Chemodivergent, enantio- and regioselective couplings of alkynes, aldehydes and silanes enabled by nickel/N-heterocyclic carbene catalysis

Jia-Ming Liu; Xuexiang Ma; Guang Chen; Wang Wan; Zhiyang Li; Youjun Xu; Dongju Zhang; Shi-Liang Shi

doi:10.1016/j.scib.2024.12.023

Chemodivergent, enantio- and regioselective couplings of alkynes, aldehydes and silanes enabled by nickel/N-heterocyclic carbene catalysis

Sci Bull (Beijing). 2024 Dec 21:S2095-9273(24)00930-7. doi: 10.1016/j.scib.2024.12.023. Online ahead of print.

Authors

Jia-Ming Liu¹, Xuexiang Ma², Guang Chen³, Wang Wan³, Zhiyang Li³, Youjun Xu⁴, Dongju Zhang⁵, Shi-Liang Shi⁶

Affiliations

¹ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China; School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
² Key Lab of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China.
³ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China.
⁴ School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, Shenyang 110016, China.
⁵ Key Lab of Colloid and Interface Chemistry, Ministry of Education, Institute of Theoretical Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China. Electronic address: zhangdj@sdu.edu.cn.
⁶ State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200032, China. Electronic address: shiliangshi@sioc.ac.cn.

PMID: 39755465
DOI: 10.1016/j.scib.2024.12.023

Abstract

Divergent synthesis of valuable molecules through common starting materials and metal catalysis represents a longstanding challenge and a significant research goal. We here describe chemodivergent, highly enantio- and regioselective nickel-catalyzed reductive and dehydrogenative coupling reactions of alkynes, aldehydes, and silanes. A single chiral Ni-based catalyst is leveraged to directly prepare three distinct enantioenriched products (silyl-protected trisubstituted chiral allylic alcohols, oxasilacyclopentenes, and silicon-stereogenic oxasilacyclopentenes) in a single chemical operation. The use of a bulky C₂-symmetric N-heterocyclic carbene (NHC) ligand for nickel catalyst is the key to enable simultaneous exceptional control of stereo- and regioselectivity (up to 99% enantiomeric excess (ee), >99:1 regiomeric ratio (rr), >99:1 E/Z) and high efficiency (up to 99% yield). Computational studies elucidate the origin of chemodivergency and reveal the critical role of NHC in the enantioselectivity- and rate-determining oxidative cyclization step via an η²-aldehyde η²-alkyne Ni five-centered transition state. We expected that the enantioselective η²-activation mode be widely applicable in other Ni-catalyzed carbonyl couplings.

Keywords: Asymmetric catalysis; Carbonyl addition; Divergent synthesis; Multicomponent reaction; Nickel catalysis; Reductive coupling.