Quinim配体的探索及其在镍催化烯烃的不对称胺甲酰基-烷基化反应的应用

Exploration of Quinim Ligand in Ni-Catalyzed Enantioselective Reductive Carbamoyl-Alkylation of Alkene

发展手性配体是不对称催化的核心任务之一.本工作报道了镍催化1,1-二取代烯烃衍生的胺甲酰氯与烷基碘代物的不对称还原胺甲酰基-烷基化反应,构建了一系列对映选择性富集的α,α-双烷基取代的吡咯烷酮化合物.通过对Quinim配体的广泛探索,发现p-tolQuinim至1-NapQuinim配体的革新是该反应成功的关键,能以高收率、高对映选择性及出色的官能团容忍性得到多样的α-位含有季碳中心的γ-内酰胺化合物.此外,研究发现,新发展的Ni/1-NapQuinim催化体系也能提高α-单烷基取代γ-内酰胺的合成效率及对映选择性.

The development of new chiral ligand constitutes the cornerstone of asymmetric catalysis.An asymmetric synthesis ofα,α-dialkylated pyrrolidinones enabled by Ni-catalyzed reductive carbamoyl-alkylation of 1,1-disubstituted alkenetethered carbamoyl chlorides and primary alkyl iodides is presented.After extensive investigation of Quinim ligands,it is found that the evolution of chiral ligand p-tolQuinim to 1-NapQuinim is critical for formation of the all-carbon quaternary center in high yield and enantioselectivity and broad functional group tolerance.The newly developed catalytic system that combines nickel salts and the 1-NapQuinim ligand also improves both the yield and enantioselectivity in the synthesis ofα-monoalkylatedγ-lactams.