Development of Enantioselective Lithium-Isothiourea-Boronate–Catalyzed Matteson Homologations

Abstract

Our group’s discovery of lithium-isothiourea-boronate–catalyzed Matteson homologations is chronicled. Chiral thiourea dual–hydrogen bond donors were initially found to promote enantioselective dichloromethyl boronate rearrangements, albeit with poor reproducibility. Systematic investigations of the fate of the thiourea led to the discovery that lithium-isothiourea-boronate derivatives were being generated in situ as highly enantioselective catalytically active species. The optimal lithium-isothiourea-boronate catalyst displays significant generality in the rearrangement of primary alkyl migrating groups, affording synthetically valuable α-chloro boronic ester products with consistently high enantioselectivities. The catalyst is proposed to act as a structurally rigid chiral framework that precisely positions two lithium cations to enable a dual-lithium–mediated chloride abstraction.

1 Introduction

2 Reaction Development

3 Discovery of Isothiourea-Boronate Catalysts

4 Synthetic Application

5 Mechanistic and Computational Studies

6 Conclusions and Outlook

Key words

boronic ester - boronate rearrangement - anion abstraction - lithium-isothiourea-boronate - Lewis acid catalysis

Publication History

Received: 29 April 2023

Accepted after revision: 24 May 2023

Accepted Manuscript online:
24 May 2023

Article published online:
02 August 2023

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