Insights into Organoamine-Catalyzed Asymmetric Synthesis of Axially Chiral Allenoates Using Morita–Baylis–Hillman Carbonates and Trisubstituted Allenoates: Mechanism and Origin of Stereoselectivity

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.

Highlighting the Rich Chemistry of the Allenone Moiety

“…Initial deprotonation of 2 and S N reaction with α‐bromoketones 599 lead to allenyl diketones 600 , which in situ undergo TBAF‐assisted hydration to yield the experimentally observed tricarbonyl compounds 601 (Scheme 102a) [255] . Treatment of allenones 2 with MgBr 2 in the presence of the electrophilic tosylimino acetates 602 results in a formal aza‐Morita‐Bailys‐Hillman reaction affording mixtures of two adducts 603 and 604 (Scheme 102b) [256,257] . The formation of allenone‐decorated aminoesters 603 can be explained from the attack of C2 carbon atom in intermediate 605 through path a , while compounds 604 are probably obtained through the attack of the terminal carbon atom following path b from the same reaction intermediate (Scheme 102b) [256,257] …”

Unraveling origin of chemoselectivity and regioselectivity of iridium‐catalyzed B(4)–H functionalization of o‐carborane by alkyne

“…Because of the reliability of DFT on the mechanistic studies of organocatalytic reactions, [31][32][33][34] transition metal-catalyzed reactions [35][36][37][38][39] and enzyme-catalyzed reactions, [40] all the calculations were performed with the Gaussian 09 program by using DFT. The geometries of all stationary points were optimized by using the B3LYP [41] density functional and the 6-31G(d, p) [29,42] basis set (denoted as Level 1).…”

A DFT study on the mechanism and regioselectivity of NHC-catalyzed double acylation of aromatic 1,2-diketones with α,β-unsaturated ketones

“…We believe that this work can systematically solve the above questions based on our previous research experience. [33][34][35][36][37][38][39][40][41][42][43][44] Due to the reliability of density functional theory (DFT) 45 in the study of the mechanism of organocatalytic and transition metal catalytic reactions, M06-2X 46 in conjunction with the standard 6-31G(d,p) basis set was employed for all geometry optimizations. The solvent effect was considered using the implicit SMD model, and N,N-dimethylformamide 47 was the reaction solvent used in calculations.…”