Enantioselective Synthesis of Unnatural Carbamate-Protected α-Alkyl Amino Esters via N–H Bond Insertion Reactions
You Li, Yu‐Xuan Su, Yutao Zhao, Lu Liu, Mao‐Lin Li, Shou‐Fei Zhu
Abstract
We have developed a method for highly enantioselective N–H bond insertion reactions of α-alkyl-α-diazoacetates and various carbamates cooperatively catalyzed by TpCu, where Tp = (hydrotris(4,5-bromopyrazolyl)borate), and a chiral spiro phosphoric acid. These reactions provide straightforward access to unnatural optically active N-carbonate α-alkyl-α-amino esters, which are widely used in artificial peptide synthesis. This mild method uses readily available starting materials and features a broad substrate scope, good functional group tolerance, good to high yields (58–88%), and high enantioselectivities (90–96% ee). The combination of the neutral copper catalyst TpCu and the chiral spiro phosphoric acid ensures the success of the reaction by inhibiting a β-H migration reaction of a copper carbene intermediate and by promoting enantioselective proton transfer to an enolate intermediate.