Chiral Aldehyde/Palladium Catalysis Enables Asymmetric Branched-Selective Ring-Opening Functionalization of Methylenecyclopropanes with Amino Acid Esters
Fang Zhu, Hui He, Wen Wei, H.‐P. GUAN, Zhu‐Lian Wu, Tian Cai, Shao‐Fei Ni, Qi‐Xiang Guo
Abstract
Achieving catalytic asymmetric functionalization of methylenecyclopropanes (MCPs) by selective C–C bond cleavage is a notable challenge due to the intricate reaction partners involved. In this work, we report that chiral aldehyde/palladium combined catalysis enables the asymmetric functionalization of MCPs with NH 2 -unprotected amino acid esters. This reaction proceeds through a regiospecific branched ring-opening mechanism, resulting in optically active α,α-disubstituted α-amino acid esters bearing nonconjugated terminal alkene units. Mechanism studies indicate that the ring-opening pathways are irreversible and the ultimate regioselectivity is governed by palladium catalysis. The products can be utilized in the construction of chiral dihydropyrazoles, α-methyl aspartic acid derivatives, and analogues of VPC01091 and BMS-986104.