Vinyl and Alkynyl Substituted Heterocycles as Privileged Scaffolds in Transition Metal Promoted Stereoselective Synthesis

Accounts of Chemical Research, Год журнала: 2024, Номер 57(5), С. 726 - 738

Опубликована: Фев. 22, 2024

ConspectusBiologically active compounds and pharmaceutically relevant intermediates often feature sterically congested stereogenic centers, in particular, carbon stereocenters that are either tertiary tetrasubstituted ones or quaternary nature. Synthons comprise such bulky structurally complex core units of high synthetic value represent important incentives for communities connected to drug discovery development. Streamlined approaches give access a diverse set incorporating acyclic relatively limited, though vital. They enable further exploration three-dimensional entities can be designed implemented programs, thereby extending the pool molecular properties is inaccessible flat molecules. However, lack modular substrates particular areas chemical space inspired us consider functionalized heterocycles known as cyclic carbonates carbamates productive way create crowded alkenes stereocenters.In this Account, we describe major approximations followed over course 8 years using transition metal (TM) catalysis an instrument control stereochemical various allylic propargylic substitution processes related transformations. Allylic reactions empowered by Pd-catalysis utilizing variety nucleophiles discussed, with amination being seed all combined work. These procedures build on vinyl-substituted (VCCs) simple easy-to-access precursors highly nature compared synthetically limited vinyl oxiranes. Overall these decarboxylative conversions take place "linear" "branched" regioselectivities ligand controlled offer wide scope functional scaffolds. Alternative approaches, including dual TM/photocatalyzed transformations, allowed expand repertoire challenging stereoselective conversions. This was achieved through key single-electron pathways via formal umpolung intermediates, resulting new types carbon–carbon bond formation significantly expanding reactions.Heterocyclic substrate variants have triple groups were also difficult-to-promote TM catalysis. In processes, Nishibayashi laboratory their seminal findings area, discovered reactivity patterns. provided range different stereodefined building blocks 1,2-diborylated 1,3-dienes α-allenols under Cu- Ni-catalysis. realm, use lactone-derived gives elusive chiral γ-amino acids lactams stereofidelity good structural diversity.Apart from efforts, elucidated some pertinent mechanistic manifolds operative transformations better understand limitations opportunities specifically synthons. We both theoretical experimental investigations lead several unexpected outcomes terms enantioinduction models, catalyst preactivation, intimately rationales observed selectivity profiles. The work communicated offers insight into unique carbonates/carbamates acting privileged precursors. It may inspire other members widen toward novel added development academic commercial settings.

Язык: Английский

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Stereospecific Construction of Quaternary Carbon Stereocenters from Quaternary Carbon Stereocenters

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(16), С. 7066 - 7071

Опубликована: Апрель 12, 2022

Organoaluminum species promote a smooth nucleophilic substitution at the quaternary carbon stereocenter of stereodefined polysubstituted cyclopropyl methyl phosphate with complete inversion configuration, even when more reactive functional groups are present. The regio- and diastereoselectivity is attributed to existence bicyclobutonium intermediate.

Язык: Английский

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A Domino Dearomative ipso-Annulation/Desymmetrization Approach: Stereoselective Access to Tricyclic Alkaloid Skeletons

Organic Letters, Год журнала: 2024, Номер 26(23), С. 4904 - 4909

Опубликована: Июнь 5, 2024

Herein, we reveal an unprecedented domino annulation of

Язык: Английский

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Synthesis of Cyclopentenones with C4-Quaternary Stereocenters via Stereospecific [3,3]-Sigmatropic Rearrangement and Applications in Total Synthesis of Sesquiterpenoids

Journal of the American Chemical Society, Год журнала: 2021, Номер 143(42), С. 17348 - 17353

Опубликована: Окт. 18, 2021

A cationic gold(I)-catalyzed asymmetric [3,3]-sigmatropic rearrangement of sulfonium leads after cyclization to cyclopentenones with a C4-quaternary stereocenter. Starting simple vinyl sulfoxides and propargyl silane, numerous compounds were isolated moderate good yields excellent enantiomeric excesses (26 examples). The application this methodology allowed the efficient total synthesis five natural sesquiterpenoids, including enokipodin B, hitoyopodin A, lagopodin isocuparene-3,4-diol.

Язык: Английский

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Nickel-Catalyzed Enantioselective Reductive Conjugate Arylation and Heteroarylation via an Elementary Mechanism of 1,4-Addition

Journal of the American Chemical Society, Год журнала: 2022, Номер 144(44), С. 20249 - 20257

Опубликована: Окт. 31, 2022

A nickel complex of isoquinox promoted enantioselective conjugate arylation and heteroarylation enones using aryl heteroaryl halides directly. The reaction was successfully applied to stereoselective syntheses ar-turmerone, chiral fragments (+)-tolterodine AZD5672. Mechanistically, experiments calculations supported that an arylnickel(I) inserted via elementary 1,4-addition.

Язык: Английский

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Copper(I)-Catalyzed Asymmetric Conjugate Addition of 1,4-Dienes to β-Substituted Alkenyl Azaarenes

Journal of the American Chemical Society, Год журнала: 2023, Номер 145(3), С. 1749 - 1758

Опубликована: Янв. 9, 2023

Chiral azaarene compounds are extremely important due to their prevalence in pharmaceutical ingredients. Herein, an array of chiral molecules bearing azaaryl groups is synthesized moderate-to-excellent yields with Z/E ratios, high dr, and excellent enantioselectivity by a copper(I)-catalyzed asymmetric conjugate addition 1,4-dienes (E)-β-substituted alkenyl azaarenes. The reaction carried out under mild proton-transfer conditions, which enjoys very atom economy. Moreover, the features broad substrate scope on (E)-α,β-unsaturated azaarenes as various well tolerated, such benzothiazole, thiazole, N-methyl-benzimidazole, benzoxazole, quinoline, isoquinoline, pyrimidine, pyrazine, triazine. Interestingly, (Z)-α,β-unsaturated affords same products results but reversed absolute configuration. DFT calculations indicate that C-C bond-forming nucleophilic Z-/E- enantio-selectivities-determining step provides rationale for origin selectivities. At last, synthetic utilities product showcased several transformations, including olefin metathesis, [4 + 2] cyclization, [2 1] cleavage benzothiazole ring.

Язык: Английский

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Catalytic Enantioselective Construction of 6‐4 Ring‐Junction All‐Carbon Stereocenters and Mechanistic Insights

Chinese Journal of Chemistry, Год журнала: 2022, Номер 40(15), С. 1767 - 1776

Опубликована: Апрель 20, 2022

Comprehensive Summary Developing reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at bridgehead position is highly desired, considering existence such skeletons in natural products biological activities potential using these molecules downstream studies chemical biology medicinal chemistry. Report here accessing target high chemo‐, regio‐ enantio‐selectivities through Pd(II)/chiral N , ’‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction yne‐allenones arylboronic acids. Realization skeleton ring‐junction all‐carbon stereocenter one‐step process while synthesizing two‐step process, which begins intramolecular [2 + 2] allenes alkynes, followed by Pd‐catalyzed addition acids to cyclic enones generated first step. Noteworthy that Bim ligand as C 2 ‐symmetric ’‐bidentateanionic ligand, designed us, coordinating Pd catalyst was applied catalyze 1,4‐conjugate catalytic performance (the can be carried out air). DFT calculations have been understand how take place, origins enantioselectivity, relative reactivities different substrates.

Язык: Английский

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Recent advances in the asymmetric catalytic construction of oxa-quaternary carbon centers

Organic Chemistry Frontiers, Год журнала: 2023, Номер 10(12), С. 3110 - 3129

Опубликована: Янв. 1, 2023

This review focuses on the very recent advances (from 2020 to beginning of 2023) in enantioselective catalytic reactions for construction oxa-quaternary stereocenters.

Язык: Английский

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An Intramolecular Umpolung Cascade Kukhtin–Ramirez Reaction/Michael Addition-Initiated Cyclization: Stereoselective Synthesis of Tetrasubstituted Cyclopropane Fused 1-Indanones

Organic Letters, Год журнала: 2023, Номер 25(11), С. 1946 - 1951

Опубликована: Март 15, 2023

Herein, we disclose a fascinating highly stereoselective P(NMe2)3 mediated intramolecular deoxygenative umpolung cascade Michael addition-initiated cyclopropanation with diverse substrate adaptability. This methodology creates new horizon for expedient access to valuable 6,5,3-fused scaffolds having an all-carbon quaternary stereocenter via Kukhtin-Ramirez (K-R) adduct formation, excellent diastereoselectivity and yields under metal-free ambient conditions. A few functional group transformations have also been performed successfully. Additionally, asymmetric catalytic attempt using (R)-(+)-H8-BINOL has delivered good enantioselectivity.

Язык: Английский

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Stereoconvergent Approach to the Enantioselective Construction of α‐Quaternary Alcohols by Radical Epoxide Allylation

Angewandte Chemie International Edition, Год журнала: 2024, Номер 63(29)

Опубликована: Апрель 26, 2024

Abstract We describe a highly stereoconvergent radical epoxide allylation towards diastereomerically and enantiomerically enriched α ‐quaternary alcohols in two steps from olefins. Our approach combines the stereospecifity enantioselectivity of Shi epoxidation with unprecedented Ti(III)‐promoted intramolecular group transfer epoxides. A directional isomerization step via configurationally labile intermediates enables selective preparation all‐carbon quaternary stereocenters unique fashion.

Язык: Английский

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