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Search for "nitrile" in Full Text gives 253 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
One-step synthesis of imidazoles from Asmic (anisylsulfanylmethyl isocyanide)
- Louis G. Mueller,
- Allen Chao,
- Embarek AlWedi and
- Fraser F. Fleming
Beilstein J. Org. Chem. 2021, 17, 1499–1502, doi:10.3762/bjoc.17.106
- Substituted imidazoles are readily prepared by condensing the versatile isocyanide Asmic, anisylsulfanylmethylisocyanide, with nitrogenous π-electrophiles. Deprotonating Asmic with lithium hexamethyldisilazide effectively generates a potent nucleophile that efficiently intercepts nitrile and imine
- to imidazoles [11][12], the condensation of metalated isocyanides with nitrogenous π-electrophiles is distinguished by excellent efficiency and modularity. Deprotonating an isocyanide 1 affords an isocyanide-stabilized anion 2 whose condensation with an imidate or nitrile generates a transient imine
- fewer steps on at least 20 g scale [18], applicable for the synthesis of several heterocycles [19][20], and able to generate imidazoles from a broad array of nitrile and imidate electrophiles. Results and Discussion Exploratory deprotonation of Asmic (5) with BuLi followed by addition of butyronitrile
Graphical Abstract
Figure 1: Representative imidazole-containing pharmaceuticals.
Scheme 1: Asmic-condensation approach to imidazoles.
Scheme 2: Asmic condensation with methyl N-phenylformimidate.
Scheme 3: Anisylsulfanylimidazole reduction to monosubstituted imidazoles.
Heterogeneous photocatalytic cyanomethylarylation of alkenes with acetonitrile: synthesis of diverse nitrogenous heterocyclic compounds
- Guanglong Pan,
- Qian Yang,
- Wentao Wang,
- Yurong Tang and
- Yunfei Cai
Beilstein J. Org. Chem. 2021, 17, 1171–1180, doi:10.3762/bjoc.17.89
- loss of photocatalytic activity when applied in the cyanomethylarylation of N-arylallylamine 1a with acetonitrile. We also utilized this strategy to test n-butyl nitrile under the standard conditions. As shown in Scheme 6a, the corresponding oxindole 11 was obtained in 45% yield. The synthetic utility
Graphical Abstract
Scheme 1: CN-K-Catalyzed cyanomethylarylation of alkenes to access diverse heterocyclic compounds.
Scheme 2: CN-K-catalyzed cyanomethylarylation of N-arylallylamines for the synthesis of indolines. Reaction c...
Scheme 3: CN-K-catalyzed cyanomethylarylation of N-benzoylallylamines for the synthesis of isoquinolinones. R...
Scheme 4: CN-K-catalyzed cyanomethylarylation of N-aryl acrylamides for the synthesis of oxindoles. Reaction ...
Scheme 5: CN-K-catalyzed cyanomethylarylation of N-benzoyl acrylamides for the synthesis of isoquinolinedione...
Figure 1: Evaluation of catalyst recycling. Reaction conditions: 1a (0.1 mmol, 1 equiv), 2d (0.2 mmol, 2 equi...
Scheme 6: Further survey of reaction scope and derivatization studies of 8a.
Scheme 7: Experiments for the mechanistic study.
Scheme 8: Plausible mechanism of the CN-K-catalyzed cyanomethylarylation of alkenes.
Synthetic accesses to biguanide compounds
- Oleksandr Grytsai,
- Cyril Ronco and
- Rachid Benhida
Beilstein J. Org. Chem. 2021, 17, 1001–1040, doi:10.3762/bjoc.17.82
- nucleophilic amines, which led to undesired side reactions on the terminal amine of the cyanoguanidine. This issue was partly solved by using TMSCl to activate the nitrile function of the cyanoguanidine, along with shortening the reaction times to 10 min. Recently, this approach was used under classical
- Štrukil et al. who reported the addition of aniline hydrochloride to N1-cyano-N2,N3-diisopropylguanidine in water at 125 °C within 30 min [48]. In this case, the desired N1,N4,N5-trisubstituted product was obtained in gratifying 89% yield (Scheme 17B). The activation of the nitrile group of
- functions and products formed. Addition of amines to dicyanamide (pathway b) The second main route to synthesize biguanides relies on the use of sodium dicyanamide by double addition of amines on the two nitrile groups. The first synthesis following this pathway was described by Rose et al. in 1956 for the
Graphical Abstract
Figure 1: Tautomeric forms of biguanide.
Figure 2: Illustrations of neutral, monoprotonated, and diprotonated structures biguanide.
Figure 3: The main approaches for the synthesis of biguanides. The core structure is obtained via the additio...
Scheme 1: The three main preparations of biguanides from cyanoguanidine.
Scheme 2: Synthesis of butylbiguanide using CuCl2 [16].
Scheme 3: Synthesis of biguanides by the direct fusion of cyanoguanidine and amine hydrochlorides [17,18].
Scheme 4: Synthesis of ethylbiguanide and phenylbiguanide as reported by Smolka and Friedreich [14].
Scheme 5: Synthesis of arylbiguanides through the reaction of cyanoguanidine with anilines in water [19].
Scheme 6: Synthesis of aryl- and alkylbiguanides by adaptations of Cohn’s procedure [20,21].
Scheme 7: Microwave-assisted synthesis of N1-aryl and -dialkylbiguanides [22,23].
Scheme 8: Synthesis of aryl- and alkylbiguanides by trimethylsilyl activation [24,26].
Scheme 9: Synthesis of phenformin analogs by TMSOTf activation [27].
Scheme 10: Synthesis of N1-(1,2,4-triazolyl)biguanides [28].
Scheme 11: Synthesis of 2-guanidinobenzazoles by addition of ortho-substituted anilines to cyanoguanidine [30,32] and...
Scheme 12: Synthesis of 2,4-diaminoquinazolines by the addition of 2-cyanoaniline to cyanoguanidine and from 3...
Scheme 13: Reactions of anthranilic acid and 2-mercaptobenzoic acid with cyanoguanidine [24,36,37].
Scheme 14: Synthesis of disubstituted biguanides with Cu(II) salts [38].
Scheme 15: Synthesis of an N1,N2,N5-trisubstituted biguanide by fusion of an amine hydrochloride and 2-cyano-1...
Scheme 16: Synthesis of N1,N5-disubstituted biguanides by the addition of anilines to cyanoguanidine derivativ...
Scheme 17: Microwave-assisted additions of piperazine and aniline hydrochloride to substituted cyanoguanidines ...
Scheme 18: Synthesis of N1,N5-alkyl-substituted biguanides by TMSOTf activation [27].
Scheme 19: Additions of oxoamines hydrochlorides to dimethylcyanoguanidine [49].
Scheme 20: Unexpected cyclization of pyridylcyanoguanidines under acidic conditions [50].
Scheme 21: Example of industrial synthesis of chlorhexidine [51].
Scheme 22: Synthesis of symmetrical N1,N5-diarylbiguanides from sodium dicyanamide [52,53].
Scheme 23: Synthesis of symmetrical N1,N5-dialkylbiguanides from sodium dicyanamide [54-56].
Scheme 24: Stepwise synthesis of unsymmetrical N1,N5-trisubstituted biguanides from sodium dicyanamide [57].
Scheme 25: Examples for the synthesis of unsymmetrical biguanides [58].
Scheme 26: Examples for the synthesis of an 1,3-diaminobenzoquinazoline derivative by the SEAr cyclization of ...
Scheme 27: Major isomers formed by the SEAr cyclization of symmetric biguanides derived from 2- and 3-aminophe...
Scheme 28: Lewis acid-catalyzed synthesis of 8H-pyrrolo[3,2-g]quinazoline-2,4-diamine [63].
Scheme 29: Synthesis of [1,2,4]oxadiazoles by the addition of hydroxylamine to dicyanamide [49,64].
Scheme 30: Principle of “bisamidine transfer” and analogy between the reactions with N-amidinopyrazole and N-a...
Scheme 31: Representative syntheses of N-amidino-amidinopyrazole hydrochloride [68,69].
Scheme 32: First examples of biguanide syntheses using N-amidino-amidinopyrazole [66].
Scheme 33: Example of “biguanidylation” of a hydrazide substrate [70].
Scheme 34: Example for the synthesis of biguanides using S-methylguanylisothiouronium iodide as “bisamidine tr...
Scheme 35: Synthesis of N-substituted N1-cyano-S-methylisothiourea precursors.
Scheme 36: Addition routes on N1-cyano-S-methylisothioureas.
Scheme 37: Synthesis of an hydroxybiguanidine from N1-cyano-S-methylisothiourea [77].
Scheme 38: Synthesis of an N1,N2,N3,N4,N5-pentaarylbiguanide from the corresponding triarylguanidine and carbo...
Scheme 39: Reactions of N,N,N’,N’-tetramethylguanidine (TMG) with carbodiimides to synthesize hexasubstituted ...
Scheme 40: Microwave-assisted addition of N,N,N’,N’-tetramethylguanidine to carbodiimides [80].
Scheme 41: Synthesis of N1-aryl heptasubstituted biguanides via a one-pot biguanide formation–copper-catalyzed ...
Scheme 42: Formation of 1,2-dihydro-1,3,5-triazine derivatives by the reaction of guanidine with excess carbod...
Scheme 43: Plausible mechanism for the spontaneous cyclization of triguanides [82].
Scheme 44: a) Formation of mono- and disubstituted (iso)melamine derivatives by the reaction of biguanides and...
Scheme 45: Reactions of 2-aminopyrimidine with carbodiimides to synthesize 2-guanidinopyrimidines as “biguanid...
Scheme 46: Non-catalyzed alternatives for the addition of 2-aminopyrimidine derivatives to carbodiimides. A) h...
Scheme 47: Addition of guanidinomagnesium halides to substituted cyanamides [90].
Scheme 48: Microwave-assisted synthesis of [11C]metformin by the reaction of 11C-labelled dimethylcyanamide an...
Scheme 49: Formation of 4-amino-6-dimethylamino[1,3,5]triazin-2-ol through the reaction of Boc-guanidine and d...
Scheme 50: Formation of 1,3,5-triazine derivatives via the addition of guanidines to substituted cyanamides [92].
Scheme 51: Synthesis of biguanide by the reaction of O-alkylisourea and guanidine [93].
Scheme 52: Aromatic nucleophilic substitution of guanidine on 2-O-ethyl-1,3,5-triazine [95].
Scheme 53: Synthesis of N1,N2-disubstituted biguanides by the reaction of guanidine and thioureas in the prese...
Scheme 54: Cyclization reactions involving condensations of guanidine(-like) structures with thioureas [97,98].
Scheme 55: Condensations of guanidine-like structures with thioureas [99,100].
Scheme 56: Condensations of guanidines with S-methylisothioureas [101,102].
Scheme 57: Addition of 2-amino-1,3-diazaaromatics to S-alkylisothioureas [103,104].
Scheme 58: Addition of guanidines to 2-(methylsulfonyl)pyrimidines [105].
Scheme 59: An example of a cyclodesulfurization reaction to a fused 3,5-diamino-1,2,4-triazole [106].
Scheme 60: Ring-opening reactions of 1,3-diaryl-2,4-bis(arylimino)-1,3-diazetidines [107].
Scheme 61: Formation of 3,5-diamino-1,2,4-triazole derivatives via addition of hydrazines to 1,3-diazetidine-2...
Scheme 62: Formation of a biguanide via the addition of aniline to 1,2,4-thiadiazol-3,5-diamines, ring opening...
Figure 4: Substitution pattern of biguanides accessible by synthetic pathways a–h.
Microwave-assisted multicomponent reactions in heterocyclic chemistry and mechanistic aspects
- Shivani Gulati,
- Stephy Elza John and
- Nagula Shankaraiah
Beilstein J. Org. Chem. 2021, 17, 819–865, doi:10.3762/bjoc.17.71
- adduct B. Adduct B then undergoes in situ cyclization through an intramolecular addition of nitrogen on amide which acts as a nucleophile to the nitrile and give intermediate C. The tautomerization of the imino to an amino group and subsequent auto-oxidation followed by aromatization affords the required
Graphical Abstract
Figure 1: Marketed drugs with acridine moiety.
Scheme 1: Synthesis of 4-arylacridinediones.
Scheme 2: Proposed mechanism for acridinedione synthesis.
Scheme 3: Synthesis of tetrahydrodibenzoacridinones.
Scheme 4: Synthesis of naphthoacridines.
Scheme 5: Plausible mechanism for naphthoacridines.
Figure 2: Benzoazepines based potent molecules.
Scheme 6: Synthesis of azepinone.
Scheme 7: Proposed mechanism for azepinone formation.
Scheme 8: Synthesis of benzoazulenen-1-one derivatives.
Scheme 9: Proposed mechanism for benzoazulene-1-one synthesis.
Figure 3: Indole-containing pharmacologically active molecules.
Scheme 10: Synthesis of functionalized indoles.
Scheme 11: Plausible mechanism for the synthesis of functionalized indoles.
Scheme 12: Synthesis of spirooxindoles.
Scheme 13: Synthesis of substituted spirooxindoles.
Scheme 14: Plausible mechanism for the synthesis of substituted spirooxindoles.
Scheme 15: Synthesis of pyrrolidinyl spirooxindoles.
Scheme 16: Proposed mechanism for pyrrolidinyl spirooxindoles.
Figure 4: Pyran-containing biologically active molecules.
Scheme 17: Synthesis of functionalized benzopyrans.
Scheme 18: Plausible mechanism for synthesis of benzopyran.
Scheme 19: Synthesis of indoline-spiro-fused pyran derivatives.
Scheme 20: Proposed mechanism for indoline-spiro-fused pyran.
Scheme 21: Synthesis of substituted naphthopyrans.
Figure 5: Marketed drugs with pyrrole ring.
Scheme 22: Synthesis of tetra-substituted pyrroles.
Scheme 23: Mechanism for silica-supported PPA-SiO2-catalyzed pyrrole synthesis.
Scheme 24: Synthesis of pyrrolo[1,10]-phenanthrolines.
Scheme 25: Proposed mechanism for pyrrolo[1,10]-phenanthrolines.
Figure 6: Marketed drugs and molecules containing pyrimidine and pyrimidinones skeletons.
Scheme 26: MWA-MCR pyrimidinone synthesis.
Scheme 27: Two proposed mechanisms for pyrimidinone synthesis.
Scheme 28: MWA multicomponent synthesis of dihydropyrimidinones.
Scheme 29: Proposed mechanism for dihydropyrimidinones.
Figure 7: Biologically active fused pyrimidines.
Scheme 30: MWA- MCR for the synthesis of pyrrolo[2,3-d]pyrimidines.
Scheme 31: Proposed mechanism for pyrrolo[2,3-d]pyrimidines.
Scheme 32: Synthesis of substituted pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 33: Probable pathway for pyrrolo[2,3-d]pyrimidine-2,4-diones.
Scheme 34: Synthesis of pyridopyrimidines.
Scheme 35: Plausible mechanism for the synthesis of pyridopyrimidines.
Scheme 36: Synthesis of dihydropyridopyrimidine and dihydropyrazolopyridine.
Scheme 37: Proposed mechanism for the formation of dihydropyridopyrimidine.
Scheme 38: Synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 39: Plausible mechanism for the synthesis of thiopyrano[4,3-d]pyrimidines.
Scheme 40: Synthesis of decorated imidazopyrimidines.
Scheme 41: Proposed mechanism for imidazopyrimidine synthesis.
Figure 8: Pharmacologically active molecules containing purine bases.
Scheme 42: Synthesis of aza-adenines.
Scheme 43: Synthesis of 5-aza-7-deazapurines.
Scheme 44: Proposed mechanism for deazapurines synthesis.
Figure 9: Biologically active molecules containing pyridine moiety.
Scheme 45: Synthesis of steroidal pyridines.
Scheme 46: Proposed mechanism for steroidal pyridine.
Scheme 47: Synthesis of N-alkylated 2-pyridones.
Scheme 48: Two possible mechanisms for pyridone synthesis.
Scheme 49: Synthesis of pyridone derivatives.
Scheme 50: Postulated mechanism for synthesis of pyridone.
Figure 10: Biologically active fused pyridines.
Scheme 51: Benzimidazole-imidazo[1,2-a]pyridines synthesis.
Scheme 52: Mechanism for the synthesis of benzimidazole-imidazo[1,2-a]pyridines.
Scheme 53: Synthesis of pyrazolo[3,4-b]pyridine-5-spirocycloalkanedione derivatives.
Scheme 54: Proposed mechanism for spiro-pyridines.
Scheme 55: Functionalized macrocyclane-fused pyrazolo[3,4-b]pyridine derivatives.
Scheme 56: Mechanism postulated for macrocyclane-fused pyrazolo[3,4-b]pyridine.
Scheme 57: Generation of pyrazolo[3,4-b]pyridines.
Scheme 58: Proposed mechanism for the synthesis of pyrazolo[3,4-b]pyridines.
Scheme 59: Proposed mechanism for the synthesis of azepinoindole.
Figure 11: Pharmaceutically important molecules with quinoline moiety.
Scheme 60: Povarov-mediated quinoline synthesis.
Scheme 61: Proposed mechanism for Povarov reaction.
Scheme 62: Synthesis of pyrazoloquinoline.
Scheme 63: Plausible mechanism for pyrazoloquinoline synthesis.
Figure 12: Quinazolinones as pharmacologically significant scaffolds.
Scheme 64: Four-component reaction for dihydroquinazolinone.
Scheme 65: Proposed mechanism for dihydroquinazolinones.
Scheme 66: Synthesis purine quinazolinone and PI3K-δ inhibitor.
Scheme 67: Synthesis of fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 68: Proposed mechanism for fused benzothiazolo/benzoimidazoloquinazolinones.
Scheme 69: On-water reaction for synthesis of thiazoloquinazolinone.
Scheme 70: Proposed mechanism for the thiazoloquinazolinone synthesis.
Scheme 71: β-Cyclodextrin-mediated synthesis of indoloquinazolinediones.
Scheme 72: Proposed mechanism for synthesis of indoloquinazolinediones.
Figure 13: Triazoles-containing marketted drugs and pharmacologically active molecules.
Scheme 73: Cu(I) DAPTA-catalyzed 1,2,3-triazole formation.
Scheme 74: Mechanism for Cu(I) DAPTA-catalyzed triazole formation.
Scheme 75: Synthesis of β-hydroxy-1,2,3-triazole.
Scheme 76: Proposed mechanism for synthesis of β-hydroxy-1,2,3-triazoles.
Scheme 77: Synthesis of bis-1,2,4-triazoles.
Scheme 78: Proposed mechanism for bis-1,2,4-triazoles synthesis.
Figure 14: Thiazole containing drugs.
Scheme 79: Synthesis of a substituted thiazole ring.
Scheme 80: Synthesis of pyrazolothiazoles.
Figure 15: Chromene containing drugs.
Scheme 81: Magnetic nanocatalyst-mediated aminochromene synthesis.
Scheme 82: Proposed mechanism for the synthesis of chromenes.
Synthesis of N-perfluoroalkyl-3,4-disubstituted pyrroles by rhodium-catalyzed transannulation of N-fluoroalkyl-1,2,3-triazoles with terminal alkynes
- Olga Bakhanovich,
- Viktor Khutorianskyi,
- Vladimir Motornov and
- Petr Beier
Beilstein J. Org. Chem. 2021, 17, 504–510, doi:10.3762/bjoc.17.44
- general trend in the efficiency of the reaction or product selectivity was observed. Hex-5-ynenitrile was used in the transannulation with 1a with the aim to assess the relative propensity of nitrile and alkyne groups in the reaction. The triple bond reacted in the transannulation about two times faster
- than the nitrile group and again the 3,4-disubstituted pyrrole 4 regioisomer dominated over the 2,4-disubstitued pyrrole 4’ (Scheme 4). To demonstrate the compatibility of the formed N-perfluoroalkylpyrroles with the conditions of pyrrole derivatization by metalation in position two and reaction with
Graphical Abstract
Figure 1: Selected pyrrole-containing natural products, drugs, agrochemicals, and functional materials.
Scheme 1: Transformation of N-sulfonyl-1,2,3-triazoles to pyrroles via metal iminocarbenes.
Scheme 2: Transannulation of triazoles 2 with phenylacetylene.
Scheme 3: Transannulation of N-perfluoroalkyl-1,2,3-triazoles with aliphatic alkynes.
Scheme 4: Reaction of 1a with hex-5-ynenitrile.
Scheme 5: Metalation and carboxylation of in situ-prepared pyrrole 2a.
Scheme 6: Plausible mechanism for rhodium-catalyzed transannulation of N-perfluoroalkyl-1,2,3-triazoles with ...
Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives
- Alexander Leslie,
- Thomas S. Moody,
- Megan Smyth,
- Scott Wharry and
- Marcus Baumann
Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33
- furthermore allowed the ester/nitrile moieties to be unaffected. Indeed, it was established subsequently that alkaline hydrolysis of the ester group requires a prolonged reaction time at an elevated temperature (Scheme 6). Importantly this can be achieved selectively without a concomitant cleavage of the
Graphical Abstract
Scheme 1: The continuous flow set-up used.
Figure 1: Scope of Cbz-carbamate products obtained via flow process (*tRes = 60 min, **T = 80 °C; isolated yi...
Scheme 2: Side reaction during formation of product 3m.
Scheme 3: Flow set-up for the CALB-mediated impurity tagging approach.
Scheme 4: Strategies towards accessing β-amino acid derivatives 8.
Scheme 5: Complementary flow approaches towards the β-amino acid derivatives 8.
Scheme 6: Batch hydrolysis of the ester group in the presence of the carbamate.
Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines
- Wilfred J. M. Lewis,
- David M. Shaw and
- Jeremy Robertson
Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31
- of further C(7a)-hydroxylated bacterial pyrrolizidines and related molecules. Pyrrolizidine 14 (Scheme 1), the key intermediate in Snider’s improved route to jenamidine A and Bode’s preparation of pyrrolizixenamides A (9) and D (12), is formed by N-cyclization onto the nitrile group in cyano-β
Graphical Abstract
Figure 1: The clazamycins, and selected bacterial pyrrolizidines of the vinylogous urea type. For consistency...
Figure 2: Key species in the biosynthesis of legonmycins A (3) and B (4), and the pyrrolizixenamides A–D (9–12...
Scheme 1: Preparation of the legonmycin core.
Scheme 2: Hypothesis for the oxidative hydrolysis of diacylated pyrrolizidinone 18 (R = iBu).
Scheme 3: Preparation of C(7a)-functionalized pyrrolizinone derivatives and synthesis of legonmycins A and B.
The preparation and properties of 1,1-difluorocyclopropane derivatives
- Kymbat S. Adekenova,
- Peter B. Wyatt and
- Sergazy M. Adekenov
Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25
- nitrile 63 could be obtained by the reaction of phenylacetonitrile (61) with 1,2-dibromo-1,1-difluoroethane (62) using sodium amide as the base (Scheme 27) [69]. However, the yield of this reaction was only 10%. The gem-difluorocyclopropanes 65 were synthesized from the reaction of gem-difluoroolefins 64
- nitrile hydratase–amidase-containing biocatalytic system and showed a high chemo-, regio-, and enantioselectivity in the hydrolysis of nitriles and dinitriles. The biocatalytic transformations of nitrile 81 (Scheme 33) supplied an effective route to optically active 2,2-difluorosubstituted 3
- by the two attached fluorine atoms. The nucleophilic attack of the nitrile, followed by cyclization and aromatization could then give the pyrrole derivatives 142. Later, Xiao et al. performed another ring-opening reaction of gem-difluorocyclopropyl ketones 143, this time mediated by BX3 (X = F, Cl
Graphical Abstract
Scheme 1: Synthesis of 1,1-difluoro-2,3-dimethylcyclopropane (2).
Scheme 2: Cyclopropanation via dehydrohalogenation of chlorodifluoromethane.
Scheme 3: Difluorocyclopropanation of methylstyrene 7 using dibromodifluoromethane and zinc.
Scheme 4: Synthesis of difluorocyclopropanes from the reaction of dibromodifluoromethane and triphenylphosphi...
Scheme 5: Generation of difluorocarbene in a catalytic two-phase system and its addition to tetramethylethyle...
Scheme 6: The reaction of methylstyrene 7 with chlorodifluoromethane (11) in the presence of a tetraarylarson...
Scheme 7: Pyrolysis of sodium chlorodifluoroacetate (12) in refluxing diglyme in the presence of alkene 13.
Scheme 8: Synthesis of boron-substituted gem-difluorocyclopropanes 16.
Scheme 9: Addition of sodium bromodifluoroacetate (17) to alkenes.
Scheme 10: Addition of sodium bromodifluoroacetate (17) to silyloxy-substituted cyclopropanes 20.
Scheme 11: Synthesis of difluorinated nucleosides.
Scheme 12: Addition of butyl acrylate (26) to difluorocarbene generated from TFDA (25).
Scheme 13: Addition of difluorocarbene to propargyl esters 27 and conversion of the difluorocyclopropenes 28 t...
Scheme 14: The generation of difluorocyclopropanes using MDFA 30.
Scheme 15: gem-Difluorocyclopropanation of styrene (32) using difluorocarbene generated from TMSCF3 (31) under...
Scheme 16: Synthesis of a gem-difluorocyclopropane derivative using HFPO (41) as a source of difluorocarbene.
Scheme 17: Cyclopropanation of (Z)-2-butene in the presence of difluorodiazirine (44).
Scheme 18: The cyclopropanation of 1-octene (46) using Seyferth's reagent (45) as a source of difluorocarbene.
Scheme 19: Alternative approaches for the difluorocarbene synthesis from trimethyl(trifluoromethyl)tin (48).
Scheme 20: Difluorocyclopropanation of cyclohexene (49).
Scheme 21: Synthesis of difluorocyclopropane derivative 53 using bis(trifluoromethyl)cadmium (51) as the diflu...
Scheme 22: Addition of difluorocarbene generated from tris(trifluoromethyl)bismuth (54).
Scheme 23: Addition of a stable (trifluoromethyl)zinc reagent to styrenes.
Scheme 24: The preparation of 2,2-difluorocyclopropanecarboxylic acids of type 58.
Scheme 25: Difluorocyclopropanation via Michael cyclization.
Scheme 26: Difluorocyclopropanation using N-acylimidazolidinone 60.
Scheme 27: Difluorocyclopropanation through the cyclization of phenylacetonitrile (61) and 1,2-dibromo-1,1-dif...
Scheme 28: gem-Difluoroolefins 64 for the synthesis of functionalized cyclopropanes 65.
Scheme 29: Preparation of aminocyclopropanes 70.
Scheme 30: Synthesis of fluorinated methylenecyclopropane 74 via selenoxide elimination.
Scheme 31: Reductive dehalogenation of (1R,3R)-75.
Scheme 32: Synthesis of chiral monoacetates by lipase catalysis.
Scheme 33: Transformation of (±)-trans-81 using Rhodococcus sp. AJ270.
Scheme 34: Transformation of (±)-trans-83 using Rhodococcus sp. AJ270.
Scheme 35: Hydrogenation of difluorocyclopropenes through enantioselective hydrocupration.
Scheme 36: Enantioselective transfer hydrogenation of difluorocyclopropenes with a Ru-based catalyst.
Scheme 37: The thermal transformation of trans-1,2-dichloro-3,3-difluorocyclopropane (84).
Scheme 38: cis–trans-Epimerization of 1,1-difluoro-2,3-dimethylcyclopropane.
Scheme 39: 2,2-Difluorotrimethylene diradical intermediate.
Scheme 40: Ring opening of stereoisomers 88 and 89.
Scheme 41: [1,3]-Rearrangement of alkenylcyclopropanes 90–92.
Scheme 42: Thermolytic rearrangement of 2,2-difluoro-1-vinylcyclopropane (90).
Scheme 43: Thermal rearrangement for ethyl 3-(2,2-difluoro)-3-phenylcyclopropyl)acrylates 93 and 95.
Scheme 44: Possible pathways of the ring opening of 1,1-difluoro-2-vinylcyclopropane.
Scheme 45: Equilibrium between 1,1-difluoro-2-methylenecyclopropane (96) and (difluoromethylene)cyclopropane 97...
Scheme 46: Ring opening of substituted 1,1-difluoro-2,2-dimethyl-3-methylenecyclopropane 98.
Scheme 47: 1,1-Difluorospiropentane rearrangement.
Scheme 48: Acetolysis of (2,2-difluorocyclopropyl)methyl tosylate (104) and (1,1-difluoro-2-methylcyclopropyl)...
Scheme 49: Ring opening of gem-difluorocyclopropyl ketones 106 and 108 by thiolate nucleophiles.
Scheme 50: Hydrolysis of gem-difluorocyclopropyl acetals 110.
Scheme 51: Ring-opening reaction of 2,2-difluorocyclopropyl ketones 113 in the presence of ionic liquid as a s...
Scheme 52: Ring opening of gem-difluorocyclopropyl ketones 113a by MgI2-initiated reaction with diarylimines 1...
Scheme 53: Ring-opening reaction of gem-difluorocyclopropylstannanes 117.
Scheme 54: Preparation of 1-fluorovinyl vinyl ketone 123 and the synthesis of 2-fluorocyclopentenone 124. TBAT...
Scheme 55: Iodine atom-transfer ring opening of 1,1-difluoro-2-(1-iodoalkyl)cyclopropanes 125a–c.
Scheme 56: Ring opening of bromomethyl gem-difluorocyclopropanes 130 and formation of gem-difluoromethylene-co...
Scheme 57: Ring-opening aerobic oxidation reaction of gem-difluorocyclopropanes 132.
Scheme 58: Dibrominative ring-opening functionalization of gem-difluorocyclopropanes 134.
Scheme 59: The selective formation of (E,E)- and (E,Z)-fluorodienals 136 and 137 from difluorocyclopropyl acet...
Scheme 60: Proposed mechanism for the reaction of difluoro(methylene)cyclopropane 139 with Br2.
Scheme 61: Thermal rearrangement of F2MCP 139 and iodine by CuI catalysis.
Scheme 62: Synthesis of 2-fluoropyrroles 142.
Scheme 63: Ring opening of gem-difluorocyclopropyl ketones 143 mediated by BX3.
Scheme 64: Lewis acid-promoted ring-opening reaction of 2,2-difluorocyclopropanecarbonyl chloride (148).
Scheme 65: Ring-opening reaction of the gem-difluorocyclopropyl ketone 106 by methanolic KOH.
Scheme 66: Hydrogenolysis of 1,1-difluoro-3-methyl-2-phenylcyclopropane (151).
Scheme 67: Synthesis of monofluoroalkenes 157.
Scheme 68: The stereoselective Ag-catalyzed defluorinative ring-opening diarylation of 1-trimethylsiloxy-2,2-d...
Scheme 69: Synthesis of 2-fluorinated allylic compounds 162.
Scheme 70: Pd-catalyzed cross-coupling reactions of gem-difluorinated cyclopropanes 161.
Scheme 71: The (Z)-selective Pd-catalyzed ring-opening sulfonylation of 2-(2,2-difluorocyclopropyl)naphthalene...
Figure 1: Structures of zosuquidar hydrochloride and PF-06700841.
Scheme 72: Synthesis of methylene-gem-difluorocyclopropane analogs of nucleosides.
Figure 2: Anthracene-difluorocyclopropane hybrid derivatives.
Figure 3: Further examples of difluorcyclopropanes in modern drug discovery.
All-carbon [3 + 2] cycloaddition in natural product synthesis
- Zhuo Wang and
- Junyang Liu
Beilstein J. Org. Chem. 2020, 16, 3015–3031, doi:10.3762/bjoc.16.251
- underwent successive intramolecular Michael addition and hydrolytic nitrile reduction to give 79 in 46% yield in two steps. Extensive studies of the nitrile reduction eventually identified that Et3Al and DIBAL-H could effectively reduce the nitrile group to the corresponding aldehyde and treatment with
Graphical Abstract
Figure 1: Highly-substituted five-membered carbocycle in biologically significant natural products.
Figure 2: Natural product synthesis featuring the all-carbon [3 + 2] cycloaddition. (Quaternary carbon center...
Scheme 1: Representative natural product syntheses that feature the all-carbon [3 + 2] cyclization as the key...
Scheme 2: (A) An intramolecular trimethylenemethane diyl [3 + 2] cycloaddition with allenyl diazo compound 38...
Scheme 3: (A) Palladium-catalyzed intermolecular carboxylative TMM cycloaddition [36]. (B) The proposed mechanism....
Scheme 4: Natural product syntheses that make use of palladium-catalyzed intermolecular [3 + 2] cycloaddition...
Scheme 5: (A) Phosphine-catalyzed [3 + 2] cycloaddition [17]. (B) The proposed mechanism.
Scheme 6: Lu’s [3 + 2] cycloaddition in natural product synthesis. (A) Synthesis of longeracinphyllin A (10) [41]...
Scheme 7: (A) Phosphine-catalyzed [3 + 2] annulation of unsymmetric isoindigo 100 with allene in the preparat...
Scheme 8: (A) Rhodium-catalyzed intracmolecular [3 + 2] cycloaddition [49]. (B) The proposed catalytic cycle of t...
Scheme 9: Total synthesis of natural products reported by Yang and co-workers applying rhodium-catalyzed intr...
Scheme 10: (A) Platinum(II)-catalyzed intermolecular [3 + 2] cycloaddition of propargyl ether 139 and n-butyl ...
Scheme 11: (A) Platinum-catalyzed intramolecular [3 + 2] cycloaddition of propargylic ketal derivative 142 to ...
Scheme 12: (A) Synthesis of phyllocladanol (21) features a Lewis acid-catalyzed formal intramolecular [3 + 2] ...
Scheme 13: The recent advances of [3 + 2] annulation in natural product synthesis. (A) The preparation of melo...
Naphthalonitriles featuring efficient emission in solution and in the solid state
- Sidharth Thulaseedharan Nair Sailaja,
- Iván Maisuls,
- Jutta Kösters,
- Alexander Hepp,
- Andreas Faust,
- Jens Voskuhl and
- Cristian A. Strassert
Beilstein J. Org. Chem. 2020, 16, 2960–2970, doi:10.3762/bjoc.16.246
- considerations: (1) the p-phenyl substituents act as electron-donor units and as AIE activators; (2) the nitrile groups provide a significant π-acceptor strength, and also promote hydrogen bonding in the aggregates [39][40][41][42]. By varying the substituents at the phenyl groups ranging from mild π-donors
- some intermolecular CH…π interactions between the C–H units of the residual tolyl group and the central ring of the naphthalonitrile bearing two nitrile groups with a CH/π-ring distance of 2.780 Å (Figure 2A). Even though the naphthalonitrile planes of two adjacent head-to-tail-arranged molecules are
- together by C–H…N intermolecular hydrogen bonds with distances of 3.006 Å for C–H(2e)/N(6) and 3.083 Å for C–H(2d)/N(6) while involving hydrogen atoms of the tolyl moieties and the nitrogen atoms of nitrile groups. Then, these dimeric substructures are linked by C–H…N intermolecular interactions to
Graphical Abstract
Scheme 1: A) Structures of the six investigated 2,3-disubstituted-6,7-diphenylnaphthalene derivatives with va...
Scheme 2: Synthesis of p-phenyl-6,7-disubstituted naphthalene-2,3-dicarbonitrile.
Figure 1: Molecular structure in the crystal of Me as obtained by X-ray diffractometric analysis. Thermal dis...
Figure 2: A) Intermolecular CH…π interactions for compound Me. B) Weak intermolecular π–π stacking interactio...
Figure 3: Normalized absorption spectra of the evaluated compounds in fluid THF at rt. All solutions were opt...
Figure 4: Normalized emission spectra of the evaluated compounds in fluid THF at rt (left) and in a frozen gl...
Figure 5: A) Photographs of H at different THF/H2O ratios under UV excitation (λ = 365 nm). B) Photoluminesce...
Ultrasound-assisted Strecker synthesis of novel 2-(hetero)aryl-2-(arylamino)acetonitrile derivatives
- Emese Gal,
- Luiza Gaina,
- Hermina Petkes,
- Alexandra Pop,
- Castelia Cristea,
- Gabriel Barta,
- Dan Cristian Vodnar and
- Luminiţa Silaghi-Dumitrescu
Beilstein J. Org. Chem. 2020, 16, 2929–2936, doi:10.3762/bjoc.16.242
- -nitrile pharmacophoric units. In this work we report the experimental procedure for the ultrasound-assisted addition of the TMSCN nucleophile to heterocyclic aldimines. The substrates tested were mostly represented by a series of phenothiazinyl aldimines, but the scope of the new synthetic procedure was
Graphical Abstract
Scheme 1: Synthesis of α-amino-acetonitrile derivatives. Reaction conditions: Aldimine (1 equiv), TMSCN (1 eq...
Figure 1: Crystal structure of 2-phenothiazinyl-2-(p-tolylamino)acetonitrile 2a. a) ORTEP plot and b) crystal...
Figure 2: SEM images recorded at 200× for the raw reaction product 2b obtained through a) ultrasound-assisted...
Figure 3: SEM image recorded at 200× for the raw reaction product 2c obtained through a) ultrasound-assisted ...
Synthesis of 4-substituted azopyridine-functionalized Ni(II)-porphyrins as molecular spin switches
- Jannis Ludwig,
- Tobias Moje,
- Fynn Röhricht and
- Rainer Herges
Beilstein J. Org. Chem. 2020, 16, 2589–2597, doi:10.3762/bjoc.16.210
- shown that the spin switching efficiency is strongly dependent on the solvent and on the substituent at the 4-position of the pyridine unit. We now introduced thiol, disulfide, thioethers, nitrile and carboxylic acid groups and investigated their spin switching efficiency. Keywords: azopyridines; Ni(II
Graphical Abstract
Figure 1: “Record player” approach for molecular spin switching. a) General principle b) Variation of the sub...
Scheme 1: Synthesis of the nitroso compounds 3 and 6 using the two different methods described by Wegner et a...
Scheme 2: Synthesis of azopyridines 11, 14, 16 and 18 by nucleophilic aromatic substitution.
Scheme 3: Synthesis of 3-(3-bromophenylazo)-4-cyanopyridine (20), which was hydrolyzed to yield 3-(3-bromophe...
Scheme 4: Modular approach for the C–C connection of the Ni(II)-porphyrin 22 and the different 4-substituted ...
Scheme 5: Cleavage of 1f to yield disulfide 1g [34].
Figure 2: Hammett plot of the investigated pyridine substituents [36].
Figure 3: UV–vis spectra of 1e (top), 1h (left) and 1j (right) in acetone water (1:9) (solid line) and after ...
Thermodynamic and electrochemical study of tailor-made crown ethers for redox-switchable (pseudo)rotaxanes
- Henrik Hupatz,
- Marius Gaedke,
- Hendrik V. Schröder,
- Julia Beerhues,
- Arto Valkonen,
- Fabian Klautzsch,
- Sebastian Müller,
- Felix Witte,
- Kari Rissanen,
- Biprajit Sarkar and
- Christoph A. Schalley
Beilstein J. Org. Chem. 2020, 16, 2576–2588, doi:10.3762/bjoc.16.209
- the optoelectronic properties of the NDI unit. The binding properties suggest that the combination of the A1·BArF24 axle and NDIC8 is optimal for the synthesis of an NDI-containing [2]rotaxane. We applied Takata’s catalyst-free stoppering approach [58] using the nitrile oxide St for the preparation of
Graphical Abstract
Figure 1: Structures of the compounds used in this study: a) crown-8 analogs; b) crown-7 analogs; c) secondar...
Scheme 1: Schematic representation of synthetic routes towards TTFC7, exTTFC7, NDIC7, and NDIC8.
Figure 2: Solid-state structures of a) exTTFC7 (CH3CN molecule omitted for clarity), b) NDIC7 (CH3CN molecule...
Figure 3: a) Synthesis of the [2]rotaxane NDIRot. b) Stacked 1H NMR spectra (700 MHz, CDCl3, 298 K) of NDIC8 ...
Figure 4: UV–vis–NIR spectra obtained by spectroelectrochemical measurements (0.1 M n-Bu4PF6, CH2Cl2/CH3CN 1:...
Recent developments in enantioselective photocatalysis
- Callum Prentice,
- James Morrisson,
- Andrew D. Smith and
- Eli Zysman-Colman
Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197
- enolisable ketone 293 is used, enolate complex 294 can be formed in the presence of base (Scheme 49a) [116]. The complex in this example is then proposed to proceed via an oxidative quenching cycle with bromo nitrile 295 to form α-cyano radicals 295• that then add to another molecule of 294
Graphical Abstract
Scheme 1: Amine/photoredox-catalysed α-alkylation of aldehydes with alkyl bromides bearing electron-withdrawi...
Scheme 2: Amine/HAT/photoredox-catalysed α-functionalisation of aldehydes using alkenes.
Scheme 3: Amine/cobalt/photoredox-catalysed α-functionalisation of ketones and THIQs.
Scheme 4: Amine/photoredox-catalysed α-functionalisation of aldehydes or ketones with imines. (a) Using keton...
Scheme 5: Bifunctional amine/photoredox-catalysed enantioselective α-functionalisation of aldehydes.
Scheme 6: Bifunctional amine/photoredox-catalysed α-functionalisation of aldehydes using amine catalysts via ...
Scheme 7: Amine/photoredox-catalysed RCA of iminium ion intermediates. (a) Synthesis of quaternary stereocent...
Scheme 8: Bifunctional amine/photoredox-catalysed RCA of enones in a radical chain reaction initiated by an i...
Scheme 9: Bifunctional amine/photoredox-catalysed RCA reactions of iminium ions with different radical precur...
Scheme 10: Bifunctional amine/photoredox-catalysed radical cascade reactions between enones and alkenes with a...
Scheme 11: Amine/photocatalysed photocycloadditions of iminium ion intermediates. (a) External photocatalyst u...
Scheme 12: Amine/photoredox-catalysed addition of acrolein (94) to iminium ions.
Scheme 13: Dual NHC/photoredox-catalysed acylation of THIQs.
Scheme 14: NHC/photocatalysed spirocyclisation via photoisomerisation of an extended Breslow intermediate.
Scheme 15: CPA/photoredox-catalysed aza-pinacol cyclisation.
Scheme 16: CPA/photoredox-catalysed Minisci-type reaction between azaarenes and α-amino radicals.
Scheme 17: CPA/photoredox-catalysed radical additions to azaarenes. (a) α-Amino radical or ketyl radical addit...
Scheme 18: CPA/photoredox-catalysed reduction of azaarene-derived substrates. (a) Reduction of ketones. (b) Ex...
Scheme 19: CPA/photoredox-catalysed radical coupling reactions of α-amino radicals with α-carbonyl radicals. (...
Scheme 20: CPA/photoredox-catalysed Povarov reaction.
Scheme 21: CPA/photoredox-catalysed reactions with imines. (a) Decarboxylative imine generation followed by Po...
Scheme 22: Bifunctional CPA/photocatalysed [2 + 2] photocycloadditions.
Scheme 23: PTC/photocatalysed oxygenation of 1-indanone-derived β-keto esters.
Scheme 24: PTC/photoredox-catalysed perfluoroalkylation of 1-indanone-derived β-keto esters via a radical chai...
Scheme 25: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 26: Bifunctional hydrogen bonding/photocatalysed intramolecular RCA cyclisation of a quinolone.
Scheme 27: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloadditions of quinolon...
Scheme 28: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloaddition reactions. (a) First use of...
Scheme 29: Bifunctional hydrogen bonding/photocatalysed deracemisation of allenes.
Scheme 30: Bifunctional hydrogen bonding/photocatalysed deracemisation reactions. (a) Deracemisation of sulfox...
Scheme 31: Bifunctional hydrogen bonding/photocatalysed intramolecular [2 + 2] photocycloaddition of coumarins....
Scheme 32: Bifunctional hydrogen bonding/photocatalysed [2 + 2] photocycloadditions of quinolones. (a) Intramo...
Scheme 33: Hydrogen bonding/photocatalysed formal arylation of benzofuranones.
Scheme 34: Hydrogen bonding/photoredox-catalysed dehalogenative protonation of α,α-chlorofluoro ketones.
Scheme 35: Hydrogen bonding/photoredox-catalysed reductions. (a) Reduction of 1,2-diketones. (b) Reduction of ...
Scheme 36: Hydrogen bonding/HAT/photocatalysed deracemisation of cyclic ureas.
Scheme 37: Hydrogen bonding/HAT/photoredox-catalysed synthesis of cyclic sulfonamides.
Scheme 38: Hydrogen bonding/photoredox-catalysed reaction between imines and indoles.
Scheme 39: Chiral cation/photoredox-catalysed radical coupling of two α-amino radicals.
Scheme 40: Chiral phosphate/photoredox-catalysed hydroetherfication of alkenols.
Scheme 41: Chiral phosphate/photoredox-catalysed synthesis of pyrroloindolines.
Scheme 42: Chiral anion/photoredox-catalysed radical cation Diels–Alder reaction.
Scheme 43: Lewis acid/photoredox-catalysed cycloadditions of carbonyls. (a) Formal [2 + 2] cycloaddition of en...
Scheme 44: Lewis acid/photoredox-catalysed RCA reaction using a scandium Lewis acid between α-amino radicals a...
Scheme 45: Lewis acid/photoredox-catalysed RCA reaction using a copper Lewis acid between α-amino radicals and...
Scheme 46: Lewis acid/photoredox-catalysed synthesis of 1,2-amino alcohols from aldehydes and nitrones using a...
Scheme 47: Lewis acid/photocatalysed [2 + 2] photocycloadditions of enones and alkenes.
Scheme 48: Meggers’s chiral-at-metal catalysts.
Scheme 49: Lewis acid/photoredox-catalysed α-functionalisation of ketones with alkyl bromides bearing electron...
Scheme 50: Bifunctional Lewis acid/photoredox-catalysed radical coupling reaction using α-chloroketones and α-...
Scheme 51: Lewis acid/photocatalysed RCA of enones. (a) Using aldehydes as acyl radical precursors. (b) Other ...
Scheme 52: Bifunctional Lewis acid/photocatalysis for a photocycloaddition of enones.
Scheme 53: Lewis acid/photoredox-catalysed RCA reactions of enones using DHPs as radical precursors.
Scheme 54: Lewis acid/photoredox-catalysed functionalisation of β-ketoesters. (a) Hydroxylation reaction catal...
Scheme 55: Bifunctional copper-photocatalysed alkylation of imines.
Scheme 56: Copper/photocatalysed alkylation of imines. (a) Bifunctional copper catalysis using α-silyl amines....
Scheme 57: Bifunctional Lewis acid/photocatalysed intramolecular [2 + 2] photocycloaddition.
Scheme 58: Bifunctional Lewis acid/photocatalysed [2 + 2] photocycloadditions (a) Intramolecular cycloaddition...
Scheme 59: Bifunctional Lewis acid/photocatalysed rearrangement of 2,4-dieneones.
Scheme 60: Lewis acid/photocatalysed [2 + 2] cycloadditions of cinnamate esters and styrenes.
Scheme 61: Nickel/photoredox-catalysed arylation of α-amino acids using aryl bromides.
Scheme 62: Nickel/photoredox catalysis. (a) Desymmetrisation of cyclic meso-anhydrides using benzyl trifluorob...
Scheme 63: Nickel/photoredox catalysis for the acyl-carbamoylation of alkenes with aldehydes using TBADT as a ...
Scheme 64: Bifunctional copper/photoredox-catalysed C–N coupling between α-chloro amides and carbazoles or ind...
Scheme 65: Bifunctional copper/photoredox-catalysed difunctionalisation of alkenes with alkynes and alkyl or a...
Scheme 66: Copper/photoredox-catalysed decarboxylative cyanation of benzyl phthalimide esters.
Scheme 67: Copper/photoredox-catalysed cyanation reactions using TMSCN. (a) Propargylic cyanation (b) Ring ope...
Scheme 68: Palladium/photoredox-catalysed allylic alkylation reactions. (a) Using alkyl DHPs as radical precur...
Scheme 69: Manganese/photoredox-catalysed epoxidation of terminal alkenes.
Scheme 70: Chromium/photoredox-catalysed allylation of aldehydes.
Scheme 71: Enzyme/photoredox-catalysed dehalogenation of halolactones.
Scheme 72: Enzyme/photoredox-catalysed dehalogenative cyclisation.
Scheme 73: Enzyme/photoredox-catalysed reduction of cyclic imines.
Scheme 74: Enzyme/photocatalysed enantioselective reduction of electron-deficient alkenes as mixtures of (E)/(Z...
Scheme 75: Enzyme/photoredox catalysis. (a) Deacetoxylation of cyclic ketones. (b) Reduction of heteroaromatic...
Scheme 76: Enzyme/photoredox-catalysed synthesis of indole-3-ones from 2-arylindoles.
Scheme 77: Enzyme/HAT/photoredox catalysis for the DKR of primary amines.
Scheme 78: Bifunctional enzyme/photoredox-catalysed benzylic C–H hydroxylation of trifluoromethylated arenes.
Recent synthesis of thietanes
- Jiaxi Xu
Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116
Graphical Abstract
Figure 1: Examples of biologically active thietane-containing molecules.
Figure 2: The diverse methods for the synthesis of thietanes.
Scheme 1: Synthesis of 1-(thietan-2-yl)ethan-1-ol (10) from 3,5-dichloropentan-2-ol (9).
Scheme 2: Synthesis of thietanose nucleosides 2,14 from 2,2-bis(bromomethyl)propane-1,3-diol (11).
Scheme 3: Synthesis of methyl 3-vinylthietane-3-carboxylate (19).
Scheme 4: Synthesis of 1,6-thiazaspiro[3.3]heptane (24).
Scheme 5: Synthesis of 6-amino-2-thiaspiro[3.3]heptane hydrochloride (28).
Scheme 6: Synthesis of optically active thietane 31 from vitamin C.
Scheme 7: Synthesis of an optically active thietane nucleoside from diethyl L-tartrate (32).
Scheme 8: Synthesis of thietane-containing spironucleoside 40 from 5-aldo-3-O-benzyl-1,2-O-isopropylidene-α-D...
Scheme 9: Synthesis of optically active 2-methylthietane-containing spironucleoside 43.
Scheme 10: Synthesis of a double-linked thietane-containing spironucleoside 48.
Scheme 11: Synthesis of two diastereomeric thietanose nucleosides via 2,4-di(benzyloxymethyl)thietane (49).
Scheme 12: Synthesis of the thietane-containing PI3k inhibitor candidate 54.
Scheme 13: Synthesis of the spirothietane 57 as the key intermediate to Nuphar sesquiterpene thioalkaloids.
Scheme 14: Synthesis of spirothietane 61 through a direct cyclic thioetherification of 3-mercaptopropan-1-ol.
Scheme 15: Synthesis of thietanes 66 from 1,3-diols 62.
Scheme 16: Synthesis of thietanylbenzimidazolone 75 from (iodomethyl)thiazolobenzimidazole 70.
Scheme 17: Synthesis of 2-oxa-6-thiaspiro[3.3]heptane (80) from bis(chloromethyl)oxetane 76 and thiourea.
Scheme 18: Synthesis of the thietane-containing glycoside, 2-O-p-toluenesulfonyl-4,6-thioanhydro-α-D-gulopyran...
Scheme 19: Synthesis of methyl 4,6-thioanhydro-α-D-glucopyranoside (89).
Scheme 20: Synthesis of thietane-fused α-D-galactopyranoside 93.
Scheme 21: Synthesis of thietane-fused α-D-gulopyranoside 100.
Scheme 22: Synthesis of 3,5-anhydro-3-thiopentofuranosides 104.
Scheme 23: Synthesis of anhydro-thiohexofuranosides 110, 112 and 113 from from 1,2:4,5-di-O-isopropylidene D-f...
Scheme 24: Synthesis of optically active thietanose nucleosides from D- and L-xyloses.
Scheme 25: Synthesis of thietane-fused nucleosides.
Scheme 26: Synthesis of 3,5-anhydro-3-thiopentofuranosides.
Scheme 27: Synthesis of 2-amino-3,5-anhydro-3-thiofuranoside 141.
Scheme 28: Synthesis of thietane-3-ols 145 from (1-chloromethyl)oxiranes 142 and hydrogen sulfide.
Scheme 29: Synthesis of thietane-3-ol 145a from chloromethyloxirane (142a).
Scheme 30: Synthesis of thietane-3-ols 145 from 2-(1-haloalkyl)oxiranes 142 and 147 with ammonium monothiocarb...
Scheme 31: Synthesis of 7-deoxy-5(20)thiapaclitaxel 154a, a thietane derivative of taxoids.
Scheme 32: Synthesis of 5(20)-thiadocetaxel 158 from 10-deacetylbaccatin III (155).
Scheme 33: Synthesis of thietane derivatives 162 as precursors for deoxythiataxoid synthesis through oxiraneme...
Scheme 34: Synthesis of 7-deoxy 5(20)-thiadocetaxel 154b.
Scheme 35: Mechanism for the formation of the thietane ring in 171 from oxiranes with vicinal leaving groups 1...
Scheme 36: Synthesis of cis-2,3-disubstituted thietane 175 from thiirane-2-methanol 172.
Scheme 37: Synthesis of a bridged thietane 183 from aziridine cyclohexyl tosylate 179 and ammonium tetrathiomo...
Scheme 38: Synthesis of thietanes via the photochemical [2 + 2] cycloaddition of thiobenzophenone 184a with va...
Scheme 39: Synthesis of spirothietanes through the photo [2 + 2] cycloaddition of cyclic thiocarbonyls with ol...
Scheme 40: Photochemical synthesis of spirothietane-thioxanthenes 210 from thioxanthenethione (208) and butatr...
Scheme 41: Synthesis of thietanes 213 from 2,4,6-tri(tert-butyl)thiobenzaldehyde (211) with substituted allene...
Scheme 42: Photochemical synthesis of spirothietanes 216 and 217 from N-methylthiophthalimide (214) with olefi...
Scheme 43: Synthesis of fused thietanes from quadricyclane with thiocarbonyl derivatives 219.
Scheme 44: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-methyldithiosuccinimides ...
Scheme 45: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-methylthiosuccinimide/thi...
Scheme 46: Synthesis of tricyclic thietanes via the photo [2 + 2] cycloaddition of N-alkylmonothiophthalimides...
Scheme 47: Synthesis of spirothietanes from dithiosuccinimides 223 with 2,3-dimethyl-2-butene (215a).
Scheme 48: Synthesis of thietanes 248a,b from diaryl thione 184b and ketene acetals 247a,b.
Scheme 49: Photocycloadditions of acridine-9-thiones 249 and pyridine-4(1H)-thione (250) with 2-methylacrynitr...
Scheme 50: Synthesis of thietanes via the photo [2 + 2] cycloaddition of mono-, di-, and trithiobarbiturates 2...
Scheme 51: Synthesis of spirothietanes via the photo [2 + 2] cycloaddition of 1,1,3-trimethyl-2-thioxo-1,2-dih...
Scheme 52: Synthesis of spirothietanes via the photo [2 + 2] cycloaddition of thiocoumarin 286 with olefins.
Scheme 53: Photochemical synthesis of thietanes 296–299 from semicyclic and acyclic thioimides 292–295 and 2,3...
Scheme 54: Photochemical synthesis of spirothietane 301 from 1,3,3-trimethylindoline-2-thione (300) and isobut...
Scheme 55: Synthesis of spirobenzoxazolethietanes 303 via the photo [2 + 2] cycloaddition of alkyl and aryl 2-...
Scheme 56: Synthesis of spirothietanes from tetrahydrothioxoisoquinolines 306 and 307 with olefins.
Scheme 57: Synthesis of spirothietanes from 1,3-dihydroisobenzofuran-1-thiones 311 and benzothiophene-1-thione...
Scheme 58: Synthesis of 2-triphenylsilylthietanes from phenyl triphenylsilyl thioketone (316) with electron-po...
Scheme 59: Diastereoselective synthesis of spiropyrrolidinonethietanes 320 via the photo [2 + 2] cycloaddition...
Scheme 60: Synthesis of bicyclic thietane 323 via the photo [2 + 2] cycloaddition of 2,4-dioxo-3,4-dihydropyri...
Scheme 61: Photo-induced synthesis of fused thietane-2-thiones 325 and 326 from silacyclopentadiene 324 and ca...
Scheme 62: Synthesis of highly strained tricyclic thietanes 328 via the intramolecular photo [2 + 2] cycloaddi...
Scheme 63: Synthesis of tri- and pentacyclic thietanes 330 and 332, respectively, through the intramolecular p...
Scheme 64: Synthesis of tricyclic thietanes 334 via the intramolecular photo [2 + 2] cycloaddition of N-vinylt...
Scheme 65: Synthesis of tricyclic thietanes 336 via the intramolecular photo [2 + 2] cycloaddition of N-but-3-...
Scheme 66: Synthesis of tricyclic thietanes via the intramolecular photo [2 + 2] cycloaddition of N-but-3-enyl...
Scheme 67: Synthesis of tetracyclic thietane 344 through the intramolecular photo [2 + 2] cycloaddition of N-[...
Scheme 68: Synthesis of tri- and tetracyclic thietanes 348, 350, and 351, through the intramolecular photo [2 ...
Scheme 69: Synthesis of tetracyclic fused thietane 354 via the photo [2 + 2] cycloaddition of vinyl 2-thioxo-3H...
Scheme 70: Synthesis of highly rigid thietane-fused β-lactams via the intramolecular photo [2 + 2] cycloadditi...
Scheme 71: Asymmetric synthesis of a highly rigid thietane-fused β-lactam 356a via the intramolecular photo [2...
Scheme 72: Diastereoselective synthesis of the thietane-fused β-lactams via the intramolecular photo [2 + 2] c...
Scheme 73: Asymmetric synthesis of thietane-fused β-lactams 356 via the intramolecular photo [2 + 2] cycloaddi...
Scheme 74: Synthesis of the bridged bis(trifluoromethyl)thietane from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-di...
Scheme 75: Synthesis of the bridged-difluorothietane 368 from 2,2,4,4-tetrafluoro-1,3-dithietane (367) and qua...
Scheme 76: Synthesis of bis(trifluoromethyl)thietanes from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietane (3...
Scheme 77: Synthesis of 2,2-dimethylthio-4,4-di(trifluoromethyl)thietane (378) from 2,2,4,4-tetrakis(trifluoro...
Scheme 78: Formation of bis(trifluoromethyl)thioacetone (381) through nucleophilic attack of dithietane 363 by...
Scheme 79: Synthesis of 2,2-bis(trifluoromethyl)thietanes from 2,2,4,4-tetrakis(trifluoromethyl)-1,3-dithietan...
Scheme 80: Synthesis of the bridged bis(trifluoromethyl)thietane 364 from of 2,2,4,4-tetrakis(trifluoromethyl)...
Scheme 81: Synthesis of 2,4-diiminothietanes 390 from alkenimines and 4-methylbenzenesulfonyl isothiocyanate (...
Scheme 82: Synthesis of arylidene 2,4-diiminothietanes 393 starting from phosphonium ylides 391 and isothiocya...
Scheme 83: Synthesis of thietane-2-ylideneacetates 397 through a DABCO-catalyzed formal [2 + 2] cycloaddition ...
Scheme 84: Synthesis of 3-substituted thietanes 400 from (1-chloroalkyl)thiiranes 398.
Scheme 85: Synthesis of N-(thietane-3-yl)azaheterocycles 403 and 404 through reaction of chloromethylthiirane (...
Scheme 86: Synthesis of 3-sulfonamidothietanes 406 from sulfonamides and chloromethylthiirane (398a).
Scheme 87: Synthesis of N-(thietane-3-yl)isatins 408 from chloromethylthiirane (398a) and isatins 407.
Scheme 88: Synthesis of 3-(nitrophenyloxy)thietanes 410 from nitrophenols 409 and chloromethylthiirane (398a).
Scheme 89: Synthesis of N-aryl-N-(thietane-3-yl)cyanamides 412 from N-arylcyanamides 411 and chloromethylthiir...
Scheme 90: Synthesis of 1-(thietane-3-yl)pyrimidin-2,4(1H,3H)-diones 414 from chloromethylthiirane (398a) and ...
Scheme 91: Synthesis of 2,4-diiminothietanes 418 from 2-iminothiiranes 416 and isocyanoalkanes 415.
Scheme 92: Synthesis of 2-vinylthietanes 421 from thiiranes 419 and 3-chloroallyl lithium (420).
Scheme 93: Synthesis of thietanes from thiiranes 419 and trimethyloxosulfonium iodide 424.
Scheme 94: Mechanism for synthesis of thietanes 425 from thiiranes 419 and trimethyloxosulfonium iodide 424.
Scheme 95: Synthesis of functionalized thietanes from thiiranes and dimethylsulfonium acylmethylides.
Scheme 96: Mechanism for the rhodium-catalyzed synthesis of functionalized thietanes 429 from thiiranes 419 an...
Scheme 97: Synthesis of 3-iminothietanes 440 through thermal isomerization from 4,5-dihydro-1,3-oxazole-4-spir...
Scheme 98: Synthesis of thietanes 443 from 3-chloro-2-methylthiolane (441) through ring contraction.
Scheme 99: Synthesis of an optically active thietanose 447 from D-xylose involving a ring contraction.
Scheme 100: Synthesis of optically thietane 447 via the DAST-mediated ring contraction of 448.
Scheme 101: Synthesis of the optically thietane nucleoside 451 via the ring contraction of thiopentose in 450.
Scheme 102: Synthesis of spirothietane 456 from 3,3,5,5-tetramethylthiolane-2,4-dithione (452) and benzyne (453...
Scheme 103: Synthesis of thietanes 461 via photoisomerization of 2H,6H-thiin-3-ones 459.
Scheme 104: Phosphorodithioate-mediated synthesis of 1,4-diarylthietanes 465.
Scheme 105: Mechanism of the phosphorodithioate-mediated synthesis of 1,4-diarylthietanes 465.
Scheme 106: Phosphorodithioate-mediated synthesis of trisubstituted thietanes (±)-470.
Scheme 107: Mechanism on the phosphorodithioate-mediated synthesis of trisubstituted thietanes.
Scheme 108: Phosphorodithioate-mediated synthesis of thietanes (±)-475.
Scheme 109: Phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes from aldehydes 476 and acrylon...
Scheme 110: Phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes via a one-pot three-component ...
Scheme 111: Mechanism for the phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes via three-co...
Scheme 112: Phosphorodithioate-mediated synthesis of substituted 3-nitrothietanes.
Scheme 113: Mechanism on the phosphorodithioate-mediated synthesis of 1,2-disubstituted thietanes (±)-486.
Scheme 114: Asymmetric synthesis of (S)-2-phenylthietane (497).
Scheme 115: Asymmetric synthesis of optically active 2,4-diarylthietanes.
Scheme 116: Synthesis of 3-acetamidothietan-2-one 503 via the intramolecular thioesterification of 3-mercaptoal...
Scheme 117: Synthesis of 4-substituted thietan-2-one via the intramolecular thioesterification of 3-mercaptoalk...
Scheme 118: Synthesis of 4,4-disubstituted thietan-2-one 511 via the intramolecular thioesterification of the 3...
Scheme 119: Synthesis of a spirothietan-2-one 514 via the intramolecular thioesterification of 3-mercaptoalkano...
Scheme 120: Synthesis of thiatetrahydrolipstatin starting from (S)-(−)-epichlorohydrin ((S)-142a).
Scheme 121: Synthesis of 2-phenethyl-4-(propan-2-ylidene)thietane (520) from 5-bromo-6-methyl-1-phenylhept-5-en...
Scheme 122: Synthesis of 2-phenethyl-4-(propan-2-ylidene)thietane (520) directly from S-(5-bromo-6-methyl-1-phe...
Scheme 123: Synthesis of 2-alkylidenethietanes from S-(2-bromoalk-1-en-4-yl)thioacetates.
Scheme 124: Synthesis of 2-alkylidenethietanes from S-(2-bromo/chloroalk-1-en-4-yl)thiols.
Scheme 125: Synthesis of spirothietan-3-ol 548 from enone 545 and ammonium hydrosulfide.
Scheme 126: Asymmetric synthesis of the optically active thietanoside from cis-but-2-ene-1,4-diol (47).
Scheme 127: Synthesis of 2-alkylidenethietan-3-ols 557 via the fluoride-mediated cyclization of thioacylsilanes ...
Scheme 128: Synthesis of 2-iminothietanes via the reaction of propargylbenzene (558) and isothiocyanates 560 in...
Scheme 129: Synthesis of 2-benzylidenethietane 567 via the nickel complex-catalyzed electroreductive cyclizatio...
Scheme 130: Synthesis of 2-iminothietanes 569 via the photo-assisted electrocyclic reaction of N-monosubstitute...
Scheme 131: Synthesis of ethyl 3,4-diiminothietane-2-carboxylates from ethyl thioglycolate (570) and bis(imidoy...
Scheme 132: Synthesis of N-(thietan-3-yl)-α-oxoazaheterocycles from azaheterocyclethiones and chloromethyloxira...
Scheme 133: Synthesis of thietan-3-yl benzoate (590) via the nickel-catalyzed intramolecular reductive thiolati...
Scheme 134: Synthesis of 2,2-bis(trifluoromethyl)thietane from 3,3-bis(trifluoromethyl)-1,2-dithiolane.
Scheme 135: Synthesis of thietanes from enamines and sulfonyl chlorides.
Scheme 136: Synthesis of spirothietane 603 via the [2 + 3] cycloaddition of 2,2,4,4-tetramethylcyclobutane-1,3-...
Scheme 137: Synthesis of thietane (605) from 1-bromo-3-chloropropane and sulfur.
Oxime radicals: generation, properties and application in organic synthesis
- Igor B. Krylov,
- Stanislav A. Paveliev,
- Alexander S. Budnikov and
- Alexander O. Terent’ev
Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107
- corresponding to the free iminoxyl radical, which indicates the reversibility of dimerization [53]. During the oxidation of pivalic aldoxime 1e by Ag2O, the formation of nitrile oxide 6e was observed, which then slowly dimerized to the corresponding furoxan 7e. The kinetics of the decomposition of dialkyl
- ruthenium catalyst. This possible reaction pathway was confirmed by a control experiment in which the hydroxyiminomethylisoxazoline was transformed to a nitrile in the presence of [RuCl2(p-cymene)]2. Aromatic oximes with various substituents, as well as heteroaromatic oximes, give cyano-substituted
- oximes (products 147e,f) were successfully used. Oxidative cyclization of unsaturated oximes with the formation of isoxazolines or cyclic nitrones and the introduction of a nitrile group was achieved using the CuCN/N,N,N′,N′′,N′′-pentamethyldiethyltriamine (PMDETA)/TBHP system (Scheme 50) [139]. Other
Graphical Abstract
Figure 1: Imine-N-oxyl radicals (IV) discussed in the present review and other classes of N-oxyl radicals (I–...
Figure 2: The products of decomposition of iminoxyl radicals generated from oximes by oxidation with Ag2O.
Scheme 1: Generation of oxime radicals and study of the kinetics of their decay by photolysis of the solution...
Scheme 2: Synthesis of di-tert-butyliminoxyl radical and its decomposition products.
Scheme 3: The proposed reaction pathway of the decomposition of di-tert-butyliminoxyl radical (experimentally...
Scheme 4: Monomolecular decomposition of the tert-butyl(triethylmethyl)oxime radical.
Scheme 5: The synthesis and stability of the most stable dialkyl oxime radicals – di-tert-butyliminoxyl and d...
Scheme 6: The formation of iminoxyl radicals from β-diketones under the action of NO2.
Scheme 7: Synthesis of the diacetyliminoxyl radical.
Scheme 8: Examples of long-living oxime radicals with electron-withdrawing groups and the conditions for thei...
Figure 3: The electronic structure iminoxyl radicals and their geometry compared to the corresponding oximes.
Figure 4: Bond dissociation enthalpies (kcal/mol) of oximes and N,N-disubstituted hydroxylamines calculated o...
Scheme 9: Examples demonstrating the low reactivity of the di-tert-butyliminoxyl radical towards the substrat...
Scheme 10: The reactions of di-tert-butyliminoxyl radical with unsaturated hydrocarbons involving hydrogen ato...
Scheme 11: Possible mechanisms of reaction of di-tert-butyliminoxyl radical with alkenes.
Scheme 12: Products of the reaction between di-tert-butyliminoxyl radical and phenol derivatives.
Scheme 13: The reaction of di-tert-butyliminoxyl radical with amines.
Scheme 14: Reaction of di-tert-butyliminoxyl radicals with organolithium reagents.
Scheme 15: Cross-dehydrogenative C–O coupling of 1,3-dicarbonyl compounds with oximes under the action of mang...
Scheme 16: Cross-dehydrogenative C–O coupling of 1,3-dicarbonyl compounds with oximes under the action of Cu(BF...
Scheme 17: Oxidative C–O coupling of benzylmalononitrile (47) with 3-(hydroxyimino)pentane-2,4-dione (19).
Scheme 18: The proposed mechanism of the oxidative coupling of benzylmalononitrile (47) with diacetyl oxime (19...
Scheme 19: Oxidative C–O coupling of pyrazolones with oximes under the action of Fe(ClO4)3.
Scheme 20: The reaction of diacetyliminoxyl radical with pyrazolones.
Scheme 21: Oxidative C–O coupling of oximes with acetonitrile, ketones, and esters.
Scheme 22: Intramolecular cyclizations of oxime radicals to form substituted isoxazolines or cyclic nitrones.
Scheme 23: TEMPO-mediated oxidative cyclization of oximes with C–H bond cleavage.
Scheme 24: Proposed reaction mechanism of oxidative cyclization of oximes with C–H bond cleavage.
Scheme 25: Selectfluor/Bu4NI-mediated C–H oxidative cyclization of oximes.
Scheme 26: Oxidative cyclization of N-benzyl amidoximes to 1,2,4-oxadiazoles.
Scheme 27: The formation of quinazolinone 73a from 5-phenyl-4,5-dihydro-1,2,4-oxadiazole 74 under air.
Scheme 28: DDQ-mediated oxidative cyclization of thiohydroximic acids.
Scheme 29: Plausible mechanism of the oxidative cyclization of thiohydroximic acids.
Scheme 30: Silver-mediated oxidative cyclization of α-halogenated ketoximes and 1,3-dicarbonyl compounds.
Scheme 31: Possible pathway of one-pot oxidative cyclization of α-halogenated ketoximes and 1,3-dicarbonyl com...
Scheme 32: T(p-F)PPT-catalyzed oxidative cyclization of oximes with the formation of 1,2,4-oxadiazolines.
Scheme 33: Intramolecular cyclization of iminoxyl radicals involving multiple C=C and N=N bonds.
Scheme 34: Oxidative cyclization of β,γ- and γ,δ-unsaturated oximes employing the DEAD or TEMPO/DEAD system wi...
Scheme 35: Cobalt-catalyzed aerobic oxidative cyclization of β,γ-unsaturated oximes.
Scheme 36: Manganese-catalyzed aerobic oxidative cyclization of β,γ-unsaturated oximes.
Scheme 37: Visible light photocatalytic oxidative cyclization of β,γ-unsaturated oximes.
Scheme 38: TBAI/TBHP-mediated radical cascade cyclization of the β,γ-unsaturated oximes.
Scheme 39: TBAI/TBHP-mediated radical cascade cyclization of vinyl isocyanides with β,γ-unsaturated oximes.
Scheme 40: tert-Butylnitrite-mediated oxidative cyclization of unsaturated oximes with the introduction of an ...
Scheme 41: Transformation of unsaturated oxime to oxyiminomethylisoxazoline via the confirmed dimeric nitroso ...
Scheme 42: tert-Butylnitrite-mediated oxidative cyclization of unsaturated oximes with the introduction of a n...
Scheme 43: Synthesis of cyano-substituted oxazolines from unsaturated oximes using the TBN/[RuCl2(p-cymene)]2 ...
Scheme 44: Synthesis of trifluoromethylthiolated isoxazolines from unsaturated oximes.
Scheme 45: Copper-сatalyzed oxidative cyclization of β,γ-unsaturated oximes with the introduction of an azido ...
Scheme 46: TBHP-mediated oxidative cascade cyclization of β,γ-unsaturated oximes and unsaturated N-arylamides.
Scheme 47: Copper-сatalyzed oxidative cyclization of unsaturated oximes with the introduction of an amino grou...
Scheme 48: TEMPO-mediated oxidative cyclization of unsaturated oximes followed by elimination.
Scheme 49: Oxidative cyclization of β,γ-unsaturated oximes with the introduction of a trifluoromethyl group.
Scheme 50: Oxidative cyclization of unsaturated oximes with the introduction of a nitrile group.
Scheme 51: Oxidative cyclization of β,γ-unsaturated oximes to isoxazolines with the introduction of a nitrile ...
Scheme 52: Oxidative cyclization of β,γ-unsaturated oximes to isoxazolines with the introduction of a sulfonyl...
Scheme 53: Oxidative cyclization of β,γ- and γ,δ-unsaturated oximes to isoxazolines with the introduction of a...
Scheme 54: Oxidative cyclization of β,γ-unsaturated oximes to isoxazolines with the introduction of a thiocyan...
Scheme 55: PhI(OAc)2-mediated oxidative cyclization of oximes with C–S and C–Se bond formation.
Scheme 56: PhI(OAc)2-mediated oxidative cyclization of unsaturated oximes accompanied by alkoxylation.
Scheme 57: PhI(OAc)2-mediated cyclization of unsaturated oximes to methylisoxazolines.
Scheme 58: Oxidative cyclization-alkynylation of unsaturated oximes.
Scheme 59: TEMPO-mediated oxidative cyclization of C-glycoside ketoximes to C-glycosylmethylisoxazoles.
Scheme 60: Silver-сatalyzed oxidative cyclization of β,γ-unsaturated oximes with formation of fluoroalkyl isox...
Scheme 61: Oxidative cyclization of β,γ-unsaturated oximes with the formation of haloalkyl isoxazolines.
Scheme 62: Cyclization of β,γ-unsaturated oximes into haloalkyl isoxazolines under the action of the halogenat...
Scheme 63: Synthesis of haloalkyl isoxazoles and cyclic nitrones via oxidative cyclization and 1,2-halogen shi...
Scheme 64: Electrochemical oxidative cyclization of diaryl oximes.
Scheme 65: Copper-сatalyzed cyclization and dioxygenation oximes containing a triple C≡C bond.
Scheme 66: Photoredox-catalyzed sulfonylation of β,γ-unsaturated oximes by sulfonyl hydrazides.
Scheme 67: Oxidative cyclization of β,γ-unsaturated oximes with introduction of sulfonate group.
Scheme 68: Ultrasound-promoted oxidative cyclization of β,γ-unsaturated oximes.
Fluorinated phenylalanines: synthesis and pharmaceutical applications
- Laila F. Awad and
- Mohammed Salah Ayoup
Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91
- nitrile 48a with 30% HCl aq/acetic acid, gave the 4-fluorophenylalanine·HCl 49a in a good overall yield (67%) [47] (Scheme 11). 1.4. Hydrolysis of Erlenmeyer’s azalactone A multistep Erlenmeyer azalactone synthesis was reported as an important method for the synthesis of fluorinated α-amino acids 53a–h
- (126). Then, reaction of 127 (1.0 mmol) with 1.5/1.0 equiv of diethylaluminum cyanide (Et2AlCN)/iPrOH at −78 °C in THF gave nitrile 128. Deprotection of the latter, followed by hydrolysis of the nitrile group afforded syn-(2S,3S)-(+)-3-fluorophenylalanine (129) [65] (Scheme 28) . 2.3. Multistep
- ] (Scheme 41). An alternative approach to the difluorinated compound 168a was achieved by the condensation of 164a with (S)-1-phenylethylamine (169), to give the imine 170. Heating of imine 170 with TMSCN in the presence of zinc iodide [82] generated the nitrile 171 as a 1:1 mixture of diastereoisomers
Graphical Abstract
Figure 1: Categories I–V of fluorinated phenylalanines.
Scheme 1: Synthesis of fluorinated phenylalanines via Jackson’s method.
Scheme 2: Synthesis of all-cis-tetrafluorocyclohexylphenylalanines.
Scheme 3: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine (nPt: neopentyl, TCE: trichloroethyl).
Scheme 4: Synthesis of ʟ-4-[sulfono(difluoromethyl)]phenylalanine derivatives 17.
Scheme 5: Synthesis of fluorinated Phe analogues from Cbz-protected aminomalonates.
Scheme 6: Synthesis of tetrafluorophenylalanine analogues via the 3-methyl-4-imidazolidinone auxiliary 25.
Scheme 7: Synthesis of tetrafluoro-Phe derivatives via chiral auxiliary 31.
Scheme 8: Synthesis of 2,5-difluoro-Phe and 2,4,5-trifluoro-Phe via Schöllkopf reagent 34.
Scheme 9: Synthesis of 2-fluoro- and 2,6-difluoro Fmoc-Phe derivatives starting from chiral auxiliary 39.
Scheme 10: Synthesis of 2-[18F]FPhe via chiral auxiliary 43.
Scheme 11: Synthesis of FPhe 49a via photooxidative cyanation.
Scheme 12: Synthesis of FPhe derivatives via Erlenmeyer azalactone synthesis.
Scheme 13: Synthesis of (R)- and (S)-2,5-difluoro Phe via the azalactone method.
Scheme 14: Synthesis of 3-bromo-4-fluoro-(S)-Phe (65).
Scheme 15: Synthesis of [18F]FPhe via radiofluorination of phenylalanine with [18F]F2 or [18F]AcOF.
Scheme 16: Synthesis of 4-borono-2-[18F]FPhe.
Scheme 17: Synthesis of protected 4-[18F]FPhe via arylstannane derivatives.
Scheme 18: Synthesis of FPhe derivatives via intermediate imine formation.
Scheme 19: Synthesis of FPhe derivatives via Knoevenagel condensation.
Scheme 20: Synthesis of FPhe derivatives 88a,b from aspartic acid derivatives.
Scheme 21: Synthesis of 2-(2-fluoroethyl)phenylalanine derivatives 93 and 95.
Scheme 22: Synthesis of FPhe derivatives via Zn2+ complexes.
Scheme 23: Synthesis of FPhe derivatives via Ni2+ complexes.
Scheme 24: Synthesis of 3,4,5-trifluorophenylalanine hydrochloride (109).
Scheme 25: Synthesis of FPhe derivatives via phenylalanine aminomutase (PAM).
Scheme 26: Synthesis of (R)-2,5-difluorophenylalanine 115.
Scheme 27: Synthesis of β-fluorophenylalanine via 2-amino-1,3-diol derivatives.
Scheme 28: Synthesis of β-fluorophenylalanine derivatives via the oxazolidinone chiral auxiliary 122.
Scheme 29: Synthesis of β-fluorophenylalanine from pyruvate hemiketal 130.
Scheme 30: Synthesis of β-fluorophenylalanine (136) via fluorination of β-hydroxyphenylalanine (137).
Scheme 31: Synthesis of β-fluorophenylalanine from aziridine derivatives.
Scheme 32: Synthesis of β-fluorophenylalanine 136 via direct fluorination of pyruvate esters.
Scheme 33: Synthesis of β-fluorophenylalanine via fluorination of ethyl 3-phenylpyruvate enol using DAST.
Scheme 34: Synthesis of β-fluorophenylalanine derivatives using photosensitizer TCB.
Scheme 35: Synthesis of β-fluorophenylalanine derivatives using Selectflour and dibenzosuberenone.
Scheme 36: Synthesis of protected β-fluorophenylalanine via aziridinium intermediate 150.
Scheme 37: Synthesis of β-fluorophenylalanine derivatives via fluorination of α-hydroxy-β-aminophenylalanine d...
Scheme 38: Synthesis of β-fluorophenylalanine derivatives from α- or β-hydroxy esters 152a and 155.
Scheme 39: Synthesis of a series of β-fluoro-Phe derivatives via Pd-catalyzed direct fluorination of β-methyle...
Scheme 40: Synthesis of series of β-fluorinated Phe derivatives using quinoline-based ligand 162 in the Pd-cat...
Scheme 41: Synthesis of β,β-difluorophenylalanine derivatives from 2,2-difluoroacetaldehyde derivatives 164a,b....
Scheme 42: Synthesis of β,β-difluorophenylalanine derivatives via an imine chiral auxiliary.
Scheme 43: Synthesis of α-fluorophenylalanine derivatives via direct fluorination of protected Phe 174.
Figure 2: Structures of PET radiotracers of 18FPhe derivatives.
Figure 3: Structures of melfufen (179) and melphalan (180) anticancer drugs.
Figure 4: Structure of gastrazole (JB95008, 181), a CCK2 receptor antagonist.
Figure 5: Dual CCK1/CCK2 antagonist 182.
Figure 6: Structure of sitagliptin (183), an antidiabetic drug.
Figure 7: Structure of retaglpitin (184) and antidiabetic drug.
Figure 8: Structure of evogliptin (185), an antidiabetic drug.
Figure 9: Structure of LY2497282 (186) a DPP-4 inhibitor for the treatment of type II diabetes.
Figure 10: Structure of ulimorelin (187).
Figure 11: Structure of GLP1R (188).
Figure 12: Structures of Nav1.7 blockers 189 and 190.
Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches
- Rodrigo Costa e Silva,
- Luely Oliveira da Silva,
- Aloisio de Andrade Bartolomeu,
- Timothy John Brocksom and
- Kleber Thiago de Oliveira
Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83
- using 4 mol % of tetra-n-butylammonium fluoride (TBAF) as an activator of TMSCN (conditions B). Following this second protocol, the primary α-aminonitriles were rapidly prepared in relevant yields (up to 87%) and converted to the corresponding α-amino acids by hydrolysis of the nitrile (Scheme 57
Graphical Abstract
Figure 1: Chemical structures of the porphyrinoids and their absorption spectra: in bold are highlighted the ...
Figure 2: Photophysical and photochemical processes (Por = porphyrin). Adapted from [12,18].
Figure 3: Main dual photocatalysts and their oxidative/reductive excited state potentials, including porphyri...
Scheme 1: Photoredox alkylation of aldehydes with diazo acetates using porphyrins and a Ru complex. aUsing a ...
Scheme 2: Proposed mechanism for the alkylation of aldehydes with diazo acetates in the presence of TPP.
Scheme 3: Arylation of heteroarenes with aryldiazonium salts using TPFPP as photocatalyst, and corresponding ...
Scheme 4: A) Scope with different aryldiazonium salts and enol acetates. B) Photocatalytic cycles and compari...
Scheme 5: Photoarylation of isopropenyl acetate A) Comparison between batch and continuous-flow approaches an...
Scheme 6: Dehalogenation induced by red light using thiaporphyrin (STPP).
Scheme 7: Applications of NiTPP as both photoreductant and photooxidant.
Scheme 8: Proposed mechanism for obtaining tetrahydroquinolines by reductive quenching.
Scheme 9: Selenylation and thiolation of anilines.
Scheme 10: NiTPP as photoredox catalyst in oxidative and reductive quenching, in comparison with other photoca...
Scheme 11: C–O bond cleavage of 1-phenylethanol using a cobalt porphyrin (CoTMPP) under visible light.
Scheme 12: Hydration of terminal alkynes by RhIII(TSPP) under visible light irradiation.
Scheme 13: Regioselective photocatalytic hydro-defluorination of perfluoroarenes by RhIII(TSPP).
Scheme 14: Formation of 2-methyl-2,3-dihydrobenzofuran by intramolecular hydro-functionalization of allylpheno...
Scheme 15: Photocatalytic oxidative hydroxylation of arylboronic acids using UNLPF-12 as heterogeneous photoca...
Scheme 16: Photocatalytic oxidative hydroxylation of arylboronic acids using MOF-525 as heterogeneous photocat...
Scheme 17: Preparation of the heterogeneous photocatalyst CNH.
Scheme 18: Photoinduced sulfonation of alkenes with sulfinic acid using CNH as photocatalyst.
Scheme 19: Sulfonic acid scope of the sulfonation reactions.
Scheme 20: Regioselective sulfonation reaction of arimistane.
Scheme 21: Synthesis of quinazolin-4-(3H)-ones.
Scheme 22: Selective photooxidation of aromatic benzyl alcohols to benzaldehydes using Pt/PCN-224(Zn).
Scheme 23: Photooxidation of benzaldehydes to benzoic acids using Pt or Pd porphyrins.
Scheme 24: Photocatalytic reduction of various nitroaromatics using a Ni-MOF.
Scheme 25: Photoinduced cycloadditions of CO2 with epoxides by MOF1.
Figure 4: Electronic configurations of the species of oxygen. Adapted from [66].
Scheme 26: TPP-photocatalyzed generation of 1O2 and its application in organic synthesis. Adapted from [67-69].
Scheme 27: Pericyclic reactions involving singlet oxygen and their mechanisms. Adapted from [67].
Scheme 28: First scaled up ascaridole preparation from α-terpinene.
Scheme 29: Antimalarial drug synthesis using an endoperoxidation approach.
Scheme 30: Photooxygenation of colchicine.
Scheme 31: Synthesis of (−)-pinocarvone from abundant (+)-α-pinene.
Scheme 32: Seeberger’s semi-synthesis of artemisinin.
Scheme 33: Synthesis of artemisinin using TPP and supercritical CO2.
Scheme 34: Synthesis of artemisinin using chlorophyll a.
Scheme 35: Quercitol stereoisomer preparation.
Scheme 36: Photocatalyzed preparation of naphthoquinones.
Scheme 37: Continuous endoperoxidation of conjugated dienes and subsequent rearrangements leading to oxidized ...
Scheme 38: The Opatz group total synthesis of (–)-oxycodone.
Scheme 39: Biomimetic syntheses of rhodonoids A, B, E, and F.
Scheme 40: α-Photooxygenation of chiral aldehydes.
Scheme 41: Asymmetric photooxidation of indanone β-keto esters by singlet oxygen using PTC as a chiral inducer...
Scheme 42: Asymmetric photooxidation of both β-keto esters and β-keto amides by singlet oxygen using PTC-2 as ...
Scheme 43: Bifunctional photo-organocatalyst used for the asymmetric oxidation of β-keto esters and β-keto ami...
Scheme 44: Mechanism of singlet oxygen oxidation of sulfides to sulfoxides.
Scheme 45: Controlled oxidation of sulfides to sulfoxides using protonated porphyrins as photocatalysts. aIsol...
Scheme 46: Photochemical oxidation of sulfides to sulfoxides using PdTPFPP as photocatalyst.
Scheme 47: Controlled oxidation of sulfides to sulfoxides using SnPor@PAF as a photosensitizer.
Scheme 48: Syntheses of 2D-PdPor-COF and 3D-Pd-COF.
Scheme 49: Photocatalytic oxidation of A) thioanisole to methyl phenyl sulfoxide and B) various aryl sulfides,...
Scheme 50: General mechanism for oxidation of amines to imines.
Scheme 51: Oxidation of secondary amines to imines.
Scheme 52: Oxidation of secondary amines using Pd-TPFPP as photocatalyst.
Scheme 53: Oxidative amine coupling using UNLPF-12 as heterogeneous photocatalyst.
Scheme 54: Synthesis of Por-COF-1 and Por-COF-2.
Scheme 55: Photocatalytic oxidation of amines to imines by Por-COF-2.
Scheme 56: Photocyanation of primary amines.
Scheme 57: Synthesis of ᴅ,ʟ-tert-leucine hydrochloride.
Scheme 58: Photocyanation of catharanthine and 16-O-acetylvindoline using TPP.
Scheme 59: Photochemical α-functionalization of N-aryltetrahydroisoquinolines using Pd-TPFPP as photocatalyst.
Scheme 60: Ugi-type reaction with 1,2,3,4-tetrahydroisoquinoline using molecular oxygen and TPP.
Scheme 61: Ugi-type reaction with dibenzylamines using molecular oxygen and TPP.
Scheme 62: Mannich-type reaction of tertiary amines using PdTPFPP as photocatalyst.
Scheme 63: Oxidative Mannich reaction using UNLPF-12 as heterogeneous photocatalyst.
Scheme 64: Transformation of amines to α-cyanoepoxides and the proposed mechanism.
Recent advances in Cu-catalyzed C(sp3)–Si and C(sp3)–B bond formation
- Balaram S. Takale,
- Ruchita R. Thakore,
- Elham Etemadi-Davan and
- Bruce H. Lipshutz
Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67
- attached to the triflate bearing carbon. In this way, different classes of substrates bearing either a nitrile (17) or ethyl ester (21) easily underwent conversion to the corresponding silylated products 18–20 in moderate to good yields (Scheme 5). This method was extended to the use of enantiomerically
Graphical Abstract
Scheme 1: Pharmaceuticals possessing a silicon or boron atom.
Scheme 2: The first Cu-catalyzed C(sp3)–Si bond formation.
Scheme 3: Conversion of benzylic phosphate 6 to the corresponding silane.
Scheme 4: Conversion of alkyl triflates to alkylsilanes.
Scheme 5: Conversion of secondary alkyl triflates to alkylsilanes.
Scheme 6: Conversion of alkyl iodides to alkylsilanes.
Scheme 7: Trapping of intermediate radical through cascade reaction.
Scheme 8: Radical pathway for conversion of alkyl iodides to alkylsilanes.
Scheme 9: Conversion of alkyl ester of N-hydroxyphthalimide to alkylsilanes.
Scheme 10: Conversion of gem-dibromides to bis-silylalkanes.
Scheme 11: Conversion of imines to α-silylated amines (A) and the reaction pathway (B).
Scheme 12: Conversion of N-tosylimines to α-silylated amines.
Scheme 13: Screening of diamine ligands.
Scheme 14: Conversion of N-tert-butylsulfonylimines to α-silylated amines.
Scheme 15: Conversion of aldimines to nonracemic α-silylated amines.
Scheme 16: Conversion of N-tosylimines to α-silylated amines.
Scheme 17: Reaction pathway [A] and conversion of aldehydes to α-silylated alcohols [B].
Scheme 18: Conversion of aldehydes to benzhydryl silyl ethers.
Scheme 19: Conversion of ketones to 1,2-diols (A) and conversion of imines to 1,2-amino alcohols (B).
Scheme 20: Ligand screening (A) and conversion of aldehydes to α-silylated alcohols (B).
Scheme 21: Conversion of aldehydes to α-silylated alcohols.
Scheme 22: 1,4-Additions to α,β-unsaturated ketones.
Scheme 23: 1,4-Additions to unsaturated ketones to give β-silylated derivatives.
Scheme 24: Additions onto α,β-unsaturated lactones to give β-silylated lactones.
Scheme 25: Conversion of α,β-unsaturated to β-silylated lactams.
Scheme 26: Conversion of N-arylacrylamides to silylated oxindoles.
Scheme 27: Conversion of α,β-unsaturated carbonyl compounds to silylated tert-butylperoxides.
Scheme 28: Catalytic cycle for Cu(I) catalyzed α,β-unsaturated compounds.
Scheme 29: Conversion of p-quinone methides to benzylic silanes.
Scheme 30: Conversion of α,β-unsaturated ketimines to regio- and stereocontrolled allylic silanes.
Scheme 31: Conversion of α,β-unsaturated ketimines to enantioenriched allylic silanes.
Scheme 32: Regioselective conversion of dienedioates to allylic silanes.
Scheme 33: Conversion of alkenyl-substituted azaarenes to β-silylated adducts.
Scheme 34: Conversion of conjugated benzoxazoles to enantioenriched β-silylated adducts.
Scheme 35: Conversion of α,β-unsaturated carbonyl indoles to α-silylated N-alkylated indoles.
Scheme 36: Conversion of β-amidoacrylates to α-aminosilanes.
Scheme 37: Conversion of α,β-unsaturated ketones to enantioenriched β-silylated ketones, nitriles, and nitro d...
Scheme 38: Regio-divergent silacarboxylation of allenes.
Scheme 39: Silylation of diazocarbonyl compounds, (A) asymmetric and (B) racemic.
Scheme 40: Enantioselective hydrosilylation of alkenes.
Scheme 41: Conversion of 3-acylindoles to indolino-silanes.
Scheme 42: Proposed mechanism for the silylation of 3-acylindoles.
Scheme 43: Silyation of N-chlorosulfonamides.
Scheme 44: Conversion of acyl silanes to α-silyl alcohols.
Scheme 45: Conversion of N-tosylaziridines to β-silylated N-tosylamines.
Scheme 46: Conversion of N-tosylaziridines to silylated N-tosylamines.
Scheme 47: Conversion of 3,3-disubstituted cyclopropenes to silylated cyclopropanes.
Scheme 48: Conversion of conjugated enynes to 1,3-bis(silyl)propenes.
Scheme 49: Proposed sequence for the Cu-catalyzed borylation of substituted alkenes.
Scheme 50: Cu-catalyzed synthesis of nonracemic allylic boronates.
Scheme 51: Cu–NHC catalyzed synthesis of α-substituted allylboronates.
Scheme 52: Synthesis of α-chiral (γ-alkoxyallyl)boronates.
Scheme 53: Cu-mediated formation of nonracemic cis- or trans- 2-substituted cyclopropylboronates.
Scheme 54: Cu-catalyzed synthesis of γ,γ-gem-difluoroallylboronates.
Scheme 55: Cu-catalyzed hydrofunctionalization of internal alkenes and vinylarenes.
Scheme 56: Cu-catalyzed Markovnikov and anti-Markovnikov borylation of alkenes.
Scheme 57: Cu-catalyzed borylation/ortho-cyanation/Cope rearrangement.
Scheme 58: Borylfluoromethylation of alkenes.
Scheme 59: Cu-catalyzed synthesis of tertiary nonracemic alcohols.
Scheme 60: Synthesis of densely functionalized and synthetically versatile 1,2- or 4,3-borocyanated 1,3-butadi...
Scheme 61: Cu-catalyzed trifunctionalization of allenes.
Scheme 62: Cu-catalyzed selective arylborylation of arenes.
Scheme 63: Asymmetric borylative coupling between styrenes and imines.
Scheme 64: Regio-divergent aminoboration of unactivated terminal alkenes.
Scheme 65: Cu-catalyzed 1,4-borylation of α,β-unsaturated ketones.
Scheme 66: Cu-catalyzed protodeboronation of α,β-unsaturated ketones.
Scheme 67: Cu-catalyzed β-borylation of α,β-unsaturated imines.
Scheme 68: Cu-catalyzed synthesis of β-trifluoroborato carbonyl compounds.
Scheme 69: Asymmetric 1,4-borylation of α,β-unsaturated carbonyl compounds.
Scheme 70: Cu-catalyzed ACB and ACA reactions of α,β-unsaturated 2-acyl-N-methylimidazoles.
Scheme 71: Cu-catalyzed diborylation of aldehydes.
Scheme 72: Umpolung pathway for chiral, nonracemic tertiary alcohol synthesis (top) and proposed mechanism for...
Scheme 73: Cu-catalyzed synthesis of α-hydroxyboronates.
Scheme 74: Cu-catalyzed borylation of ketones.
Scheme 75: Cu-catalyzed borylation of unactivated alkyl halides.
Scheme 76: Cu-catalyzed borylation of allylic difluorides.
Scheme 77: Cu-catalyzed borylation of cyclic and acyclic alkyl halides.
Scheme 78: Cu-catalyzed borylation of unactivated alkyl chlorides and bromides.
Scheme 79: Cu-catalyzed decarboxylative borylation of carboxylic acids.
Scheme 80: Cu-catalyzed borylation of benzylic, allylic, and propargylic alcohols.
Synthesis of organic liquid crystals containing selectively fluorinated cyclopropanes
- Zeguo Fang,
- Nawaf Al-Maharik,
- Peer Kirsch,
- Matthias Bremer,
- Alexandra M. Z. Slawin and
- David O’Hagan
Beilstein J. Org. Chem. 2020, 16, 674–680, doi:10.3762/bjoc.16.65
- relative to other polar substituents such as nitrile and ester groups, and this reduces intermolecular interactions leading to lower viscosities and thus increased life time reliability [4][5]. A significant effort has been devoted to the development of liquid crystals with either positive or negative
Graphical Abstract
Figure 1: Examples of liquid crystal candidates with negative values for dielectric anisotropy (Δε) [6-10].
Figure 2: Synthetic candidate LC targets 8–11.
Scheme 1: Synthesis of 8. Reagents and conditions: a) TMSCF3, NaI, THF, reflux, 55% [13,14].
Scheme 2: Synthesis of 9. Reagents and conditions: a) NBS, HF·Py, DCM; b) t-BuOK, DCM, 42% in two steps [15]; c) ...
Scheme 3: Synthesis of compound 10. Reagents and conditions: a) NaBH4, MeOH, rt, 45%; b) C4H9OCH=CH2, Pd(TFA)2...
Scheme 4: Synthesis of compounds 11. Reagents and conditions: a) PPh3CH3Br, t-BuOK, diethyl ether, 0 °C to rt...
Figure 3: Theory study exploring the relative energies for different conformers of 11a.
Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles
- Ming-Xi Bi,
- Shuai Liu,
- Yangen Huang,
- Xiu-Hua Xu and
- Feng-Ling Qing
Beilstein J. Org. Chem. 2020, 16, 657–662, doi:10.3762/bjoc.16.62
- effect of the substitution on the indole ring. Both electron-donating and withdrawing groups at different positions of the indole ring produced the bis(trifluoromethylthiolated) products 2a–o in moderate to good yields. A wide range of functionalities such as alkyl, alkoxy, nitro, nitrile, ester
- were subjected to the standard conditions, the cascade trifluoromethylthiolation and cyclization occurred to yield trifluoromethylthiolated pyrrolo[1,2-a]indol-3-ones (4a–d) in moderate yields (Scheme 3). The functionalities including alkyl, aryl, nitrile, and acyl were also well tolerated in this
Graphical Abstract
Figure 1: Representative examples of biologically active pyrrolo[1,2-a]indol-3-one derivatives.
Scheme 1: Radical cascade trifluoromethylthiolation and cyclization reactions.
Scheme 2: Cascade bis(trifluoromethylthiolation) and cyclization of N-[(3-aryl)propioloyl]indoles 1. Reaction...
Scheme 3: Cascade trifluoromethylthiolation and cyclization of N-[(3-aryl)propioloyl]indoles 3. Reaction cond...
Scheme 4: Proposed reaction mechanism.
Architecture and synthesis of P,N-heterocyclic phosphine ligands
- Wisdom A. Munzeiwa,
- Bernard Omondi and
- Vincent O. Nyamori
Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35
- the quinazoline ring (Scheme 17) and the phosphine was introduced via metal-catalyzed phosphorylation. The ligands were synthesized in eight steps with relatively good yield. The reaction between substituted nitrile derivatives 87 and anthranilic acid (88) catalyzed by sodium methoxide formed
Graphical Abstract
Scheme 1: Synthesis of pyridylphosphine ligands.
Figure 1: Pyridylphosphine ligands.
Scheme 2: Synthesis of piperidyl- and oxazinylphosphine ligands.
Scheme 3: Synthesis of linear multi-chelate pyridylphosphine ligands.
Scheme 4: Synthesis of chiral acetal pyridylphosphine ligands.
Scheme 5: Synthesis of diphenylphosphine-substituted triazine ligands.
Scheme 6: Synthesis of (pyridine-2-ylmethyl)phosphine ligands.
Scheme 7: Synthesis of diphosphine pyrrole ligands.
Scheme 8: Synthesis of 4,5-diazafluorenylphosphine ligands.
Scheme 9: Synthesis of thioether-containing pyridyldiphosphine ligands starting from ethylene sulfide and dip...
Scheme 10: Synthesis of monoterpene-derived phosphine pyridine ligands.
Scheme 11: Synthesis of N-phenylphosphine-substituted imidazole ligands.
Scheme 12: Synthesis of triazol-4-ylphosphine ligands.
Scheme 13: Synthesis of phosphanyltriazolopyridines and product selectivity depending on the substituents’ eff...
Scheme 14: Synthesis of PTA-phosphine ligands.
Scheme 15: Synthesis of isomeric phosphine dipyrazole ligands by varying the reaction temperature.
Scheme 16: Synthesis of N-tethered phosphine imidazolium ligands (route A) and diphosphine imidazolium ligands...
Scheme 17: Synthesis of {1-[2-(pyridin-2-yl)- (R = CH) and {1-[2-(pyrazin-2-yl)quinazolin-4-yl]naphthalen-2-yl...
Scheme 18: Synthesis of oxazolylindolylphosphine ligands 102.
Scheme 19: Synthesis of pyrrolylphosphine ligands.
Scheme 20: Synthesis of phosphine guanidinium ligands.
Scheme 21: Synthesis of a polydentate aminophosphine ligand.
Scheme 22: Synthesis of quinolylphosphine ligands.
Scheme 23: Synthesis of N-(triazolylmethyl)phosphanamine ligands.
Figure 2: Triazolylphosphanamine ligands synthesized by Wassenaar’s method [22].
Scheme 24: Synthesis of oxazaphosphorines.
Scheme 25: Synthesis of paracyclophane pyridylphosphine ligands.
Scheme 26: Synthesis of triazolylphosphine ligands.
Figure 3: Click-phosphine ligands.
Scheme 27: Ferrocenyl pyridylphosphine imine ligands.
Scheme 28: Synthesis of phosphinooxazolines (PHOX).
Scheme 29: Synthesis of ferrocenylphosphine oxazoles.
The use of isoxazoline and isoxazole scaffolding in the design of novel thiourea and amide liquid-crystalline compounds
- Itamar L. Gonçalves,
- Rafaela R. da Rosa,
- Vera L. Eifler-Lima and
- Aloir A. Merlo
Beilstein J. Org. Chem. 2020, 16, 175–184, doi:10.3762/bjoc.16.20
- , 8, 9, 12 and 13 were then prepared by [3 + 2]-1,3-dipolar cycloaddition of nitrile oxide (ArCNO) formed in situ from oximes and a number of alkenes as dipolarophiles, to yield the precursors of the cycloadducts isoxazolines 2, 7 and 11 regioselectively. The cycloadducts were subjected to SnCl2
Graphical Abstract
Scheme 1: Amines 3, 4, 8, 9, 12 and 13 installed on 5-membered isoxazoline and isoxazole rings.
Scheme 2: Synthesis of acylisoxazolinylthioureas 17a–c and acylisoxazolylthioureas 18a–c. (i) SOCl2, reflux, ...
Scheme 3: Synthesis of amides. Part A: (i) SOCl2, reflux; (ii) KOCN, acetone, reflux; (iii) amines 3, 4, 8 an...
Figure 1: Optical textures observed on POM for thioureas 17a (a), 17b (b), 18a (c), 18b (d) and 18c (e,f). Al...
Figure 2: Optical textures observed on POM of amide 19. (a) Fan-shaped focal conic texture of the SmA mesopha...
Figure 3: DSC curves for the thiourea 17a (A), amide 19 (B) and 20 (C) upon the first heating and cooling cur...
Figure 4: TGA analysis for thiourea 18c; and amides 20 and 22.
Efficient method for propargylation of aldehydes promoted by allenylboron compounds under microwave irradiation
- Jucleiton J. R. Freitas,
- Queila P. S. B. Freitas,
- Silvia R. C. P. Andrade,
- Juliano C. R. Freitas,
- Roberta A. Oliveira and
- Paulo H. Menezes
Beilstein J. Org. Chem. 2020, 16, 168–174, doi:10.3762/bjoc.16.19
- or nitrile group were used, the corresponding products 2q and 2r were obtained in good yields. The use of a heteroaromatic or an aliphatic aldehyde as substrates under the optimized conditions gave the corresponding homopropargylic alcohols 2s,t in moderate yields. The development of a solvent-free
Graphical Abstract
Scheme 1: Scope of the propargylation reaction. Reactions were performed with the appropriate aldehyde (1 mmo...
Scheme 2: Synthesis of potassium allenyltrifluoroborate (4).
Scheme 3: Propargylation of aldehydes using potassium allenyltrifluoroborate (4).
Synthesis of 3-alkenylindoles through regioselective C–H alkenylation of indoles by a ruthenium nanocatalyst
- Abhijit Paul,
- Debnath Chatterjee,
- Srirupa Banerjee and
- Somnath Yadav
Beilstein J. Org. Chem. 2020, 16, 140–148, doi:10.3762/bjoc.16.16
- tolerated several functional groups, including bromine and nitrile units, which provide ample scope for further manipulation of the products from the perspective of medicinal chemistry. The catalyst can be easily recovered and recycled in a colloidal solid form, enabling catalytic recycling and reusability
Graphical Abstract
Figure 1: Biologically and medicinally important 3-alkenylindoles.
Scheme 1: a) Previous and b) present work related to the synthesis of 3-alkenylindoles.
Scheme 2: Substrate scope for the C–H alkenylation of the indoles 1. Reaction conditions: 1 (1 mmol), 2 (2 mm...
Scheme 3: a) Three-phase test to determine a homogeneous or heterogeneous catalytic mechanism of action for t...
Scheme 4: Probable catalytic mechanism for the transformation of 1a by the RuNC.
