Enantioselective Synthesis of cis‐Decalins by Merging the Birch Reduction and Inverse‐Electron‐Demand Diels–Alder Reaction

Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse‐electron‐demand Diels–Alder reaction of 2‐pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis‐decalin scaffolds. Ena...

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Published in:Angewandte Chemie International Edition 2023-08, Vol.62 (32), p.e202303876-n/a
Main Authors: Si, Xu‐Ge, Feng, Shi‐Xiong, Wang, Zhuo‐Yan, Chen, Xiaoyu, Xu, Meng‐Meng, Zhang, Yu‐Zhen, He, Jun‐Xiong, Yang, Limin, Cai, Quan
Format: Article
Language:English
Subjects:
Anisole
Asymmetric Catalysis
Birch Reduction
cis-Decalin
Decalin
Diels-Alder reactions
Enantiomers
Intermediates
Inverse-Electron-Demand Diels–Alder Reaction
Reduction
Scaffolds
Substrates
Synthesis
Triterpenes
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Summary:Herein, we show that the combination of the Birch reduction of readily available anisole derivatives and the catalytic asymmetric inverse‐electron‐demand Diels–Alder reaction of 2‐pyrones can serve as a powerful platform for the diverse synthesis of synthetically important cis‐decalin scaffolds. Enabled by a well‐modified chiral bis(oxazoline) ligand/CuII complex, a wide range of polysubstituted cis‐decalin scaffolds with up to six contiguous stereocenters were generated efficiently. The synthetic potential of this method is demonstrated by the concise synthesis of the sesquiterpene (+)‐occidentalol and a key intermediate for seven triterpenes. Mechanistic studies suggest the 1,3‐cyclohexadienes formed in situ are the key intermediates, and efficient kinetic resolution occurs when C2‐ and/or C3‐substituted 1,4‐cyclohexadienes are utilized as substrates. DFT calculations elucidated that the Diels–Alder reaction proceeds in a stepwise fashion and revealed the origins of the stereoselectivities. Asymmetric synthesis of highly functionalized chiral cis‐decalins was realized by merging Birch reduction and a tandem olefin migration/asymmetric IEDDA reaction. Up to six contiguous and two quaternary stereocenters could be formed in one step by efficient kinetic resolution. The synthetic value of the approach is illustrated by the concise total synthesis of (+)‐occidentalol and the synthesis of a key intermediate for seven triterpenes.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.202303876