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Search for "sustainability" in Full Text gives 113 result(s) in Beilstein Journal of Organic Chemistry.
Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions
- Francesco Mele,
- Ana M. Constantin,
- Andrea Porcheddu,
- Raimondo Maggi,
- Giovanni Maestri,
- Nicola Della Ca’ and
- Luca Capaldo
Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33
- Francesco Mele Ana M. Constantin Andrea Porcheddu Raimondo Maggi Giovanni Maestri Nicola Della Ca' Luca Capaldo SynCat Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy Dipartimento di Scienze
- Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy 10.3762/bjoc.21.33 Abstract Photomechanochemistry, i.e., the merger of light energy and mechanical forces, is emerging as a new trend in organic synthesis, enabling unique reactivities of fleeting excited states under solvent
- turn demands large volumes of solvents, negatively impacting the sustainability of light-mediated synthesis as it transitions from academic curiosity to industrial application. Moreover, since the solvent is the reaction component with the highest concentration, competitive side-reactions such as
Graphical Abstract
Figure 1: The Grotthuss–Draper, Einstein–Stark, and Beer–Lambert laws. T: transmittance; ε: molar attenuation...
Figure 2: The benefits of merging photochemistry with mechanochemical setups (top). Most common setups for ph...
Scheme 1: Mechanochemically triggered pedal-like motion in solid-state [2 + 2] photochemical cycloaddition fo...
Scheme 2: Mechanically promoted [2 + 2] photodimerization of trans-1,2-bis(4-pyridyl)ethylene (2.1) via supra...
Scheme 3: Photo-thermo-mechanosynthesis of quinolines [65].
Scheme 4: Study of the mechanically assisted [2 + 2] photodimerization of chalcone [66].
Scheme 5: Liquid-assisted vortex grinding (LAVG) for the synthesis of [2.2]paracyclophane [68].
Scheme 6: Photomechanochemical approach for the riboflavin tetraacetate-catalyzed photocatalytic oxidation of...
Scheme 7: Photomechanochemical oxidation of 1,2-diphenylethyne to benzil. The photo in Scheme 7 was republished with ...
Scheme 8: Photomechanochemical borylation of aryldiazonium salts. The photo in Scheme 8 was reproduced from [72] (© 2017 ...
Scheme 9: Photomechanochemical control over stereoselectivity in the [2 + 2] dimerization of acenaphthylene. ...
Scheme 10: Photomechanochemical synthesis of polyaromatic compounds using UV light. The photo in Scheme 10 was reproduc...
Scheme 11: Mechanically assisted photocatalytic reactions: A) atom-transfer-radical addition, B) pinacol coupl...
Scheme 12: Use of mechanoluminescent materials as photon sources for photomechanochemistry. SAOED: SrAl2O4:Eu2+...
Figure 3: SWOT (strengths, weaknesses, opportunities, threats) analysis of photomechanochemistry.
Red light excitation: illuminating photocatalysis in a new spectrum
- Lucas Fortier,
- Corentin Lefebvre and
- Norbert Hoffmann
Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22
- growing concerns around environmental sustainability, there is increasing interest in developing photocatalysts that are more accessible, tunable, and eco-friendly. Each section of this document discusses a specific approach to red-light photocatalysis, reflecting the field’s evolution and exploring
- integrity over extended reaction times, even under high substrate concentrations and continuous flow conditions, achieving high turnover numbers of over 50000. This stability allowed for solvent-free reactions, significantly enhancing the sustainability of the process. Additionally, the authors have
Graphical Abstract
Figure 1: Influence of the metal center M (Fe, Ru, Os) on the position of the MLCT and MC (metal-centered) ab...
Scheme 1: Red-light-mediated ring-closing metathesis through activation of a ruthenium catalyst by an osmium ...
Scheme 2: Photocatalyzed polymerization of dicylopentadiene mediated with red or blue light.
Figure 2: Comparison between [Ru(bpy)3]2+ and [Os(tpy)2]2+ in a photocatalyzed trifluoromethylation reaction:...
Scheme 3: Red-light photocatalyzed C–N cross-coupling reaction by T. Rovis et al. (SET = single-electron tran...
Figure 3: Red-light-mediated aryl oxidative addition with a bismuthinidene complex.
Scheme 4: Red-light-mediated reduction of aryl derivatives by O. S. Wenger et al. (PC = photocatalyst, anh = ...
Scheme 5: Red-light-mediated aryl halides reduction with an isoelectronic chromium complex (TDAE = tetrakis(d...
Scheme 6: Red-light-photocatalyzed trifluoromethylation of styrene derivatives with Umemoto’s reagent and a p...
Scheme 7: Red-light-mediated energy transfer for the cross-dehydrogenative coupling of N-phenyltetrahydroisoq...
Scheme 8: Red-light-mediated oxidative cyanation of tertiary amines with a phthalocyanin zinc complex.
Scheme 9: Formation of dialins and tetralins via a red-light-photocatalyzed reductive decarboxylation mediate...
Scheme 10: Oxidation of β-citronellol (28) via energy transfer mediated by a red-light activable silicon phtha...
Scheme 11: Formation of alcohol derivatives 32 from boron compounds 31 using chlorophyll (chl) as a red-light-...
Scheme 12: Red-light-driven reductive dehalogenation of α-halo ketones mediated by a thiaporphyrin photocataly...
Figure 4: Photoinduced electron transfer-reversible addition-fragmentation chain transfer polymerization medi...
Figure 5: Recent examples of red-light-mediated photocatalytic reactions with traditional organic dyes.
Figure 6: Squaraine photocatalysts used by Goddard et al. and aza-Henry reaction with squaraine-based photoca...
Figure 7: Reactions described by Goddard et al. involving 40 as the photocatalyst.
Figure 8: Various structures of squaraine derivatives used to initiate photopolymerizations.
Figure 9: Naturally occurring cyanins.
Figure 10: Influence of the structure on the photophysical properties of a cyanin dye.
Figure 11: NIR-light-mediated aza-Henry reaction photocatalyzed by 46.
Scheme 13: Photocatalyzed arylboronic acids oxidation by 46.
Figure 12: Cyanin structures synthetized and characterized by Goddard et al. (redox potentials given against s...
Figure 13: N,N′-Di-n-propyl-1,13-dimethoxyquinacridinium (55) with its redox potentials at its ground state an...
Scheme 14: Dual catalyzed C(sp2)–H arylation of 57 using DMQA 55 as the red-light-absorbing photocatalyst.
Scheme 15: Red-light-mediated aerobic oxidation of arylboronic acids 59 into phenols 60 via the use of DMQA as...
Figure 14: Red-light-photocatalyzed reactions proposed by Gianetti et al. using DMQA as the photocatalyst.
Scheme 16: Simultaneous release of NO and production of superoxide (O2•−) and their combination yielding the p...
Figure 15: Palladium porphyrin complex as the photoredox catalyst and the NO releasing substrate are linked in...
Scheme 17: Uncaging of compound 69 which is a microtubule depolymerizing agent using near IR irradiation. The ...
Scheme 18: Photochemical uncaging of drugs protected with a phenylboronic acid derivative using near IR irradi...
Scheme 19: Photoredox catalytical generation of aminyl radicals with near IR irradiation for the transfer of b...
Scheme 20: Photoredox catalytical fluoroalkylation of tryptophan moieties.
Figure 16: Simultaneous absorption of two photons of infrared light of low energy enables electronic excitatio...
Scheme 21: Uncaging Ca2+ ions using two-photon excitation with near infrared light.
Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide
- Marios Zingiridis,
- Danae Papachristodoulou,
- Despoina Menegaki,
- Konstantinos G. Froudas and
- Constantinos G. Neochoritis
Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13
- molecules, contributing significantly to sustainability, innovation and economic growth across various sectors. In this study, we present an efficient and rapid method for synthesizing a variety of heteroannulated pyrimidones using cyanoacetamide-based multicomponent reaction (MCR) chemistry. By utilizing
Graphical Abstract
Figure 1: Heteroannulated pyrimidones in drug discovery: blockbuster drugs that are based on the privileged p...
Scheme 1: Strategies towards targeted adducts: A) Niementowski quinazoline synthesis utilizing anthranilic ac...
Scheme 2: Access to the key building blocks 2–4 by employing three different nonisocyanide-based MCRs. Divers...
Scheme 3: Synthesis of N-substituted thienopyrimidones 5a–e by a Gewald three-component reaction employing 2-...
Scheme 4: Synthesis of N-substituted quinolinopyrimidones 6a–e from 2-aminoindoles 3a–e and formamide as C1 s...
Scheme 5: Synthesis of N-substituted indolopyrimidones 7a–e from 2-aminoindoles 4a–e and formamide as C1 sour...
Figure 2: Representative fluorescence spectrum of compounds 5b (λex = 330 nm) and 6e (λex = 430 nm) at 0.2 M ...
Figure 3: Molecular geometry observed within the crystal structure of compound 7b (CCDC 2376493).
Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations
- Seungmin Lee,
- Minsuk Kim,
- Hyewon Han and
- Jongwoo Son
Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12
- catalysts have been gaining increasing attention owing to their abundance, cost-effectiveness, and sustainability. Recently, these catalytic systems have been applied to the chemical transformation of dioxazolones, conferring a convenient protocol towards amidated products. This review highlights recent
- . Moreover, copper-catalyzed asymmetric C(sp3)–N bond-forming transformations are still underexplored except for elegant studies by the research groups of Buchwald [98] and Chang [74]. Given the versatility and sustainability of the copper-catalyzed transformation of dioxazolones, further investigations for
Graphical Abstract
Scheme 1: Formation of isocyanates and amidated arenes from dioxazolones.
Scheme 2: Copper-catalyzed synthesis of δ-lactams via open-shell copper nitrenoid transfer. aCuBr (10 mol %) ...
Figure 1: Proposed reaction pathway for the copper-catalyzed synthesis of δ-lactams from dioxazolones.
Scheme 3: Copper(II)-catalyzed synthesis of 1,2,4-triazole derivatives.
Figure 2: Proposed reaction mechanism for the copper-catalyzed synthesis of 1,2,4-triazole analogues from dio...
Scheme 4: Copper(I)-catalyzed synthesis of N-acyl amidines from dioxazolones, acetylenes, and amines. aPerfor...
Figure 3: Proposed reaction mechanism for the copper(I)-catalyzed synthesis of N-acyl amidines.
Scheme 5: Preparation of N-arylamides from dioxazolones and boronic acids using a copper salt.
Figure 4: Proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones.
Scheme 6: Copper-catalyzed preparation of N-acyl iminophosphoranes from dioxazolones.
Figure 5: Proposed reaction pathway for the copper-catalyzed synthesis of N-acyl iminophosphoranes from dioxa...
Scheme 7: Copper-catalyzed synthesis of N-acyl sulfenamides. a1.0 equiv of 18 and 2.0 equiv of 19 were used. b...
Figure 6: Proposed reaction mechanism for the copper-catalyzed S-amidation of thiols.
Scheme 8: Copper-catalyzed asymmetric hydroamidation of vinylarenes. a4 mol % + 2 mol % catalyst was used. b4...
Figure 7: Proposed reaction mechanism for the copper-catalyzed hydroamidation of vinylarenes.
Scheme 9: Copper-catalyzed anti-Markovnikov hydroamidation of alkynes.
Figure 8: Proposed reaction mechanism for the copper-catalyzed amidation of alkynes.
Scheme 10: Copper-catalyzed preparation of primary amides through N–O bond reduction using reducing agent.
Figure 9: Proposed catalytic cycle for the copper-catalyzed reduction of dioxazolones.
Recent advances in electrochemical copper catalysis for modern organic synthesis
- Yemin Kim and
- Won Jun Jang
Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9
- ’ and Fu’s asymmetric C–N bond cross-coupling reactions by merging photoredox catalysis with copper catalysis [29][30]. Building on the success of photoredox catalysis, electrochemistry has emerged as a complementary and attractive strategy for promoting sustainability of organic synthesis. By offering
Graphical Abstract
Figure 1: General mechanisms of traditional and radical-mediated cross-coupling reactions.
Figure 2: Types of electrocatalysis (using anodic oxidation).
Figure 3: Recent developments and features of electrochemical copper catalysis.
Figure 4: Scheme and proposed mechanism for Cu-catalyzed alkynylation and annulation of benzamide.
Figure 5: Scheme and proposed mechanism for Cu-catalyzed asymmetric C–H alkynylation.
Figure 6: Scheme for Cu/TEMPO-catalyzed C–H alkenylation of THIQs.
Figure 7: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical enantioselective cyanation of b...
Figure 8: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical asymmetric heteroarylcyanation ...
Figure 9: Scheme and proposed mechanism for Cu-catalyzed enantioselective regiodivergent cross-dehydrogenativ...
Figure 10: Scheme and proposed mechanism for Cu/Ni-catalyzed stereodivergent homocoupling of benzoxazolyl acet...
Figure 11: Scheme and proposed mechanism for Cu-catalyzed electrochemical amination.
Figure 12: Scheme and proposed mechanism for Cu-catalyzed electrochemical azidation of N-arylenamines and annu...
Figure 13: Scheme and proposed mechanism for Cu-catalyzed electrochemical halogenation.
Figure 14: Scheme and proposed mechanism for Cu-catalyzed asymmetric cyanophosphinoylation of vinylarenes.
Figure 15: Scheme and proposed mechanism for Cu/Co dual-catalyzed asymmetric hydrocyanation of alkenes.
Figure 16: Scheme and proposed mechanism for Cu-catalyzed electrochemical diazidation of olefins.
Figure 17: Scheme and proposed mechanism for Cu-catalyzed electrochemical azidocyanation of alkenes.
Figure 18: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical asymmetric decarboxylative cyan...
Figure 19: Scheme and proposed mechanism for electrocatalytic Chan–Lam coupling.
Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning
- Pablo Quijano Velasco,
- Kedar Hippalgaonkar and
- Balamurugan Ramalingam
Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3
- Technological University, Singapore 639798, Republic of Singapore Institute for Functional Intelligent Materials, National University of Singapore, 4 Science Drive 2, Singapore 117544, Republic of Singapore Institute of Sustainability for Chemicals, Energy and Environment (ISCE2), Agency for Science Technology
Graphical Abstract
Figure 1: A high-level representation of the workflow and framework used for the optimization of organic reac...
Figure 2: (a) Photograph showing a Chemspeed HTE platform using 96-well reaction blocks. (b) Mobile robot equ...
Figure 3: (a) Description of a slug flow platform developed using segments of gas as separation medium for hi...
Figure 4: Schematic representation (a) and photograph (b) of the flow parallel synthesizer intelligently desi...
Figure 5: (a) Schematic representation of an ASFR for obtaining an optimal solution with minimal human interv...
Figure 6: (a) A modular flow platform developed for a wider variety of chemical syntheses. (b) Various catego...
Figure 7: Implementation of four complementary PATs into the optimization process of a three-step synthesis.
Figure 8: Overlay of several Raman spectra of a single condition featuring the styrene vinyl region (a) and t...
Figure 9: (a) Schematic description of the process of chemical reaction optimization through ML methods. (b) ...
Figure 10: (a) Comparison between a standard GP (single-task) and a multitask GP. Training an auxiliary task u...
Figure 11: Comparison of the reaction yield between optimizations campaign where the catalyst ligand selection...
Hypervalent iodine-mediated intramolecular alkene halocyclisation
- Charu Bansal,
- Oliver Ruggles,
- Albert C. Rowett and
- Alastair J. J. Lennox
Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258
- and co-workers reported a mild, metal free-synthesis of fluorobenzoxazepines 30 in 2016 (Scheme 13) [37]. Using 1-fluoro-3,3-dimethylbenziodoxole (12) and 4 Å molecular sieves, a range of benzamides 29 were successfully cyclised in good yields. The sustainability of the reaction was improved by
Graphical Abstract
Figure 1: Example bioactive compounds containing cyclic scaffolds potentially accessible by HVI chemistry.
Figure 2: A general mechanism for HVI-mediated endo- or exo-halocyclisation.
Scheme 1: Metal-free synthesis of β-fluorinated piperidines 6. Ts = tosyl.
Scheme 2: Intramolecular aminofluorination of unactivated alkenes with a palladium catalyst.
Scheme 3: Aminofluorination of alkenes in the synthesis of enantiomerically pure β-fluorinated piperidines. P...
Scheme 4: Synthesis of β-fluorinated piperidines.
Scheme 5: Intramolecular fluoroaminations of unsaturated amines published by Li.
Scheme 6: Intramolecular aminofluorination of unsaturated amines using 1-fluoro-3,3-dimethylbenziodoxole (12)...
Scheme 7: 3-fluoropyrrolidine synthesis. aDiastereomeric ratio (cis/trans) determined by 19F NMR analysis.
Scheme 8: Kitamura’s synthesis of 3-fluoropyrrolidines. Values in parentheses represent the cis:trans ratio.
Scheme 9: Jacobsen’s enantio- and diastereoselective protocol for the synthesis of syn-β-fluoroaziridines 15.
Scheme 10: Different HVI reagents lead to different diastereoselectivity in aminofluorination competing with c...
Scheme 11: Fluorocyclisation of unsaturated alcohols and carboxylic acids to make tetrahydrofurans, fluorometh...
Scheme 12: Oxyfluorination of unsaturated alcohols.
Scheme 13: Synthesis and mechanism of fluoro-benzoxazepines.
Scheme 14: Intramolecular fluorocyclisation of unsaturated carboxylic acids. Yield of isolated product within ...
Scheme 15: Synthesis of fluorinated tetrahydrofurans and butyrolactone.
Scheme 16: Synthesis of fluorinated oxazolines 32. aReaction time increased to 40 hours. Yields refer to isola...
Scheme 17: Electrochemical synthesis of fluorinated oxazolines.
Scheme 18: Electrochemical synthesis of chromanes.
Scheme 19: Synthesis of fluorinated oxazepanes.
Scheme 20: Enantioselective oxy-fluorination with a chiral aryliodide catayst.
Scheme 21: Catalytic synthesis of 5‑fluoro-2-aryloxazolines using BF3·Et2O as a source of fluoride and an acti...
Scheme 22: Intramolecular carbofluorination of alkenes.
Scheme 23: Intramolecular chlorocyclisation of unsaturated amines.
Scheme 24: Synthesis of chlorinated cyclic guanidines 44.
Scheme 25: Synthesis of chlorinated pyrido[2,3-b]indoles 46.
Scheme 26: Chlorolactonization and chloroetherification reactions.
Scheme 27: Proposed mechanism for the synthesis of chloromethyl oxazolines 49.
Scheme 28: Oxychlorination to form oxazine and oxazoline heterocycles promoted by BCl3.
Scheme 29: Aminobromocyclisation of homoallylic sulfonamides 53. The cis:trans ratios based on the 1H NMR of t...
Scheme 30: Synthesis of cyclic imines 45.
Scheme 31: Synthesis of brominated pyrrolo[2,3-b]indoles 59.
Scheme 32: Bromoamidation of alkenes.
Scheme 33: Synthesis of brominated cyclic guanidines 61 and 61’.
Scheme 34: Intramolecular bromocyclisation of N-oxyureas.
Scheme 35: The formation of 3-bromoindoles.
Scheme 36: Bromolactonisation of unsaturated acids 68.
Scheme 37: Synthesis of 5-bromomethyl-2-oxazolines.
Scheme 38: Synthesis of brominated chiral morpholines.
Scheme 39: Bromoenolcyclisation of unsaturated dicarbonyl groups.
Scheme 40: Brominated oxazines and oxazolines with BBr3.
Scheme 41: Synthesis of 5-bromomethtyl-2-phenylthiazoline.
Scheme 42: Intramolecular iodoamination of unsaturated amines.
Scheme 43: Formation of 3-iodoindoles.
Scheme 44: Iodoetherification of 2,2-diphenyl-4-penten-1-carboxylic acid (47’) and 2,2-diphenyl-4-penten-1-ol (...
Scheme 45: Synthesis of 5-iodomethyl-2-oxazolines.
Scheme 46: Synthesis of chiral iodinated morpholines. aFrom the ʟ-form of the amino acid starting material. Th...
Scheme 47: Iodoenolcyclisation of unsaturated dicarbonyl compounds 74.
Scheme 48: Synthesis of 5-iodomethtyl-2-phenylthiazoline (87).
Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts
- Mandeep K. Chahal
Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257
- macrocycles as electrocatalysts Development of efficient renewable technologies is a driving force in the efforts to achieve sustainability with the same or even increasing demands for energy worldwide. In this context, transition-metal complexes of tetraazamacrocycles (N4-macrocycle) such as porphyrins
Graphical Abstract
Figure 1: Chemical structures of the main tetrapyrrolic macrocycles studied in this review for their role as ...
Figure 2: Calix[4]pyrroles 3 and 4 and an their acyclic analogue 5 used for the transformation of Danishefsky...
Figure 3: Calixpyrrole-based organocatalysts 11 and 12 for the diastereoselective addition reaction of TMSOF ...
Figure 4: (a) Chemical structures of macrocyclic organocatalysts used for the synthesis of cyclic carbonates ...
Figure 5: Cuprous chloride-catalyzed aziridination of styrene (22) by chloramine-T (23) providing 1-tosyl-2-p...
Figure 6: Chemical structures of the various porphyrin macrocycles (18, 25–41) screened as potential catalyst...
Figure 7: Organocatalytic activity of distorted porphyrins explored by Senge and co-workers. Planar macrocycl...
Figure 8: Chemical structures of H2EtxTPP (x = 0, 2, 4, 6, 8) compounds with incrementally increasing nonplan...
Figure 9: Chemical structures of OxP macrocycles tested as potential organocatalysts for the conjugate additi...
Figure 10: a) Fundamental structure of the J-aggregates of diprotonated TPPS3 53 and b) its use as a catalyst ...
Figure 11: Chemical structures of amphiphilic porphyrin macrocycles used as pH-switchable catalysts based on i...
Figure 12: a) Chemical structures of porphyrin macrocycles for the cycloaddition of CO2 to N-alkyl/arylaziridi...
Figure 13: Electron and energy-transfer processes typical for excited porphyrin molecules (Por = porphyrin mac...
Figure 14: Proposed mechanism for the light-induced α-alkylation of aldehydes with EDA in the presence of H2TP...
Figure 15: a) Chemical structures of porphyrins screened as photoredox catalysts, b) model reaction of furan (...
Figure 16: Porphyrin macrocycles H2TPP (18) and PPIX 78 as photoreductants for the red light-induced C–H aryla...
Figure 17: Porphyrin macrocycles H2TPP (18) and PPIX 78 as photoredox catalyst for (a) α-alkylation of an alde...
Figure 18: Corrole macrocycles 98–100 as photoredox catalysts for C–H arylation and borylation reactions. Adap...
Figure 19: Proposed catalytic cycle of electrocatalytic generation of H2 evolution using tetrapyrrolic macrocy...
Figure 20: a) Chemical structures of tetrapyrrolic macrocycles 109, 73, and 110 used for oxygen reductions in ...
Figure 21: a) Absorption spectra (left) of the air-saturated DCE solutions containing: 5 × 10−5 M H2TPP (black...
Figure 22: Chemical structures of N,N’-dimethylated saddle-distorted porphyrin isomers, syn-Me2P 111 and anti-...
Figure 23: Reaction mechanisms for the two-electron reduction of O2 by a) syn-Me2Iph 113 and b) anti-Me2Iph 114...
Figure 24: O2/H2O2 interconversion using methylated saddle-distorted porphyrin and isophlorin (reduced porphyr...
Figure 25: Chemical structures of distorted dodecaphenylporphyrin macrocycle 117 and its diprotonated form 118...
Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures
- Yosuke Akae
Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252
- conditions) that facilitate sustainability [1][2][3][4][5][6][7][8][9][10]. In this regard, the rotaxane framework represents an attractive motif for implementing substantial property changes triggered by certain stimuli owing to its higher dynamic nature than those of conventional materials [11][12][13][14
Graphical Abstract
Figure 1: Overview of the CD-based rotaxane as a polymer material covered in this review.
Figure 2: CD structure.
Figure 3: Typical pathway for synthesizing CD-based rotaxanes.
Scheme 1: (A) Synthesis of α-CD-based [2]rotaxane via a metal–ligand complex. (B) Chemical structures of meth...
Scheme 2: Synthesis of α-CD-based polyrotaxane.
Scheme 3: Facile [3]rotaxane synthesis by the urea end-capping method.
Figure 4: (A) Single-crystal structure of α-CD-based [3]rotaxane 3 and PMα-CD-based [3]rotaxane 4. (B) Schema...
Figure 5: Structural control of CD-based [2]rotaxane via (A) light irradiation and (B) light irradiation and ...
Figure 6: Relationship among the plus–minus signs of ICD, the position of the guest molecule, and the axis of...
Figure 7: Structural control of CD-based rotaxane via (A) redox reaction and (B) in a solvent.
Scheme 4: (A) Synthesis of pseudopolyrotaxane bearing an ABA triblock copolymer as an axle. (B) Two synthetic...
Scheme 5: Slippage of size-complementary rotaxanes.
Figure 8: (A) Reversible formation of the CD-based [2]rotaxane. (B) Deslipping reaction of the CD-based size-...
Figure 9: (A) Chemical structures of [3]rotaxanes 2 and 3. (B) Schematic of the deslipping reaction of [3]rot...
Figure 10: (A) Modification of the axle ends of [3]rotaxane by (1) bromination and (2) the Suzuki coupling rea...
Figure 11: (A) ICD spectra of [3]rotaxanes bearing acylated (top) and conventional (bottom) CDs. (B) Schematic...
Figure 12: Synthesis of macromolecular[3]rotaxane via a size-complementary protocol.
Figure 13: Conjugated polymer insulated by (A) β-CD. (B) Triphenylamine-substituted β-CD.
Figure 14: Synthesis of the VSC and successive rotaxane-crosslinked polymer (RCP) preparation.
Figure 15: (A) Chemical structure of the [3]rotaxane crosslinker (RC). (B) Schematic of the synthesis and de-c...
Figure 16: (A) Random vinylation of the CD-based [3]rotaxane; (B) Schematic of the reaction between α-CD and m...
Figure 17: (A) Aggregation of CD-based [3]rotaxane. (B) Schematic of the plausible mechanism of the aggregatio...
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
- fundamental to advancing technologies that address global challenges in health, sustainability, and beyond. By enabling the production of complex molecules with specific functions, chemical synthesis and catalysis play a key role in innovation across the above-mentioned fields and thus improve our quality of
A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis
- Nian Li,
- Ruzal Sitdikov,
- Ajit Prabhakar Kale,
- Joost Steverlynck,
- Bo Li and
- Magnus Rueping
Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214
- industrial settings. An anodic oxidation is frequently employed for C–H functionalization, which can simplify late-stage functionalization strategies. Additionally, many of these synthetic methods do not require precious metals, enhancing their appeal in terms of sustainability and cost-effectiveness
Graphical Abstract
Figure 1: Classification of LSF reactions in this review.
Scheme 1: C(sp2)–H trifluoromethylation of heteroarenes.
Scheme 2: C(sp2)–H and C(sp3)–H alkylation of complex molecules.
Scheme 3: Electrochemical oxidation-induced intermolecular aromatic C–H sulfonamidation.
Scheme 4: Bioconjugation of tyrosine with (a) phenothiazine and (b) urazole derivatives.
Scheme 5: Electrochemical iodoamination of indoles using unactivated amines.
Scheme 6: Allylic C(sp3)–H aminations with sulfonamides.
Scheme 7: Electrochemical benzylic oxidation of C–H bonds.
Scheme 8: Site-selective electrooxidation of methylarenes to aromatic acetals.
Scheme 9: Electrochemical activation of C–H by electron-deficient W2C nanocrystals.
Scheme 10: α-Acyloxy sulfide preparation via C–H/OH cross-dehydrogenative coupling.
Scheme 11: Aromatic C–H-bond thiolation.
Scheme 12: C(sp2)–H functionalization for the installation of sulfonamide groups.
Scheme 13: Preparation of (hetero)aryl chlorides and vinyl chloride with 1,2-dichloroethane. aCu(OAc)2 (0.05 e...
Scheme 14: Electrochemical dual-oxidation enables access to α-chlorosulfoxides.
Scheme 15: Regio- and chemoselective formyloxylation–bromination/chlorination/trifluoromethylation of alkenes.
Scheme 16: Aziridine formation by coupling amines and alkenes.
Scheme 17: Formation of iminosulfide ethers via difunctionalization of an isocyanide.
Scheme 18: Synthesis of 1,3-difunctionalized molecules via C–C-bond cleavage of arylcyclopropane.
Scheme 19: Electrooxidative amino- and oxyselenation of alkenes. VBImBr = 1-butyl-3-vinylimidazolium bromide.
Scheme 20: Electrooxidative dehydrogenative [4 + 2] annulation of indole derivatives.
Scheme 21: Electrochemical cyclization combined with alkoxylation of triticonazole.
Scheme 22: Electrochemically tuned oxidative [4 + 2] annulation of olefins with hydroxamic acids.
Scheme 23: Electrosynthesis of indole derivatives via cyclization of 2-ethynylanilines.
Scheme 24: Allylic C–H oxidation of mono-, di-, and sesquiterpenes.
Scheme 25: Oxidation of unactivated C–H bonds.
Scheme 26: Fluorination of C(sp3)–H bonds. rAP = rapid alternating polarity.
Scheme 27: C(sp3)–H α-cyanation of secondary piperidines.
Scheme 28: Selective electrochemical hydrolysis of hydrosilanes to silanols.
Scheme 29: Organocatalytic electrochemical amination of benzylic C–H bonds.
Scheme 30: Iodide ion-initiated anodic oxidation reactions.
Scheme 31: Mn(III/IV) electro-catalyzed C(sp3)–H azidation.
Scheme 32: Tailored cobalt–salen complexes enable electrocatalytic intramolecular allylic C–H functionalizatio...
Scheme 33: Cobalt–salen complexes-induced electrochemical (cyclo)additions.
Scheme 34: Electrochemical 1,2-diarylation of alkenes enabled by direct dual C–H functionalization of electron...
Scheme 35: Cobalt-electrocatalyzed atroposelective C–H annulation.
Scheme 36: Nickel-electrocatalyzed C(sp2)–H alkoxylation with secondary alcohols.
Scheme 37: Nickel-catalyzed electrochemical enantioselective amination.
Scheme 38: Ruthenium-electrocatalyzed C(sp2)–H mono- and diacetoxylation.
Scheme 39: Rhodium(III)-catalyzed aryl-C–H phosphorylation enabled by anodic oxidation-induced reductive elimi...
Scheme 40: Asymmetric Lewis-acid catalysis for the synthesis of non-racemic 1,4-dicarbonyl compounds.
Scheme 41: Electrochemical enantioselective C(sp3)–H alkenylation.
Scheme 42: Palladium-catalyzed electrochemical dehydrogenative cross-coupling.
Scheme 43: Ir-electrocatalyzed vinylic C(sp2)–H activation for the annulation between acrylic acids and alkyne...
Scheme 44: Electrochemical gold-catalyzed C(sp3)–C(sp) coupling of alkynes and arylhydrazines.
Scheme 45: Photoelectrochemical alkylation of C–H heteroarenes using organotrifluoroborates.
Scheme 46: Mn-catalyzed photoelectro C(sp3)–H azidation.
Scheme 47: Photoelectrochemical undirected C–H trifluoromethylations of (Het)arenes.
Scheme 48: Photoelectrochemical dehydrogenative cross-coupling of heteroarenes with aliphatic C–H bonds.
Scheme 49: C–H amination via photoelectrochemical Ritter-type reaction.
Scheme 50: Photoelectrochemical multiple oxygenation of C–H bonds.
Scheme 51: Accelerated C(sp3)–H heteroarylations by the f-EPC system.
Scheme 52: Photoelectrochemical cross-coupling of amines.
Scheme 53: Birch electroreduction of arenes. GSW = galvanized steel wire.
Scheme 54: Electroreductive deuterations.
Scheme 55: Chemoselective electrosynthesis using rapid alternating polarity.
Scheme 56: Electroreductive olefin–ketone coupling.
Scheme 57: Electroreductive approach to radical silylation.
Scheme 58: Electrochemical borylation of alkyl halides. CC = carbon close.
Scheme 59: Radical fluoroalkylation of alkenes.
Scheme 60: Electrochemical defluorinative hydrogenation/carboxylation.
Scheme 61: Electrochemical decarboxylative olefination.
Scheme 62: Electrochemical decarboxylative Nozaki–Hiyama–Kishi coupling.
Scheme 63: Nickel-catalyzed electrochemical reductive relay cross-coupling.
Scheme 64: Electrochemical chemo- and regioselective difunctionalization of 1,3-enynes.
Scheme 65: Electrocatalytic doubly decarboxylative crosscoupling.
Scheme 66: Electrocatalytic decarboxylative crosscoupling with aryl halides.
Scheme 67: Nickel-catalyzed electrochemical reductive coupling of halides.
Scheme 68: Nickel-electrocatalyzed enantioselective carboxylation with CO2.
Scheme 69: Reductive electrophotocatalysis for borylation.
Scheme 70: Electromediated photoredox catalysis for selective C(sp3)–O cleavages of phosphinated alcohols to c...
Scheme 71: Stereoselective electro-2-deoxyglycosylation from glycals. MFE = methyl nonafluorobutyl ether.
Scheme 72: Electrochemical peptide modifications.
Scheme 73: Electrochemical α-deuteration of amides.
Scheme 74: Electrochemical synthesis of gem-diselenides.
Scheme 75: Site-selective electrochemical aromatic C–H amination.
Scheme 76: Electrochemical coupling of heteroarenes with heteroaryl phosphonium salts.
Scheme 77: Redox-neutral strategy for the dehydroxyarylation reaction.
Scheme 78: Nickel-catalyzed electrochemical C(sp3)–C(sp2) cross-coupling of benzyl trifluoroborate and halides....
Scheme 79: Paired electrocatalysis for C(sp3)–C(sp2) coupling.
Scheme 80: Redox-neutral strategy for amination of aryl bromides.
Scheme 81: Redox-neutral cross-coupling of aryl halides with weak N-nucleophiles. aProtocol with (+) RVC | RVC...
Scheme 82: Nickel-catalyzed N-arylation of NH-sulfoximines with aryl halides.
Scheme 83: Esterification of carboxylic acids with aryl halides.
Scheme 84: Electrochemically promoted nickel-catalyzed carbon–sulfur-bond formation. GFE = graphite felt elect...
Scheme 85: Electrochemical deoxygenative thiolation by Ni-catalysis. GFE = graphite felt electrode; NFE = nick...
Scheme 86: Electrochemical coupling of peptides with aryl halides.
Scheme 87: Paired electrolysis for the phosphorylation of aryl halides. GFE = graphite felt electrode, FNE = f...
Scheme 88: Redox-neutral alkoxyhalogenation of alkenes.
Machine learning-guided strategies for reaction conditions design and optimization
- Lung-Yi Chen and
- Yi-Pei Li
Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212
- models across various laboratories and contexts. Such global collaboration is instrumental in addressing widespread challenges like climate change and sustainability through smarter chemical processes. By focusing on these directions, we anticipate a future where ML not only supports but significantly
Graphical Abstract
Figure 1: Schematic diagram illustrating the data mining and preprocessing steps for chemical reaction datase...
Figure 2: A comparison of three types of reaction embedding methods: (A) descriptor-based, which use predefin...
Figure 3: A schematic diagram of how ML algorithms can be combined with HTE platforms to optimize reaction co...
Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis
- Stefan P. Schmid,
- Leon Schlosser,
- Frank Glorius and
- Kjell Jorner
Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196
Graphical Abstract
Figure 1: Schematic depiction of available data sources for predictive modelling, each with its advantages an...
Figure 2: Schematic depiction of different kinds of molecular representations for fluoronitroethane. Among th...
Figure 3: Depiction of the energy diagram of a generic enantioselective reaction. In the centre, catalyst and...
Figure 4: Hammett parameters are derived from the equilibrium constant of substituted benzoic acids (example ...
Figure 5: Selected examples of popular descriptors applied to model organocatalytic reactions. Descriptors en...
Figure 6: Example bromocyclization reaction from Toste and co-workers using a DABCOnium catalyst system and C...
Figure 7: Example from Neel et al. using a chiral ion pair catalyst for the selective fluorination of allylic...
Figure 8: Data set created by Denmark and co-workers for the CPA-catalysed thiol addition to N-acylimines [67]. T...
Figure 9: Selected examples of ML developments that used the dataset from Denmark and co-workers [67]. (A) Varnek...
Figure 10: Study from Reid and Sigman developing statistical models for CPA-catalysed nucleophilic addition re...
Figure 11: Selected examples of studies where mechanistic transferability was exploited to model multiple reac...
Figure 12: Generality approach by Denmark and co-workers [132] for the iodination of arylpyridines. From the releva...
Figure 13: Betinol et al. [133] clustered the relevant chemical space and then evaluated the average ee for every c...
Figure 14: Corminboeuf and co-workers [134] chose a representative subset of the reaction space (indicated by dark ...
Figure 15: Example for data-driven modelling to improve substrate and catalyst design. (A) C–N coupling cataly...
Figure 16: Example for utilising a genetic algorithm for catalyst design. (A) Morita–Baylis–Hillman reaction s...
Figure 17: Organocatalysed synthesis of spirooxindole analogues by Kondo et al. [171] (A) Reaction scheme of dienon...
Figure 18: Schematic depiction of required developments in order to overcome current limitations of ML for org...
Hetero-polycyclic aromatic systems: A data-driven investigation of structure–property relationships
- Sabyasachi Chakraborty,
- Eduardo Mayo Yanes and
- Renana Gershoni-Poranne
Beilstein J. Org. Chem. 2024, 20, 1817–1830, doi:10.3762/bjoc.20.160
- Sabyasachi Chakraborty Eduardo Mayo Yanes Renana Gershoni-Poranne Schulich Faculty of Chemistry and the Resnick Sustainability Center for Catalysis, Technion – Israel Institute of Technology, Haifa 32000, Israel 10.3762/bjoc.20.160 Abstract Polycyclic aromatic systems (PASs) are pervasive
Graphical Abstract
Figure 1: A) The building blocks used in the COMPAS-2 datasets. B) Possible annulation types formed when comb...
Figure 2: Roadmap of the work described in this article. Three main criteria are defined in increasing struct...
Figure 3: Comparison between COMPAS-1 (blue) and COMPAS-2 (purple). A) Principal Moments of Inertia shape dis...
Figure 4: Distributions of electronic properties of the dataset. KDE plots of HOMO, LUMO, Gap, AIP, and AEA c...
Figure 5: KDE distributions of the HOMO, LUMO, and Gap separated and colored by the longest L for: A) all 9-r...
Figure 6: Distributions of molecular properties for 4n and (4n + 2) π-electron count systems, divided by the ...
Figure 7: Stacked histograms showing the prevalence of the different heteroatoms across different areas of th...
Figure 8: Distributions of electronic properties of the dataset. KDE plots of A) HOMO, B) LUMO, C) Gap, D) AI...
Figure 9: A) Scatter plot of the HOMO (x-axis) and LUMO (y-axis) values of the molecules in COMPAS-2. In each...
Figure 10: The effect of multiple heterocycles of a certain type on the A) HOMO, B) LUMO, and C) Gap. For all ...
Harnessing unprotected deactivated amines and arylglyoxals in the Ugi reaction for the synthesis of fused complex nitrogen heterocycles
- Javier Gómez-Ayuso,
- Pablo Pertejo,
- Tomás Hermosilla,
- Israel Carreira-Barral,
- Roberto Quesada and
- María García-Valverde
Beilstein J. Org. Chem. 2024, 20, 1758–1766, doi:10.3762/bjoc.20.154
- the most desirable strategy from the point-of view of sustainability. This has been achieved following two different approaches: the blockage of the amine group throughout the reaction by the incorporation of an additional group on the carbonyl component [16][17][18] or the use of amine groups with a
Graphical Abstract
Figure 1: Fused heterocycles containing the piperazine and diazepine core.
Scheme 1: Synthesis of benzodiazepinones 5 from anthranilic acid derivatives.
Scheme 2: Diastereoselective one-pot synthesis of benzodiazepinones 6.
Scheme 3: Synthesis of bis-1,4-benzodiazepines 7.
Scheme 4: Synthesis of benzodiazepinone 5c and pyrrolobenzodiazepinone 8 from anthranilic acid and 3-bromopro...
Scheme 5: Synthesis of pyrrolopiperazinones 9 from pyrrole and indole carboxylic acids.
Scheme 6: Synthesis of pyrrolopiperazinones 10 from N-phenylglicine.
Figure 2: X-ray diffraction structures of pyrrolopiperazinones 9a (left) and 10a (right). The thermal ellipso...
Scheme 7: Synthesis of pyrrolopiperazinone 11 using (S)-α-methylbenzylamine.
Scheme 8: Proposed mechanism in the spontaneous cyclization of Ugi adducts obtained from arylglyoxals and dea...
Scheme 9: Synthesis of pyrrolopiperazinoquinazolines 13.
Scheme 10: Synthesis of piperazinoquinazoline 14.
Scheme 11: Synthesis of dipyrrolopiperazinones 12.
Figure 3: X-ray diffraction structure of dipyrrolopiperazinone 12c. The thermal ellipsoid plot (Olex2) is at ...
Synthetic applications of the Cannizzaro reaction
- Bhaskar Chatterjee,
- Dhananjoy Mondal and
- Smritilekha Bera
Beilstein J. Org. Chem. 2024, 20, 1376–1395, doi:10.3762/bjoc.20.120
- furnishing the corresponding alcohol (D) and acid molecule (E). Review Modernization of the Cannizzaro reaction Researchers have always aimed to improve the efficiency, selectivity, and sustainability of reaction processes. The development of reagents, solvents, and application of modern technology frame the
- also simplifies product isolation and purification and improves the overall sustainability of the process [23][24]. However; specific reaction requirements ensure efficient and selective utilization of solvents. Marvi and Talakoubi carried out the Cannizzaro reaction [25] using montmorillonite K-10 and
Graphical Abstract
Figure 1: Types and mechanism of the Cannizzaro reaction.
Figure 2: Various approaches of the Cannizzaro reaction.
Figure 3: Representative molecules synthesized via the Cannizzaro reaction.
Scheme 1: Intramolecular Cannizzaro reaction of aryl glyoxal hydrates using TOX catalysts.
Scheme 2: Intramolecular Cannizzaro reaction of aryl methyl ketones using ytterbium triflate/selenium dioxide....
Scheme 3: Intramolecular Cannizzaro reaction of aryl glyoxals using Cr(ClO4)3 as catalyst.
Scheme 4: Cu(II)-PhBox-catalyzed asymmetric Cannizzaro reaction.
Scheme 5: FeCl3-based chiral catalyst applied for the enantioselective intramolecular Cannizzaro reaction rep...
Scheme 6: Copper bis-oxazoline-catalysed intramolecular Cannizzaro reaction and proposed mechanism.
Scheme 7: Chiral Fe catalysts-mediated enantioselective Cannizzaro reaction.
Scheme 8: Ruthenium-catalyzed Cannizzaro reaction of aromatic aldehydes.
Scheme 9: MgBr2·Et2O-assisted Cannizzaro reaction of aldehydes.
Scheme 10: LiBr-catalyzed intermolecular Cannizzaro reaction of aldehydes.
Scheme 11: γ-Alumina as a catalyst in the Cannizzaro reaction.
Scheme 12: AlCl3-mediated Cannizzaro disproportionation of aldehydes.
Scheme 13: Ru–N-heterocyclic carbene catalyzed dehydrogenative synthesis of carboxylic acids.
Figure 4: Proposed catalytic cycle for the dehydrogenation of alcohols.
Scheme 14: Intramolecular desymmetrization of tetraethylene glycol.
Scheme 15: Desymmetrization of oligoethylene glycol dialdehydes.
Scheme 16: Intramolecular Cannizzaro reaction of calix[4]arene dialdehydes.
Scheme 17: Desymmetrization of dialdehydes of symmetrical crown ethers using Ba(OH)2.
Scheme 18: Synthesis of ottelione A (proposed) via intramolecular Cannizzaro reaction.
Scheme 19: Intramolecular Cannizzaro reaction for the synthesis of pestalalactone.
Scheme 20: Synthetic strategy towards nigricanin involving an intramolecular Cannizzaro reaction.
Scheme 21: Spiro-β-lactone-γ-lactam part of oxazolomycins via aldol crossed-Cannizzaro reaction.
Scheme 22: Synthesis of indole alkaloids via aldol crossed-Cannizzaro reaction.
Scheme 23: Aldol and crossed-Cannizzaro reaction towards the synthesis of ertuliflozin.
Scheme 24: Synthesis of cyclooctadieneones using a Cannizzaro reaction.
Scheme 25: Microwave-assisted crossed-Cannizzaro reaction for the synthesis of 3,3-disubstituted oxindoles.
Scheme 26: Synthesis of porphyrin-based rings using the Cannizzaro reaction.
Scheme 27: Synthesis of phthalides and pestalalactone via Cannizarro–Tishchenko-type reaction.
Scheme 28: Synthesis of dibenzoheptalene bislactones via a double intramolecular Cannizzaro reaction.
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
- recent photocatalysis methodologies in the field of C–O bond activation. As conventional techniques, such as Barton decarboxylation, create hazardous wastes, the use of alternative feedstocks, including alcohols and acids, has been encouraged to achieve sustainability. The recent advancements not only
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.
The Ugi4CR as effective tool to access promising anticancer isatin-based α-acetamide carboxamide oxindole hybrids
- Carolina S. Marques,
- Aday González-Bakker and
- José M. Padrón
Beilstein J. Org. Chem. 2024, 20, 1213–1220, doi:10.3762/bjoc.20.104
- with remarkable atom economy, cost and time-effective and mainly diminishing waste production is a conscientious boost for structural diversity and sustainability [1][2][3]. The well-known Passerini, Ugi, Mannich, Biginelli, Hantzsch and Strecker reactions are some examples of the classic MCRs
- isatin-based Ugi reaction [16][20][21][22][23] and the potential of the bis-amide-oxindole type derivatives as anticancer agents, a second family was synthesized, and screened for their anticancer activities (Scheme 1B). Results and Discussion Synthesis Underlining sustainability and economically favored
Graphical Abstract
Figure 1: (A) Accessing libraries of oxindole hybrids using commercially available isatin as starting materia...
Scheme 1: (A) Library of isatin-based α-acetamide carboxamide oxindole derivatives obtained using an Ugi four...
Scheme 2: Library of α-acetamide carboxamide oxindole hybrids 5 accessed via the Ugi4CR.
Figure 2: Carboxylic acids 2 and aldehydes/ketones 3 used in the Ugi4CR.
Scheme 3: Microwave-assisted CuAAC reaction to access α-acetamide carboxamide 1,2,3-triazole oxindole hybrid 7...
Scheme 4: Library of α-acetamide carboxamide isatin hybrids 8 easy accessed via deprotection reaction on the ...
Figure 3: GI50 range plot against human solid tumor cell lines of investigated α-acetamide carboxamide isatin...
Manganese-catalyzed C–C and C–N bond formation with alcohols via borrowing hydrogen or hydrogen auto-transfer
- Mohd Farhan Ansari,
- Atul Kumar Maurya,
- Abhishek Kumar and
- Saravanakumar Elangovan
Beilstein J. Org. Chem. 2024, 20, 1111–1166, doi:10.3762/bjoc.20.98
- , expensive, and limited in availability. Hence, replacing them with the first row of transition metals would increase the sustainability and profitability of this procedure [13]. Indeed, many 3d-metal-based homogeneous catalysts have been documented for BH reactions [14][15] since these metals are
Graphical Abstract
Scheme 1: General scheme of the borrowing hydrogen (BH) or hydrogen auto-transfer (HA) methodology.
Scheme 2: General scheme for C–N bond formation. A) Traditional cross-couplings with alkyl or aryl halides. B...
Figure 1: Manganese pre-catalysts used for the N-alkylation of amines with alcohols.
Scheme 3: Manganese(I)-pincer complex Mn1 used for the N-alkylation of amines with alcohols and methanol.
Scheme 4: N-Methylation of amines with methanol using Mn2.
Scheme 5: C–N-Bond formation with amines and methanol using PN3P-Mn complex Mn3 reported by Sortais et al. [36]. a...
Scheme 6: Base-assisted synthesis of amines and imines with Mn4. Reaction assisted by A) t-BuOK and B) t-BuON...
Scheme 7: Coupling of alcohols and hydrazine via the HB approach reported by Milstein et al. [38]. aReaction time...
Scheme 8: Proposed mechanism for the coupling of alcohols and hydrazine catalyzed by Mn5.
Scheme 9: Phosphine-free manganese catalyst for N-alkylation of amines with alcohols reported by Balaraman an...
Scheme 10: N-Alkylation of sulfonamides with alcohols.
Scheme 11: Mn–NHC catalyst Mn6 applied for the N-alkylation of amines with alcohols. a3 mol % of Mn6 were used....
Scheme 12: N-Alkylation of amines with primary and secondary alcohols. a80 °C, b100 °C.
Scheme 13: Manganese(III)-porphyrin catalyst for synthesis of tertiary amines.
Scheme 14: Proposed mechanism for the alcohol dehydrogenation with Mn(III)-porphyrin complex Mn7.
Scheme 15: N-Methylation of nitroarenes with methanol using catalyst Mn3.
Scheme 16: Mechanism of manganese-catalyzed methylation of nitroarenes using Mn3 as the catalyst.
Scheme 17: Bidentate manganese complex Mn8 applied for the N-alkylation of primary anilines with alcohols. aOn...
Scheme 18: N-Alkylation of amines with alcohols in the presence of manganese salts and triphenylphosphine as t...
Scheme 19: N-Alkylation of diazo compounds with alcohols using catalyst Mn9.
Scheme 20: Proposed mechanism for the amination of alcohols with diazo compounds catalyzed by catalyst Mn9.
Scheme 21: Mn1 complex-catalyzed synthesis of polyethyleneimine from ethylene glycol and ethylenediamine.
Scheme 22: Bis-triazolylidene-manganese complex Mn10 for the N-alkylation of amines with alcohols.
Figure 2: Manganese complexes applied for C-alkylation reactions of ketones with alcohols.
Scheme 23: General scheme for the C–C bond formation with alcohols and ketones.
Scheme 24: Mn1 complex-catalyzed α-alkylation of ketones with primary alcohols.
Scheme 25: Mechanism for the Mn1-catalyzed alkylation of ketones with alcohols.
Scheme 26: Phosphine-free in situ-generated manganese catalyst for the α-alkylation of ketones with primary al...
Scheme 27: Plausible mechanism for the Mn-catalyzed α-alkylation of ketones with alcohols.
Scheme 28: α-Alkylation of esters, ketones, and amides using alcohols catalyzed by Mn11.
Scheme 29: Mono- and dialkylation of methylene ketones with primary alcohols using the Mn(acac)2/1,10-phenanth...
Scheme 30: Methylation of ketones with methanol and deuterated methanol.
Scheme 31: Methylation of ketones and esters with methanol. a50 mol % of t-BuOK were used, bCD3OD was used ins...
Scheme 32: Alkylation of ketones and secondary alcohols with primary alcohols using Mn4.
Scheme 33: Bidentate manganese-NHC complex Mn6 applied for the synthesis of alkylated ketones using alcohols.
Scheme 34: Mn1-catalyzed synthesis of substituted cycloalkanes by coupling diols and secondary alcohols or ket...
Scheme 35: Proposed mechanism for the synthesis of cycloalkanes via BH method.
Scheme 36: Synthesis of various cycloalkanes from methyl ketones and diols catalyze by Mn13. aReaction time wa...
Scheme 37: N,N-Amine–manganese complex (Mn13)-catalyzed alkylation of ketones with alcohols.
Scheme 38: Naphthyridine‑N‑oxide manganese complex Mn14 applied for the alkylation of ketones with alcohols. a...
Scheme 39: Proposed mechanism of the naphthyridine‑N‑oxide manganese complex (Mn14)-catalyzed alkylation of ke...
Scheme 40: α-Methylation of ketones and indoles with methanol using Mn15.
Scheme 41: α-Alkylation of ketones with primary alcohols using Mn16. aNMR yield.
Figure 3: Manganese complexes used for coupling of secondary and primary alcohols.
Scheme 42: Alkylation of secondary alcohols with primary alcohols catalyzed by phosphine-free catalyst Mn17. a...
Scheme 43: PNN-Manganese complex Mn18 for the alkylation of secondary alcohols with primary alcohols.
Scheme 44: Mechanism for the Mn-pincer catalyzed C-alkylation of secondary alcohols with primary alcohols.
Scheme 45: Upgrading of ethanol with methanol for isobutanol production.
Scheme 46: Mn-Pincer catalyst Mn19 applied for the β-methylation of alcohols with methanol. a2.0 mol % of Mn19...
Scheme 47: Functionalized ketones from primary and secondary alcohols catalyzed by Mn20. aMn20 (5 mol %), NaOH...
Scheme 48: Synthesis of γ-disubstituted alcohols and β-disubstituted ketones through Mn9-catalyzed coupling of...
Scheme 49: Proposed mechanism for the Mn9-catalyzed synthesis of γ-disubstituted alcohols and β-disubstituted ...
Scheme 50: Dehydrogenative coupling of ethylene glycol and primary alcohols catalyzed by Mn4.
Scheme 51: Mn18-cataylzed C-alkylation of unactivated esters and amides with alcohols.
Scheme 52: Alkylation of amides and esters using Mn21.
Scheme 53: α-Alkylation of nitriles with primary alcohols using in situ-generated manganese catalyst.
Scheme 54: Proposed mechanism for the α-alkylation of nitriles with primary alcohols.
Scheme 55: Mn9-catalyzed α-alkylation of nitriles with primary alcohols. a1,4-Dioxane was used as solvent, 24 ...
Figure 4: Manganese complexes used for alkylation of heterocyclic compounds.
Scheme 56: Aminomethylation of aromatic compounds with secondary amines and methanol catalyzed by Mn22.
Scheme 57: Regioselective alkylation of indolines with alcohols catalyzed by Mn9. aMn9 (4 mol %), 48 h.
Scheme 58: Proposed mechanism for the C- and N-alkylation of indolines with alcohols.
Scheme 59: C-Alkylation of methyl N-heteroarenes with primary alcohols catalyzed by Mn1. aTime was 60 h.
Scheme 60: C-Alkylation of oxindoles with secondary alcohols.
Scheme 61: Plausible mechanism for the Mn23-catalyzed C-alkylation of oxindoles with secondary alcohols.
Scheme 62: Synthesis of C-3-alkylated products by coupling alcohols with indoles and aminoalcohols.
Scheme 63: C3-Alkylation of indoles using Mn1.
Scheme 64: C-Methylation of indoles with Mn15 and methanol.
Scheme 65: α-Alkylation of 2-oxindoles with primary and secondary alcohols catalyzed by Mn25. aReaction carrie...
Scheme 66: Dehydrogenative alkylation of indolines with Mn1. aMn1 (5.0 mol %) was used.
Scheme 67: Synthesis of bis(indolyl)methane derivatives from indoles and alcohols catalyzed by Mn26. aMn26 (5....
Scheme 68: One-pot synthesis of pyrimidines via BH.
Scheme 69: Synthesis of pyrroles from alcohols and aminoalcohols using Mn4.
Scheme 70: Synthesis of pyrroles via multicomponent reaction catalyzed by Mn12.
Scheme 71: Friedländer quinoline synthesis using an in situ-generated phosphine-free manganese catalyst.
Scheme 72: Quinoline synthesis using bis-N-heterocyclic carbene-manganese catalyst Mn6.
Scheme 73: Quinoline synthesis using manganese(III)-porphyrin catalyst Mn7.
Scheme 74: Manganese-catalyzed tetrahydroquinoline synthesis via borrowing BH.
Scheme 75: Proposed mechanism for the manganese-catalyzed tetrahydroquinoline synthesis.
Scheme 76: Synthesis of C3-alkylated indoles using Mn24.
Scheme 77: Synthesis of C-3-alkylated indoles using Mn1.
Scheme 78: C–C Bond formation by coupling of alcohols and ylides.
Scheme 79: C-Alkylation of fluorene with alcohols catalyzed by Mn24.
Scheme 80: Proposed mechanism for the C-alkylation of fluorene with alcohols catalyzed by Mn24.
Scheme 81: α-Alkylation of sulfones using Mn-PNN catalyst Mn28.
Light on the sustainable preparation of aryl-cored dibromides
- Fabrizio Roncaglia,
- Alberto Ughetti,
- Nicola Porcelli,
- Biagio Anderlini,
- Andrea Severini and
- Luca Rigamonti
Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95
- significant importance as reactive building blocks in polymer and materials chemistry. Their preparation primarily relies on established synthetic methods using molecular bromine or N-bromosuccinimide, known for their reliability and effectiveness. However, from a sustainability perspective, these methods
- be employed in two variants modulated by light irradiation. This external switch can be used to selectively trigger side-chain or core halogenation. Keywords: aryl halides; benzyl halides; bromination; sustainability; Introduction Activation through halogens has become a key strategy in achieving
- results on various substrates, the direct use of molecular bromine poses sustainability challenges. Its innate reactivity requires stringent safety protocols during transportation, storage, and handling [24]. A related concern involves the stability of the diluting media, often requiring the use of toxic
Graphical Abstract
Figure 1: Comparison between the light-initiated radical halogenation of toluene (right), and the Ar-SE bromi...
Figure 2: Toluene halogenation mediated by NBS in absence (left) or exposed to light (right).
Figure 3: Scifinder® reaction hits for the structure “as drawn” (January 2024).
Figure 4: Yields obtained in the preparation of aryl-cored halides.
Innovative synthesis of drug-like molecules using tetrazole as core building blocks
- Jingyao Li,
- Ajay L. Chandgude,
- Qiang Zheng and
- Alexander Dömling
Beilstein J. Org. Chem. 2024, 20, 950–958, doi:10.3762/bjoc.20.85
- pathways in terms of economy, sustainability, generalizability, step-count, reaction simplicity, and yields. With these tetrazole building blocks in hand, we next aimed to investigate the scope and limitations by assembling smaller compound libraries with a high degree of complexity and skeletal diversity
Graphical Abstract
Figure 1: Tetrazole drugs, current assembly strategies, and novel building block strategy.
Scheme 1: Synthesis of tetrazole building blocks. Isolated yields.
Scheme 2: Substrate scope of Passerini products 3. Isolated yields.
Scheme 3: Substrate scope of Ugi products 4 and 5. Isolated yields.
Scheme 4: Synthesis of tetrazole building block 6. Isolated yield.
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
- structural scope of modern agrochemical research and to address sustainability goals, e.g., overcoming herbicide resistance and meeting demanding environmental safety goals. Experimental Synthesis Representative procedure for the synthesis of 6-bromo-5-(2-fluorophenyl)-2,3-dihydro[1,3]thiazolo[4,5-b]pyridine
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...
A new analog of dihydroxybenzoic acid from Saccharopolyspora sp. KR21-0001
- Rattiya Janthanom,
- Yuta Kikuchi,
- Hiroki Kanto,
- Tomoyasu Hirose,
- Arisu Tahara,
- Takahiro Ishii,
- Arinthip Thamchaipenet and
- Yuki Inahashi
Beilstein J. Org. Chem. 2024, 20, 497–503, doi:10.3762/bjoc.20.44
- and biotechnological innovations. Continued research in this area has the potential to uncover valuable compounds that contribute to human health, pharmaceutical industry, and environmental sustainability. Experimental Taxonomic analysis Saccharopolyspora sp. KR21-0001 was isolated from soil in Ōha
Graphical Abstract
Figure 1: Neighbor-joining tree based on 16S rRNA gene sequences between KR21-0001 and members of the genus S...
Scheme 1: Fermentation of Saccharopolyspora sp. KR21-0001 and isolation procedure of KR21-0001A (1).
Figure 2: Structure of KR21-0001A (1). (a) 1H,1H COSY and HMBC correlations and (b) absolute configuration.
Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles
- Periklis X. Kolagkis,
- Eirini M. Galathri and
- Christoforos G. Kokotos
Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36
- synthetic pathways in organic chemistry [32][33][34]. Common organic syntheses require the use of harmful chemicals, such as toxic solvents, hazardous reagents, catalysts and reaction conditions, which contribute to environmental pollution and soil degradation [35][36]. Wanting to enhance the sustainability
- just 0.06 mol % in just 25 minutes [101][102]. Furthermore, the nanocatalyst could be easily retrieved by applying a magnetic field on the reaction mixture, where it could be reused for at least 8 cycles, before there was a noticeable drop in effectiveness. This boosted the sustainability of this
Graphical Abstract
Scheme 1: Examples of BIMs used for their medicinal properties.
Scheme 2: Mechanisms for the synthesis of BIMs using protic or Lewis acids as catalysts.
Scheme 3: Synthesis of bis(indolyl)methanes using DBDMH.
Scheme 4: Competition experiments and synthesis of bis(indolyl)methanes using DBDMH.
Scheme 5: Proposed mechanism for formation of BIM of using DBDMH.
Scheme 6: Synthesis of bis(indolyl)methanes using I2.
Scheme 7: General reaction mechanism upon halogen bonding.
Scheme 8: Synthesis of bis(indolyl)methanes using I2, introduced by Ji.
Scheme 9: Synthesis of bis(indolyl)methanes using Br2 in CH3CN.
Scheme 10: Βidentate halogen-bond donors.
Scheme 11: Synthesis of bis(indolyl)methanes using bidentate halogen-bond donor 26.
Scheme 12: Proposed reaction mechanism.
Scheme 13: Synthesis of bis(indolyl)methanes using iodoalkyne as catalyst.
Scheme 14: Proposed reaction mechanism.
Scheme 15: Optimized reaction conditions used by Ramshini.
Scheme 16: Activation of the carbonyl group by HPA/TPI-Fe3O4.
Scheme 17: Synthesis of BIMs in the presence of nanoAg-Pt/SiO2-doped silicate.
Scheme 18: Mechanism of action proposed by Khalafi-Nezhad et al.
Scheme 19: Activation of the carbonyl group by the Cu–isatin Schiff base complex.
Scheme 20: Optimum reaction conditions published by Jain.
Scheme 21: Organocatalytic protocol utilizing nanoparticles introduced by Bankar.
Scheme 22: Activation of the carbonyl group by the AlCl3·6H2O-SDS-SiO2 complex.
Scheme 23: Optimal reaction conditions for the aforementioned nano-Fe3O4 based catalysts.
Scheme 24: Nanocatalytic protocol proposed by Kaur et al.
Scheme 25: Microwave approach introduced by Yuan.
Scheme 26: Microwave approach introduced by Zahran et al.
Scheme 27: Microwave irradiation protocol introduced by Bindu.
Scheme 28: Silica-supported microwave irradiation protocol.
Scheme 29: Proposed mechanism for formation of BIM by Nongkhlaw.
Scheme 30: Microwave-assisted synthesis of BIMs catalyzed by succinic acid.
Scheme 31: Proposed mechanism of action of MMO-4.
Scheme 32: Catalytic approach introduced by Muhammadpoor-Baltork et al.
Scheme 33: Reaction conditions used by Xiao-Ming.
Scheme 34: Ultrasonic irradiation-based protocol published by Saeednia.
Scheme 35: Pyruvic acid-mediated synthesis of BIMs proposed by Thopate.
Scheme 36: Synthesis of BIMs using [bmim]BF4 or [bmim]PF6 ionic liquids.
Scheme 37: Synthesis of BIMs utilizing In(OTf)3 in octylmethylimidazolium hexafluorophosphate as ionic liquid.
Scheme 38: FeCl3·6H2O-catalyzed synthesis of BIMs with use of ionic liquid.
Scheme 39: Synthesis of BIMs utilizing the [hmim]HSO4/EtOH catalytic system.
Scheme 40: Synthesis of BIMs utilizing acidic ionic liquid immobilized on silica gel (ILIS-SO2Cl).
Scheme 41: The [bmim][MeSO4]-catalyzed reaction of indole with various aldehydes.
Scheme 42: The role of [bmim][MeSO4] in catalyzing the reaction of indole with aldehydes.
Scheme 43: Synthesis of BIMs utilizing FeCl3-based ionic liquid ([BTBAC]Cl-FeCl3) as catalyst.
Scheme 44: Synthesis of BIMs using [Msim]Cl at room temperature.
Scheme 45: [Et3NH][H2PO4]-catalyzed synthesis of bis(indolyl)methanes.
Scheme 46: PILs-catalyzed synthesis of bis(indolyl)methanes.
Scheme 47: FSILs-mediated synthesis of bis(indolyl)methanes.
Scheme 48: Possible “release and catch” catalytic process.
Scheme 49: Synthesis of bis(indolyl)methanes by [DABCO-H][HSO4].
Scheme 50: Synthesis of bis(indolyl)methanes by [(THA)(SO4)].
Scheme 51: Synthesis of BBSI-Cl and BBSI-HSO4.
Scheme 52: Synthesis of BIMs in the presence of BBSI-Cl and BBSI-HSO4.
Scheme 53: Chemoselectivity of the present method.
Scheme 54: Synthesis of BIMs catalyzed by chitosan-supported ionic liquid.
Scheme 55: Proposed mechanism of action of CSIL.
Scheme 56: Optimization of the reaction in DESs.
Scheme 57: Synthesis of BIMs using ChCl/SnCl2 as DES.
Scheme 58: Synthesis of BIMs derivatives in presence of DES.
Scheme 59: BIMs synthesis in choline chloride/urea (CC/U).
Scheme 60: Flow chemistry-based synthesis of BIMs by Ley.
Scheme 61: Flow chemistry-based synthesis of BIMs proposed by Nam et al.
Scheme 62: Amino-catalyzed reaction of indole with propionaldehyde.
Scheme 63: Aminocatalytic synthesis of BIMs.
Scheme 64: Proposed mechanism for the aminocatalytic synthesis of BIMs.
Scheme 65: Enzymatic reaction of indole with aldehydes.
Scheme 66: Proposed mechanism for the synthesis of BIMs catalyzed by TLIM.
Scheme 67: Proposed reaction mechanism by Badsara.
Scheme 68: Mechanism proposed by D’Auria.
Scheme 69: Photoinduced thiourea catalysis.
Scheme 70: Proposed mechanism of photoacid activation.
Scheme 71: Proposed mechanism of action for CF3SO2Na.
Scheme 72: Proposed mechanism for the synthesis of BIMs by Mandawad.
Scheme 73: Proposed mechanism for the (a) acid generation and (b) synthesis of BIMs.
Scheme 74: a) Reaction conditions employed by Khaksar and b) activation of the carbonyl group by HFIP.
Scheme 75: Activation of the carbonyl group by the PPy@CH2Br through the formation of a halogen bond.
Scheme 76: Reaction conditions utilized by Mhaldar et al.
Scheme 77: a) Reaction conditions employed by López and b) activation of the carbonyl group by thiourea.
Scheme 78: Infrared irradiation approach introduced by Luna-Mora and his research group.
Scheme 79: Synthesis of BIMs with the use of the Fe–Zn BMOF.
A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen
- Gyula Dargó,
- Dóra Erdélyi,
- Balázs Molnár,
- Péter Kisszékelyi,
- Zsófia Garádi and
- József Kupai
Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133
- ). During solvent selection, both the catalytic performance and green chemistry aspects were addressed. For this purpose, we followed GSK’s solvent sustainability guide [34], which ranks solvents according to their properties, such as waste generation, environmental and health impacts, and boiling point
- literature [41]. Application of cinchona squaramide 1 and recyclable, lipophilic cinchona squaramide organocatalysts 2 in a new, gram-scale stereoselective synthesis of baclofen precursor. Classification of the tested non-polar solvents according to the GSK’s solvent sustainability guide [34]. Recycling of
Graphical Abstract
Figure 1: Application of cinchona squaramide 1 and recyclable, lipophilic cinchona squaramide organocatalysts ...
Scheme 1: Synthesis of demethylated cinchona squaramide organocatalyst and the incorporation of the flexible ...
Scheme 2: Synthesis of the lipophilic tag from methyl gallate (8) and attachment to the cinchona squaramide.
Figure 2: Classification of the tested non-polar solvents according to the GSK’s solvent sustainability guide ...
Figure 3: Recycling of the lipophilic organocatalyst in the stereoselective Michael addition by replacing the...
Scheme 3: A new, stereoselective synthetic route for baclofen.
Scheme 4: Gram-scale synthesis of (S)-baclofen hydrochloride.
