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

Comprehensive Summary Developing reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at the bridgehead position is highly desired, considering the existence of such skeletons in natural products with biological activities and the potential of using thes...

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Bibliographic Details
Published in:Chinese journal of chemistry 2022-08, Vol.40 (15), p.1767-1776
Main Authors: Wang, Jia‐Yin, Li, Chen‐Long, Xu, Ting, Li, Meng‐Fan, Hao, Wen‐Juan, Tu, Shu‐Jiang, Wang, Jianyi, Li, Guigen, Yu, Zhi‐Xiang, Jiang, Bo
Format: Article
Language:English
Subjects:
Alkynes
Asymmetric catalysis
Asymmetry
Carbon
Catalysts
Chemical synthesis
Chiral cyclobutenes
Enantiomers
Ligands
Mechanism
Michael addition
Natural products
Palladium
Substrates
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Summary:Comprehensive Summary Developing reactions for the synthesis of 6‐6‐4 and 6‐4 carbocyclic scaffolds with a chiral quaternary center at the bridgehead position is highly desired, considering the existence of such skeletons in natural products with biological activities and the potential of using these molecules for downstream studies in chemical biology and medicinal chemistry. Report here is accessing these target skeletons with high chemo‐, regio‐ and enantio‐selectivities through Pd(II)/chiral N,N’‐disulfonyl bisimidazoline (Bim) ligand‐catalyzed asymmetric reaction of yne‐allenones and arylboronic acids. Realization of 6‐6‐4 skeleton with a ring‐junction all‐carbon stereocenter is a one‐step process while synthesizing 6‐4 skeleton is a two‐step process, which begins with intramolecular [2 + 2] reaction of allenes with alkynes, followed by Pd‐catalyzed asymmetric addition of arylboronic acids to cyclic enones generated in the first step. Noteworthy is that chiral Bim ligand as a C2‐symmetric N,N’‐bidentateanionic ligand, designed by us, in coordinating with Pd catalyst was first applied to catalyze asymmetric 1,4‐conjugate addition reaction with the high catalytic performance (the reaction can be carried out in air). DFT calculations have been applied to understand how these reactions take place, the origins of enantioselectivity, and relative reactivities of different substrates.
ISSN:1001-604X
1614-7065
DOI:10.1002/cjoc.202200211