Stereoselective Allylic Alkylation of 1-Pyrroline-5-carboxylic Esters via a Pd/Cu Dual Catalysis

• DOI: 10.1021/acs.orglett.8b02902
• Publication Date: 2018-10-10T14:12:59Z
• Authors: Penglin Liu; Xiaohong Huo; Bowen Li; Rui He; Jiacheng Zhang; Tianhong Wang; Fang Xie; Wanbin Zhang
• Keywords: 01 natural sciences; 0104 chemical sciences

The asymmetric allylation of 1-pyrroline-5-carboxylic esters has been accomplished through a synergistic Pd/Cu catalyst system under mild reaction conditions. The mechanistic studies suggested that (1) nucleophilic attack is the enantiodiscriminating step; (2) the cooperative action of two chiral reactive species, N-metalated azomethine ylides and π-allylpalladium, is most likely responsible for its high reactivity and excellent enantioselectivity (up to >99% ee); and (3) the steric hindrance and electronic factors of the allylic electrophiles and imino ester substrates are crucial for the formation of the linear products. A series of 3,4-2 H-pyrrole derivatives bearing a quaternary stereogenic center were easily synthesized in high yields and with high to excellent regioselectivity and enantioselectivity.