open access

https://hdl.handle.net/2115/96068

A DFT Mechanistic Study on the Aza-Aldol Reaction of Boron Aza-Enolates : Relative Stability of Six-Membered Transition State and Its Relevance to the Coordination Mode of the Leaving Group

英語

2024-09-18

American Chemical Society

Journal of organic chemistry

89(19)

13913-13922

The mechanism of the aza-aldol reaction between boron aza-enolate and benzaldehyde is investigated by using density functional theory calculations. The result shows that the syn-E isomer is preferentially formed, consistent with experimental observations. The six-membered ring transition state (TS) with the boat form leads to the E isomer, while the more unstable chair TS does to the Z isomer. The preference of the syn isomer is determined by the interactions between the substituents of aza-enolate and benzaldehyde. Structural distortion and intrinsic reaction coordinate analyses of simplified model systems provide insights into the origin of the relative stability of the rate-determining TS with boat and chair forms. The boat TS is an early TS; thus, minimal structural distortions of the reactant are required to reach this TS. The Lewis pair interactions between the boron and imine groups during B-N elimination also influenced the relative stability of the TSs. This interaction involves the nitrogen lone pair in the boat TS, while the pi(N=C) orbital is involved in the chair TS. The Lewis pair with the lone pair stabilizes the TS more than that with the pi orbital. The boron aza-enolate with 9-BBN generates an ate complex and forms C-C bonds sequentially, whereas that with Bpin does not generate an ate complex and exhibits the concerted formation of B-O and C-C bonds. Thus, the higher electrophilicity of boron such as 9-BBN enhances the reactivity by facilitating the formation of the ate complex. A reaction design is proposed to reverse the syn/anti selectivity. Proof-of-concept DFT calculations suggested that the modification of the imine group would change the relative stability of the boat/chair TSs and give the anti-product.

学術雑誌論文

Accepted Manuscript

This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of organic chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/articlesonrequest/AOR-DAUXBVF9PYPPFTUEDHPJ.

0022-3263