Liu Jia-Ming, Ma Xuexiang, Chen Guang, Wan Wang, Li Zhiyang, Xu Youjun, Zhang Dongju, Shi Shi-Liang
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.
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.
Sci Bull (Beijing). 2025 Mar 15;70(5):674-682. doi: 10.1016/j.scib.2024.12.023. Epub 2024 Dec 21.
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 C-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 η-aldehyde η-alkyne Ni five-centered transition state. We expected that the enantioselective η-activation mode be widely applicable in other Ni-catalyzed carbonyl couplings.
通过常见起始原料和金属催化实现有价值分子的发散合成是一项长期挑战和重要研究目标。我们在此描述了炔烃、醛和硅烷的化学发散、高度对映和区域选择性的镍催化还原和脱氢偶联反应。利用单一手性镍基催化剂，通过单一化学操作直接制备三种不同的对映体富集产物（硅基保护的三取代手性烯丙醇、氧杂硅环戊烯和硅立体中心氧杂硅环戊烯）。使用大位阻的C对称N-杂环卡宾（NHC）配体作为镍催化剂是实现对立体和区域选择性同时进行卓越控制（对映体过量高达99%（ee），区域异构体比例>99:1（rr），E/Z>99:1）和高效率（产率高达99%）的关键。计算研究阐明了化学发散的起源，并揭示了NHC在通过η-醛η-炔镍五中心过渡态的对映选择性和速率决定氧化环化步骤中的关键作用。我们预期对映选择性η-活化模式将广泛应用于其他镍催化的羰基偶联反应中。
