Insights into Organoamine-Catalyzed Asymmetric Synthesis of Axially Chiral Allenoates Using Morita–Baylis–Hillman Carbonates and Trisubstituted Allenoates: Mechanism and Origin of Stereoselectivity
Jiaming Zhang, Jing Luo, Xue Li, Qiaoyu Zhang, Zhou-Jie Wu, Yu Lan, Donghui Wei
Abstract
A computational study was performed to explore the possible mechanisms of β-isocinchonine-catalyzed asymmetric C(sp2)-H allylation of trisubstituted allenoates using Morita–Baylis–Hillman (MBH) carbonates for synthesis of axially chiral tetrasubstituted allenoates. The calculated results indicate that the most energetically favorable pathway includes (1) nucleophilic attack on MBH carbonate by β-isocinchonine, (2) BocO– dissociation, (3) stereoselective formation of the C–C bond, and (4) regeneration of the catalyst. By tracking the orbital overlap/interaction changes, the half shoulder-to-head orbital overlap mode can be smoothly switched to a head-to-head orbital overlap mode for the key C–C σ bond formation, which is also identified as the stereoselectivity-determining process. Further distortion/interaction, noncovalent interaction (NCI), and atom-in-molecule (AIM) analyses demonstrate that C–H···O and C–H···π interactions should be key for controlling the axial and central chirality. This work would be useful for rational design of organocatalytic allylic alkylation reactions for synthesis of axially chiral compounds in the future.