Chemistry and Physics Faculty Articles

Title

An Asymmetric SN2 Dynamic Kinetic Resolution

Document Type

Article

Publication Date

5-4-2021

Publication Title

Journal of the American Chemical Society

Keywords

adducts, substitution reactions, indoles, oxidation, molecular structure

ISSN

1520-5126

Volume

143

Issue/No.

19

First Page

7509

Last Page

7520

Abstract

The SN2 reaction exhibits the classic Walden inversion, indicative of the stereospecific backside attack of the nucleophile on the stereogenic center. Observation of the inversion of the stereocenter provides evidence for an SN2-type displacement. However, this maxim is contingent on substitution proceeding on a discrete stereocenter. Here we report an SN2 reaction that leads to enantioenrichment of product despite starting from a racemic mixture of starting material. The enantioconvergent reaction proceeds through a dynamic Walden cycle, involving an equilibrating mixture of enantiomers, initiated by a chiral aminocatalyst and terminated by a stereoselective SN2 reaction at a tertiary carbon to provide a quaternary carbon stereocenter. A combination of computational, kinetic, and empirical studies elucidates the multifaceted role of the chiral organocatalyst to provide a model example of the Curtin–Hammett principle. These examples challenge the notion of enantioenriched products exclusively arising from predefined stereocenters when operating through an SN2 mechanism. Based on these principles, examples are included to highlight the generality of the mechanism. We anticipate the asymmetric SN2 dynamic kinetic resolution to be used for a variety of future reactions.

ORCID ID

0000-0002-0566-0820

ResearcherID

V-6501-2018

DOI

10.1021/jacs.1c02193

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