Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes

Abstract Enantioenriched unsymmetric dialkyl carbinol derivatives are of importance in natural products, bioactive molecules, and functional organic materials. However, the catalytic asymmetric synthesis of dialkyl carbinol derivatives remains challenging due to the similar steric and electronic pro...

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Main Authors: Quan‐Xing Zi, Wei Shu
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:Advanced Science
Subjects:
Online Access:https://doi.org/10.1002/advs.202409592
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author Quan‐Xing Zi
Wei Shu
author_facet Quan‐Xing Zi
Wei Shu
author_sort Quan‐Xing Zi
collection DOAJ
description Abstract Enantioenriched unsymmetric dialkyl carbinol derivatives are of importance in natural products, bioactive molecules, and functional organic materials. However, the catalytic asymmetric synthesis of dialkyl carbinol derivatives remains challenging due to the similar steric and electronic properties of two alkyl substituents. Herein, an unprecedented synthesis of chiral dialkyl carbinol ester derivatives from Ni‐catalyzed reductive‐oxidative relay cross‐coupling of two alkenes is developed for the first time. The reaction features the use of enol esters and unactivated alkenes as two different alkyl equivalents to undergo head‐to‐tail and enantioselective alkyl‐alkyl cross‐coupling. The reaction undergoes two‐electron reduction and single electron oxidation in the presence of both reductants and oxidants. The use of an allyl bromide as single electron acceptor is crucial for the success of this non‐trivial asymmetric cross‐coupling, providing a new reaction mode for asymmetric alkyl‐alkyl bond‐forming event in the absence of stoichiometric alkyl electrophiles.
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spelling doaj-art-ee490fb4cacd490cbcf52442bc8e576e2025-08-20T02:01:00ZengWileyAdvanced Science2198-38442024-12-011148n/an/a10.1002/advs.202409592Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct AlkenesQuan‐Xing Zi0Wei Shu1Guangming Advanced Research Institute Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis Southern University of Science and Technology Shenzhen Grubbs Institute Shenzhen Guangdong 518055 P. R. ChinaGuangming Advanced Research Institute Department of Chemistry and Guangdong Provincial Key Laboratory of Catalysis Southern University of Science and Technology Shenzhen Grubbs Institute Shenzhen Guangdong 518055 P. R. ChinaAbstract Enantioenriched unsymmetric dialkyl carbinol derivatives are of importance in natural products, bioactive molecules, and functional organic materials. However, the catalytic asymmetric synthesis of dialkyl carbinol derivatives remains challenging due to the similar steric and electronic properties of two alkyl substituents. Herein, an unprecedented synthesis of chiral dialkyl carbinol ester derivatives from Ni‐catalyzed reductive‐oxidative relay cross‐coupling of two alkenes is developed for the first time. The reaction features the use of enol esters and unactivated alkenes as two different alkyl equivalents to undergo head‐to‐tail and enantioselective alkyl‐alkyl cross‐coupling. The reaction undergoes two‐electron reduction and single electron oxidation in the presence of both reductants and oxidants. The use of an allyl bromide as single electron acceptor is crucial for the success of this non‐trivial asymmetric cross‐coupling, providing a new reaction mode for asymmetric alkyl‐alkyl bond‐forming event in the absence of stoichiometric alkyl electrophiles.https://doi.org/10.1002/advs.202409592alkene‐alkene couplingasymmetric alkyl‐alkyl couplingdialkyl carbinolsnickel catalysisreductive‐oxidative relay
spellingShingle Quan‐Xing Zi
Wei Shu
Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes
Advanced Science
alkene‐alkene coupling
asymmetric alkyl‐alkyl coupling
dialkyl carbinols
nickel catalysis
reductive‐oxidative relay
title Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes
title_full Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes
title_fullStr Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes
title_full_unstemmed Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes
title_short Asymmetric Synthesis of Dialkyl Carbinols by Ni‐Catalyzed Reductive‐Oxidative Relay of Distinct Alkenes
title_sort asymmetric synthesis of dialkyl carbinols by ni catalyzed reductive oxidative relay of distinct alkenes
topic alkene‐alkene coupling
asymmetric alkyl‐alkyl coupling
dialkyl carbinols
nickel catalysis
reductive‐oxidative relay
url https://doi.org/10.1002/advs.202409592
work_keys_str_mv AT quanxingzi asymmetricsynthesisofdialkylcarbinolsbynicatalyzedreductiveoxidativerelayofdistinctalkenes
AT weishu asymmetricsynthesisofdialkylcarbinolsbynicatalyzedreductiveoxidativerelayofdistinctalkenes