Enantioselective Relay Coupling of Perfluoroalkyl and Vinylogous Ketyl Radicals DOI Creative Commons
Yuxin Zhao, Yichi Zhang, Yong Huang

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(35)

Published: June 12, 2024

Abstract β‐Chiral carboxylic acids and their derivatives are highly valuable structural motifs in the fields of asymmetric synthesis medicinal chemistry. However, introduction a sterically demanding sidechain to β‐carbon, such as an all‐carbon quaternary center, remains significant challenge classical polar processes. Recently, N ‐heterocyclic carbene (NHC) mediated coupling reactions involving persistent ketyl radicals have emerged promising strategy assemble crowded carbon‐carbon bonds. Nevertheless, achieving enantioselectivity these challenging. In this work, we report our recent progress controlling for relay perfluoroalkyl vinylogous radicals. We developed chiral bifunctional NHC‐squaramide catalyst that achieves high facial selectivity critical bond‐forming event congested tertiary carbon radical radical. Chiral carboxylates bearing center at β‐position can be prepared good yield excellent enantiomeric excess. Results from density functional theory (DFT) calculations nuclear Overhauser effect (NOE) experiments indicate , N’ ‐diaryl squaramide motif adopts unusual syn ‐ conformation, enabling hydrogen bonding interactions with enolate oxygen, thereby rigidifying overall conformation transition state.

Language: Английский

Catalytic Asymmetric Redox‐Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer DOI

Wenhui Wei,

Chunyang Li, Yifan Fan

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(30)

Published: April 30, 2024

Abstract Consecutive photoinduced electron transfer (ConPET) is a powerful and atom‐economical protocol to overcome the limitations of intrinsic redox potential visible light‐absorbing photosensitizers, thereby considerably improving substrate reaction types. Likely because such an exothermic single‐electron (SET) process usually does not require aid chiral catalysts, resulting in inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on viability cooperative ConPET hydrogen‐bonding catalysis for [3+2] photocycloaddition cyclopropyl ketones with vinylazaarenes. In addition enabling first use olefins that preferentially interact this platform paves way efficient synthesis pharmaceutically synthetically important cyclopentyl functionalized by azaarenes high yields, ees dr. The robust capacity method can be further highlighted low loading catalyst (1.0 mol %), good compatibility both 2‐azaarene 3‐pyridine‐based olefins, successful concurrent construction three stereocenters cyclopentane rings involving elusive but all‐carbon quaternary.

Language: Английский

Citations

11
Radical Cross Coupling and Enantioselective Protonation through Asymmetric Photoredox Catalysis DOI Creative Commons

Manman Kong,

Zhuoxi Wang,

Xu Ban

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: 11(12)

Published: Jan. 17, 2024

Abstract An unprecedented enantioselective protonation reaction enabled by photoredox catalytic radical coupling is developed. Under cooperative dicynopyrazine‐derived chromophore (DPZ) as a photosensitizer and chiral phosphoric acid catalyst, Hantzsch ester sacrificial reductant, the transformations between α‐substituted enones cyanoazaarenes or 2‐(chloromethyl)azaaren‐1‐iums can proceed tandem reduction, coupling, process efficiently. Two classes of pharmaceutically important enantioenriched azaarene variants, which contain synthetically versatile ketone‐substituted tertiary carbon stereocenter at β ‐ γ ‐position azaarenes, are synthesized with high yields ees.

Language: Английский

Citations

9
Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N‐Arylquinazolinones DOI
Yilin Liu,

Mengqi Chu,

Xiangtao Li

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: unknown

Published: July 24, 2024

Visible light-driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of allenes have been established, where the activated energy photosensitizer should surpass that substrates, representing intrinsic requirement. Accordingly, this method not applicable axially chiral molecules with significantly high triplet energies. In study, we present a photoredox catalytic approach enables efficient valuable yet challenging-to-access 2-azaarene-functionalized quinazolinones. The substrate scope extensive, allowing both 3-axis unmet 1-axis assembly through facile oxidation diverse central 2,3-dihydroquinazolin-4(1H)-ones can be easily prepared achieve enantiomer enrichment via deracemization. Mechanistic studies reveal importance selection in attaining excellent chemoselectivity highlight indispensability Brønsted acid enabling enantioselective protonation accomplish

Language: Английский

Citations

5
Photoredox cobalt-catalyzed asymmetric desymmetric reductive coupling of cyclobutenes with alkynes DOI Creative Commons

Tianlong Zeng,

Yezeng He, Ying Li

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: April 1, 2025

Catalytic methods to couple alkynes and alkenes are highly valuable in synthetic chemistry. The cobalt-catalyzed intermolecular reductive coupling of is particularly attractive due the unique reactivity cost-effectiveness cobalt catalysts. However, enantioselective transformations this kind less developed. limited successful examples restricted use electronically biased activated olefins as partners. Herein, we report an asymmetric desymmetric unbiased succinimide-containing cyclobutenes with synthesize enantioenriched, synthetically important vinyl cyclobutanes via photoredox dual catalysis. Excellent enantioselectivities, good diastereoselectivities regioselectivities obtained. Preliminary mechanistic studies suggest that Hantzsch ester a better reducing reagent when used combination Et3N. Density functional theory calculations reveal reaction proceeds more likely through Co(III)-H migratory insertion mechanism. Here, authors internal

Language: Английский

Citations

0
Enantioselective Hydroaminoalkylation of Azaaryl Ketones through Asymmetric Photoredox Catalysis DOI

Xiangbin Bai,

Jialu Yao,

Wenxian Li

et al.

Organic Letters, Journal Year: 2024, Volume and Issue: 26(23), P. 5037 - 5042

Published: June 5, 2024

An enantioselective hydroaminoalkylation of azaaryl ketones under a transition-metal-free asymmetric photoredox catalysis platform is reported. A series valuable azaarene-functionalized 1,2-amino alcohols featuring attractive quaternary carbon stereocenters have been synthesized in high yields with good to excellent enantioselectivities. The viability readily accessible N-aryl glycines as reaction partners facilitates the conjugate modification these products into important derivatives, thereby enhancing synthetic utility current approach.

Language: Английский

Citations

3
Enantioselective Relay Coupling of Perfluoroalkyl and Vinylogous Ketyl Radicals DOI Creative Commons
Yuxin Zhao, Yichi Zhang, Yong Huang

et al.

Angewandte Chemie International Edition, Journal Year: 2024, Volume and Issue: 63(35)

Published: June 12, 2024

Abstract β‐Chiral carboxylic acids and their derivatives are highly valuable structural motifs in the fields of asymmetric synthesis medicinal chemistry. However, introduction a sterically demanding sidechain to β‐carbon, such as an all‐carbon quaternary center, remains significant challenge classical polar processes. Recently, N ‐heterocyclic carbene (NHC) mediated coupling reactions involving persistent ketyl radicals have emerged promising strategy assemble crowded carbon‐carbon bonds. Nevertheless, achieving enantioselectivity these challenging. In this work, we report our recent progress controlling for relay perfluoroalkyl vinylogous radicals. We developed chiral bifunctional NHC‐squaramide catalyst that achieves high facial selectivity critical bond‐forming event congested tertiary carbon radical radical. Chiral carboxylates bearing center at β‐position can be prepared good yield excellent enantiomeric excess. Results from density functional theory (DFT) calculations nuclear Overhauser effect (NOE) experiments indicate , N’ ‐diaryl squaramide motif adopts unusual syn ‐ conformation, enabling hydrogen bonding interactions with enolate oxygen, thereby rigidifying overall conformation transition state.

Language: Английский

Citations

1
Photoredox Catalytic Deracemization Enabled Enantioselective and Modular Access to Axially Chiral N‐Arylquinazolinones DOI Open Access
Yilin Liu,

Mengqi Chu,

Xiangtao Li

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(43)

Published: July 24, 2024

Abstract Visible light‐driven photocatalytic deracemization is highly esteemed as an ideal tool for organic synthesis due to its exceptional atom economy and synthetic efficiency. Consequently, successful instances of allenes have been established, where the activated energy photosensitizer should surpass that substrates, representing intrinsic requirement. Accordingly, this method not applicable axially chiral molecules with significantly high triplet energies. In study, we present a photoredox catalytic approach enables efficient valuable yet challenging‐to‐access 2‐azaarene‐functionalized quinazolinones. The substrate scope extensive, allowing both 3‐axis unmet 1‐axis assembly through facile oxidation diverse central 2,3‐dihydroquinazolin‐4(1 H )‐ones can be easily prepared achieve enantiomer enrichment via deracemization. Mechanistic studies reveal importance selection in attaining excellent chemoselectivity highlight indispensability Brønsted acid enabling enantioselective protonation accomplish

Language: Английский

Citations

1
Catalytic Asymmetric Redox‐Neutral [3+2] Photocycloadditions of Cyclopropyl Ketones with Vinylazaarenes Enabled by Consecutive Photoinduced Electron Transfer DOI

Wenhui Wei,

Chunyang Li, Yifan Fan

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(30)

Published: April 30, 2024

Abstract Consecutive photoinduced electron transfer (ConPET) is a powerful and atom‐economical protocol to overcome the limitations of intrinsic redox potential visible light‐absorbing photosensitizers, thereby considerably improving substrate reaction types. Likely because such an exothermic single‐electron (SET) process usually does not require aid chiral catalysts, resulting in inevitable racemic background reaction, notably, no enantioselective manifolds have been reported. Herein, we report on viability cooperative ConPET hydrogen‐bonding catalysis for [3+2] photocycloaddition cyclopropyl ketones with vinylazaarenes. In addition enabling first use olefins that preferentially interact this platform paves way efficient synthesis pharmaceutically synthetically important cyclopentyl functionalized by azaarenes high yields, ees dr. The robust capacity method can be further highlighted low loading catalyst (1.0 mol %), good compatibility both 2‐azaarene 3‐pyridine‐based olefins, successful concurrent construction three stereocenters cyclopentane rings involving elusive but all‐carbon quaternary.

Language: Английский

Citations

0
Enantioselective Relay Coupling of Perfluoroalkyl and Vinylogous Ketyl Radicals DOI Creative Commons
Yuxin Zhao, Yichi Zhang, Yong Huang

et al.

Angewandte Chemie, Journal Year: 2024, Volume and Issue: 136(35)

Published: June 12, 2024

Abstract β‐Chiral carboxylic acids and their derivatives are highly valuable structural motifs in the fields of asymmetric synthesis medicinal chemistry. However, introduction a sterically demanding sidechain to β‐carbon, such as an all‐carbon quaternary center, remains significant challenge classical polar processes. Recently, N ‐heterocyclic carbene (NHC) mediated coupling reactions involving persistent ketyl radicals have emerged promising strategy assemble crowded carbon‐carbon bonds. Nevertheless, achieving enantioselectivity these challenging. In this work, we report our recent progress controlling for relay perfluoroalkyl vinylogous radicals. We developed chiral bifunctional NHC‐squaramide catalyst that achieves high facial selectivity critical bond‐forming event congested tertiary carbon radical radical. Chiral carboxylates bearing center at β‐position can be prepared good yield excellent enantiomeric excess. Results from density functional theory (DFT) calculations nuclear Overhauser effect (NOE) experiments indicate , N’ ‐diaryl squaramide motif adopts unusual syn ‐ conformation, enabling hydrogen bonding interactions with enolate oxygen, thereby rigidifying overall conformation transition state.

Language: Английский

Citations

0