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Search for "conjugate addition" in Full Text gives 162 result(s) in Beilstein Journal of Organic Chemistry.
Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B
- Si-Chen Yao,
- Jing-Si Cao,
- Jian Xiao,
- Ya-Wen Wang and
- Yu Peng
Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197
- Abstract The total synthesis of bioactive (+)-aglacin B was achieved. The key steps include an asymmetric conjugate addition reaction induced by a chiral auxiliary and a nickel-promoted reductive tandem cyclization of the elaborated β-bromo acetal, which led to the efficient construction of the
- aryltetralin[2,3-c]furan skeleton embedded in this natural product. Keywords: aryltetralin; conjugate addition; cyclolignan; nickel; reductive coupling; Introduction Proksch and co-workers isolated aglacins A, B, C, and E (1–4, Figure 1) from the methanolic extract of stem bark of Aglaia cordata Hiern from
- that the diarylmethine stereocenter at C7′ in 6 could be formed by an Evans’ auxiliary-induced asymmetric conjugate addition of α,β-unsaturated acyl oxazolidinone 7 with 3,4,5-trimethoxyphenylmagnesium bromide (8). Both of these two building blocks could be conveniently prepared from commercially
Graphical Abstract
Figure 1: The structures of aglacins A, B, C, and E.
Scheme 1: Retrosynthetic analysis of (+)-aglacin B (2).
Scheme 2: Synthesis of cyclization precursor 5.
Scheme 3: Synthesis of (+)-aglacin B (2).
Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA
- Grant D. Walby,
- Brandon R. Tessier,
- Tristan L. Mabee,
- Jennah M. Hoke,
- Hallie M. Bleam,
- Angelina Giglio-Tos,
- Emily E. Harding,
- Vladislavs Baskevics,
- Martins Katkevics,
- Eriks Rozners and
- James A. MacKay
Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193
- . Db3 Synthesis The synthesis of Db3 was originally envisioned to be completed with an unprotected aniline nitrogen, however, this proved problematic in the PNA synthesis. The ultimate route was developed to have an N-Boc protected monomer (Scheme 3). The synthesis started with a conjugate addition of m
Graphical Abstract
Figure 1: (a) Structure of a PNA oligomer with the N-(2-aminoethyl)glycine backbone (in red); (b) Representat...
Figure 2: Representative extended nucleobase triples through Hoogsteen hydrogen bonding (blue dashed lines). ...
Figure 3: Evolution of the strategy for U–A recognition.
Figure 4: Isoorotamide-derived nucleobases for A–U recognition.
Figure 5: Proposed isoorotamide distal binding (Db) nucleobases designed from the Io5 core. Hydrogen bonding ...
Scheme 1: Synthesis of the Db1 monomer (8).
Scheme 2: Synthesis of Db2 monomer 15.
Scheme 3: Synthesis of Db3 monomer 21.
Figure 6: Sequences for RNA hairpins and PNA ligands used for binding studies.
Figure 7: Major-groove view of hydrogen-bonding interactions in the (A) Db1*U–A triplet, (B) Db2*U–A triplet,...
An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives
- Elizaveta V. Gradova,
- Nikita A. Ozhegov,
- Roman O. Shcherbakov,
- Alexander G. Tkachenko,
- Larisa Y. Nesterova,
- Elena Y. Mendogralo and
- Maxim G. Uchuskin
Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183
- , a highly diastereoselective method for the synthesis of dihydrospiro[indoline-3,2'-pyrrole]-2-ones has been developed (Scheme 1, path a) [7]. This transformation proceeds via a Lewis acid-mediated conjugate addition of vinyl azides to electron-deficient alkenes, followed by denitrogenative
Graphical Abstract
Figure 1: Natural and synthetic bioactive spiro[indoline-3,2'-pyrrolidine] derivatives.
Scheme 1: Previous approaches and our work.
Scheme 2: The reaction of 2-arylindoles 1 with α,β-unsaturated ketones 2. aIsolated yield of the 5 mmol scale...
Scheme 3: The scope of the Fe-catalyzed spirocyclization. aIsolated yield of the 4.2 mmol scale experiment.
Scheme 4: The proposed mechanism of product 4 formation.
Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications
- Jullyane Emi Matsushima,
- Khushbu,
- Zuliah Abdulsalam,
- Udyogi Navodya Kulathilaka Conthagamage and
- Víctor García-López
Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179
- . The photoisomerization of the hydrazone modulates the position of the tetraamide macrocycle around the pyrrolidine, breaking its symmetry and switching its handedness. This dynamic control was used to adjust the enantioselectivity of an enamine-mediated conjugate addition. In 2024, the same group
Graphical Abstract
Figure 1: Schematic of common rotaxanes (left) and depiction of the macrocycle shuttling (right).
Figure 2: Structure of some common photoswitches integrated into rotaxanes.
Figure 3: Rotaxane with an acridane photoswitch on the axle modulates the translation of a CBQT4+ macrocycle ...
Figure 4: Hydrogel composed of [2]rotaxanes featuring a central azobenzene in the axle and a cyclodextrin mac...
Figure 5: Dendrimer composed of [2]rotaxane with an azobenzene photoswitch functioning as a macroscopic actua...
Figure 6: (a) Structure of the [2]rotaxane and (b) mechanism for K+ cations transport across lipid bilayers. Figure 6...
Figure 7: Dithienylethene-based [2]rotaxane used in writing patterning applications: (a) rotaxane with open d...
Figure 8: Dithienylethene-based [1]rotaxane shuttling motion triggered by pH changes (top). Dithienylethene p...
Figure 9: Depiction of a fumaramide-based [2]rotaxane photoswitching cycle and deposition on glass and mica s...
Figure 10: Hydrazone-based rotaxane controls helical pitch in a liquid crystal. Figure 10 was adapted from [73] (© 2024 S. ...
Figure 11: (a) Light- and pH-responsive Förster resonance energy transfer observed on a spiropyran-based [2]ro...
Figure 12: Photoresponsive bending of artificial muscle with [c2]daisy chain reported by Harada and collaborat...
Figure 13: Light-responsive shuttling motion of [2]rotaxane based on a stiff-stilbene photoswitch. Figure 13 was reprod...
Figure 14: Azobenzene-based rotaxane modulating lipid bilayers upon photoisomerization. Figure 14 was adapted from [23] (© ...
Figure 15: Depiction of fluorescence quenching processes upon external stimuli of a dithienylethene-based [2]r...
Figure 16: Diagrammatic illustration of rotaxane 1-H-SP depicting interconversions between the four isomeric s...
Figure 17: Representation of [2]rotaxane chloride binding modulated by photoisomerization of a stiff-stilbene. ...
Comparative analysis of complanadine A total syntheses
- Reem Al-Ahmad and
- Mingji Dai
Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178
- in four steps. Subsequent conjugate addition of the lithium anion of TMS-acetonitrile to 15, followed by careful one-pot protonation of the resulting enolate with ethyl salicylate and TMS removal with CsF, gave 16 bearing three properly arranged substituents. Grignard 1,2-addition to ketone 16
- underwent ketone release and amine-ketone condensation to form iminium ion 27. Under the same acidic conditions, enamide 26 underwent hydrolysis and tautomerization to form enol 28. Conjugate addition of enol 28 to iminium ion 27 gave 29 for the subsequent intramolecular Mannich cyclization to deliver 30
- TMSN3 recently developed by Xu and co-workers [34]. Mukaiyama conjugate addition between 60 and 61 promoted by Tf2NH followed by a one-pot enol ether hydrolysis gave 62 as a mixture of inconsequential stereoisomers. Subsequent oxidative cleavage of the terminal olefin of 62 using ozonolysis followed by
Graphical Abstract
Scheme 1: Complanadine natural products and their plausible biosynthesis.
Scheme 2: The Siegel total synthesis of complanadine A enabled by [2 + 2 + 2] cycloadditions.
Scheme 3: The Sarpong total synthesis of complanadine A enabled by a biomimetic strategy and C–H activation.
Scheme 4: The Tsukano total synthesis of complanadine A enabled by Diels–Alder cycloaddition, Heck cyclizatio...
Scheme 5: The Dai total synthesis of complanadine A using single-atom skeletal editing.
Scheme 6: Comparative summary of the four complanadine A total syntheses.
Enantioselective radical chemistry: a bright future ahead
- Anna C. Renner,
- Sagar S. Thorat,
- Hariharaputhiran Subramanian and
- Mukund P. Sibi
Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174
- [22][23]. In these studies, alkyl radicals underwent conjugate addition to N-enoyloxazolidinones. Sibi later described enantioselective tandem radical conjugate addition–trapping reactions that formed two carbon–carbon bonds and created two vicinal stereocenters in a single transformation (Scheme 1
- ) [40]. The reactions were catalyzed by chiral Lewis acids and involved conjugate addition of a nucleophilic alkyl radical to an α,β-unsaturated substrate containing an oxazolidinone or pyrrolidinone template. The resulting α-radical was trapped with an allylstannane and the addition and trapping
Graphical Abstract
Figure 1: Methods of radical generation (A) and general types of radical reactions (B).
Figure 2: Chiral catalysis in enantioselective radical chemistry [13-37].
Scheme 1: Diastereo- and enantioselective additions of nucleophilic radicals to N-enoyloxazolidinone and pyrr...
Scheme 2: Organocatalyzed formal [3 + 2] cycloadditions affording substituted pyrrolidines.
Scheme 3: Synthesis of a hexacyclic compound via an organocatalyzed enantioselective polyene cyclization.
Scheme 4: Nickel-catalyzed asymmetric cross-coupling reactions.
Scheme 5: Chiral cobalt–porphyrin metalloradical-catalyzed radical cyclization reactions.
Scheme 6: Enantioselective radical chaperone catalysis.
Scheme 7: Enantioselective radical addition by decatungstate/iminium catalysis.
Scheme 8: An ene-reductase-catalyzed photoenzymatic enantioselective radical cyclization/enantioselective HAT...
Scheme 9: Photoenzymatic oxidative C(sp3)–C(sp3) coupling reactions between organoboron compounds and amino a...
Scheme 10: Electrochemical α-alkenylation reactions of 2-acylimidazoles catalyzed by a chiral-at-rhodium Lewis...
Scheme 11: Regio- and enantioselective electrochemical reactions of silyl polyenolates catalyzed by a chiral n...
The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products
- Dong-Xing Tan and
- Fu-She Han
Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164
- of 96 with CrO3/3,5-DMP produced ketone 100. The 1,4-conjugate addition of 100 with MeI followed by Luche reduction provided the secondary alcohol 101. A-ring modifications in 101 completed the first total synthesis of (−)-conidiogenone E (20). One the other hand, a two-step transformation involving
- the 1,4-conjugate addition utilizing vinylMgBr and Luche reduction, 100 was converted to secondary alcohol 102 (dr = 2:1). Finally, functional group modifications of A- and D-rings furnished the total syntheses of (−)-conidiogenone C (18) and (−)-12β-hydroxyconidiogenone C (22), respectively. Total
Graphical Abstract
Figure 1: Several representative terpenoid and alkaloid natural products synthesized by applying desymmetric ...
Figure 2: Selected terpenoid and alkaloid natural products synthesized by applying desymmetric enantioselecti...
Scheme 1: The total synthesis of (+)-aplysiasecosterol A (6) by Li [14].
Scheme 2: The total synthesis of (−)-cyrneine A by Han [31].
Scheme 3: The total syntheses of three cyrneine diterpenoids by Han [31,32].
Scheme 4: The total synthesis of (−)-hamigeran B and (−)-4-bromohamigeran B by Han [51].
Scheme 5: The total synthesis of (+)-randainin D by Baudoin [53].
Scheme 6: The total synthesis of (−)-hunterine A and (−)-aspidospermidine by Stoltz [58].
Scheme 7: The total synthesis of (+)-toxicodenane A by Han [65,66].
Scheme 8: The formal total synthesis of (−)-conidiogeone B and total synthesis of (−)-conidiogeone F by Lee a...
Scheme 9: The total syntheses of four conidiogenones natural products by Lee and Han [72].
Scheme 10: The total synthesis of (−)-platensilin by Lou and Xu [82].
Scheme 11: The total synthesis of (−)-platencin and (−)-platensimycin by Lou and Xu [82].
Scheme 12: The total synthesis of (+)-isochamaecydin and (+)-chamaecydin by Han [86].
Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity
- Madara Darzina,
- Anna Lielpetere and
- Aigars Jirgensons
Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136
- -wise process [22]. The first step involves addition of the oxazoline nitrogen to TsNCO leading to a zwitterionic intermediate A, which undergoes 1,4-conjugate addition forming a cyclic intermediate B. Subsequently, the electron-rich double bond in intermediate B reacts with a second equivalent of TsNCO
Graphical Abstract
Scheme 1: Proposed approach for the preparation of vinyloxazoline 6.
Scheme 2: Synthesis of furfuryl amino alcohols S-2d and R-2d and their electrochemical oxidation to esters S-...
Scheme 3: Cleavage of the N-Alloc group leading to a mixture of isomers cis-S-5 and trans-S-5.
Scheme 4: Cleavage of the N-Alloc group with PdCl2(S-BINAP) leading to trans-S-5 and trans-R-5.
Scheme 5: Cyclization of amides trans-S-5 and trans-R-5 to oxazolines S-6 and R-6.
Scheme 6: aza-Diels–Alder reaction of vinyloxazoline S-6 with TsNCO.
Scheme 7: The proposed mechanism of product 7 formation.
Oxetanes: formation, reactivity and total syntheses of natural products
- Peter Gabko,
- Martin Kalník and
- Maroš Bella
Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101
- still runs smoothly, if the aryl is substituted for cyclohexyl. The proposed mechanism, supported by control experiments, deuterium exchange studies and energy calculations, consists of the following steps: conjugate addition of the carbene to the allenoate, regioselective addition of the resulting
Graphical Abstract
Figure 1: Bond lengths and bond angles in oxetane at 140 K [2].
Figure 2: Analogy of 3-substituted oxetanes to carbonyl and gem-dimethyl groups [12].
Figure 3: Use of oxetanes in drug design – selected examples.
Figure 4: Examples of oxetane-containing natural products.
Scheme 1: Synthetic strategies towards construction of the oxetane ring.
Scheme 2: Overview of intramolecular Williamson etherification and competing Grob fragmentation.
Scheme 3: Synthesis of spiro-oxetanes via 1,4-C–H insertion and Williamson etherification.
Scheme 4: Use of phenyl vinyl selenone in the synthesis of spirooxindole oxetanes.
Scheme 5: Synthesis of bicyclic 3,5-anhydrofuranoses via double epoxide opening/etherification.
Scheme 6: Preparation of spirooxetanes by cycloisomerisation via MHAT/RPC.
Scheme 7: Oxetane synthesis via alcohol C–H functionalisation.
Scheme 8: Access to oxetanes 38 from α-acetyloxy iodides.
Scheme 9: The kilogram-scale synthesis of oxetane intermediate 41.
Scheme 10: Overview of the intramolecular opening of 3-membered rings.
Scheme 11: Synthesis of 4,7-dioxatricyclo[3.2.1.03,6]octane skeletons.
Scheme 12: Silicon-directed electrophilic cyclisation of homoallylic alcohols.
Scheme 13: Hydrosilylation–iodocyclisation of homopropargylic alcohols.
Scheme 14: Cu-catalysed intramolecular O-vinylation of γ-bromohomoallylic alcohols.
Scheme 15: Cu-catalysed intramolecular cross-coupling of hydroxyvinylstannanes.
Scheme 16: Isomerisation of oxiranyl ethers containing weakly carbanion-stabilising groups.
Scheme 17: Cyclisation of diethyl haloalkoxymalonates.
Scheme 18: Synthesis of oxetanes through a 1,5-HAT/radical recombination sequence.
Scheme 19: General approach to oxetanes via [2 + 2] cycloadditions.
Scheme 20: Synthesis of tricyclic 4:4:4 oxetanes through a photochemical triple cascade reaction.
Scheme 21: Iridium-catalysed Paternò–Büchi reaction between α-ketoesters and simple alkenes.
Scheme 22: Three-step synthesis of spirocyclic oxetanes 83 via Paternò–Büchi reaction, nucleophilic ring openi...
Scheme 23: Enantioselective Paternò–Büchi reaction catalysed by a chiral iridium photocatalyst.
Scheme 24: Synthesis of polysubstituted oxetanes 92 via Cu(II)-mediated formal [2 + 2] cycloadditions.
Scheme 25: Synthesis of alkylideneoxetanes via NHC- and DBU-mediated formal [2 + 2] cycloadditions.
Scheme 26: Use of sulphur-stabilised carbanions in ring expansions.
Scheme 27: Synthesis of α,α-difluoro(arylthio)methyl oxetanes.
Scheme 28: Ring expansion in an industrial synthesis of PF-06878031.
Scheme 29: Ring contraction of triflated 2-hydroxy-γ-lactones.
Scheme 30: Ring contraction in an industrial synthesis of PF-06878031.
Scheme 31: Photochemical ring contraction of 2,5-dihydrofurans by aryldiazoacetic acid esters.
Scheme 32: Synthesis of 3-oxetanones via O-H insertion of carbenes.
Scheme 33: Synthesis of phosphonate oxetanones via gold-mediated alkyne oxidation/O–H insertion.
Scheme 34: Syntheses and common derivatisations of 3-oxetanone.
Scheme 35: SN1 substitution of 3-aryloxetan-3-ols by thiols and alcohols.
Scheme 36: Fe–Ni dual-catalytic olefin hydroarylation towards 3-alkyl-3-(hetero)aryloxetanes.
Scheme 37: Synthesis of 3-aryloxetan-3-carboxylic acids.
Scheme 38: Decarboxylative alkylation of 3-aryloxetan-3-carboxylic acids.
Scheme 39: Synthesis of 3-amino-3-aryloxetanes via photoredox/nickel cross-coupling catalysis.
Scheme 40: Intermolecular cross-selective [2 + 2] photocycloaddition towards spirooxetanes.
Scheme 41: Synthesis of 3-aryl-3-aminooxetanes via defluorosulphonylative coupling.
Scheme 42: Two-step synthesis of amide bioisosteres via benzotriazolyl Mannich adducts 170.
Scheme 43: Functionalisation of oxetanyl trichloroacetimidates 172.
Scheme 44: Synthesis of oxetane-amino esters 176.
Scheme 45: Tandem Friedel–Crafts alkylation/intramolecular ring opening of 3-aryloxetan-3-ols.
Scheme 46: Synthesis of polysubstituted furans and pyrroles.
Scheme 47: Synthesis of oxazolines and bisoxazolines.
Scheme 48: Tandem, one-pot syntheses of various polycyclic heterocycles.
Scheme 49: Synthesis of 1,2-dihydroquinolines via skeletal reorganisation of oxetanes.
Scheme 50: Synthesis of benzoindolines and 2,3-dihydrobenzofurans and their derivatisations.
Scheme 51: Synthesis of polysubstituted 1,4-dioxanes.
Scheme 52: Preparation of various lactones via ring opening of oxetane-carboxylic acids 219.
Scheme 53: Tsuji-Trost allylation/ring opening of 3-aminooxetanes.
Scheme 54: Arylative skeletal rearrangement of 3-vinyloxetan-3-ols to 2,5-dihydrofurans.
Scheme 55: Reductive opening of oxetanes using catalytic Mg–H species.
Scheme 56: Opening of oxetanes by silyl ketene acetals.
Scheme 57: Rhodium-catalysed hydroacylation of oxetanes.
Scheme 58: Generation of radicals from oxetanes mediated by a vitamin B12-derived cobalt catalyst.
Scheme 59: Reductive opening of oxetanes by B–Si frustrated Lewis pairs.
Scheme 60: Zirconocene-mediated reductive opening of oxetanes.
Scheme 61: Enantioselective syntheses of small and medium-size rings using chiral phosphoric acids.
Scheme 62: Asymmetric synthesis of 2,3-dihydrobenzo[b]oxepines catalysed by a chiral scandium complex.
Scheme 63: Enantioselective synthesis of 1,3-bromohydrins under a chiral squaramide catalysis.
Scheme 64: Enantioselective opening of 2-aryl-2-ethynyloxetanes by anilines.
Scheme 65: Ru-catalysed insertion of diazocarbonyls into oxetanes.
Scheme 66: Ring expansion of oxetanes by stabilised carbenes generated under blue light irradiation.
Scheme 67: Expansion of oxetanes via nickel-catalysed insertion of alkynyltrifluoroborates.
Scheme 68: Nickel-catalysed expansion of oxetanes into ε-caprolactones.
Scheme 69: Expansion of oxetanes via cobalt-catalysed carbonyl insertion.
Scheme 70: Gold-catalysed intramolecular 1,1-carboalkoxylation of oxetane-ynamides.
Scheme 71: Expansion of oxetanes by stabilised sulphoxonium ylides.
Scheme 72: Cu-catalysed ring expansion of 2-vinyloxetanes by diazoesters.
Scheme 73: Total synthesis of (+)-oxetin.
Scheme 74: Total synthesis of racemic oxetanocin A.
Scheme 75: Total synthesis of (−)-merrilactone A.
Scheme 76: Total synthesis of (+)-dictyoxetane.
Scheme 77: Total synthesis of ent-dichrocephone B.
Scheme 78: Total synthesis of (−)-mitrephorone A.
Scheme 79: Total synthesis of (−)-taxol.
Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents
- Jiangfei Chen,
- Yi-Lin Qu,
- Ming Yuan,
- Xiang-Mei Wu,
- Heng-Pei Jiang,
- Ying Fu and
- Shengrong Guo
Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98
Graphical Abstract
Scheme 1: DTBP-mediated oxidative alkylarylation of activated alkenes.
Scheme 2: Iron-catalyzed oxidative 1,2-alkylarylation.
Scheme 3: Possible mechanism for the iron-catalyzed oxidative 1,2-alkylation of activated alkenes.
Scheme 4: A metal-free strategy for synthesizing 3,3-disubstituted oxindoles.
Scheme 5: Iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkenes.
Scheme 6: Proposed mechanism for the iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkene...
Scheme 7: Bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 8: Possible reaction mechanism for the bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 9: Radical cyclization of N-arylacrylamides with isocyanides.
Scheme 10: Plausible mechanism for the radical cyclization of N-arylacrylamides with isocyanides.
Scheme 11: Electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 12: Plausible mechanism for the dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 13: Photocatalyzed cyclization of N-arylacrylamide and N,N-dimethylaniline.
Scheme 14: Proposed mechanism for the photocatalyzed cyclization of N-arylacrylamides and N,N-dimethylanilines....
Scheme 15: Electrochemical monofluoroalkylation cyclization of N-arylacrylamides with dimethyl 2-fluoromalonat...
Scheme 16: Proposed mechanism for the electrochemical radical cyclization of N-arylacrylamides with dimethyl 2...
Scheme 17: Photoelectrocatalytic carbocyclization of unactivated alkenes using simple malonates.
Scheme 18: Plausible mechanism for the photoelectrocatalytic carbocyclization of unactivated alkenes with simp...
Scheme 19: Bromide-catalyzed electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 20: Proposed mechanism for the electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 21: Visible light-mediated trifluoromethylarylation of N-arylacrylamides.
Scheme 22: Plausible reaction mechanism for the visible light-mediated trifluoromethylarylation of N-arylacryl...
Scheme 23: Electrochemical difluoroethylation cyclization of N-arylacrylamides with sodium difluoroethylsulfin...
Scheme 24: Electrochemical difluoroethylation cyclization of N-methyacryloyl-N-alkylbenzamides with sodium dif...
Scheme 25: Photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)su...
Scheme 26: Proposed mechanism for the photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamide...
Scheme 27: Visible-light-induced domino difluoroalkylation/cyclization of N-cyanamide alkenes.
Scheme 28: Proposed mechanism of photoredox-catalyzed radical domino difluoroalkylation/cyclization of N-cyana...
Scheme 29: Palladium-catalyzed oxidative difunctionalization of alkenes.
Scheme 30: Two possible mechanisms of palladium-catalyzed oxidative difunctionalization.
Scheme 31: Silver-catalyzed oxidative 1,2-alkyletherification of unactivated alkenes with α-bromoalkylcarbonyl...
Scheme 32: Photochemical radical cascade cyclization of dienes.
Scheme 33: Proposed mechanism for the photochemical radical cascade 6-endo cyclization of dienes with α-carbon...
Scheme 34: Photocatalyzed radical coupling/cyclization of N-arylacrylamides and.
Scheme 35: Photocatalyzed radical-type couplings/cyclization of N-arylacrylamides with sulfoxonium ylides.
Scheme 36: Possible mechanism of visible-light-induced radical-type couplings/cyclization of N-arylacrylamides...
Scheme 37: Visible-light-promoted difluoroalkylated oxindoles systhesis via EDA complexes.
Scheme 38: Possible mechanism for the visible-light-promoted radical cyclization of N-arylacrylamides with bro...
Scheme 39: A dicumyl peroxide-initiated radical cascade reaction of N-arylacrylamide with DCM.
Scheme 40: Possible mechanism of radical cyclization of N-arylacrylamides with DCM.
Scheme 41: An AIBN-mediated radical cascade reaction of N-arylacrylamides with perfluoroalkyl iodides.
Scheme 42: Possible mechanism for the reaction with perfluoroalkyl iodides.
Scheme 43: Photoinduced palladium-catalyzed radical annulation of N-arylacrylamides with alkyl halides.
Scheme 44: Radical alkylation/cyclization of N-Alkyl-N-methacryloylbenzamides with alkyl halides.
Scheme 45: Possible mechanism for the alkylation/cyclization with unactivated alkyl chlorides.
Scheme 46: Visible-light-driven palladium-catalyzed radical cascade cyclization of N-arylacrylamides with unac...
Scheme 47: NHC-catalyzed radical cascade cyclization of N-arylacrylamides with alkyl bromides.
Scheme 48: Possible mechanism of NHC-catalyzed radical cascade cyclization.
Scheme 49: Electrochemically mediated radical cyclization reaction of N-arylacrylamides with freon-type methan...
Scheme 50: Proposed mechanistic pathway of electrochemically induced radical cyclization reaction.
Scheme 51: Redox-neutral photoinduced radical cascade cylization of N-arylacrylamides with unactivated alkyl c...
Scheme 52: Proposed mechanistic hypothesis of redox-neutral radical cascade cyclization.
Scheme 53: Thiol-mediated photochemical radical cascade cylization of N-arylacrylamides with aryl halides.
Scheme 54: Proposed possible mechanism of thiol-mediated photochemical radical cascade cyclization.
Scheme 55: Visible-light-induced radical cascade bromocyclization of N-arylacrylamides with NBS.
Scheme 56: Possible mechanism of visible-light-induced radical cascade cyclization.
Scheme 57: Decarboxylation/radical C–H functionalization by visible-light photoredox catalysis.
Scheme 58: Plausible mechanism of visible-light photoredox-catalyzed radical cascade cyclization.
Scheme 59: Visible-light-promoted tandem radical cyclization of N-arylacrylamides with N-(acyloxy)phthalimides....
Scheme 60: Plausible mechanism for the tandem radical cyclization reaction.
Scheme 61: Visible-light-induced aerobic radical cascade alkylation/cyclization of N-arylacrylamides with alde...
Scheme 62: Plausible mechanism for the aerobic radical alkylarylation of electron-deficient amides.
Scheme 63: Oxidative decarbonylative [3 + 2]/[5 + 2] annulation of N-arylacrylamide with vinyl acids.
Scheme 64: Plausible mechanism for the decarboxylative (3 + 2)/(5 + 2) annulation between N-arylacrylamides an...
Scheme 65: Rhenium-catalyzed alkylarylation of alkenes with PhI(O2CR)2.
Scheme 66: Plausible mechanism for the rhenium-catalyzed decarboxylative annulation of N-arylacrylamides with ...
Scheme 67: Visible-light-induced one-pot tandem reaction of N-arylacrylamides.
Scheme 68: Plausible mechanism for the visible-light-initiated tandem synthesis of difluoromethylated oxindole...
Scheme 69: Copper-catalyzed redox-neutral cyanoalkylarylation of activated alkenes with cyclobutanone oxime es...
Scheme 70: Plausible mechanism for the copper-catalyzed cyanoalkylarylation of activated alkenes.
Scheme 71: Photoinduced alkyl/aryl radical cascade for the synthesis of quaternary CF3-attached oxindoles.
Scheme 72: Plausible photoinduced electron-transfer (PET) mechanism.
Scheme 73: Photoinduced cerium-mediated decarboxylative alkylation cascade cyclization.
Scheme 74: Plausible reaction mechanism for the decarboxylative radical-cascade alkylation/cyclization.
Scheme 75: Metal-free oxidative tandem coupling of activated alkenes.
Scheme 76: Control experiments and possible mechanism for 1,2-carbonylarylation of alkenes with carbonyl C(sp2...
Scheme 77: Silver-catalyzed acyl-arylation of activated alkenes with α-oxocarboxylic acids.
Scheme 78: Proposed mechanism for the decarboxylative acylarylation of acrylamides.
Scheme 79: Visible-light-mediated tandem acylarylation of olefines with carboxylic acids.
Scheme 80: Proposed mechanism for the radical cascade cyclization with acyl radical via visible-light photored...
Scheme 81: Erythrosine B-catalyzed visible-light photoredox arylation-cyclization of N-arylacrylamides with ar...
Scheme 82: Electrochemical cobalt-catalyzed radical cyclization of N-arylacrylamides with arylhydrazines or po...
Scheme 83: Proposed mechanism of radical cascade cyclization via electrochemical cobalt catalysis.
Scheme 84: Copper-catalyzed oxidative tandem carbamoylation/cyclization of N-arylacrylamides with hydrazinecar...
Scheme 85: Proposed reaction mechanism for the radical cascade cyclization by copper catalysis.
Scheme 86: Visible-light-driven radical cascade cyclization reaction of N-arylacrylamides with α-keto acids.
Scheme 87: Proposed mechanism of visible-light-driven cascade cyclization reaction.
Scheme 88: Peroxide-induced radical carbonylation of N-(2-methylallyl)benzamides with methyl formate.
Scheme 89: Proposed cyclization mechanism of peroxide-induced radical carbonylation with N-(2-methylallyl)benz...
Scheme 90: Persulfate promoted carbamoylation of N-arylacrylamides and N-arylcinnamamides.
Scheme 91: Proposed mechanism for the persulfate promoted radical cascade cyclization reaction of N-arylacryla...
Scheme 92: Photocatalyzed carboacylation with N-arylpropiolamides/N-alkyl acrylamides.
Scheme 93: Plausible mechanism for the photoinduced carboacylation of N-arylpropiolamides/N-alkyl acrylamides.
Scheme 94: Electrochemical Fe-catalyzed radical cyclization with N-arylacrylamides.
Scheme 95: Plausible mechanism for the electrochemical Fe-catalysed radical cyclization of N-phenylacrylamide.
Scheme 96: Substrate scope of the selective functionalization of various α-ketoalkylsilyl peroxides with metha...
Scheme 97: Proposed reaction mechanism for the Fe-catalyzed reaction of alkylsilyl peroxides with methacrylami...
Scheme 98: EDA-complex mediated C(sp2)–C(sp3) cross-coupling of TTs and N-methyl-N-phenylmethacrylamides.
Scheme 99: Proposed mechanism for the synthesis of oxindoles via EDA complex.
Correction: Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates
- Deepa Nair,
- Abhishek Tiwari,
- Banamali Laha,
- Lakshminarayana Satham and
- Irishi N. N. Namboothiri
Beilstein J. Org. Chem. 2025, 21, 1170–1170, doi:10.3762/bjoc.21.93
Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes
- Patricia Gómez-Roibás,
- Andrea Chaves-Pouso and
- Martín Fañanás-Mastral
Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71
- different diastereoselectivity observed when other bases featuring different metal cations were used (Table 1, entry 2 vs entry 5), and the absence of any significant stereochemical influence from the copper complex (Table 1, entries 9–14). Lithium enolate C would then undergo a diastereoselective conjugate
- addition to a second molecule of 1. Given the negative results observed for other crotonate derivatives (Scheme 3c), coordination between the Li cation and the two chlorine atoms via proposed transition state D may be crucial not only for diastereoselective control but also for the viability of this step
Graphical Abstract
Scheme 1: Chemodivergent reactivity observed in copper-catalyzed borylative couplings of allylic gem-dichlori...
Scheme 2: Cu-Bpin-mediated dimerization of 4,4-dichoro-2-butenoic acid derivatives.
Scheme 3: Control experiments.
Scheme 4: Proposed mechanism for the Cu-catalyzed dimerization of 4,4-dichoro-2-butenoic acid derivatives.
Scheme 5: a) KOt-Bu-mediated intramolecular cyclization of 9. b) Direct formation of cyclopropane 20 from gem...
Photocatalyzed elaboration of antibody-based bioconjugates
- Marine Le Stum,
- Eugénie Romero and
- Gary A. Molander
Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49
- particularly useful and important tool in which azides and other dipolar species engage with reactive alkenes and alkynes on non-canonical amino acids [20]. Transition-metal-mediated processes, including metathesis reactions, aryl cross-coupling reactions, and conjugate addition reactions with dehydroalanine
Graphical Abstract
Figure 1: Representation of an antibody–drug conjugate. The antibody shown in this figure is from https://www...
Figure 2: a. Photoredox catalytic cycles; b. absorption spectrum of photosensitizers. Therapeutic window indi...
Figure 3: Graph representing the average number of publications focusing on photoredox chemistry applied to p...
Figure 4: Schematic procedure developed by Sato et al. on histidine photoinduced modification. The antibody s...
Figure 5: Schematic procedure of the divergent method developed by Sato et al. on histidine/tyrosine photoind...
Figure 6: Schematic procedure developed by Bräse et al. on photoinduced disulfide rebridging method.
Figure 7: Schematic procedure developed by Lang et al. on a photoinduced dual nickel photoredox-catalyzed app...
Figure 8: Schematic of the procedure developed by Chang et al. on photoinduced high affinity IgG Fc-binding s...
Figure 9: Potential advantages of photoredox chemistry for bioconjugation applied to antibodies. The antibody...
Figure 10: Representation of the photoinduced control of the DAR. The antibody shown in this figure is from ht...
Figure 11: Representation of a photoinduced control of multi-payloads ADC strategy. The antibody shown in this...
Cu(OTf)2-catalyzed multicomponent reactions
- Sara Colombo,
- Camilla Loro,
- Egle M. Beccalli,
- Gianluigi Broggini and
- Marta Papis
Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7
- . Electron-poor and electron-rich aromatic aldehydes gave good results, whereas aliphatic aldehydes gave moderate yields (Scheme 11) [24]. The asymmetric conjugate addition of dialkylzinc and benzaldehyde to unsaturated carbonyls under copper catalysis in the presence of optically pure phosphanes was
Graphical Abstract
Figure 1: Plausible general catalytic activation for ionic or radical mechanisms.
Scheme 1: Synthesis of α-aminonitriles 1.
Scheme 2: Synthesis of β-amino ketone or β-amino ester derivatives 3.
Scheme 3: Synthesis of 1-(α-aminoalkyl)-2-naphthol derivatives 4.
Scheme 4: Synthesis of thioaminals 5.
Scheme 5: Synthesis of aryl- or amine-containing alkanes 6 and 7.
Scheme 6: Synthesis of 1-aryl-2-sulfonamidopropanes 8.
Scheme 7: Synthesis of α-substituted propargylamines 10.
Scheme 8: Synthesis of N-propargylcarbamates 11.
Scheme 9: Synthesis of (E)-vinyl sulfones 12.
Scheme 10: Synthesis of o-halo-substituted aryl chalcogenides 13.
Scheme 11: Synthesis of α-aminophosphonates 14.
Scheme 12: Synthesis of unsaturated furanones and pyranones 15–17.
Scheme 13: Synthesis of substituted dihydropyrimidines 18.
Scheme 14: Regioselective synthesis of 1,4-dihydropyridines 20.
Scheme 15: Synthesis of tetrahydropyridines 21.
Scheme 16: Synthesis of furoquinoxalines 22.
Scheme 17: Synthesis of 2,4-substituted quinolines 23.
Scheme 18: Synthesis of cyclic ether-fused tetrahydroquinolines 24.
Scheme 19: Practical route for 1,2-dihydroisoquinolines 25.
Scheme 20: Synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives 26.
Scheme 21: Synthesis of polysubstituted pyrroles 27.
Scheme 22: Enantioselective synthesis of polysubstituted pyrrolidines 30 directed by the copper complex 29.
Scheme 23: Synthesis of 4,5-dihydropyrazoles 31.
Scheme 24: Synthesis of 2 arylisoindolinones 32.
Scheme 25: Synthesis of imidazo[1,2-a]pyridines 33.
Scheme 26: Synthesis of isoxazole-linked imidazo[1,2-a]azines 35.
Scheme 27: Synthesis of 2,3-dihydro-1,2,4-triazoles 36.
Scheme 28: Synthesis of naphthopyrans 37.
Scheme 29: Synthesis of benzo[g]chromene derivatives 38.
Scheme 30: Synthesis of naphthalene annulated 2-aminothiazoles 39, piperazinyl-thiazoloquinolines 40 and thiaz...
Scheme 31: Synthesis of furo[3,4-b]pyrazolo[4,3-f]quinolinones 42.
Scheme 32: Synthesis of spiroindoline-3,4’-pyrano[3,2-b]pyran-4-ones 43.
Scheme 33: Synthesis of N-(α-alkoxy)alkyl-1,2,3-triazoles 44.
Scheme 34: Synthesis of 4-(α-tetrasubstituted)alkyl-1,2,3-triazoles 45.
Recent advances in organocatalytic atroposelective reactions
- Henrich Szabados and
- Radovan Šebesta
Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6
- transformation is an asymmetric conjugate addition leading to a central chiral intermediate that tautomerizes to the axially chiral product. Chiral phosphoric acid C33 was utilized in the construction of products 136 bearing both axial and central chirality (Scheme 40) [68] through the reaction of bisindoles 134
Graphical Abstract
Scheme 1: Formation of axially chiral styrenes 3 via iminium activation.
Scheme 2: Synthesis of axially chiral 2-arylquinolines 6.
Scheme 3: Atroposelective intramolecular (4 + 2) annulation leading to aryl-substituted indolines.
Scheme 4: Atroposelective formation of biaryl via twofold aldol condensation.
Scheme 5: Strategy towards diastereodivergent formation of axially chiral oligonaphthylenes.
Scheme 6: Atroposelective formation of chiral biaryls based on a Michael/Henry domino reaction.
Scheme 7: Organocatalytic Michael/aldol cascade followed by oxidative aromatization.
Scheme 8: Atroposelective formation of C(sp2)–C(sp3) axially chiral compounds.
Scheme 9: NHC-catalyzed synthesis of axially chiral styrenes 26.
Scheme 10: NHC-catalyzed synthesis of biaxial chiral pyranones.
Scheme 11: Formation of bridged biaryls with eight-membered lactones.
Scheme 12: The NHC-catalyzed (3 + 2) annulation of urazoles 37 and ynals 36.
Scheme 13: NHC-catalyzed synthesis of axially chiral 4‑aryl α‑carbolines 41.
Scheme 14: NHC-catalyzed construction of N–N-axially chiral pyrroles and indoles.
Scheme 15: NHC-catalyzed oxidative Michael–aldol cascade.
Scheme 16: NHC-catalyzed (4 + 2) annulation for the synthesis of benzothiophene-fused biaryls.
Scheme 17: NHC-catalyzed desymmetrization of N-aryl maleimides.
Scheme 18: NHC-catalyzed deracemization of biaryl hydroxy aldehydes 55a–k into axially chiral benzonitriles 56a...
Scheme 19: NHC-catalyzed desymmetrization of 2-aryloxyisophthalaldehydes.
Scheme 20: NHC-catalyzed DKR of 2-arylbenzaldehydes 62.
Scheme 21: Atroposelective biaryl amination.
Scheme 22: CPA-catalyzed atroposelective amination of 2-anilinonaphthalenes.
Scheme 23: Atroposelective DKR of naphthylindoles.
Scheme 24: CPA-catalyzed kinetic resolution of binaphthylamines.
Scheme 25: Atroposelective amination of aromatic amines with diazodicarboxylates.
Scheme 26: Atroposelective Friedländer heteroannulation.
Scheme 27: CPA-catalyzed formation of axially chiral 4-arylquinolines.
Scheme 28: CPA-catalyzed Friedländer reaction of arylketones with cyclohexanones.
Scheme 29: CPA-catalyzed atroposelective Povarov reaction.
Scheme 30: Atroposelective CPA-catalyzed Povarov reaction.
Scheme 31: Paal–Knorr formation of axially chiral N-pyrrolylindoles and N-pyrrolylpyrroles.
Scheme 32: Atroposelective Paal–Knorr reaction leading to N-pyrrolylpyrroles.
Scheme 33: Atroposelective Pictet–Spengler reaction of N-arylindoles with aldehydes.
Scheme 34: Atroposelective Pictet–Spengler reaction leading to tetrahydroisoquinolin-8-ylanilines.
Scheme 35: Atroposelective formation of arylindoles.
Scheme 36: CPA-catalyzed arylation of naphthoquinones with indolizines.
Scheme 37: Atroposelective reaction of o-naphthoquinones.
Scheme 38: CPA-catalyzed formation of axially chiral arylquinones.
Scheme 39: CPA-catalyzed axially chiral N-arylquinones.
Scheme 40: Atroposelective additions of bisindoles to isatin-based 3-indolylmethanols.
Scheme 41: CPA-catalyzed synthesis of axially chiral arylindolylindolinones.
Scheme 42: CPA-catalyzed reaction between bisindoles and ninhydrin-derived 3-indoylmethanols.
Scheme 43: Atroposelective reaction of bisindoles and isatin-derived imines.
Scheme 44: CPA-catalyzed formation of axially chiral bisindoles.
Scheme 45: Atroposelective reaction of 2-naphthols with alkynylhydroxyisoindolinones.
Scheme 46: CPA-catalyzed reaction of indolylnaphthols with propargylic alcohols.
Scheme 47: Atroposelective formation of indolylpyrroloindoles.
Scheme 48: Atroposelective reaction of indolylnaphthalenes with alkynylnaphthols.
Scheme 49: CPA-catalyzed addition of naphthols to alkynyl-2-naphthols and 2-naphthylamines.
Scheme 50: CPA-catalyzed formation of axially chiral aryl-alkene-indoles.
Scheme 51: CPA-catalyzed formation of axially chiral styrenes.
Scheme 52: Atroposelective formation of alkenylindoles.
Scheme 53: Atroposelective formation of axially chiral arylquinolines.
Scheme 54: Atroposelective (3 + 2) cycloaddition of alkynylindoles with azonaphthalenes.
Scheme 55: CPA-catalyzed formation of axially chiral 3-(1H-benzo[d]imidazol-2-yl)quinolines.
Scheme 56: Atroposelective cyclization of 3-(arylethynyl)-1H-indoles.
Scheme 57: Atroposelective three-component heteroannulation.
Scheme 58: CPA-catalyzed formation of arylbenzimidazols.
Scheme 59: CPA-catalyzed reaction of N-naphthylglycine esters with nitrosobenzenes.
Scheme 60: CPA-catalyzed formation of axially chiral N-arylbenzimidazoles.
Scheme 61: CPA-catalyzed formation of axially chiral arylbenzoindoles.
Scheme 62: CPA-catalyzed formation of pyrrolylnaphthalenes.
Scheme 63: CPA-catalyzed addition of naphthols and indoles to nitronaphthalenes.
Scheme 64: Atroposelective reaction of heterobiaryl aldehydes and aminobenzamides.
Scheme 65: Atroposelective cyclization forming N-arylquinolones.
Scheme 66: Atroposelective formation of 9H-carbazol-9-ylnaphthalenes and 1H-indol-1-ylnaphthalene.
Scheme 67: CPA-catalyzed formation of pyrazolylnaphthalenes.
Scheme 68: Atroposelective addition of diazodicarboxamides to azaborinephenols.
Scheme 69: Catalytic formation of axially chiral arylpyrroles.
Scheme 70: Atroposelective coupling of 1-azonaphthalenes with 2-naphthols.
Scheme 71: CPA-catalyzed formation of axially chiral oxindole-based styrenes.
Scheme 72: Atroposelective electrophilic bromination of aminonaphthoquinones.
Scheme 73: Atroposelective bromination of dienes.
Scheme 74: CPA-catalyzed formation of axially chiral 5-arylpyrimidines.
Scheme 75: Atroposelective hydrolysis of biaryloxazepines.
Scheme 76: Atroposelective opening of dinaphthosiloles.
Scheme 77: Atroposelective reduction of naphthylenals.
Scheme 78: Atroposelective allylic substitution with 2-naphthols.
Scheme 79: Atroposelective allylic alkylation with phosphinamides.
Scheme 80: Atroposelective allylic substitution with aminopyrroles.
Scheme 81: Atroposelective allylic substitution with aromatic sulfinamides.
Scheme 82: Atroposelective sulfonylation of naphthylynones.
Scheme 83: Squaramide-catalyzed reaction of alkynyl-2-naphthols with 5H-oxazolones.
Scheme 84: Formation of axially chiral styrenes via sulfonylative opening of cyclopropanols.
Scheme 85: Atroposelective organo-photocatalyzed sulfonylation of alkynyl-2-naphthols.
Scheme 86: Thiourea-catalyzed atroposelective cyclization of alkynylnaphthols.
Scheme 87: Squaramide-catalyzed formation of axially chiral naphthylisothiazoles.
Scheme 88: Atroposelective iodo-cyclization catalyzed by squaramide C69.
Scheme 89: Squaramide-catalyzed formation of axially chiral oligoarenes.
Scheme 90: Atroposelective ring-opening of cyclic N-sulfonylamides.
Scheme 91: Thiourea-catalyzed kinetic resolution of naphthylpyrroles.
Scheme 92: Atroposelective ring-opening of arylindole lactams.
Scheme 93: Atroposelective reaction of 1-naphthyl-2-tetralones and diarylphosphine oxides.
Scheme 94: Atroposelective reaction of iminoquinones with indoles.
Scheme 95: Kinetic resolution of binaphthylalcohols.
Scheme 96: DKR of hydroxynaphthylamides.
Scheme 97: Atroposelective N-alkylation with phase-transfer catalyst C75.
Scheme 98: Atroposelective allylic substitution via kinetic resolution of biarylsulfonamides.
Scheme 99: Atroposelective bromo-functionalization of alkynylarenes.
Scheme 100: Sulfenylation-induced atroposelective cyclization.
Scheme 101: Atroposelective O-sulfonylation of isochromenone-indoles.
Scheme 102: NHC-catalyzed atroposelective N-acylation of anilines.
Scheme 103: Peptide-catalyzed atroposelective ring-opening of lactones.
Scheme 104: Peptide-catalyzed coupling of 2-naphthols with quinones.
Scheme 105: Atroposelective nucleophilic aromatic substitution of fluoroarenes.
Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines
- Sergio Torres-Oya and
- Mercedes Zurro
Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268
- , they can be attacked by a nucleophile and undergo a 1,2-addition or conjugate addition leading to the production of allylic amines or aliphatic imines, respectively. They can also behave as C4 synthons in cycloaddition reactions such as the aza-Diels–Alder reaction, giving access to nitrogen-containing
Graphical Abstract
Figure 1: Reactivity of α,β-unsaturated imines and variety of structures.
Figure 2: The hetero-Diels–Alder and inverse electron demand hetero-Diels–Alder reactions.
Figure 3: Different strategies to promote the activation of dienes and dienophiles in IEDADA reactions.
Figure 4: Examples of non-covalent interactions in organocatalysis.
Scheme 1: Enantioselective bifunctional thiourea-catalyzed inverse electron demand Diels–Alder reaction of N-...
Scheme 2: Cinchona-derived thiourea-catalyzed stereoselective (3 + 2) reaction of α,β-unsaturated imines and ...
Scheme 3: Cinchona-derived thiourea-catalyzed stereoselective (3 + 2)/(4 + 2) cascade reaction of α,β-unsatur...
Scheme 4: Enantioselective bifunctional squaramide-catalyzed formal [4 + 2] cycloaddition of malononitrile wi...
Scheme 5: Bifunctional squaramide-catalyzed IEDADA reaction of saccharin-derived 1-azadienes and azlactones.
Scheme 6: Chiral guanidine-catalyzed enantioselective (4+1) cyclization of benzofuran-derived azadienes with ...
Scheme 7: Bifunctional squaramide-catalyzed [4 + 2] cyclization of benzofuran-derived azadienes and azlactone...
Scheme 8: Chiral bifunctional squaramide-catalyzed domino Mannich/formal [4 + 2] cyclization of 2-benzothiazo...
Scheme 9: Chiral bifunctional thiourea-catalyzed formal IEDADA reaction of β,γ-unsaturated ketones and benzof...
Scheme 10: Dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates and ...
Scheme 11: Enantioselective squaramide-catalyzed asymmetric IEDADA reaction of benzofuran-derived azadienes an...
Scheme 12: Scale up and derivatizations of benzofuran-fused 2-piperidinol derivatives.
Scheme 13: Dihydroquinine-derived squaramide-catalyzed Mannich-type reaction of isocyanoacetates with N-(2-ben...
Figure 5: Structure of a cinchona alkaloid and (DHQD)2PHAL.
Scheme 14: Enantioselective modified cinchona alkaloid-catalyzed [4 + 2] annulation of γ-butenolides and sacch...
Scheme 15: Chiral tertiary amine-catalyzed [2 + 4] annulation of cyclic 1-azadiene with γ-nitro ketones.
Scheme 16: Inverse electron demand aza-Diels–Alder reaction (IEDADA) of 1-azadienes with enecarbamates catalyz...
Scheme 17: Phosphoric acid-catalyzed enantioselective [4 + 2] cycloaddition of benzothiazolimines and enecarba...
Scheme 18: Phosphoric acid-catalyzed enantioselective inverse electron demand aza-Diels–Alder reaction of in s...
Scheme 19: Proposed reaction mechanism for the phosphoric acid-catalyzed enantioselective inverse electron dem...
Scheme 20: Enantioselective dearomatization of indoles by a (3 + 2) cyclization with azoalkenes catalyzed by a...
Scheme 21: Synthetic applicability of the pyrroloindoline derivatives.
Scheme 22: Chiral phosphoric acid-catalyzed (2 + 3) dearomative cycloaddition of 3-alkyl-2-vinylindoles with a...
Scheme 23: Chiral phosphoric acid-catalyzed asymmetric [4 + 2] cycloaddition of aurone-derived 1-azadienes and...
Scheme 24: Phosphoric acid-catalyzed enantioselective formal [4 + 2] cycloaddition of dienecarbamates and 2-be...
Scheme 25: Chiral phosphoric acid-catalyzed asymmetric inverse electron demand aza-Diels–Alder reaction of 1,3...
Scheme 26: Chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and ...
Scheme 27: Synthetic applicability of the NPNOL derivatives.
Scheme 28: Chiral phosphoric acid-catalyzed asymmetric intermolecular formal (3 + 2) cycloaddition of azoalken...
Scheme 29: Enantioselective [4 + 2] cyclization of α,β-unsaturated imines and azlactones.
Scheme 30: Catalytic cycle for the chiral phosphoric acid-catalyzed enantioselective [4 + 2] cyclization of α,...
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
- 1,4-conjugate addition (Michael addition) of 2,4-pentanedione (51) to β-nitrostyrene (50) (Figure 9) [63]. The OxP-macrocycles turned out to combine the advantages of porphyrins and calix[4]pyrroles. Due to their nonplanar geometry, OxPs have easily accessible inner –NH groups, similarly to calix[4
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...
Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction
- Yuta Kabumoto,
- Eiichiro Yoshimoto,
- Bing Xiaohuan,
- Masato Morita,
- Motohiro Yasui,
- Shigeyuki Yamada and
- Tsutomu Konno
Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233
- published that the asymmetric conjugate addition of 4-methylphenylboronic acid towards (E)-5-bromo-4,4,5,5-tetrafluoro-1-phenyl-2-penten-1-one (8) in the presence of a rhodium catalyst coordinated with (S)-BINAP gave the corresponding Michael adduct 9 in 94% enantiomeric excess (reaction 2, Scheme 1) [22
Graphical Abstract
Figure 1: Various applications of tetrafluoroethylenated molecules.
Scheme 1: Precedent synthetic approaches to optically active compounds possessing a tetrafluoroethylene group...
Scheme 2: Synthetic strategy for preparing fluorine-containing amines via [1,3]-proton shift reactions.
Scheme 3: Preparation of the substrates used in this study.
Scheme 4: Derivatization of (S)-20b to (S)-23b for determining the optical purity of (S)-20b.
Scheme 5: Substrate scope for the present [1,3]-proton shift reaction. aYields are determined by 19F NMR spec...
Scheme 6: Proposed reaction mechanism.
Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols
- Smaher E. Butt,
- Konrad Kepski,
- Jean-Marc Sotiropoulos and
- Wesley J. Moran
Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209
- important area of study as this ring system is prevalent in many useful molecules. Typical literature procedures include multistep derivations of proline itself, e.g., the destruction of the stereocenter and then its reinstallation by an enantioselective conjugate addition [9]. Other methods include the
- enantioselective conjugate addition to α,β-unsaturated pyroglutamic acid derivatives followed by deoxygenation [10], and the enantioselective organocatalytic reaction between 2-acylaminomalonates and α,β-unsaturated aldehydes [11][12]. The development of new synthetic methods using hypervalent iodine reagents has
Graphical Abstract
Figure 1: Functional molecules containing a substituted pyrrolidine core.
Scheme 1: A) Our previous report on N-alkenylamide cyclizations. B) An overview of the present work.
Scheme 2: Calculated mechanism for the cyclization of amide 3a optimized at the B3LYP/ 6-31+G(d,p) level of t...
Scheme 3: Scope of cyclization reaction.
Scheme 4: Reactions of di- and trisubstituted alkene substrates.
Natural resorcylic lactones derived from alternariol
- Joachim Podlech
Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187
Graphical Abstract
Figure 1: Examples of compounds covered in this review categorized in six sub-classes (see text).
Figure 2: Examples of compounds not covered in this review.
Figure 3: Wrongly assigned and thus obsolete structures (details will be discussed in the respective chapters...
Figure 4: Alternariol with the correct IUPAC numbering and an occasionally used numbering based on the biphen...
Figure 5: Alternariol O-methyl ethers.
Figure 6: Alternariol O-glycosides.
Figure 7: Alternariol O-acetates and O-sulfates.
Figure 8: 2-Hydroxy- and 4-hydroxy-substituted alternariol and its O-methyl ethers.
Figure 9: Chloro- and amino-substituted alternariol and its O-methyl ethers.
Figure 10: Presumed alternariol derivatives with non-canonical substitution pattern.
Figure 11: Alternariol derivatives with the 1-methyl group hydroxylated.
Figure 12: Verrulactones: pseudo-dimeric derivatives of altertenuol and related compounds.
Figure 13: Biaryls formed by reductive lactone opening and/or by decarboxylation.
Figure 14: Altenuene and its diastereomers.
Figure 15: 9-O-Demethylated altenuene diastereomers.
Figure 16: Acetylated and methylated altenuene diastereomers.
Figure 17: Altenuene diastereomers modified with lactic acid, pyruvic acid, or acetone.
Figure 18: Neoaltenuene and related compounds.
Figure 19: Dehydroaltenusin and its derivatives.
Scheme 1: Equilibrium of dehydroaltenusin in polar solvents [278].
Figure 20: Further quinoid derivatives.
Figure 21: Dehydroaltenuenes.
Figure 22: Complex aggregates containing dehydroaltenuene substructures and related compounds.
Figure 23: Dihydroaltenuenes.
Figure 24: Altenuic acids and related compounds.
Figure 25: Cyclopentane- and cyclopentene-fused derivatives.
Figure 26: Cyclopentenone-fused derivatives.
Figure 27: Spiro-fused derivatives and a related ring-opened derivative.
Figure 28: Lactones-fused and lactone-substituted derivatives.
Scheme 2: Biosynthesis of alternariol [324].
Scheme 3: Biosynthesis of alternariol and its immediate successors with the genes involved in the respective ...
Scheme 4: Presumed formation of altenuene and its diastereomers and of botrallin.
Scheme 5: Presumed formation of altenuic acids and related compounds.
Scheme 6: A selection of plausible biosynthetic paths to cyclopenta-fused metabolites. (No stereochemistry is...
Scheme 7: Biomimetic synthesis of alternariol (1) by Harris and Hay [66].
Scheme 8: Total synthesis of alternariol (1) by Subba Rao et al. using a Diels–Alder approach [34].
Scheme 9: Total synthesis of alternariol (1) using a Suzuki strategy by Koch and Podlech [62], improved by Kim et...
Scheme 10: Total synthesis of alternariol (1) using an intramolecular biaryl coupling by Abe et al. [63].
Scheme 11: Total synthesis of altenuene (54) and isoaltenuene (55) by Podlech et al. [249].
Scheme 12: Total synthesis of neoaltenuene (69) by Podlech et al. [35].
Scheme 13: Total synthesis of TMC-264 (79) by Tatsuta et al. [185].
Scheme 14: Total synthesis of cephalosol (99) by Koert et al. [304].
Factors influencing the performance of organocatalysts immobilised on solid supports: A review
- Zsuzsanna Fehér,
- Dóra Richter,
- Gyula Dargó and
- József Kupai
Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183
- the conjugate addition of propanal (22) and trans-β-nitrostyrene (11) catalysed by a simple solid-supported peptidic catalyst 24 using a continuous flow reactor. To overcome the diffusion limitations, elevated pressure was applied. Increasing the pressure from atmospheric to 60 bar resulted in a 12
Graphical Abstract
Scheme 1: Esterification of oleic acid (1) with propylsulfonic acid (Pr-SO3H)-functionalised mesoporous silic...
Scheme 2: Using confinement of organocatalytic units for improving the enantioselectivity of silica-supported...
Scheme 3: Michael addition catalysed by cinchona thiourea immobilised on magnetic nanoparticles (13).
Scheme 4: Michael addition catalysed by cinchona thiourea in the presence of magnetic nanoparticles.
Scheme 5: Benzoin condensation catalysed by N-benzylthiazolium salt attached to mesoporous material.
Scheme 6: Photoinduced RAFT polymerisation of n-butyl acrylate (19) catalysed by silica nanoparticle-supporte...
Scheme 7: Pressure and temperature dependence of the 1,4-addition of propanal to trans-β-nitrostyrene under c...
Scheme 8: α-Amination of ethyl 2-oxocyclopentanecarboxylate catalysed by PS-THU which could be recycled over ...
Scheme 9: Preparation of supported catalysts C29–C31 from cinchona squaramides 29–31 modified with a primary ...
Scheme 10: Application of PGMA-supported organocatalysts C29–C31 in the asymmetric Michael addition of pentane...
Scheme 11: Alcoholytic desymmetrisation of a cyclic anhydride 34 catalysed by polyamide-supported cinchona sul...
Diastereoselective synthesis of highly substituted cyclohexanones and tetrahydrochromene-4-ones via conjugate addition of curcumins to arylidenemalonates
- Deepa Nair,
- Abhishek Tiwari,
- Banamali Laha and
- Irishi N. N. Namboothiri
Beilstein J. Org. Chem. 2024, 20, 2016–2023, doi:10.3762/bjoc.20.177
Graphical Abstract
Figure 1: Biologically active derivatives of cyclohexanones.
Scheme 1: The Michael donor–acceptor reactivity of curcumin: previous vs present work.
Scheme 2: A plausible reaction mechanism.
Figure 2: X-ray structure of 4a (CCDC 2351387).
Figure 3: Origin of stereoselectivity in the double Michael addition.
Scheme 3: Scale-up reaction.
Primary amine-catalyzed enantioselective 1,4-Michael addition reaction of pyrazolin-5-ones to α,β-unsaturated ketones
- Pooja Goyal,
- Akhil K. Dubey,
- Raghunath Chowdhury and
- Amey Wadawale
Beilstein J. Org. Chem. 2024, 20, 1518–1526, doi:10.3762/bjoc.20.136
- the conjugate addition product 3aa in 58–62% yield with 74% ee (Table 1, entry 1). On the other hand, 9-amino-9-deoxyepicinchonine (II) [30] furnished the opposite enantiomer ent-3aa in 62% yield and 66% ee (Table 1, entry 2). Among the screened organocatalysts (see Table S1 in Supporting Information
- %) furnished ent-3aa in 76% yield and 87.5% ee (Table 1, entry 13). With the optimal reaction conditions at hands, the 1,4-conjugate addition reaction of a series of α,β-unsaturated ketones 1 with pyrazolin-5-one (2a) were studied next (Scheme 2). Aryl α,β-unsaturated ketones bearing a halogen, electron
- ). Representative examples of asymmetric organocatalytic conjugate addition of pyrazolin-5-ones to α,β-unsaturated ketones and present study. Scope of substrates. Reaction conditions: 1 (0.3 mmol), 2 (0.2 mmol), 15 mol % of catalyst I, 30 mol % A5 (for 3) or 15 mol % catalyst II, 30 mol % A5 (for ent-3) in 1.0 mL
Graphical Abstract
Figure 1: Selected examples of drugs and bioactive molecules bearing a pyrazole core.
Scheme 1: Representative examples of asymmetric organocatalytic conjugate addition of pyrazolin-5-ones to α,β...
Scheme 2: Scope of substrates. Reaction conditions: 1 (0.3 mmol), 2 (0.2 mmol), 15 mol % of catalyst I, 30 mo...
Scheme 3: Synthesis of pyrazole-benzofuran and pyrazole–indole hybrid molecules. Reaction conditions: 1m or 1n...
Scheme 4: Synthesis of 3aa on preparative scale.
Figure 2: Single crystal X-ray structure of ent-3ba (CCDC 2234286).
Scheme 5: Proposed reaction mechanism.
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
- bond activation of benzyl alcohols. Deoxygenative arylation of alcohols using NHC to activate alcohols. Deoxygenative conjugate addition of alcohol using NHC as alcohol activator. Synthesis of polysubstituted aldehydes. Funding The author thanks SERB, India (CRG/2021/000402) for financial assistance.
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.
(Bio)isosteres of ortho- and meta-substituted benzenes
- H. Erik Diepers and
- Johannes C. L. Walker
Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78
- 1,4-BCHs (Scheme 11B) [55]. From carboxylic acid 100e, Curtius rearrangement led to amine 101 and a photoredox decarboxylative conjugate addition to diester 102. From boronate ester 100f, oxidative deborylation led to alcohol 103, arylation led to furan 104 and Matteson homologation to boronate ester
Graphical Abstract
Figure 1: Scaffolds commonly reported as bioisosteric replacements of para-substituted benzene and examples p...
Figure 2: 1,2-BCPs as isosteres for ortho-and meta-substituted benzenes: comparison of reported exit vector p...
Scheme 1: 1,2-Disubstituted bicyclo[1.1.1]pentanes as isosteres of ortho-substituted benzenes. A: Baran, Coll...
Scheme 2: Synthesis of 1,2-BCPs from BCP 15 by bridge C–H bromination as reported by MacMillan and co-workers ...
Figure 3: Comparative physicochemical data of telmisartan, lomitapide and their BCP isosteres [26,33]. Shake flask d...
Figure 4: 1,2-Disubstituted bicyclo[2.1.1]hexanes as isosteres of ortho-benzenes: Exit vector parameters of t...
Scheme 3: Synthesis of 1,2-disubstituted bicyclo[2.1.1]hexanes via alkene insertion into bicyclo[1.1.0]butane...
Scheme 4: Synthesis of 1,2-disubstituted bicyclo[2.1.1]hexanes via intramolecular crossed [2 + 2] cycloadditi...
Figure 5: Comparison of physicochemical data of fluxapyroxad and boscalid and their 1,2-BCH bioisosteres [36]. Sh...
Figure 6: Antifungal activity of fluxapyroxad, its 1,5-BCH bioisostere (±)-55, boscalid and its bioisostere 1...
Figure 7: 1,5-Disubstituted bicyclo[2.1.1]hexanes as isosteres of ortho-substituted benzenes. Comparison of e...
Scheme 5: Synthesis of 1,5-disubstituted bicyclo[2.1.1]hexanes as isosteres of ortho-benzenes via intramolecu...
Figure 8: Comparison of physicochemical data of fluxapyroxad and boscalid and their 1,5-BCH bioisosteres [45]. Sh...
Figure 9: Antifungal activity of fluxapyroxad, its 1,5-BCH bioisostere (±)-64, boscalid and its bioisostere 1...
Figure 10: 1,5-Disubstituted 3-oxabicylco[2.1.1]hexanes as isosteres for ortho-benzenes: Comparison of exit ve...
Scheme 6: Synthesis of 1,5-disubstituted 3-oxabicyclo[2.1.1]hexanes as isosteres for ortho-benzenes via intra...
Figure 11: Comparison of physicochemical data of fluxapyroxad and boscalid and their 3-oxa-1,5-BCH bioisostere...
Figure 12: Antifungal activity of fluxapyroxad and boscalid and their 3-oxa-1,5-BCH bioisosteres (±)-75 and (±...
Figure 13: 1,2-Disubstituted bicyclo[3.1.1]heptanes as isosteres of ortho-benzenes. Schematic representation o...
Scheme 7: Synthesis of 1,2-disubstituted bicyclo[3.1.1]heptanes as isosteres for ortho-benzenes via alkene in...
Figure 14: 1,2-Disubstituted stellanes as ortho-benzene isosteres: Comparison of selected exit vector paramete...
Scheme 8: Synthesis of 1,2-disubstituted stellanes as isosteres for ortho-benzenes reported by Ryabukhin, Vol...
Figure 15: 1,2-Disubstituted cubanes as ortho-benzene isosteres: Comparison of substituent distances and angle...
Scheme 9: Synthesis of 1,2-disubsituted cubanes as isosteres for ortho-benzenes. A: Synthesis of 1,2-cubane d...
Figure 16: 1,3-Disubstituted bicyclo[2.1.1]hexanes as isosteres of meta-benzenes: comparative exit vector para...
Scheme 10: Synthesis of 1,3-disubstituted bicyclo[2.1.1]hexanes as isosteres for meta-benzenes reported by Wal...
Figure 17: 1,4-Disubstituted bicyclo[2.1.1]hexanes as isosteres of meta-benzenes: comparative exit vector para...
Scheme 11: Synthesis of 1,4-disubstituted bicyclo[2.1.1}hexanes as isosteres for ortho-benzenes via intramolec...
Figure 18: 1,4-Disubstituted-2-oxabicyclo[2.1.1]hexanes as meta-benzene isosteres: comparison of selected exit...
Scheme 12: Synthesis of 1,4-disubstituted 2-oxabicyclo[2.1.1]hexanes as isosteres for meta-benzenes. A: Mykhai...
Figure 19: Comparative physicochemical data for 2- and 3-oxa-1,4-BCHs and para-substituted benzene equivalents...
Figure 20: 1,5-Disubstituted bicyclo[3.1.1]heptanes as isosteres of meta-benzenes: comparison of exit vector p...
Scheme 13: Synthesis of [3.1.1]propellane as a precursor for 1,5-disubsituted bicyclo[3.1.1]heptanes. A: aGass...
Scheme 14: Synthesis of iodine-substituted 1,5-disubstituted bicyclo[3.1.1]heptanes as isosteres for meta-benz...
Scheme 15: Synthesis of nitrogen-, chalcogen- and tin-substituted 1,5-disubstituted bicyclo[3.1.1]heptanes as ...
Figure 21: Comparative physicochemical data of URB597 and 1,5-BCHep isostere 146 [27]. Kinetic aqueous solubility ...
Figure 22: [2]-Ladderanes as isosteres of meta-benzenes: comparison of reported exit vector parameters [63].
Scheme 16: Synthesis of cis-2,6-disubstituted bicyclo[2.2.0]hexanes as isosteres for meta-benzenes. A: Brown a...
Figure 23: Comparative physicochemical data of meta-benzene 158 and [2]-ladderane isostere 159 [63]. Partition coe...
Figure 24: 1,3-Disubstituted cubanes as isosteres of meta-benzenes: comparison of selected exit vector paramet...
Scheme 17: Synthesis of 1,3-disubsituted cubanes as isosteres for meta-benzenes. A: MacMillan and co-workers’ ...
Figure 25: Comparative physicochemical data of lumacaftor and its 1,3-cubane bioisostere 183 [51]. Distribution co...
Figure 26: 1,3-Disubstituted cuneanes as isosteres of meta-benzenes: comparison of selected exit vector parame...
Scheme 18: Synthesis of 1,3-cuneanes as isosteres of meta-benzene. A: Synthesis of 1,3-cuneanes reported by La...
Figure 27: Comparative physicochemical data of sonidegib and its 1,3-cuneane isostere 190 [71]. aSolubility was to...
Figure 28: Exemplary polysubstituted scaffolds related to disubstituted scaffolds suggested as isosteres of or...
