Synthesis of Enantioenriched 1,2-cis Disubstituted Cycloalkanes by Convergent NiH Catalysis

Changpeng Chen; Wenqing Guo; Deyong Qiao; Shaolin Zhu

doi:10.1002/anie.202308320

Synthesis of Enantioenriched 1,2-cis Disubstituted Cycloalkanes by Convergent NiH Catalysis

Angew Chem Int Ed Engl. 2023 Sep 4;62(36):e202308320. doi: 10.1002/anie.202308320. Epub 2023 Jul 31.

Authors

Changpeng Chen¹, Wenqing Guo¹, Deyong Qiao¹, Shaolin Zhu^{1

2

3}

Affiliations

¹ State Key Laboratory of Coordination Chemistry, Jiangsu Key Laboratory of Advanced Organic Materials, Chemistry and Biomedicine Innovation Center (ChemBIC), School of Chemistry and Chemical Engineering, Nanjing University, 210093, Nanjing, China.
² School of Chemistry and Chemical Engineering, Henan Normal University, 453007, Xinxiang, China.
³ Shanghai Key Laboratory for Molecular Engineering of Chiral Drugs, Shanghai Jiao Tong University, 200240, Shanghai, China.

PMID: 37470299
DOI: 10.1002/anie.202308320

Abstract

Enantioenriched multi-substituted cycloalkanes constitute an essential class of compounds in pharmaceuticals, natural products and agrochemicals. Here we report an NiH-catalyzed asymmetric migratory hydroalkylation process for the efficient and selective construction of such compounds. Through a dynamic kinetic asymmetric transformation (DYKAT), easily accessible racemic and isomeric mixtures of cycloalkenes could be directly utilized as starting materials, convergently producing thermo-dynamically disfavored chiral 1,2-cis disubstituted cycloalkanes bearing vicinal stereocenters with high levels of regio-, diastereo- and enantioselectivity. In addition, prochiral cyclic alkenes can be also employed, and deliver chiral 1,2-cis disubstituted cycloalkanes through desymmetrization process.

Keywords: Alkenes; Alkylation; Asymmetric Catalysis; Isomerization; Nickel.

Abstract

Grants and funding