Issue 21, 2023

Computational molecular refinement to enhance enantioselectivity by reinforcing hydrogen bonding interactions in major reaction pathway

Abstract

Computational analyses have revealed that the distortion of a catalyst and the substrates and their interactions are key to determining the stability of the transition state. Hence, two strategies “distortion strategy” and “interaction strategy” can be proposed for improving enantiomeric excess in enantioselective reactions. The “distortion strategy” is used as a conventional approach that destabilizes the TS (transition state) of the minor pathway. On the other hand, the “interaction strategy” focuses on the stabilization of the TS of the major pathway in which an enhancement of the reaction rate is expected. To realize this strategy, we envisioned the TS stabilization of the major reaction pathway by reinforcing hydrogen bonding and adopted the chiral phosphoric acid-catalysed enantioselective Diels–Alder reaction of 2-vinylquinolines with dienylcarbamates. The intended “interaction strategy” led to remarkable improvements in the enantioselectivity and reaction rate.

Graphical abstract: Computational molecular refinement to enhance enantioselectivity by reinforcing hydrogen bonding interactions in major reaction pathway

Supplementary files

Article information

Article type
Edge Article
Submitted
29 Mar 2023
Accepted
29 Apr 2023
First published
02 May 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2023,14, 5712-5721

Computational molecular refinement to enhance enantioselectivity by reinforcing hydrogen bonding interactions in major reaction pathway

T. Nakanishi and M. Terada, Chem. Sci., 2023, 14, 5712 DOI: 10.1039/D3SC01637D

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