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Search for "retro-Michael" in Full Text gives 12 result(s) in Beilstein Journal of Organic Chemistry.
Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction
- James Guevara-Pulido,
- Fernando González-Pérez,
- José M. Andrés and
- Rafael Pedrosa
Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34
- low catalyst loadings and mild reaction conditions. This research focuses on the kinetic resolution of 1,5-dicarbonyl compounds using a retro-Michael reaction, co-catalyzed at room temperature with 20 mol % of the Jørgensen–Hayashi catalyst and PNBA. The study highlights the importance of conducting
- the kinetic resolution at a concentration of approximately ten millimolar (mM) to prevent the Michael retro-Michael equilibrium from affecting the process. Keywords: 1,5-dicarbonyl; equilibrium; kinetic resolution; organocatalysis; retro-Michael; Introduction For many years, enantiomers have been
- racemization when treated with inorganic bases [25], which had led us to check the equilibrium between Michael and the retro-Michael reaction (Scheme 1). These observations have prompted us to conduct further research into this reaction for potential applications in the kinetic resolution of these adducts. In
Graphical Abstract
Scheme 1: Previous work.
Scheme 2: Hypothesis, retro-Michael reaction, and its application in kinetic resolution.
Scheme 3: Model reaction.
Scheme 4: Kinetic resolution of the Michael adduct 1.
Scheme 5: Chemical correlation of 3 with 19.
Scheme 6: Epimerization of the anti-1 adduct promoted by A.
Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts
- Beatriz Dedeiras,
- Catarina S. Caldeira,
- José C. Cunha,
- Clara S. B. Gomes and
- M. Manuel B. Marques
Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272
- ) [32][33]. To investigate the reactivity of the BBXs in this electrophilic amination reaction, the generated compound 4 was subjected to a retro-Michael addition to produce the sulfenate anion intermediate, followed by the addition of BBX 2. Based on our experience with HIRs, the reaction of 2 with
- nucleophiles is more effective when a pre-formed nucleophile is used [4]. Thus, HIR 2 was added to the reaction mixture after the in situ formation of the sulfenate anion (by retro-Michael addition). First experiments were carried out under the previously described conditions for BBX electrophilic amination
- is more favorable at higher temperatures [4]. Due to the reversibility of the retro-Michael addition, an experiment was carried out using an excess of tert-butyl 3-(p-tolylsulfinyl)propanoate (4a) leading to an increase in the yield of the corresponding sulfonamide 5aa by 38% (Table 1, entry 6). A
Graphical Abstract
Figure 1: Examples of cyclic HIRs with a nitrogen-based group transfer [4,10,13-20].
Scheme 1: Electrophilic α‑amination of indanone-based β-ketoesters [4].
Scheme 2: Scope of the different (benzylamino)benziodoxolones (BBXs) 2 with ORTEP-3 diagram of compound 2d, u...
Scheme 3: Scope of the different β-sulfinyl esters 4 [32,33]. Isolated yields. rt – room temperature.
Scheme 4: Scope of the primary amine electrophilic reaction of sulfenate salts. Reaction conditions: 4 (2 equ...
Scheme 5: Electrophilic amination reaction in the presence of TEMPO. Reaction conditions: 4a (2 equiv), NaH (...
Scheme 6: Mechanism proposed for sulfonamide 5, β-sulfinyl ester 4, disulfide 7, and sulfide 3 formations. Th...
Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts
- Ritu Mamgain,
- Kokila Sakthivel and
- Fateh V. Singh
Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243
- base-mediated deprotonation of substrates 86 produces the corresponding ester enolate. This enolate undergoes a retro-Michael reaction, generating sulfenate anion A. The sulfenate anion A then nucleophilically attacks the diaryliodonium salts 16, forming hypervalent iodine intermediates B. Finally
Graphical Abstract
Figure 1: Various structures of iodonium salts.
Scheme 1: Αrylation of α-fluoroacetoacetamides 5 to α-aryl-α-fluoroacetoacetamides 7 and α-fluoroacetamides 8...
Scheme 2: Proposed mechanism for the arylation of α-fluoroacetoacetamides 5 to α-aryl-α-fluoroacetoacetamides ...
Scheme 3: α-Arylation of α-nitro- and α-cyano derivatives of α-fluoroacetamides 9 employing unsymmetrical DAI...
Scheme 4: Synthesis of α,α-difluoroketones 13 by reacting α,α-difluoro-β-keto acid esters 11 with aryl(TMP)io...
Scheme 5: Coupling reaction of arynes generated by iodonium salts 6 and arynophiles 14 for the synthesis of t...
Scheme 6: Metal-free arylation of quinoxalines 17 and quinoxalinones 19 with DAISs 16.
Scheme 7: Transition-metal-free, C–C cross-coupling of 2-naphthols 21 to 1-arylnapthalen-2-ols 22 employing d...
Scheme 8: Arylation of vinyl pinacol boronates 23 to trans-arylvinylboronates 24 in presence of hypervalent i...
Scheme 9: Light-induced selective arylation at C2 of quinoline N-oxides 25 and pyridine N-oxides 28 in the pr...
Scheme 10: Plaussible mechanism for the light-induced selective arylation of N-heterobiaryls.
Scheme 11: Photoinduced arylation of heterocycles 31 with the help of diaryliodonium salts 16 activated throug...
Scheme 12: Arylation of MBH acetates 33 with DIPEA and DAIRs 16.
Scheme 13: Aryl sulfonylation of MBH acetates 33 with DABSO and diphenyliodonium triflates 16.
Scheme 14: Synthesis of oxindoles 37 from N-arylacrylamides 36 and diaryliodonium salts 26.
Scheme 15: Mechanically induced N-arylation of amines 38 using diaryliodonium salts 16.
Scheme 16: o-Fluorinated diaryliodonium salts 40-mediated diarylation of amines 38.
Scheme 17: Proposed mechanism for the diarylation of amines 38 using o-fluorinated diaryliodonium salts 40.
Scheme 18: Ring-opening difunctionalization of aliphatic cyclic amines 41.
Scheme 19: N-Arylation of amino acid esters 44 using hypervalent iodonium salts 45.
Scheme 20: Regioselective N-arylation of triazole derivatives 47 by hypervalent iodonium salts 48.
Scheme 21: Regioselective N-arylation of tetrazole derivatives 50 by hypervalent iodonium salt 51.
Scheme 22: Selective arylation at nitrogen and oxygen of pyridin-2-ones 53 by iodonium salts 16 depending on t...
Scheme 23: N-Arylation using oxygen-bridged acyclic diaryliodonium salt 56.
Scheme 24: The successive C(sp2)–C(sp2)/O–C(sp2) bond formation of naphthols 58.
Scheme 25: Synthesis of diarylethers 62 via in situ generation of hypervalent iodine salts.
Scheme 26: O-Arylated galactosides 64 by reacting protected galactosides 63 with hypervalent iodine salts 16 i...
Scheme 27: Esterification of naproxen methyl ester 65 via formation and reaction of naproxen-containing diaryl...
Scheme 28: Etherification and esterification products 72 through gemfibrozil methyl ester-derived diaryliodoni...
Scheme 29: Synthesis of iodine containing meta-substituted biaryl ethers 74 by reacting phenols 61 and cyclic ...
Scheme 30: Plausible mechanism for the synthesis of meta-functionalized biaryl ethers 74.
Scheme 31: Intramolecular aryl migration of trifluoromethane sulfonate-substituted diaryliodonium salts 75.
Scheme 32: Synthesis of diaryl ethers 80 via site-selective aryl migration.
Scheme 33: Synthesis of O-arylated N-alkoxybenzamides 83 using aryl(trimethoxyphenyl)iodonium salts 82.
Scheme 34: Synthesis of aryl sulfides 85 from thiols 84 using diaryliodonium salts 16 in basic conditions.
Scheme 35: Base-promoted synthesis of diarylsulfoxides 87 via arylation of general sulfinates 86.
Scheme 36: Plausible mechanism for the arylation of sulfinates 86 via sulfenates A to give diaryl sulfoxides 87...
Scheme 37: S-Arylation reactions of aryl or heterocyclic thiols 88.
Scheme 38: Site-selective S-arylation reactions of cysteine thiol groups in 91 and 94 in the presence of diary...
Scheme 39: The selective S-arylation of sulfenamides 97 using diphenyliodonium salts 98.
Scheme 40: Plausible mechanism for the synthesis of sulfilimines 99.
Scheme 41: Synthesis of S-arylxanthates 102 by reacting DAIS 101 with potassium alkyl xanthates 100.
Figure 2: Structured of the 8-membered and 4-membered heterotetramer I and II.
Scheme 42: S-Arylation by diaryliodonium cations 103 using KSCN (104) as a sulfur source.
Scheme 43: S-Arylation of phosphorothioate diesters 107 through the utilization of diaryliodonium salts 108.
Scheme 44: Transfer of the aryl group from the hypervalent iodonium salt 108 to phosphorothioate diester 107.
Scheme 45: Synthesis of diarylselenides 118 via diarylation of selenocyanate 115.
Scheme 46: Light-promoted arylation of tertiary phosphines 119 to quaternary phosphonium salts 121 using diary...
Scheme 47: Arylation of aminophosphorus substrate 122 to synthesize phosphine oxides 123 using aryl(mesityl)io...
Scheme 48: Reaction of diphenyliodonium triflate (16) with DMSO (124) via thia-Sommelet–Hauser rearrangement.
Scheme 49: Synthesis of biaryl compounds 132 by reacting diaryliodonium salts 131 with arylhydroxylamines 130 ...
Scheme 50: Synthesis of substituted indazoles 134 and 135 from N-hydroxyindazoles 133.
Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles
- Bilge Banu Yagci,
- Selin Ezgi Donmez,
- Onur Şahin and
- Yunus Emre Türkmen
Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6
- reaction. This type of olefin E–Z isomerization is likely to take place after the N-acyliminium formation, possibly via a Michael/retro-Michael addition sequence between the chloride (Cl−) anion and the electron-deficient olefin of the N-acyliminium intermediate at 80 °C (Scheme 9c). In conclusion, these
Graphical Abstract
Scheme 1: Examples of aza-Nazarov reactions.
Scheme 2: Aza-Nazarov cyclization on gram scale.
Scheme 3: Scope of the aza-Nazarov cyclization with acyclic imines. aThe syntheses of aza-Nazarov products 19b...
Figure 1: X-ray crystal structure of compound 19l.
Scheme 4: Proposed mechanism for the formation of diastereomers 19 and 22.
Scheme 5: Preparation of acyl chloride 23.
Scheme 6: Aza-Nazarov reaction tested using β-TMS-substituted acyl chloride 23.
Scheme 7: Hydrolysis of N-acyliminium intermediates.
Scheme 8: (a) Two possible pathways for the formation of 7 and (b) investigation of the reaction between imin...
Scheme 9: (a) Preparation of acyl chlorides 6ba and 6bb in diastereomerically pure forms, (b) aza-Nazarov cyc...
Pauson–Khand reaction of fluorinated compounds
- Jorge Escorihuela,
- Daniel M. Sedgwick,
- Alberto Llobat,
- Mercedes Medio-Simón,
- Pablo Barrio and
- Santos Fustero
Beilstein J. Org. Chem. 2020, 16, 1662–1682, doi:10.3762/bjoc.16.138
- in wet nitromethane under reflux, clean conjugate addition/detrifluoromethylation was observed, in this case followed by retro-Michael reaction of nitromethane achieving enones 65 in moderate to good yields (Scheme 37). Interestingly, the overall reaction sequence results in the formal inversion of
Graphical Abstract
Scheme 1: Schematic representation of the Pauson–Khand reaction.
Scheme 2: Substrates included in this review.
Scheme 3: Commonly accepted mechanism for the Pauson–Khand reaction.
Scheme 4: Regioselectivity of the PKR.
Scheme 5: Variability at the acetylenic and olefinic counterpart.
Scheme 6: Pauson–Khand reaction of fluoroolefinic enynes reported by the group of Ishizaki [46].
Scheme 7: PKR of enynes bearing fluorinated groups on the alkynyl moiety, reported by the group of Ishizaki [46]....
Scheme 8: Intramolecular PKR of 1,7-enynes reported by the group of Billard [47].
Scheme 9: Intramolecular PKR of 1,7-enynes reported by the group of Billard [48].
Scheme 10: Intramolecular PKR of 1,7-enynes by the group of Bonnet-Delpon [49]. Reaction conditions: i) Co(CO)8 (1...
Scheme 11: Intramolecular PKR of 1,6-enynes reported by the group of Ichikawa [50].
Scheme 12: Intramolecular Rh(I)-catalyzed PKR reported by the group of Hammond [52].
Scheme 13: Intramolecular PKR of allenynes reported by the group of Osipov [53].
Scheme 14: Intramolecular PKR of 1,7-enynes reported by the group of Osipov [53].
Scheme 15: Intramolecular PKR of fluorine-containing 1,6-enynes reported by the Konno group [54].
Scheme 16: Diastereoselective PKR with enantioenriched fluorinated enynes 34 [55].
Scheme 17: Intramolecular PKR reported by the group of Martinez-Solorio [56].
Scheme 18: Fluorine substitution at the olefinic counterpart.
Scheme 19: Synthesis of fluorinated enynes 37 [59].
Scheme 20: Fluorine-containing substrates in PKR [59].
Scheme 21: Pauson Khand reaction for fluorinated enynes by the Fustero group: scope and limitations [59].
Scheme 22: Synthesis of chloro and bromo analogues [59].
Scheme 23: Dimerization pathway [59].
Scheme 24: Synthesis of fluorine-containing N-tethered 1,7-enynes [61].
Scheme 25: Intramolecular PKR of chiral N-tethered fluorinated 1,7-enynes [61].
Scheme 26: Examples of further modifications to the Pauson−Khand adducts [61].
Scheme 27: Asymmetric synthesis the fluorinated enynes 53.
Scheme 28: Intramolecular PKR of chiral N-tethered 1,7-enynes 53 [64].
Scheme 29: Intramolecular PKR of chiral N-tethered 1,7-enyne bearing a vinyl fluoride [64].
Scheme 30: Catalytic intramolecular PKR of chiral N-tethered 1,7-enynes [64].
Scheme 31: Model fluorinated alkynes used by Riera and Fustero [70].
Scheme 32: PKR with norbornadiene and fluorinated alkynes 58 [71].
Scheme 33: Nucleophilic addition/detrifluoromethylation and retro Diels-Alder reactions [70].
Scheme 34: Tentative mechanism for the nucleophilic addition/retro-aldol reaction sequence.
Scheme 35: Catalytic PKR with norbornadiene [70].
Scheme 36: Scope of the PKR of trifluoromethylalkynes with norbornadiene [72].
Scheme 37: DBU-mediated detrifluoromethylation [72].
Scheme 38: A simple route to enone 67, a common intermediate in the total synthesis of α-cuparenone.
Scheme 39: Effect of the olefin partner in the regioselectivity of the PKR with trifluoromethyl alkynes [79].
Scheme 40: Intermolecular PKR of trifluoromethylalkynes with 2-norbornene reported by the group of Konno [54].
Scheme 41: Intermolecular PKR of diarylalkynes with 2-norbornene reported by the group of Helaja [80].
Scheme 42: Intermolecular PKR reported by León and Fernández [81].
Scheme 43: PKR reported with cyclopropene 73 [82].
Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones
- Alexander N. Reznikov,
- Anastasiya E. Sibiryakova,
- Marat R. Baimuratov,
- Eugene V. Golovin,
- Victor B. Rybakov and
- Yuri N. Klimochkin
Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127
- diastereomer 8a was dissolved in chloroform-d and the formation of the second diastereomer 9a was monitored by 1H NMR. Surprisingly, we found that, along with the epimerization of (2R,3S)-8a to (2S,3S)-9a, retro-Michael reaction occurred (Figure 4). It is noteworthy that firstly the formation of sulfone 5a was
- solution, but also as a result of dynamic equilibrium between the Michael/retro-Michael products. This assumption is confirmed by a partial racemization of sulfones 8 at a prolonged storage, passing both the stereocenter at position 2 and the stereocenter at the position 3 (according to the HPLC data
- the reaction was observed. Рharmacologically active sulfones. Structures of the ligands L1–L8. Evolution of the conversion of 5 and diastereomeric composition of the products of reaction of 5a with 6a in the presence of catalyst 7a (2 mol %) in chloroform-d. Time profile of epimerization and retro
Graphical Abstract
Figure 1: Рharmacologically active sulfones.
Figure 2: Structures of the ligands L1–L8.
Figure 3: Evolution of the conversion of 5 and diastereomeric composition of the products of reaction of 5a w...
Figure 4: Time profile of epimerization and retro-Michael reaction of (2R,3S)-8a in chloroform-d solution.
Figure 5: ORTEP diagram of (2R,3S)-8d.
Scheme 1: The proposed mechanism of asymmetric addition of β-ketosulfones to nitroalkenes.
Scheme 2: Transition state models for asymmetric addition of β-ketosulfones to nitroalkenes.
(Thio)urea-mediated synthesis of functionalized six-membered rings with multiple chiral centers
- Giorgos Koutoulogenis,
- Nikolaos Kaplaneris and
- Christoforos G. Kokotos
Beilstein J. Org. Chem. 2016, 12, 462–495, doi:10.3762/bjoc.12.48
- ) pathway of a Michael–retro-Michael–Michael–Michael reaction. The same year Zhao and co-workers reported a novel domino Michael–Knoevenagel reaction between 2-mercaptobenzaldehydes 163 and easily accessible Michael acceptors 169 catalyzed by 9-epi-aminoquinine thiourea 57 (Scheme 55) [76]. Various adducts
Graphical Abstract
Scheme 1: Activation of carbonyl compounds via enamine and iminium intermediates [2].
Scheme 2: Electronic and steric interactions present in enamine activation mode [2].
Scheme 3: Electrophilic activation of carbonyl compounds by a thiourea moiety.
Scheme 4: Asymmetric synthesis of dihydro-2H-pyran-6-carboxylate 3 using organocatalyst 4 [16].
Scheme 5: Possible hydrogen-bonding for the reaction of (E)-methyl 2-oxo-4-phenylbut-3-enoate [16].
Scheme 6: Asymmetric desymmetrization of 4,4-cyclohexadienones using the Michael addition reaction with malon...
Scheme 7: The enantioselective synthesis of α,α-disubstituted cycloalkanones using catalyst 11 [18].
Scheme 8: The enantioselective synthesis of indolo- and benzoquinolidine compounds through aza-Diels–Alder re...
Scheme 9: Enantioselective [5 + 2] cycloaddition [20].
Scheme 10: Asymmetric synthesis of oxazine derivatives 26 [21].
Scheme 11: Asymmetric synthesis of bicyclo[3.3.1]nonadienone, core 30 present in (−)-huperzine [22].
Scheme 12: Asymmetric inverse electron-demand Diels-Alder reaction catalyzed by amine-thiourea 34 [23].
Scheme 13: Asymmetric entry to morphan skeletons, catalyzed by amine-thiourea 37 [24].
Scheme 14: Asymmetric transformation of (E)-2-nitroallyl acetate [25].
Scheme 15: Proposed way of activation.
Scheme 16: Asymmetric synthesis of nitrobicyclo[3.2.1]octan-2-one derivatives [26].
Scheme 17: Asymmetric tandem Michael–Henry reaction catalyzed by 50 [27].
Scheme 18: Asymmetric Diels–Alder reactions of 3-vinylindoles 51 [29].
Scheme 19: Proposed transition state and activation mode of the asymmetric Diels–Alder reactions of 3-vinylind...
Scheme 20: Desymmetrization of meso-anhydrides by Chin, Song and co-workers [30].
Scheme 21: Desymmetrization of meso-anhydrides by Connon and co-workers [31].
Scheme 22: Asymmetric intramolecular Michael reaction [32].
Scheme 23: Asymmetric addition of malonate to 3-nitro-2H-chromenes 67 [33].
Scheme 24: Intramolecular desymmetrization through an intramolecular aza-Michael reaction [34].
Scheme 25: Enantioselective synthesis of (−)-mesembrine [34].
Scheme 26: A novel asymmetric Michael–Michael reaction [35].
Scheme 27: Asymmetric three-component reaction catalyzed by Takemoto’s catalyst 77 [46].
Scheme 28: Asymmetric domino Michael–Henry reaction [47].
Scheme 29: Asymmetric domino Michael–Henry reaction [48].
Scheme 30: Enantioselective synthesis of derivatives of 3,4-dihydro-2H-pyran 89 [49].
Scheme 31: Asymmetric addition of α,α-dicyano olefins 90 to 3-nitro-2H-chromenes 91 [50].
Scheme 32: Asymmetric three-component reaction producing 2,6-diazabicyclo[2.2.2]octanones 95 [51].
Scheme 33: Asymmetric double Michael reaction producing substituted chromans 99 [52].
Scheme 34: Enantioselective synthesis of multi-functionalized spiro oxindole dienes 106 [53].
Scheme 35: Organocatalyzed Michael aldol cyclization [54].
Scheme 36: Asymmetric synthesis of dihydrocoumarins [55].
Scheme 37: Asymmetric double Michael reaction en route to tetrasubstituted cyclohexenols [56].
Scheme 38: Asymmetric synthesis of α-trifluoromethyl-dihydropyrans 121 [58].
Scheme 39: Tyrosine-derived tertiary amino-thiourea 123 catalyzed Michael hemiaketalization reaction [59].
Scheme 40: Enantioselective entry to bicyclo[3.2.1]octane unit [60].
Scheme 41: Asymmetric synthesis of spiro[4-cyclohexanone-1,3’-oxindoline] 126 [61].
Scheme 42: Kinetic resolution of 3-nitro-2H-chromene 130 [62].
Scheme 43: Asymmetric synthesis of chromanes 136 [63].
Scheme 44: Wang’s utilization of β-unsaturated α-ketoesters 87 [64,65].
Scheme 45: Asymmetric entry to trifluoromethyl-substituted dihydropyrans 144 [66].
Scheme 46: Phenylalanine-derived thiourea-catalyzed domino Michael hemiaketalization reaction [67].
Scheme 47: Asymmetric synthesis of α-trichloromethyldihydropyrans 149 [68].
Scheme 48: Takemoto’s thiourea-catalyzed domino Michael hemiaketalization reaction [69].
Scheme 49: Asymmetric synthesis of densely substituted cyclohexanes [70].
Scheme 50: Enantioselective synthesis of polysubstituted chromeno [4,3-b]pyrrolidine derivatines 157 [71].
Scheme 51: Enantioselective synthesis of spiro-fused cyclohexanone/5-oxazolone scaffolds 162 [72].
Scheme 52: Utilizing 2-mercaptobenzaldehydes 163 in cascade processes [73,74].
Scheme 53: Proposed transition state of the initial sulfa-Michael step [74].
Scheme 54: Asymmetric thiochroman synthesis via dynamic kinetic resolution [75].
Scheme 55: Enantioselective synthesis of thiochromans [76].
Scheme 56: Enantioselective synthesis of chromans and thiochromans synthesis [77].
Scheme 57: Enantioselective sulfa-Michael aldol reaction en route to spiro compounds [78].
Scheme 58: Enantioselective synthesis of 4-aminobenzo(thio)pyrans 179 [79].
Scheme 59: Asymmetric synthesis of tetrahydroquinolines [80].
Scheme 60: Novel asymmetric Mannich–Michael sequence producing tetrahydroquinolines 186 [81].
Scheme 61: Enantioselective synthesis of biologically interesting chromanes 190 and 191 [82].
Scheme 62: Asymmetric tandem Henry–Michael reaction [83].
Scheme 63: An asymmetric synthesis of substituted cyclohexanes via a dynamic kinetic resolution [84].
Scheme 64: Three component-organocascade initiated by Knoevenagel reaction [85].
Scheme 65: Asymmetric Michael reaction catalyzed by catalysts 57 and 211 [86].
Scheme 66: Proposed mechanism for the asymmetric Michael reaction catalyzed by catalysts 57 and 211 [86].
Scheme 67: Asymmetric facile synthesis of hexasubstituted cyclohexanes [87].
Scheme 68: Dual activation catalytic mechanism [87].
Scheme 69: Asymmetric Michael–Michael/aldol reaction catalyzed by catalysts 57, 219 and 214 [88].
Scheme 70: Asymmetric synthesis of substituted cyclohexane derivatives, using catalysts 57 and 223 [89].
Scheme 71: Asymmetric synthesis of substituted piperidine derivatives, using catalysts 223 and 228 [90].
Scheme 72: Asymmetric synthesis of endo-exo spiro-dihydropyran-oxindole derivatives catalyzed by catalyst 232 [91]....
Scheme 73: Asymmetric synthesis of carbazole spiroxindole derivatives, using catalyst 236 [92].
Scheme 74: Enantioselective formal [2 + 2] cycloaddition of enal 209 with nitroalkene 210, using catalysts 23 ...
Scheme 75: Asymmetric synthesis of polycyclized hydroxylactams derivatives, using catalyst 242 [94].
Scheme 76: Asymmetric synthesis of product 243, using catalyst 246 [95].
Scheme 77: Formation of the α-stereoselective acetals 248 from the corresponding enol ether 247, using catalys...
Scheme 78: Selective glycosidation, catalyzed by Shreiner’s catalyst 23 [97].
Bifunctional phase-transfer catalysis in the asymmetric synthesis of biologically active isoindolinones
- Antonia Di Mola,
- Maximilian Tiffner,
- Francesco Scorzelli,
- Laura Palombi,
- Rosanna Filosa,
- Paolo De Caprariis,
- Mario Waser and
- Antonio Massa
Beilstein J. Org. Chem. 2015, 11, 2591–2599, doi:10.3762/bjoc.11.279
- the C=O group of the lactam. A similar retro-Michael racemization mechanism can be envisioned for the Krapcho decarboxylation, in which the Lewis acid Li+ can coordinate the lactam group. In principle, racemization could also occur on 7. However, under the optimized conditions, the decarboxylation is
- isoindolinones 9 via retro-Michael process. Asymmetric synthesis of (S)-PD172938. Coupling of chiral acid 9 with p-tolylpiperazine and CuI arylation of chiral isoindolinones. Catalyst screening in asymmetric cascade reactions of 2-cyanobenzaldehyde. Optimization of the asymmetric cascade reaction. Optimization
Graphical Abstract
Figure 1: Some chiral, bioactive isoindolinones.
Scheme 1: This work: 1) trans-1,2-cyclohexane diamine-based bifunctional ammonium salts 8 in the asymmetric s...
Scheme 2: Asymmetric cascade, crystallization and decarboxylation reaction.
Scheme 3: Proposed racemization pathways of isoindolinones 9 via retro-Michael process.
Scheme 4: Asymmetric synthesis of (S)-PD172938.
Scheme 5: Coupling of chiral acid 9 with p-tolylpiperazine and CuI arylation of chiral isoindolinones.
Stereoselective, nitro-Mannich/lactamisation cascades for the direct synthesis of heavily decorated 5-nitropiperidin-2-ones and related heterocycles
- Pavol Jakubec,
- Dane M. Cockfield,
- Madeleine Helliwell,
- James Raftery and
- Darren J. Dixon
Beilstein J. Org. Chem. 2012, 8, 567–578, doi:10.3762/bjoc.8.64
- with the generally high diastereocontrol in the formation of piperidinones 1a–j and 2a–l is interesting and worthy of further commentary. With the knowledge that the retro-Michael reaction does not occur under standard reaction conditions (Scheme 4) and assuming that the final step of the cascade (the
Graphical Abstract
Figure 1: Biologically active natural products and drugs containing the piperidine ring.
Scheme 1: A general strategy to 5-nitropiperidin-2-ones and related heterocycles.
Scheme 2: The synthesis of Michael adduct model substrates for the nitro-Mannich/lactamisation cascade.
Scheme 3: Nitro-Mannich/lactamisation cascade with in situ formed imines.
Figure 2: Cyclic imines employed in nitro-Mannich/lactamisation cascade.
Scheme 4: Nitro-Mannich/lactamisation cascade of diastereomeric Michael adducts 6a, 6a’’ with cyclic imine 5a....
Scheme 5: Nitro-Mannich/lactamisation cascade with cyclic imines. aDiastereomeric ratio in a crude reaction m...
Scheme 6: Possible explanations for the observed high stereoselectivities in the nitro-Mannich/lactamisation ...
Scheme 7: Thermodynamically-driven epimerisation of 5-nitropiperidin-2-ones 2m and 2m’.
Figure 3: Thermodynamically driven epimerisation of 5-nitropiperidin-2-ones 2m and 2m’; identical diastereome...
Scheme 8: One-pot three/four-component enantioselective Michael addition/nitro-Mannich/lactamisation cascade.
Scheme 9: Protodenitration of 5-nitropiperidin-2-ones.
Scheme 10: Various reductions of denitrated heterocycles.
Michael-type addition of azoles of broad-scale acidity to methyl acrylate
- Sławomir Boncel,
- Kinga Saletra,
- Barbara Hefczyc and
- Krzysztof Z. Walczak
Beilstein J. Org. Chem. 2011, 7, 173–178, doi:10.3762/bjoc.7.24
- important drugs, have seldomly been considered as aza-Michael donors due to their poor nucleophilicity and the possible tendency of adducts to undergo retro-Michael reactions [26]. Here, we present Michael-type addition of azoles, inter alia imidazole and 1,2,4-triazole derivatives of high acidity (pKa
- retro-Michael reaction – in equilibrium with Michael-type addition. By contrast, DIPEA, with a lower pKa gave the same adducts 3a and 3b in excellent yields. For 1b (the azole with the lowest acidity) a similar yield to 1a was achieved only after a significantly prolonged reaction time due to its lower
- Michael-type addition of uracils to acrylic acceptors [27][42], where a a strongly basic catalyst (DBU) enabled control of regioselectivity via a retro-Michael reaction. Conclusion We have developed and optimised a simple and effective synthetic protocol for Michael-type addition of azoles of broad-scale
Graphical Abstract
Figure 1: Examples of azole derivatives as important therapeutic agents.
Scheme 1: Michael-type addition of azoles of broad-scale acidity 1a–h to methyl acrylate (2) under basic cond...
Scheme 2: Chemical evidence for a regioselective Michael-type addition of 4(5)-nitroimidazole (1c) to methyl ...
Mitomycins syntheses: a recent update
- Jean-Christophe Andrez
Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33
- lithium aluminum hydride and replaced by a 3-acetyl propyl group to give 168. This group was removed by hydrolysis, Pfitzner–Moffat oxidation [122] and retro-Michael (steps x, y, z). As discussed before, all the benzyl groups were removed at once to yield compound 169 after exposure to air. The key step
Graphical Abstract
Scheme 1: Aziridine containing natural products.
Scheme 2: Mitomycin structures and nomenclature.
Scheme 3: Base catalysed epimerization of mitomycin B.
Scheme 4: Biosynthesis of mitomycin C (MMC) 7.
Scheme 5: Mode of action of mitomycin C.
Scheme 6: The N–C3–C9a disconnection.
Scheme 7: Danishefsky’s Retrosynthesis of mitomycin K.
Scheme 8: Hetero Diels–Alder reaction en route to mitomycins.
Scheme 9: Nitroso Diels–Alder cycloaddition.
Scheme 10: Frank azide cycloadddition.
Scheme 11: Final steps of mitomycin K synthesis. aPDC, DCM; bPhSCH2N3, PhH, 80 °C; cL-selectride, THF, −78 °C; ...
Scheme 12: Naruta–Maruyama retrosynthesis.
Scheme 13: Synthesis of a leucoaziridinomitosane by nitrene cycloaddition. aAlCl3-Et2O; bNaH, ClCH2OMe; cn-BuL...
Scheme 14: Thermal decomposition of azidoquinone 51.
Scheme 15: Diastereoselectivity during the cycloaddition.
Scheme 16: Oxidation with iodo-azide.
Scheme 17: Williams’ approach towards mitomycins.aDEIPSCl, Imidazole, DCM; bPd/C, HCO2NH4, MeOH; cAllocCl, NaH...
Scheme 18: Synthesis of pyrrolidones by homoconjugate addition.
Scheme 19: Homoconjugate addition on the fully functionalized substrate.
Scheme 20: Introduction of the olefin.
Scheme 21: Retrosynthesis of N–C9a, N–C3 bond formation.
Scheme 22: Synthesis of the pyrrolo[1,2]indole 82 using N-PSP activation.aAc2O, Py; bAc2O, Hg(OAc)2, AcOH, 90%...
Scheme 23: Synthesis of an aziridinomitosane. am-CPBA, DCM then iPr2NH, CCl4 reflux; bK2CO3, MeOH; cBnBr, KH; d...
Scheme 24: Oxidation products of a leucoaziridinomitosane obtained from a Polonovski oxidation.
Scheme 25: Polonovski oxidation of an aziridinomitosane. am-CPBA; bPd/C, H2; cDimethoxypropane, PPTS.
Scheme 26: The C1–C9a disconnection.
Scheme 27: Ziegler synthesis of desmethoxymitomycin A.aIm2C=O, THF; bNH3; cTMSOTf, 2,6-di-tert-butylpyridine, ...
Scheme 28: Transformation of sodium erythorbate.aTBDMSCl; bNaN3; cPPh3; d(Boc)2O, DMAP; eTBAF; fTf2O, Pyr.
Scheme 29: Formation of C9,C10-unsaturation in the mitomycins. am-CPBA, DCM; bO3, MeOH; cMe2S; dKHMDS, (EtO)3P...
Scheme 30: Fragmentation mechanism.
Scheme 31: Michael addition-cyclisation.
Scheme 32: SmI2 8-endo-dig cyclisation.
Scheme 33: Synthesis of pyrrolo[1,2-a]indole by 5-exo-dig radical cyclization.
Scheme 34: The C9–C9a disconnection.
Scheme 35: Intramolecular nitrile oxide cycloaddition.
Scheme 36: Regioselectivity of the INOC.
Scheme 37: Fukuyama’s INOC strategy.
Scheme 38: Synthesis of a mitosane core by rearrangement of a 1-(1-pyrrolidinyl)-1,3-butadiene.
Scheme 39: Sulikowski synthesis of an aziridinomitosene. aPd(Tol3P)2Cl2, Bu3SnF, 140; bH2, Pd/C; cTFAA, Et3N; d...
Scheme 40: Enantioselective carbene insertion.
Scheme 41: Parson’s radical cyclization.
Scheme 42: Cha’s mitomycin B core synthesis.
Scheme 43: The N-aromatic disconnection.
Scheme 44: Kishi retrosynthesis.
Scheme 45: Kishi synthesis of a starting material. aallyl bromide, K2CO3, acetone, reflux; bN,N-Dimethylanilin...
Scheme 46: Kishi synthesis of MMC 7. aLDA, THF, −78 °C then PhSeBr, THF, −78 °C; bH2O2, THF-EtOAc; cDIBAL, DCM...
Scheme 47: Acid catalyzed degradation of MMC 7.
Scheme 48: In vivo formation of apomitomycin B.
Scheme 49: Advanced intermediate for apomitomycin B synthesis.
Scheme 50: Remers synthesis of a functionalized mitosene. aTMSCl, Et3N, ZnCl2 then NBS; bAcOK; cNH2OH; dPd/C, H...
Scheme 51: Coleman synthesis of desmethoxymitomycin A. aSnCl2, PhSH, Et3N, CH3CN; bClCO2Bn, Et3N; cPPh3, DIAD,...
Scheme 52: Transition state and pyrrolidine synthesis.
Scheme 53: Air oxidation of mitosanes and aziridinomitosanes.
Scheme 54: The C9-aromatic disconnection.
Scheme 55: Synthesis of the aziridine precursor. aLHMDS, THF; bNaOH; c(s)-α-Me-BnNH2, DCC, HOBT; dDIBAL; eK2CO3...
Scheme 56: Synthesis of 206 via enamine conjugate addition.
Scheme 57: Rapoport synthesis of an aziridinomitosene.
Scheme 58: One pot synthesis of a mitomycin analog.
Scheme 59: Synthesis of compound 218 via intramolecular Heck coupling. aEtMgCl, THF, then 220; bMsCl, Et3N; cN...
Scheme 60: Elaboration of indole 223. aEt3N, Ac2O; bAcOH; cSOCl2, Et3N; dNaN3, DMF; eH2SO4, THF; fK2CO3, MeOH; ...
Scheme 61: C9-C9a functionalization from indole.
Scheme 62: Synthesis of mitomycin K. a2 equiv. MoO5.HMPA, MeOH; bPPh3, Et3N, THF-H2O; cMeOTf, Py, DCM; dMe3SiCH...
Scheme 63: Configurational stability of mitomycin K derivatives.
Scheme 64: Epimerization of carbon C9a in compound 227b.
Scheme 65: Corey–Chaykovsky synthesis of indol 235.
Scheme 66: Cory intramolecular aza-Darzens reaction for the formation of aziridinomitosene 239.
Scheme 67: Jimenez synthesis of aziridinomitosene 242.
Scheme 68: Von Braun opening of indoline 244.
Scheme 69: C9a oxidation of an aziridinomitosane with DDQ/OsO4.
Scheme 70: Synthesis of epi-mitomycin K. aNaH, Me2SO4; bH2, Pd/C; cMitscher reagent [165]; d[(trimethylsilyl)methyl...
Scheme 71: Mitomycins rearrangement.
Scheme 72: Fukuyama’s retrosynthesis.
Scheme 73: [2+3] Cycloaddition en route to isomitomycin A. aToluene, 110 °C; bDIBAL, THF, −78 °C; cAc2O, Py.; d...
Scheme 74: Final steps of Fukuyama’s synthesis.
Scheme 75: “Crisscross annulation”.
Scheme 76: Synthesis of 274; the 8-membered ring 274 was made using a crisscross annulation. a20% Pd(OH)2/C, H2...
Scheme 77: Conformational analysis of compound 273 and 275.
Scheme 78: Synthesis of a mitomycin analog. aNa2S2O4, H2O, DCM; bBnBr (10 equiv), K2CO3, 18-crown-6 (cat.), TH...
Scheme 79: Vedejs retrosynthesis.
Scheme 80: Formation of the azomethine ylide.
Scheme 81: Vedejs second synthesis of an aziridinomitosene. aDIBAL; bTPAP, NMO; c287; dTBSCl, imidazole.
Scheme 82: Trityl deprotection and new aziridine protecting group 300.
Scheme 83: Ene reaction towards benzazocinones.
Scheme 84: Benzazocenols via homo-Brook rearrangement.
Scheme 85: Pt-catalyzed [3+2] cycloaddition.
Scheme 86: Carbonylative lactamization entry to benzazocenols. aZn(OTf)2, (+)-N-methylephedrine, Et3N, TMS-ace...
Scheme 87: 8 membered ring formation by RCM. aBOC2O, NaHCO3; bTBSCl, Imidazole, DMF; callyl bromide, NaH, DMF; ...
Scheme 88: Aziridinomitosene synthesis. aTMSN3; bTFA; cPOCl3, DMF; dNaClO2, NaH2PO4, 2-methyl-2-butene; eMeI, ...
Scheme 89: Metathesis from an indole.
Scheme 90: Synthesis of early biosynthetic intermediates of mitomycins.
Multiple hydride reduction pathways in isoflavonoids
- Auli K. Salakka,
- Tuija H. Jokela and
- Kristiina Wähälä
Beilstein J. Org. Chem. 2006, 2, No. 16, doi:10.1186/1860-5397-2-16
- of isoflavones [10][16][17][18][19][20]. Deoxybenzoins (5) and propenols (6) Isoflavanones undergo a facile retro-Michael-type ring opening [21][55] under basic conditions to give the propenone intermediate 14 (Figure 2), sometimes considered [56] to be an independent isoflavone metabolite but
- conditions, the ketone is generated, and reduced further to the saturated alcohol (NaBH4). In a nonprotic solvent, the β-aryloxyenolate will undergo a retro-Michael addition, giving the phenolate anion of the ring opened 2-propen-1-one which may undergo a 1,2- or 1,4-addition of hydride (LiAlH4, LiBH4). If
Graphical Abstract
Figure 1: Isoflavonoid subclasses.
Figure 2: 2-Isoflaven-4-ols and 1-(2-hydroxyphenyl)-2-phenyl-2-propen-1-one
Figure 3:
Dietary isoflavones and their metabolites in humans.
e R4’=OMe, R7= OH, other R groups = H
f R4’= OMe...
