Aza‐Ortho‐Quinone Methides as Reactive Intermediates: Generation and Utility in Contemporary Asymmetric Synthesis DOI
Hsuan‐Hung Liao, Shinje Miñoza, Shao‐Chi Lee

et al.

Chemistry - A European Journal, Journal Year: 2022, Volume and Issue: 28(46)

Published: June 2, 2022

Abstract The aza‐ ortho ‐quinone methide (aza‐ o ‐QM) chemistry has overwhelmingly progressed in the past few decades. This review aims to integrate various transition metal‐catalyzed and organocatalytic strategies taming aza ‐o‐ QM intermediates, including ‐vinylidene quinone ‐VQM), ‐alkynyl ‐AQM), para p ‐QM), indole‐based ‐QM analog. These transient species are often utilized for direct enantioselective synthesis of complex (hetero)polycyclic or fused‐ring molecular scaffolds such as tetrahydroquinoline indoline, among others, which abundant many natural products, bioactive compounds, pharmaceuticals.

Language: Английский

para‐Quinone Methides as Acceptors in 1,6‐Nucleophilic Conjugate Addition Reactions for the Synthesis of Structurally Diverse Molecules DOI
Carolina G. S. Lima, Fernanda P. Pauli, Dora C. S. Costa

et al.

European Journal of Organic Chemistry, Journal Year: 2020, Volume and Issue: 2020(18), P. 2650 - 2692

Published: Feb. 28, 2020

para ‐Quinone methides ( p ‐QMs) are naturally occurring molecules that have been finding increasing synthetic applications in the last few years. The presence of two electronically different exocyclic conjugate substituents their structure, carbonyl and methylidene, leads to a pronounced reactivity owing polarization molecule. In this sense, those prone undergo attack nucleophiles terminal carbon double bond, behaving as vinylogous electrophiles generating 1,6‐addition products. context, years development catalytic approaches for 1,6‐nucleophilic addition reactions involving ‐QMs has attracted considerable attention. Considering extensive such found decades reactions, review we comprehensively discuss historical field, starting with early on natural product synthesis, going through seminal non‐stereoselective processes progressing cutting‐edge asymmetric‐catalyzed approaches.

Language: Английский

Citations

197
Organocatalytic Enantioselective Synthesis of Chiral Allenes: Remote Asymmetric 1,8‐Addition of Indole Imine Methides DOI
Xingguang Li, Jianwei Sun

Angewandte Chemie International Edition, Journal Year: 2020, Volume and Issue: 59(39), P. 17049 - 17054

Published: June 18, 2020

An organocatalytic enantioconvergent synthesis of chiral tetrasubstituted allenes is disclosed. With suitable phosphoric acid catalysts, a range racemic indole-substituted propargylic alcohols reacted with nucleophiles to provide efficient access series enantioenriched high enantioselectivities. Control experiments suggested mechanism involving remotely controlled asymmetric 1,8-addition the in situ generated indole imine methide via bifunctional transition state.

Language: Английский

Citations

125
Recent Advances in Organocatalytic Enantioselective Synthesis of Axially Chiral Allenes DOI
Xing Wang, Xuling Chen, Lin Wei

et al.

Advanced Synthesis & Catalysis, Journal Year: 2022, Volume and Issue: 364(7), P. 1212 - 1222

Published: March 9, 2022

Abstract Axially chiral allenes occur on a wide range of natural products and synthetic molecules with significant biological activity. Furthermore, they are versatile building blocks in organic synthesis because their inherent chemical properties. Accordingly, catalytic enantioselective axially has been paid much attention. Benefited from the development asymmetric organocatalysis, many simple efficient methods terms different systems as well reaction partners have developed. This review will focus recent progress field organocatalytic (2000–2022), which is organized according to types catalyst system used. magnified image

Language: Английский

Citations

64
Enantio‐ and Diastereoselective Synthesis of Chiral Tetrasubstituted α‐Amino Allenoates Bearing a Vicinal All‐Carbon Quaternary Stereocenter with Dual‐Copper‐Catalysis DOI

Cheng Sheng,

Zheng Ling, Junzhe Xiao

et al.

Angewandte Chemie International Edition, Journal Year: 2023, Volume and Issue: 62(31)

Published: June 1, 2023

The skeletons of chiral tetrasubstituted allenes bearing a vicinal all-carbon quaternary stereocenter are importance but still challenging to synthesize. Herein, we report enantio- and diastereoselective γ-additions 1-alkynyl ketimines with dual-copper-catalysis under mild conditions, affording α-amino allenoates in high yields (up 99 % yield) excellent enantioselectivities ee) diastereoselectivities >20 : 1 dr). Importantly, the stereodivergent synthesis products was realized by asymmetric γ-addition reaction Grignard reagent promoted epimerization. Moreover, dual-copper-catalyzed reactions were smoothly applied gram-scale adopted introduce allenyl moieties into bioactive molecules. Mechanistic experiments density functional theory (DFT) calculations demonstrated that catalyzed double copper catalysts.

Language: Английский

Citations

27
Enantioselective synthesis of tetrasubstituted allenes via addition/arylation tandem reaction of 2-activated 1,3-enynes DOI

Yongyan Zhang,

Wu Jin, Lichao Ning

et al.

Science China Chemistry, Journal Year: 2023, Volume and Issue: 66(2), P. 526 - 533

Published: Jan. 9, 2023

Language: Английский

Citations

25
Asymmetric Synthesis of Remotely Chiral Naphthols and Naphthylamines via Naphthoquinone Methides DOI
Shuxuan Liu, Ka Lok Chan, Zhenyang Lin

et al.

Journal of the American Chemical Society, Journal Year: 2023, Volume and Issue: 145(23), P. 12802 - 12811

Published: June 5, 2023

Quinone methides are well-established intermediates in asymmetric synthesis. In contrast, their extended analogues with the carbonyl and methide units distributed across two different rings have not been exploited Herein, we achieved first process involving such intermediates. Specifically, use of suitable chiral phosphoric acids enabled situ generation 2-naphthoquinone 8-methides corresponding aza counterparts for mild one-pot nucleophilic addition. These processes provided rapid access to a wide range previously less accessible remotely naphthols naphthylamines both high efficiency excellent enantioselectivity. Control experiment DFT calculations important insights into reaction mechanism, which likely involves acid molecules enantiodetermining transition states. This work serves as proof concept exploitation new types quinone versatile synthesis, thus providing platform efficient construction remote benzylic stereogenic centers aromatic compounds.

Language: Английский

Citations

24
Enantioselective synthesis of molecules with multiple stereogenic elements DOI Creative Commons
Arthur Gaucherand, Expédite Yen‐Pon,

Antoine Domain

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(22), P. 11165 - 11206

Published: Jan. 1, 2024

This review explores the fascinating world of molecules featuring multiple stereogenic elements, unraveling different strategies designed over years for their enantioselective synthesis.

Language: Английский

Citations

15
Challenging Task of Ni-Catalyzed Highly Regio-/Enantioselective Semihydrogenation of Racemic Tetrasubstituted Allenes via a Kinetic Resolution Process DOI
Gang Liu,

Xuanliang Yang,

Pei Gu

et al.

Journal of the American Chemical Society, Journal Year: 2024, Volume and Issue: 146(11), P. 7419 - 7430

Published: March 6, 2024

The first earth-abundant transition metal Ni-catalyzed highly regio- and enantioselective semihydrogenation of racemic tetrasubstituted allenes via a kinetic resolution process as challenging task was well established. This protocol furnishes expedient access to diversity structurally important enantioenriched chiral allylic molecules with high regio-, enantio-, Z/E-selectivity. Remarkably, this proceeded one carbon–carbon double bond allenes, which regioselective complementary the Rh-catalyzed asymmetric version. Deuterium labeling experiments density functional theory (DFT) calculations were carried out reveal reasonable reaction mechanism explain regio-/stereoselectivity.

Language: Английский

Citations

13
Novel Stereo‐Induction Pattern in Pudovik Addition/Phospha‐Brook Rearrangement Towards Chiral Trisubstituted Allenes DOI

Jia‐Yan Zheng,

Handong Wang, Yan Zhang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(22)

Published: March 23, 2024

Abstract Despite the significance of chiral allene skeletons in catalysis, organic synthesis and medicinal chemistry et al., there is a scarcity reports on axially allenyl phosphorus compounds. Here, we disclosed an efficient straightforward cascade reaction between ethynyl ketones phosphine oxides, resulting broad array trisubstituted allenes incorporating moiety high yields with excellent stereoselectivities facilitated by peptide‐mimic phosphonium salt (PPS) Additionally, comprehensive series mechanistic experiments have been conducted to elucidate that this proceeds via asymmetric Pudovik addition followed subsequent phospha ‐Brook rearrangement occurs concomitantly kinetic resolution, representing stereospecific protonation process facilitating central‐to‐axial chirality transfer manner. We anticipate our research will pave way for promising exploration novel stereo‐induction pattern addition/ reaction.

Language: Английский

Citations

10
Catalytic asymmetric multiple dearomatizations of phenols enabled by a cascade 1,8-addition and Diels–Alder reaction DOI Creative Commons
Xihong Liu, Jingying Zhang,

Lutao Bai

et al.

Chemical Science, Journal Year: 2019, Volume and Issue: 11(3), P. 671 - 676

Published: Dec. 6, 2019

The first chiral phosphoric acid catalyzed asymmetric multiple dearomatizations of phenols for the synthesis bridged polycyclic compounds are reported.

Language: Английский

Citations

58