Ni‐Catalyzed Regio‐ and Enantioselective Homoallylic Coupling: Synthesis of Chiral Branched 1,5‐Dienes Featuring a Quaternary Stereogenic Center and Mechanistic Analysis
Asymmetric synthesis of small molecules comprising quaternary stereogenic carbon centers represents a challenging objective. Here regio‐ and enantioselective synthesis of chiral 1,5‐dienes featuring quaternary stereocenters is reported via nickel‐promoted by reductive homoallylic coupling. The devel...
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Published in | Angewandte Chemie International Edition Vol. 62; no. 50; pp. e202314865 - n/a |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
WEINHEIM
Wiley
11.12.2023
Wiley Subscription Services, Inc |
Edition | International ed. in English |
Subjects | |
Online Access | Get full text |
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Summary: | Asymmetric synthesis of small molecules comprising quaternary stereogenic carbon centers represents a challenging objective. Here regio‐ and enantioselective synthesis of chiral 1,5‐dienes featuring quaternary stereocenters is reported via nickel‐promoted by reductive homoallylic coupling. The developed methodology features an atypical preference for the formation of unusual branched regioisomers (rr >20 : 1) in a sterically challenging allylic substitution event and furnishes the products with enantiomeric ratios of up to 98 : 2 and with high chemo‐ and E‐selectivity. A range of experimental evidences suggest that zinc plays a dual role to generate electrophilic and nucleophilic Ni(II)‐allyl intermediates empowering a unique formal bimetallic cross‐electrophile manifold in two separate kinetic regimes.
A reductive cross‐electrophile coupling of allylic carbonates under Ni‐catalysis provides access to unique 1,5‐dienes featuring a quaternary stereogenic center under high chemo‐, regio‐, diastereo‐ and enantio‐control. Mechanistic studies align well with a catalytic cycle based on a Ni(0)/Ni(II) couple with a crucial role for divalent Zn boosting the overall kinetics and selectivity while favoring a key bimetallic C−C bond formation. |
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Bibliography: | These authors contributed equally to this work. Marie Curie Actions (MSCA) ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 1433-7851 1521-3773 |
DOI: | 10.1002/anie.202314865 |