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Search for "borane" in Full Text gives 95 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis of the aggregation pheromone of Tribolium castaneum
- Biyu An,
- Xueyang Wang,
- Ao Jiao,
- Qinghua Bian and
- Jiangchun Zhong
Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38
- olefine (5R,9R)-12, which could be obtained through Li2CuCl4-catalyzed coupling of chiral tosylate (S)-10 with a Grignard reagent derived from (R)-1-bromo-2-methylbutane ((R)-11). The key chiral building block (S)-10 was envisaged to be prepared through a sequence of hydrolyzation, decarboxylation, borane
- , geminal acid (S)-7 was decarboxylated with DMSO to yield chiral acid (S)-8 [33], followed by TiCl4-catalyzed reduction with ammonia-borane to obtain the chiral alkenyl alcohol (S)-9 [34]. The final tosylation with p-tosyl chloride provided (S)-3-methylhept-6-en-1-yl 4-methylbenzenesulfonate ((S)-10) [29
Graphical Abstract
Figure 1: The aggregation pheromone of Tribolium castaneum.
Scheme 1: Retrosynthetic analysis of the aggregation pheromone (4R,8R)-1.
Scheme 2: Synthesis of chiral tosylate (S)-10.
Scheme 3: Synthesis of chiral tosylate (R)-10.
Scheme 4: Synthesis of the aggregation pheromone of Tribolium castaneum.
Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides
- Ayesha Saeed,
- Shahana Ehsan,
- Muhammad Zia-ur-Rehman,
- Erin M. Marshall,
- Sandra Loesgen,
- Abdus Saleem,
- Simone Giovannuzzi and
- Claudiu T. Supuran
Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25
- assays [36] (Figure 1A). In continuation of this work, these derivatives have also been investigated for their remarkable anti-HIV-1 activity [37] (Figure 1B). The same research group reported the synthesis of acetamide derivatives of pyrazolo-1,2-benzothiazines as anticancer drugs using a borane-THF
Graphical Abstract
Figure 1: An overview of previously synthesized 1,2-benzothiazines [36-39].
Scheme 1: General scheme for the synthesis of pyrazolo-1,2-benzothiazine-N-aryl/benzyl/cyclohexylacetamide.
Figure 2: An example of contrasting 1H NMR signals for monoalkylated (7a) and dialkylated (7l) derivatives, (...
Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation
- Perry van der Heide,
- Michele Retini,
- Fabiola Fanini,
- Giovanni Piersanti,
- Francesco Secci,
- Daniele Mazzarella,
- Timothy Noël and
- Alberto Luridiana
Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271
- radical activation, resulting in milder and safer reaction conditions [14][15][16]. Given the toxicity of tin-based compounds, there has been significant interest in developing alternative halogen-atom-transfer reagents. Borane, alkylamine, and silane compounds have emerged as effective XAT reagents upon
Graphical Abstract
Figure 1: Giese reaction: Radical addition on olefins with an electron-withdrawing group (EWG) followed by a ...
Figure 2: Alkyl bromide and Dha derivative scope. Reaction conditions: Dha derivative (0.5 mmol), alkyl bromi...
Figure 3: Scaled-up reaction. Reaction conditions: Dha derivative (2.2 mmol), alkyl bromide (5.4 mmol), tris(...
5th International Symposium on Synthesis and Catalysis (ISySyCat2023)
- Anthony J. Burke and
- Elisabete P. Carreiro
Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227
- Suzuki couplings and the reduction of the thiazole moiety to 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a crucial intermediate, using BH3⋅NH3 and tris(pentafluorophenyl)borane as a Lewis acid, followed by treatment with formic acid. Gillie et al. reported the synthesis of a laterally fused N-heterocyclic
Computational design for enantioselective CO2 capture: asymmetric frustrated Lewis pairs in epoxide transformations
- Maxime Ferrer,
- Iñigo Iribarren,
- Tim Renningholtz,
- Ibon Alkorta and
- Cristina Trujillo
Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224
- ]. One study reported a reaction involving the asymmetric reduction of ketones using an achiral borane, denoted as B(p-HC6F4)3, paired with a chiral oxazoline, as depicted in Scheme 3 [28]. Remarkably, in this study, these FLPs demonstrated the capability to achieve high conversion rates and enantiomeric
Graphical Abstract
Scheme 1: Reaction between propylene oxide (PO) and CO2 and the five catalyst scaffolds under study. The posi...
Figure 1: Schematic representation of an (A) 2D and a (B) 3D volcano plot. The abbreviation “cat.” stands for...
Scheme 2: Capture reactions of CO2 or an epoxide by FLP.
Figure 2: (A) Structure of PO annotated with the C–O bond distances and electron densities at the BCPs. BCPs ...
Figure 3: Symmetric FLP scaffolds considered in the first study. X denotes N or P.
Figure 4: Subset of FLP scaffolds considered in the catalyst optimisation study. Substituents and labels are ...
Figure 5: Coupling reaction between PO and CO2. Depending on the catalyst considered, the reaction follows me...
Figure 6: VOLCANO plot group 1. The free energies of pre-TS01 assembly and Min2 are considered for the correl...
Figure 7: VOLCANO plot group 2. The free energies of pre-TS01 assembly and Min2 are considered for the correl...
Scheme 3: Asymmetric catalysis studied. On the left, the catalyst proposed by Gao et al. for the asymmetric h...
Figure 8: Catalysed reaction between the (S)-enantiomer of propylene oxide and CO2 resulting in the formation...
Figure 9: Schemes of the different asymmetric reactions observed. Hydrogen capable of rotation is marked in o...
Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis
- Akiya Ogawa and
- Yuki Yamamoto
Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182
- phenanthridines via silver-catalyzed radical sulfonylation–cyclization of 2-isocyanobiphenyls (Scheme 25) [98]. Wang et al. reported a radical borylative cyclization of 2-isocyanobiaryls with N-heterocyclic carbene borane (Scheme 26) [99]. The boryl radical generated via hydrogen abstraction in the presence of di
Graphical Abstract
Figure 1: Resonance structures and reactivity of carbon monoxide.
Figure 2: Resonance structures and reactivity of isocyanides.
Scheme 1: Possible three pathways of the E• formation for imidoylation.
Scheme 2: Radical addition of thiols to isocyanides.
Scheme 3: Selective thioselenation and catalytic dithiolation of isocyanides.
Scheme 4: Synthesis of carbacephem framework.
Scheme 5: Sequential addition of (PhSe)2 to ethyl propiolate and isocyanide.
Scheme 6: Isocyanide insertion reaction into carbon-tellurium bonds.
Scheme 7: Radical addition to isocyanides with disubstituted phosphines.
Scheme 8: Radical addition to phenyl isocyanides with diphosphines.
Scheme 9: Radical reaction of tin hydride and hydrosilane toward isocyanide.
Scheme 10: Isocyanide insertion into boron compounds.
Scheme 11: Isocyanide insertion into cyclic compounds containing boron units.
Scheme 12: Photoinduced hydrodefunctionalization of isocyanides.
Scheme 13: Tin hydride-mediated indole synthesis and cross-coupling.
Scheme 14: 2-Thioethanol-mediated radical cyclization of alkenyl isocyanide.
Scheme 15: Thiol-mediated radical cyclization of o-alkenylaryl isocyanide.
Scheme 16: (PhTe)2-assisted dithiolative cyclization of o-alkenylaryl isocyanide.
Scheme 17: Trapping imidoyl radicals with heteroatom moieties.
Scheme 18: Trapping imidoyl radicals with isocyano group.
Scheme 19: Quinoline synthesis via aza-Bergman cyclization.
Scheme 20: Phenanthridine synthesis via radical cyclization of 2-isocyanobiaryls.
Scheme 21: Phenanthridine synthesis by radical reactions with AIBN, DBP and TTMSS.
Scheme 22: Phenanthridine synthesis by oxidative cyclization of 2-isocyanobiaryls.
Scheme 23: Phenanthridine synthesis using a photoredox system.
Scheme 24: Phenanthridine synthesis induced by phosphorus-centered radicals.
Scheme 25: Phenanthridine synthesis induced by sulfur-centered radicals.
Scheme 26: Phenanthridine synthesis induced by boron-centered radicals.
Scheme 27: Phenanthridine synthesis by oxidative cyclization of 2-aminobiaryls.
Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations
- Ryo Tanifuji and
- Hiroki Oguri
Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151
- pentacyclic secondary amine 97 bearing the ester linker in the C1 side chain in one pot. After removal of SfmC by precipitation and centrifugation, the reaction mixture containing secondary amine 97 was subjected to the reductive amination using 2-picoline borane as a hydride source, yielding tertiary amine
Graphical Abstract
Scheme 1: Targeted natural products and key enzymatic transformations in the chemo-enzymatic total syntheses ...
Scheme 2: Biosynthetic pathway to brassicicenes in Pseudocercospora fijiensis [14]. (A) Cyclization phase catalyz...
Scheme 3: Chemo-enzymatic total synthesis of cotylenol (1) and brassicicenes. (A) Chemical cyclization phase....
Scheme 4: (A) Biosynthetic pathway for trichodimerol (2) in Penicillium chrysogenum. (B) Chemo-enzymatic tota...
Scheme 5: (A) Proposed biosynthetic pathway for chalcomoracin (3) in Morus alba. (B) Outline of the biosynthe...
Scheme 6: (A) Chemo-enzymatically synthesized natural products by using the originally identified MaDA. (B) M...
Scheme 7: Proposed biosynthetic mechanism of tylactone (4) in Streptomyces fradiae.
Scheme 8: (A) Chemical synthesis and cascade enzymatic transformations of cyclization precursors. (B) Late-st...
Scheme 9: Proposed biosynthetic mechanism of saframycin A (5) in Streptomyces lavendulae.
Scheme 10: (A) Chemo-enzymatic total synthesis of saframycin A (5) and jorunnamycin A (103). (B) Chemo-enzymat...
Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations
- Mithu Roy,
- Bitan Sardar,
- Itu Mallick and
- Dipankar Srimani
Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119
- in DMF solvent and requires ca. 18 h to finish upon irradiation with blue LEDs. The catecholboronic esters produced at first are transesterified into pinacol borane by addition of pinacol and triethylamine. The reaction proved to be useful for a wide variety of substrates, such as borneol, menthol
Graphical Abstract
Figure 1: Generation of alkyl and acyl radicals via C–O bond breaking.
Figure 2: General photocatalytic mechanism.
Scheme 1: Photoredox-catalyzed hydroacylation of olefins with aliphatic carboxylic acids.
Scheme 2: Acylation–aromatization of p-quinone methides using carboxylic acids.
Scheme 3: Visible-light-induced deoxygenation–defluorination for the synthesis of γ,γ-difluoroallylic ketones....
Scheme 4: Photochemical hydroacylation of azobenzenes with carboxylic acids.
Scheme 5: Photoredox-catalyzed synthesis of flavonoids.
Scheme 6: Synthesis of O-thiocarbamates and photocatalytic reduction of O-thiocarbamates.
Scheme 7: Deoxygenative borylation of alcohols.
Scheme 8: Trifluoromethylation of O-alkyl thiocarbonyl substrates.
Scheme 9: Redox-neutral radical coupling reactions of alkyl oxalates and Michael acceptors.
Scheme 10: Visible-light-catalyzed and Ni-mediated syn-alkylarylation of alkynes.
Scheme 11: 1,2-Alkylarylation of alkenes with aryl halides and alkyl oxalates.
Scheme 12: Deoxygenative borylation of oxalates.
Scheme 13: Coupling of N-phthalimidoyl oxalates with various acceptors.
Scheme 14: Cross-coupling of O-alkyl xanthates with aryl halides via dual photoredox and nickel catalysis.
Scheme 15: Deoxygenative borylation of secondary alcohol.
Scheme 16: Deoxygenative alkyl radical generation from alcohols under visible-light photoredox conditions.
Scheme 17: Deoxygenative alkylation via alkoxy radicals against hydrogenation or β-fragmentation.
Scheme 18: Direct C–O bond activation of benzyl alcohols.
Scheme 19: Deoxygenative arylation of alcohols using NHC to activate alcohols.
Scheme 20: Deoxygenative conjugate addition of alcohol using NHC as alcohol activator.
Scheme 21: Synthesis of polysubstituted aldehydes.
Confirmation of the stereochemistry of spiroviolene
- Yao Kong,
- Yuanning Liu,
- Kaibiao Wang,
- Tao Wang,
- Chen Wang,
- Ben Ai,
- Hongli Jia,
- Guohui Pan,
- Min Yin and
- Zhengren Xu
Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77
- , respectively. The formation of all three products 9–11 can be explained as follows (Scheme 2A) [28][29][30][31]: Due to the favorable formation of cis-5,5-fused B/C ring system, the borane reagent is preferred to approach the double bond of 1 from the α-face, to give either a secondary 1-organoborane
- the 9-organoborane intermediate IM-16 probably through borane–olefin complexes. The suprafacial nature of the boron migration allowed the boron to be α-oriented in intermediate IM-16, which would give 10 with retention of the configuration after NaOH/H2O2 oxidation. The formation of a significant
- process. Derivatization of spiroviolene for X-ray crystallography. A) Hydroboration/oxidation reaction of spiroviolene involving a borane migration process. B) Synthesis of the hydrazone derivative of spiroviolene for single-crystal X-ray diffraction. Supporting Information Supporting Information File 19
Graphical Abstract
Figure 1: Structures of spiroviolene and related natural products.
Scheme 1: Possible cyclization mechanisms for spiroviolene (1) and related natural products. A) Revised cycli...
Figure 2: Heterologous production of spiroviolene using the isopentenol utilization pathway. A) Gas chromatog...
Scheme 2: Derivatization of spiroviolene for X-ray crystallography. A) Hydroboration/oxidation reaction of sp...
Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors
- Jens Frackenpohl,
- David M. Barber,
- Guido Bojack,
- Birgit Bollenbach-Wahl,
- Ralf Braun,
- Rahel Getachew,
- Sabine Hohmann,
- Kwang-Yoon Ko,
- Karoline Kurowski,
- Bernd Laber,
- Rebecca L. Mattison,
- Thomas Müller,
- Anna M. Reingruber,
- Dirk Schmutzler and
- Andrea Svejda
Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46
- (pentafluorophenyl)borane as a strong Lewis acid. Remarkably, greenhouse trials showed that some of the target compounds outlined herein display promising control of grass weed species in preemergence application, combined with a dose response window that enables partial selectivity in certain crops. Keywords: 2,3
- temperature [23] led to the cleavage of the thiazole ring, furnishing disulfides 18b and 18c exclusively (Table 1, entries 7–10). Interestingly, the reaction of 5 with ammonia borane at elevated temperature in toluene [20] furnished three reaction products with a low yield since 2,3-dihydro[1,3]thiazolo[4,5-b
- ]pyridine 7b was formed together with disulfide 18b and aminoborane 17b (Table 1, entry 11). We thus evaluated B(C6F5)3 as a nonmetallic catalyst to activate ammonia borane in the reductive hydrogenation of the C=N-bond in [1,3]thiazolo[4,5-b]pyridines 5 and 15c. In line with reports on the hydrogenation of
Graphical Abstract
Scheme 1: Selected known inhibitors 1–3 of acyl-ACP thioesterases (belonging to the protein family of FATs) a...
Scheme 2: Preparation of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines 7a–c and 13a–c via iron-mediated sulfur rem...
Scheme 3: Evaluation of potential side reactions in the borane-mediated preparation of 2,3-dihydro[1,3]thiazo...
Figure 1: Preemergence efficacy of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine-based FAT inhibitors 7b, 7c, and 1...
Figure 2: Preemergence efficacy of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridine-based FAT inhibitors 7b, 7c, and 1...
Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes
- Michio Yamada
Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13
- addition of B(C6H5)3, which may be due to the enhancement of the dienophilic nature of the cyano group due to coordination with borane. Rotaxane synthesis Push–pull chromophores with nonplanar configurations have been reported as effective stoppering motifs for rotaxane synthesis. A rational approach
Graphical Abstract
Scheme 1: Pathway of the [2 + 2] CA–RE reaction of an electron-rich alkyne with TCNE or TCNQ. EDG = electron-...
Scheme 2: Reaction pathway for DMA-appended acetylene and TCNEO.
Scheme 3: Pathway of the [2 + 2] CA–RE reaction between 1 and DCFs.
Scheme 4: Sequential double [2 + 2] CA–RE reactions between 1 and TCNE.
Scheme 5: Divergent chemical transformation pathways of TCBD 6.
Scheme 6: Synthesis of 12.
Scheme 7: [2 + 2] CA–RE reaction of 1 with 14. TCE = 1,1,2,2-tetrachloroethane.
Scheme 8: Autocatalytic model proposed by Nielsen et al.
Scheme 9: Synthesis of anthracene-embedded TCBD compound 19.
Scheme 10: Sequence of the [2 + 2] CA–RE reaction between dibenzo-fused cyclooctyne or cyclooctadiyne and TCNE...
Scheme 11: [2 + 2] CA–RE reaction between the CPP derivatives and TCNE. THF = tetrahydrofuran.
Scheme 12: [2 + 2] CA–RE reaction between ethynylfullerenes 31 and TCNE and subsequent thermal rearrangement.
Scheme 13: Pathway of the [2 + 2] CA–RE reaction between TCNE and 34, followed by additional skeletal transfor...
Scheme 14: Synthesis scheme for heterocycle 38 from the reaction between TCNE and 1 in water and a surfactant.
Scheme 15: Synthesis scheme of the CDA product 41.
Scheme 16: Synthesis of rotaxanes 44 and 46 via the [2 + 2] CA–RE reaction.
Scheme 17: Synthesis of a CuI bisphenanthroline-based rotaxane 50.
Figure 1: Structures of the chiral push–pull chromophores 51–56.
Figure 2: Structures of the axially chiral TCBD 57 and DCNQ 58 bearing a C60 core.
Figure 3: Structures of the axially chiral SubPc–TCBD–aniline conjugates 59 and 60 and the subporphyrin–TCBD–...
Figure 4: Structures of 63 and the TCBD 64.
Figure 5: Structures of the fluorophore-containing TCBDs 65–67.
Figure 6: Structures of the fluorophore-containing TCBDs 68–72.
Figure 7: Structures of the urea-containing TCBDs 73–75.
Figure 8: Structures of the fullerene–TCBD and DCNQ conjugates 76–79 and their reference compounds 80–83.
Figure 9: Structures of the ZnPc–TCBD–aniline conjugates 84 and 85.
Figure 10: Structures of the ZnP–PCBD and TCBD conjugates 86–88.
Figure 11: Structures of the porphyrin-based donor–acceptor conjugates (89–104).
Figure 12: Structures of the porphyrin–PTZ or DMA conjugates 105–112.
Figure 13: Structures of the BODIPY–Acceptor–TPA or PTZ conjugates 113–116.
Figure 14: Structures of the corrole–TCBD conjugates 117 and 118.
Figure 15: Structure of the dendritic TCBD 119.
Figure 16: Structures of the TCBDs 120–126.
Figure 17: Structures of the precursor 127 and TCBDs 128–130.
Figure 18: Structures of 131–134 utilized for BHJ OSCs.
Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp3)–H to construct C–C bonds
- Hui Yu and
- Feng Xu
Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94
- ]. The current synthesis method depends on the reaction of organic borane with epoxy carbonyl compounds. Using the CDC reaction can save some synthesis steps [105]. Based on DDQ-mediated oxidative C–H functionalization of benzyl ethers, the mechanism can be described as a single electron transfer (SET
Graphical Abstract
Scheme 1: Research progress of coupling reactions and active compounds containing α-C(sp3)-functionalized eth...
Scheme 2: Transition-metal-catalyzed CDC pathways.
Scheme 3: CDC of active methylene compounds in the α-C(sp3) position of ethers.
Scheme 4: InCl3/Cu(OTf)2/NHPI co-catalyzed CDC reaction.
Scheme 5: CDC of cyclic benzyl ethers with aldehydes.
Scheme 6: Cu-catalyzed CDC of (a) unactivated C(sp3)–H ethers with simple ketones and (b) double C(sp3)−H fun...
Scheme 7: Cu-catalyzed CDC of C(sp3)–H/C(sp3)–H bonds.
Scheme 8: Cu-catalyzed synthesis of chiral 2-substituted tetrahydropyrans.
Scheme 9: CDC of thiazole with cyclic ethers.
Scheme 10: Cu(I)-catalyzed oxidative alkenylation of simple ethers.
Scheme 11: Cross-dehydrogenation coupling of isochroman C(sp3)–H bonds with anisole C(sp2)–H bonds.
Scheme 12: Pd(OAc)2/Cu(OTf)2-catalyzed arylation of α-C(sp3)–H bonds of ethers.
Scheme 13: Cu-catalyzed C(sp3)–H/C(sp2)–H activation strategies to construct C(sp3)–C(sp2) bonds.
Scheme 14: Cu(I)-catalyzed C(sp2)–H alkylation.
Scheme 15: Cu-catalyzed C(sp3)–H/C(sp)–H activation to construct C(sp3)–C(sp) bonds (H2BIP: 2,6-bis(benzimidaz...
Scheme 16: Fe-catalyzed CDC reaction pathways.
Scheme 17: Fe2(CO)9-catalyzed functionalization of C–H bonds.
Scheme 18: Ligand-promoted Fe-catalyzed CDC reaction of N-methylaniline with ethers.
Scheme 19: Fe-catalyzed CDC of C(sp3)–H/C(sp3)–H bonds.
Scheme 20: Fe-catalyzed hydroalkylation of α,β-unsaturated ketones with ethers.
Scheme 21: Solvent-free Fe(NO3)3-catalyzed CDC of C(sp3)–H/C(sp2)–H bonds.
Scheme 22: Alkylation of disulfide compounds to afford tetrasubstituted alkenes.
Scheme 23: Fe-catalyzed formation of 1,1-bis-indolylmethane derivatives.
Scheme 24: Alkylation of coumarins and flavonoids.
Scheme 25: Direct CDC α-arylation of azoles with ethers.
Scheme 26: CDC of terminal alkynes with C(sp3)–H bonds adjacent to oxygen, sulfur or nitrogen atoms.
Scheme 27: Alkylation of terminal alkynes.
Scheme 28: Co-catalyzed functionalization of glycine esters.
Scheme 29: Co-catalyzed construction of C(sp2)–C(sp3) bonds.
Scheme 30: Co-catalyzed CDC of imidazo[1,2-a]pyridines with isochroman.
Scheme 31: Co-catalyzed C–H alkylation of (benz)oxazoles with ethers.
Scheme 32: Cobalt-catalyzed CDC between unactivated C(sp2)–H and C(sp3)–H bonds.
Scheme 33: MnO2-catalyzed CDC of the inactive C(sp3)-H.
Scheme 34: Oxidative cross-coupling of ethers with enamides.
Scheme 35: Ni(II)-catalyzed CDC of indoles with 1,4-dioxane.
Scheme 36: Chemo- and regioselective ortho- or para-alkylation of pyridines.
Scheme 37: Asymmetric CDC of 3,6-dihydro-2H-pyrans with aldehydes.
Scheme 38: CDC of heterocyclic aromatics with ethers.
Scheme 39: Indium-catalyzed alkylation of DHPs with 1,3-dicarbonyl compounds.
Scheme 40: Rare earth-metal-catalyzed CDC reaction.
Scheme 41: Visible-light-driven CDC of cycloalkanes with benzazoles.
Scheme 42: Photoinduced alkylation of quinoline with cyclic ethers.
Scheme 43: Photocatalyzed CDC reactions between α-C(sp3)–H bonds of ethers and C(sp2)–H bonds of aromatics.
Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update
- Anup Biswas
Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72
- benzofuran-2(3H)-one derivative 144 having an aza-quaternary stereocenter. The achiral Lewis acid tris(pentafluorophenyl)borane was required as additive in the reaction system to enhance the chemical yield and enantioselectivity. After two additional steps, i.e., demethylation of the phenolic ether and ester
Graphical Abstract
Scheme 1: First organocatalyzed asymmetric aza-Friedel–Crafts reaction.
Scheme 2: Aza-Friedel–Crafts reaction between indoles and cyclic ketimines.
Scheme 3: Aza-Friedel–Crafts reaction utilizing trifluoromethyldihydrobenzoazepinoindoles as electrophiles.
Scheme 4: Aza-Friedel–Crafts reaction utilizing cyclic N-sulfimines as electrophiles.
Scheme 5: Aza-Friedel–Crafts reaction involving N-unprotected imino ester as electrophile.
Scheme 6: Aza-Friedel–Crafts and lactonization cascade.
Scheme 7: One-pot oxidation and aza-Friedel–Crafts reaction.
Scheme 8: C1 and C2-symmetric phosphoric acids as catalysts.
Scheme 9: Aza-Friedel–Crafts reaction using Nps-iminophosphonates as electrophiles.
Scheme 10: Aza-Friedel–Crafts reaction between indole and α-iminophosphonate.
Scheme 11: [2.2]-Paracyclophane-derived chiral phosphoric acids as catalyst.
Scheme 12: Aza-Friedel–Crafts reaction through ring opening of sulfamidates.
Scheme 13: Isoquinoline-1,3(2H,4H)-dione scaffolds as electrophiles.
Scheme 14: Functionalization of the carbocyclic ring of substituted indoles.
Scheme 15: Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles.
Scheme 16: Anilines and α-naphthols as potential nucleophiles.
Scheme 17: Solvent-controlled regioselective aza-Friedel–Crafts reaction.
Scheme 18: Generating central and axial chirality via aza-Friedel–Crafts reaction.
Scheme 19: Reaction between indoles and racemic 2,3-dihydroisoxazol-3-ol derivatives.
Scheme 20: Exploiting 5-aminoisoxazoles as nucleophiles.
Scheme 21: Reaction between unsubstituted indoles and 3-alkynylated 3-hydroxy-1-oxoisoindolines.
Scheme 22: Synthesis of unnatural amino acids bearing an aza-quaternary stereocenter.
Scheme 23: Atroposelective aza-Friedel–Crafts reaction.
Scheme 24: Coupling of 5-aminopyrazole and 3H-indol-3-ones.
Scheme 25: Pyrophosphoric acid-catalyzed aza-Friedel–Crafts reaction on phenols.
Scheme 26: Squaramide-assisted aza-Friedel–Crafts reaction.
Scheme 27: Thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 28: Squaramide-catalyzed reaction between β-naphthols and benzothiazolimines.
Scheme 29: Thiourea-catalyzed reaction between β-naphthol and isatin-derived ketamine.
Scheme 30: Quinine-derived molecule as catalyst.
Scheme 31: Cinchona alkaloid as catalyst.
Scheme 32: aza-Friedel–Crafts reaction by phase transfer catalyst.
Scheme 33: Disulfonamide-catalyzed reaction.
Scheme 34: Heterogenous thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 35: Total synthesis of (+)-gracilamine.
Scheme 36: Total synthesis of (−)-fumimycin.
Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles
- Péter Kisszékelyi and
- Radovan Šebesta
Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44
Graphical Abstract
Scheme 1: General scheme depicting tandem reactions based on an asymmetric conjugate addition followed by an ...
Scheme 2: Cu-catalyzed tandem conjugate addition of R2Zn/aldol reaction with chiral acetals.
Scheme 3: Cu-catalyzed asymmetric desymmetrization of cyclopentene-1,3-diones using a tandem conjugate additi...
Scheme 4: Stereocontrolled assembly of dialkylzincs, cyclic enones, and sulfinylimines utilizing a Cu-catalyz...
Scheme 5: Cu-catalyzed tandem conjugate addition/Mannich reaction (A). Access to chiral isoindolinones and tr...
Scheme 6: Cu-catalyzed tandem conjugate addition/nitro-Mannich reaction (A) with syn–anti or syn–syn selectiv...
Figure 1: Various chiral ligands utilized for the tandem conjugate addition/Michael reaction sequences.
Scheme 7: Cu-catalyzed tandem conjugate addition/Michael reaction: side-product formation with chalcone (A) a...
Scheme 8: Zn enolate trapping using allyl iodides (A), Stork–Jung vinylsilane reagents (B), and allyl bromide...
Scheme 9: Cu-catalyzed tandem conjugate addition/acylation through Li R2Zn enolate (A). A four-component coup...
Scheme 10: Selected examples for the Cu-catalyzed tandem conjugate addition/trifluoromethylthiolation sequence....
Scheme 11: Zn enolates trapped by vinyloxiranes: synthesis of allylic alcohols.
Scheme 12: Stereoselective cyclopropanation of Mg enolates formed by ACA of Grignard reagents to chlorocrotona...
Scheme 13: Domino aldol reactions of Mg enolates formed from coumarin and chromone.
Scheme 14: Oxidative coupling of ACA-produced Mg enolates.
Scheme 15: Tandem ACA of Grignard reagents to enones and Mannich reaction.
Scheme 16: Diastereodivergent Mannich reaction of Mg enolates with differently N-protected imines.
Scheme 17: Tandem Grignard–ACA–Mannich using Taddol-based phosphine-phosphite ligands.
Scheme 18: Tandem reaction of Mg enolates with aminomethylating reagents.
Scheme 19: Tandem reaction composed of Grignard ACA to alkynyl enones.
Scheme 20: Rh/Cu-catalyzed tandem reaction of diazo enoates leading to cyclobutanes.
Scheme 21: Tandem Grignard-ACA of cyclopentenones and alkylation of enolates.
Scheme 22: Tandem ACA of Grignard reagents followed by enolate trapping reaction with onium compounds.
Scheme 23: Mg enolates generated from unsaturated lactones in reaction with activated alkenes.
Scheme 24: Lewis acid mediated ACA to amides and SN2 cyclization of a Br-appended enolate.
Scheme 25: Trapping reactions of aza-enolates with Michael acceptors.
Scheme 26: Si enolates generated by TMSOTf-mediated ACA of Grignard reagents and enolate trapping reaction wit...
Scheme 27: Trapping reactions of enolates generated from alkenyl heterocycles (A) and carboxylic acids (B) wit...
Scheme 28: Reactions of heterocyclic Mg enolates with onium compounds.
Scheme 29: Synthetic transformations of cycloheptatrienyl and benzodithiolyl substituents.
Scheme 30: Aminomethylation of Al enolates generated by ACA of trialkylaluminum reagents.
Scheme 31: Trapping reactions of enolates with activated alkenes.
Scheme 32: Alkynylation of racemic aluminum or magnesium enolates.
Scheme 33: Trapping reactions of Zr enolates generated by Cu-ACA of organozirconium reagents.
Scheme 34: Chloromethylation of Zr enolates using the Vilsmeier–Haack reagent.
Scheme 35: Tandem conjugate borylation with subsequent protonation or enolate trapping by an electrophile.
Scheme 36: Tandem conjugate borylation/aldol reaction of cyclohexenones.
Scheme 37: Selected examples for the tandem asymmetric borylation/intramolecular aldol reaction; synthesis of ...
Scheme 38: Cu-catalyzed tandem methylborylation of α,β-unsaturated phosphine oxide in the presence of (R,Sp)-J...
Scheme 39: Cu-catalyzed tandem transannular conjugated borylation/aldol cyclization of macrocycles containing ...
Scheme 40: Stereoselective tandem conjugate borylation/Mannich cyclization: selected examples (A) and a multi-...
Scheme 41: Some examples of Cu-catalyzed asymmetric tandem borylation/aldol cyclization (A). Application to di...
Scheme 42: Atropisomeric P,N-ligands used in tandem conjugate borylation/aldol cyclization sequence.
Scheme 43: Selected examples for the enantioselective Cu-catalyzed borylation/intramolecular Michael addition ...
Scheme 44: Selected examples for the preparation of enantioenriched spiroindanes using a Cu-catalyzed tandem c...
Scheme 45: Enantioselective conjugate borylation of cyclobutene-1-carboxylic acid diphenylmethyl ester 175 wit...
Scheme 46: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 47: Cu-catalyzed enantioselective tandem conjugate silylation of α,β-unsaturated ketones with subsequen...
Scheme 48: Cu-catalyzed tandem conjugate silylation/aldol condensation. The diastereoselectivity is controlled...
Scheme 49: Chiral Ru-catalyzed three-component coupling reaction.
Scheme 50: Rh-Phebox complex-catalyzed reductive cyclization and subsequent reaction with Michael acceptors th...
Scheme 51: Rh-catalyzed tandem asymmetric conjugate alkynylation/aldol reaction (A) and subsequent spiro-cycli...
Scheme 52: Rh-bod complex-catalyzed tandem asymmetric conjugate arylation/intramolecular aldol addition (A). S...
Scheme 53: Co-catalyzed C–H-bond activation/asymmetric conjugate addition/aldol reaction.
Scheme 54: (Diisopinocampheyl)borane-promoted 1,4-hydroboration of α,β-unsaturated morpholine carboxamides and...
Figure 2: Some examples of total syntheses that have been recently reviewed.
Scheme 55: Stereoselective synthesis of antimalarial prodrug (+)-artemisinin utilizing a tandem conjugate addi...
Scheme 56: Amphilectane and serrulatane diterpenoids: preparation of chiral starting material via asymmetric t...
Scheme 57: Various asymmetric syntheses of pleuromutilin and related compounds based on a tandem conjugate add...
Scheme 58: Total synthesis of glaucocalyxin A utilizing a tandem conjugate addition/acylation reaction sequenc...
Scheme 59: Installation of the exocyclic double bond using a tandem conjugate addition/aminomethylation sequen...
Scheme 60: Synthesis of the taxol core using a tandem conjugate addition/enolate trapping sequence with Vilsme...
Scheme 61: Synthesis of the tricyclic core of 12-epi-JBIR-23/24 utilizing a Rh-catalyzed asymmetric conjugate ...
Scheme 62: Total synthesis of (−)-peyssonoside A utilizing a Cu-catalyzed enantioselective tandem conjugate ad...
Group 13 exchange and transborylation in catalysis
- Dominic R. Willcox and
- Stephen P. Thomas
Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28
- review will explore the use of group 13 exchange reactions as a general method for catalytic turnover, and serves to expand on the previously published review on transborylation-enabled boron catalysis to include a broader range of catalysts and turnover reagents [47]. Review Boron catalysis The borane
- catalyse the hydroboration of alkynes with HBcat [50]. Hoshi later reported that Cy2BH [51] and in situ generated bis(pentafluorophenyl)borane, Piers’ borane [52], catalysed the hydroboration of alkynes with HBpin, to give alkenyl pinacol boronic esters. Tris(2,4,6-trifluorophenyl)borane [53], tris(3,4,5
- -trifluorophenyl)borane [54], BH3 [55][56][57], and H-B-9-BBN [58] have also been reported as catalysts for the hydroboration of alkynes with HBpin (Scheme 2). Lloyd-Jones et al. investigated the mechanism of this reaction and found transborylation, group 13 exchange between boron atoms, enabled catalytic turnover
Graphical Abstract
Scheme 1: Group 13 exchange.
Scheme 2: Borane-catalysed hydroboration of alkynes and the proposed mechanism.
Scheme 3: a) Borane-catalysed hydroboration of alkenes and the proposed mechanism. b) H-B-9-BBN-catalysed dou...
Scheme 4: a) Amine-borane-catalysed C‒H borylation of heterocycles and the proposed mechanism. b) Benzoic aci...
Scheme 5: Bis(pentafluorophenyl)borane-catalysed dimerisation of allenes and the proposed mechanism.
Scheme 6: Alkoxide-promoted hydroboration of heterocycles and the proposed mechanism.
Scheme 7: Borane-catalysed reduction of indoles and the proposed mechanism.
Scheme 8: H-B-9-BBN-catalysed hydrocyanation of enones and the proposed mechanism.
Scheme 9: Borane-catalysed hydroboration of nitriles and the proposed mechanism.
Scheme 10: Myrtanylborane-catalysed asymmetric reduction of propargylic ketones and the proposed mechanism.
Scheme 11: H-B-9-BBN-catalysed C–F esterification of alkyl fluorides and the proposed mechanism.
Scheme 12: H-B-9-BBN-catalysed 1,4-hydroboration of enones and the proposed mechanism.
Scheme 13: Boric acid-promoted reduction of esters, lactones, and carbonates and the proposed mechanism.
Scheme 14: H-B-9-BBN-catalysed reductive aldol-type reaction and the proposed mechanism.
Scheme 15: H-B-9-BBN-catalysed diastereoselective allylation of ketones and the Ph-BBD-catalysed enantioselect...
Scheme 16: H-B-9-BBN-catalysed C–F arylation of benzyl fluorides and the proposed mechanism.
Scheme 17: Borane-catalysed S‒H borylation of thiols and the proposed mechanism.
Scheme 18: Borane-catalysed hydroalumination of alkenes and allenes.
Scheme 19: a) Aluminium-catalysed hydroboration of alkynes and example catalysts. b) Deprotonation mechanistic...
Scheme 20: Aluminium-catalysed hydroboration of alkenes and the proposed mechanism.
Scheme 21: Aluminium-catalysed C–H borylation of terminal alkynes and the proposed mechanism.
Scheme 22: Aluminium-catalysed dehydrocoupling of amines, alcohols, and thiols with H-B-9-BBN or HBpin and the...
Scheme 23: Aluminium-catalysed hydroboration of unsaturated compounds and the general reaction mechanism.
Scheme 24: a) Gallium-catalysed asymmetric hydroboration of ketones and the proposed mechanism. b) Gallium-cat...
Scheme 25: Gallium(I)-catalysed allylation/propargylation of acetals and aminals and the proposed mechanism.
Scheme 26: Indium(I)-catalysed allylation/propargylation of acetals, aminals, and alkyl ethers.
Scheme 27: Iron–indium cocatalysed double hydroboration of nitriles and the proposed mechanism.
Figure 1: a) The number of reports for a given group 13 exchange in catalysis. b) Average free energy barrier...
Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry
- Eric Gayon,
- Guillaume Lefèvre,
- Olivier Guerret,
- Adrien Tintar and
- Pablo Chourreu
Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15
- ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead
Scheme 1: Structure of the (8E,10Z)-tetradecadienal (1, sex pheromone of the horse-chestnut leaf miner) and r...
Scheme 2: a) Alkyl–vinyl seminal cross-coupling reaction by Kochi; b) improved procedure described by Cahiez.
Scheme 3: Iron-catalyzed cross-coupling of n-OctMgCl with a 1-butadienyl phosphate.
Scheme 4: Synthesis of several insect sex pheromones (a) red bollworm moth, b) European grapevine moth, c) ho...
Scheme 5: Cross-coupling of alkyl Grignard reagents with a) alkenyl or b) aryl halides involving EtOMgCl as a...
Scheme 6: Total synthesis of codling moth sex pheromone 4 using an iron-mediated cross-coupling between an α,...
B–N/B–H Transborylation: borane-catalysed nitrile hydroboration
- Filip Meger,
- Alexander C. W. Kwok,
- Franziska Gilch,
- Dominic R. Willcox,
- Alex J. Hendy,
- Kieran Nicholson,
- Andrew D. Bage,
- Thomas Langer,
- Thomas A. Hunt and
- Stephen P. Thomas
Beilstein J. Org. Chem. 2022, 18, 1332–1337, doi:10.3762/bjoc.18.138
- relies upon stoichiometric reagents or transition-metal catalysis. Herein, a borane-catalysed hydroboration of nitriles to give primary amines is reported. Good yields (48–95%) and chemoselectivity (e.g., ester, nitro, sulfone) were observed. DFT calculations and mechanistic studies support the proposal
- transborylation (a σ-bond metathesis turnover method) has been used for borane-catalysed reductions of N-heteroarenes [28][29], and the borane-catalysed cyanation of enones [30]. Applying B–N/B–H transborylation to the hydroboration of nitriles would enable the development of a borane-catalysed hydroboration of
- available (H3B·SMe2, [H-B-9-BBN]2, H3B·THF) and prepared borane catalysts (dicyclohexylborane) in the hydroboration of heptanenitrile with HBpin as the turnover reagent (see Supporting Information File 1 for details). All boranes were catalytically active, with H3B·SMe2 displaying the highest activity. As
Graphical Abstract
Scheme 1: a) Derivatives of primary amines in materials chemistry, pharmaceuticals, and agrochemicals; b) thi...
Scheme 2: Substrate scope of borane-catalysed nitrile hydroboration with HBpin. Conditions: nitrile (0.50 mmo...
Scheme 3: a) Proposed mechanism; b) H-B-9-BBN-catalysed heptanenitrile hydroboration (yield determined by 1H ...
Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides
- Jiaxi Xu
Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90
- electrophiles 206–209, which include three 1,3,2-oxazaphospholidine 2-oxide derivatives 206–208 and phenylphosphonic dichloride (209). The product 210 was further transformed into (1S,3R)-3-methyl-1-phenyl-2,3-dihydro-1H-benzo[c][1,2]azaphosphole 212, which can be applied as a precatalyst. However, its borane
- complex showed 23% enantiomeric excess in the asymmetric borane reduction of acetophenone in THF at room temperature (Scheme 33) [58]. The reaction of 3-(phenylaminomethylene)-2-phenylamino-6-methyl-2,3-dihydro-4H-chromen-4-one (213) and diethyl phosphite at 90–100 °C generated 2-ethoxy-6-methyl-2-oxo-1
Graphical Abstract
Figure 1: Biologically active 1,2-azaphospholine 2-oxide derivatives.
Figure 2: Diverse synthetic strategies for the preparation of 1,2-azaphospholidine and 1,2-azaphospholine 2-o...
Scheme 1: Synthesis of 1-phenyl-2-phenylamino-γ-phosphonolactam (2) from N,N’-diphenyl 3-chloropropylphosphon...
Scheme 2: Synthesis of 2-ethoxy-1-methyl-γ-phosphonolactam (6) from ethyl N-methyl-(3-bromopropyl)phosphonami...
Scheme 3: Synthesis of 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 from N-aryl-2-chlorom...
Scheme 4: Synthesis of 2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides from alkylarylphosphinyl or diarylphosph...
Scheme 5: Synthesis of 3-arylmethylidene-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides via the TBAF-mediated ...
Scheme 6: Synthesis of 2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides via the metal-free intramolecular oxida...
Scheme 7: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 42 and 44 from ethyl/benzyl 2-bromobenzy...
Scheme 8: Synthesis of azaphospholidine 2-oxides/sulfide from 1,2-oxaphospholane 2-oxides/sulfides and 1,2-th...
Scheme 9: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides/sulfides from 2-aminobenzyl(phenyl)phosp...
Scheme 10: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-sulfide (59) from zwitterionic 2-aminobenzyl(ph...
Scheme 11: Synthesis of 1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides from 2-aminobenzyl(methyl/phenyl)phosphi...
Scheme 12: Synthesis of ethyl 2-methyl-1,2-azaphospholidine-5-carboxylate 2-oxide 69 from 2-amino-4-(hydroxy(m...
Scheme 13: Synthesis of 2-methoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxide 71 from dimethyl 2-(methylamino...
Scheme 14: Synthesis of tricyclic γ-phosphonolactams via formation of the P–C bond.
Scheme 15: Synthesis of γ-phosphonolactams 85 from ethyl 2-(3-chloropropyl)aminoalkanoates with diethyl chloro...
Scheme 16: Synthesis of N-phosphoryl- and N-thiophosphoryl-1,2-azaphospholidine 2-oxides 90/2-sulfides 91 from...
Scheme 17: Synthesis of 1-methyl-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 56a and 93 from P-(chloromethyl...
Scheme 18: Synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-diallyl-vinylphosphonodia...
Scheme 19: Diastereoselective synthesis of 2-allylamino-1,5-dihydro-1,2-azaphosphole 2-oxides from N,N’-dially...
Scheme 20: Synthesis of 1-alkyl-3-benzoyl-2-ethoxy-1,3-dihydrobenzo[d][1,2]azaphosphole 2-oxides 106 from ethy...
Scheme 21: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-benzyl-N-methylphosphinamide (...
Scheme 22: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-alkyl-N-benzylphosphinamides.
Scheme 23: Synthesis of cyclohexadiene-fused γ-phosphinolactams from diphenyl-N-methyl-N-(1-phenylethyl)phosph...
Scheme 24: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-alkyl-N-benzylphosph...
Scheme 25: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-benzyl-N-methylphosp...
Scheme 26: Synthesis of carbonyl-containing benzocyclohexadiene-fused γ-phosphinolactams from dinaphth-1-yl-N-...
Scheme 27: Synthesis of benzocyclohexadiene-fused γ-phosphinolactams from dinaphthyl-N-benzyl-N-methylphosphin...
Scheme 28: Synthesis of cyclohexadiene-fused 1-(N-benzyl-N-methyl)amino-γ-phosphinolactams from aryl-N,N’-dibe...
Scheme 29: Synthesis of bis(cyclohexadiene-fused γ-phosphinolactam)s from bis(diphenyl-N-benzylphosphinamide)s....
Scheme 30: Synthesis of bis(hydroxymethyl-derived cyclohexadiene-fused γ-phosphinolactam)s from tetramethylene...
Scheme 31: Synthesis of 2-aryl/dimethylamino-1-ethoxy-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxides from ethy...
Scheme 32: Synthesis of ethyl 2-ethoxy-1,2-azaphospholidine-4-carboxylate 2-oxides from ethyl 2-((chloro(ethox...
Scheme 33: Synthesis of (1S,3R)-2-(tert-butyldiphenylsilyl)-3-methyl-1-phenyl-2,3-dihydrobenzo[c][1,2]azaphosp...
Scheme 34: Synthesis of 2,3,3a,9a-tetrahydro-4H-1,2-azaphospholo[5,4-b]chromen-4-one (215) from 3-(phenylamino...
Scheme 35: Synthesis of quinoline-fused 1,2-azaphospholine 2-oxides from 2-azidoquinoline-3-carbaldehydes and ...
Scheme 36: Synthesis of 1-hydro-1,2-azaphosphol-5-one 2-oxide from cyanoacetohydrazide with phosphonic acid an...
Scheme 37: Synthesis of chromene-fused 5-oxo-1,2-azaphospolidine 2-oxides.
Scheme 38: Synthesis of (R)-1-phenyl-2-((R)-1-phenylethyl)-2-hydrobenzo[c][1,2]azaphosphol-3-one 1-oxide (239)...
Scheme 39: Synthesis of dihydro[1,2]azaphosphole 1-oxides from aryl/vinyl-N-phenylphosphonamidates and aryl-N-...
Scheme 40: Synthesis of 1,3-dihydro-[1,2]azaphospholo[5,4-b]pyridine 2-oxides.
Post-synthesis from Lewis acid–base interaction: an alternative way to generate light and harvest triplet excitons
- Hengjia Liu and
- Guohua Xie
Beilstein J. Org. Chem. 2022, 18, 825–836, doi:10.3762/bjoc.18.83
- temperature. Figure 12 was reprinted from [29], Chemical Engineering Journal, vol. 380, by M. Zhang; G. Xie; Q. Xue; H. Wang, “Electroluminescence of intra-molecular exciplexes based on novel Lewis acid borane acceptors and a high triplet level donor”, article no. 122527, Copyright (2020), with permission
Graphical Abstract
Figure 1: Chemical structures of Lewis acid examples.
Figure 2: Chemical structures of Lewis basic fluorescent polymer poly{2,5-pyridylene-co-1,4-[2,5-bis(2-ethylh...
Figure 3: (a) Normalized PL spectra of films with compound 1 doped with different Lewis acids. (b) PL spectra...
Figure 4: Schematic diagram of a BF3·OEt2 vapor-treated device and the macroscopic gradation emissive pattern...
Figure 5: Chemical structures of Lewis basic fluorescent compounds 3–14.
Figure 6: (a) PL spectra of compound 6 in toluene after addition of 0.0 (black line), 0.1 (red line), 0.3 (gr...
Figure 7: Photos of a solution of compound 12 and B(C6F5)3 at different ratios in toluene under a 365 nm UV l...
Figure 8: Structure of small molecule 15 containing pyridine and thiazole groups reported by Bazan et al. and...
Figure 9: (a) 1H NMR spectra in the aromatic region and (b) 19F NMR spectra of compound 15 (top) and the mixt...
Figure 10: Pyrazine-containing polymers 19 and 20 investigated by Li et al.
Figure 11: (a) HOMO/LUMO orbitals and energy levels (unit: eV) and (b) electrostatic potential surface (EPS) m...
Figure 12: (a) UV–vis absorbance and (b) PL spectra (excited by 330 nm) for 35DCzPPy (compound 14), B(C6F5)3, ...
Figure 13: (a) Schematic diagram of the low-band gap materials 21 and 22. (b) Ground state geometry optimizati...
New synthesis of a late-stage tetracyclic key intermediate of lumateperone
- Mátyás Milen,
- Bálint Nyulasi,
- Tamás Nagy,
- Gyula Simig and
- Balázs Volk
Beilstein J. Org. Chem. 2022, 18, 653–659, doi:10.3762/bjoc.18.66
- a Fischer indole synthesis. The inexpensive starting material, the efficient synthetic steps, and the avoidance of the borane-based reduction step provide a reasonable potential for scalability. Keywords: drug substance; indole synthesis; key intermediate; protecting group; telescoping
Graphical Abstract
Figure 1: Structure of lumateperone.
Scheme 1: First synthetic route leading to lumateperone (1).
Scheme 2: Alternate synthesis of lumateperone.
Scheme 3: Alternate synthetic approaches leading to racemic lumateperone ((±)-1)).
Scheme 4: Planned new synthesis of key intermediate (±)-9a.
Scheme 5: New synthesis of key intermediate (±)-9a.
Scheme 6: Trifluoroacetylation of tetrahydroquinoxaline (37).
Synthetic strategies toward 1,3-oxathiolane nucleoside analogues
- Umesh P. Aher,
- Dhananjai Srivastava,
- Girij P. Singh and
- Jayashree B. S
Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182
- -1,3-oxathiolane derivative. Further, reduction of the ester functionality with borane dimethyl sulfide at −15 °C afforded the corresponding 2-(hydroxymethyl)-1,3-oxathiolane in 50% yield. It was further treated with benzoyl chloride in the presence of triethylamine (TEA), which provided the desired
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Catalyzed and uncatalyzed procedures for the syntheses of isomeric covalent multi-indolyl hetero non-metallides: an account
- Ranadeep Talukdar
Beilstein J. Org. Chem. 2021, 17, 2102–2122, doi:10.3762/bjoc.17.137
- recently found active against Parkinson’s and Alzheimer’s diseases [101][102][103]. In 2002, Jiang, while studying its synthesis, found the tris(indolyl)borane 154 instead of the desired chiral indole alcohol 155 while reacting the N-silylated 4-bromoindole 152 with n-BuLi in a failed regioselective ring
- . Syntheses of bis(indol-2-yl)selanes. Syntheses of bis(indol-3-yl)selanes. Synthesis of bis(indol-2-yl)tellane 147. Synthesis of tris(indolyl)borane 154. Synthesis of bis(indol-4-yl)amines 159. Synthesis of bis(indol-5-yl)amines. Synthesis of 6,5’/6,6’-bis(indolyl)amines. Synthesis of potent HIV-inhibitors
Graphical Abstract
Scheme 1: Synthesis of 2,2’-bis(indole)borinic ester 3.
Scheme 2: Synthesis of 2,2’-bisindole NHC·boranes by an SEAr mechanism.
Scheme 3: Syntheses of indolyl amines through Buchwald–Hartwig cross coupling.
Scheme 4: Synthesis of 3,3’-bis(indolyl) ethers.
Scheme 5: C–H silylation of indoles.
Scheme 6: n-BuLi-mediated syntheses of bis(indol-3-yl)silanes.
Scheme 7: Acid-catalyzed syntheses of bis(indol-3-yl)silanes and mechanisms.
Scheme 8: B(C6F5)3 and Al(C6F5)3-catalyzed syntheses of bis(indol-3-yl)silanes reported by Han.
Scheme 9: Base-mediated syntheses of bis and tris(indol-2-yl)phosphines.
Scheme 10: Synthesis of bis(indol-2-yl)sulfides using SL2-type reagents.
Scheme 11: Synthesis of 2,3’- and 2,2’-bis(indolyl)sulfides using disulfides as substrates.
Scheme 12: Synthesis of diindol-2-ylsulfide (84) from 2-iodoindole (92) and thiourea.
Scheme 13: Synthesis of bis(indol-3-yl)sulfides using N-silylated 3-bromoindole 93.
Scheme 14: Fischer indole synthesis of bis(indol-3-yl)sulfides using thio diketones.
Scheme 15: Oxidative synthesis of bis(indol-3-yl)sulfides using indoles and elemental sulfur.
Scheme 16: Synthesis of bis(indol-3-yl)sulfides using sulfoxides as sulfur source.
Scheme 17: Syntheses of bis(indol-2-yl)selanes.
Scheme 18: Syntheses of bis(indol-3-yl)selanes.
Scheme 19: Synthesis of bis(indol-2-yl)tellane 147.
Scheme 20: Synthesis of tris(indolyl)borane 154.
Scheme 21: Synthesis of bis(indol-4-yl)amines 159.
Scheme 22: Synthesis of bis(indol-5-yl)amines.
Scheme 23: Synthesis of 6,5’/6,6’-bis(indolyl)amines.
Scheme 24: Synthesis of potent HIV-inhibitors 6,6’-bis(indolyl) ethers.
Scheme 25: Synthesis of bis(indol-7-yl) ether.
Scheme 26: Synthesis of di(indol-5-yl)sulfide (183).
Scheme 27: Syntheses of 2,2’-diformyl-7,7’-bis(indolyl)selenides.
Correction: Amine–borane complex-initiated SF5Cl radical addition on alkenes and alkynes
- Audrey Gilbert,
- Pauline Langowski,
- Marine Delgado,
- Laurent Chabaud,
- Mathieu Pucheault and
- Jean-François Paquin
Beilstein J. Org. Chem. 2021, 17, 1725–1726, doi:10.3762/bjoc.17.120
- , France 10.3762/bjoc.17.120 Keywords: amine–borane complex; pentafluorosulfanyl chloride; pentafluorosulfanyl substituent; radical addition; radical initiation; The stereochemistry of some alkene products (2i–k) in Scheme 4 of the original publication was misattributed. The corrected structures are
Graphical Abstract
Scheme 1: Corrected Scheme 4 of the original article. Scope of the Et3B and the DICAB-initiated SF5Cl additio...
Scheme 2: Corrected graphical abstract of the original publication.
Total synthesis of ent-pavettamine
- Memory Zimuwandeyi,
- Manuel A. Fernandes,
- Amanda L. Rousseau and
- Moira L. Bode
Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99
- yield. The first step involved esterification of malic acid using methanol, followed by selective reduction of the resulting dimethyl ester using borane dimethyl sulfide (BMS) yielding diol 5 (Scheme 2) [1][14][15]. The step achieved chemo-differentiation of the carboxyl groups present in 3 whilst
Graphical Abstract
Figure 1: Structure of pavettamine 1 and its enantiomer 2.
Scheme 1: Established route for the synthesis of intermediate 4 [1].
Scheme 2: Alternative route. Reaction conditions: a) TrCl, pyridine, rt, overnight, 100%; b) DMAP, imidazole,...
Figure 2: Crystal structure of compound 9.
Scheme 3: Sequence showing the source of compound 9.
Scheme 4: Stereoselective reduction of intermediate 8 as key step towards intermediate 4. Reaction conditions...
Figure 3: Single crystal X-ray structure of compound 4.
Scheme 5: Synthesis of the C5 fragments from intermediate 4. Reaction conditions: a) i) TFAA, collidine, 0 °C...
Scheme 6: Synthesis of ent-pavettamine as the TFA salt 28. Reaction conditions: a) IBX, DMSO, rt, overnight, ...
A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries
- Guido Gambacorta,
- James S. Sharley and
- Ian R. Baxendale
Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90
Graphical Abstract
Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
Figure 2: General structure of an international fragrance company [2].
Figure 3: The Michael Edwards fragrance wheel.
Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
Figure 5: A basic depiction of batch vs flow.
Scheme 1: Examples of reactions for which flow processing outperforms batch.
Scheme 2: Some industrially important aldol-based transformations.
Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
Figure 6: Immobilised reagent column reactor types.
Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH2: primary amine-fun...
Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst® A26.
Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
Scheme 49: A collection of commonly encountered hydrogenation reactions.
Figure 7: The ThalesNano H-Cube® continuous-flow hydrogenator.
Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube® reactor.
Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube® reactor for the reduction of an alkyne.
Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube® system.
Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
Scheme 54: Recyclable heterogeneous flow hydrogenation system.
Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
Scheme 67: High-pressure in-line mixing of H2 for the asymmetric reduction of 278 at pilot scale with a 73 L p...
Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
Scheme 77: A tubular reactor design for flow photo-oxygenation.
Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
Scheme 95: Continuous oxidation of thiosulfinates using Oxone®-packed reactor.
Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
Scheme 99: Some industrially important transformations involving Grignard reagents.
Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
Scheme 115: Selected industrial applications of DA reaction.
Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
Scheme 126: Two-step continuous-flow synthesis of triazole 543.
Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
Scheme 139: Examples of FC reactions applied in F&F industry.
Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr4+-β-zeolite developed by Kob...
Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
Scheme 149: Continuous hydroformylation in scCO2.
Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
Scheme 159: Continuous-flow preparation of cyclopentenone 676.
Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
