Rapid and Scalable Halosulfonylation of Strain-Release Reagents

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2022 Oct 13

PMID 36226350

Authors

Helena D Pickford

Vasyl Ripenko

Ryan E McNamee

Serhii Holovchuk

Amber L Thompson

Russell C Smith

Pavel K Mykhailiuk

Edward A Anderson

Affiliations

Soon will be listed here.

Abstract

Sulfonylated aromatics are commonplace motifs in drugs and agrochemicals. However, methods for the direct synthesis of sulfonylated non-classical arene bioisosteres, which could improve the physicochemical properties of drug and agrochemical candidates, are limited. Here we report a solution to this challenge: a one-pot halosulfonylation of [1.1.1]propellane, [3.1.1]propellane and bicyclo[1.1.0]butanes that proceeds under practical, scalable and mild conditions. The sulfonyl halides used in this chemistry feature aryl, heteroaryl and alkyl substituents, and are conveniently generated in situ from readily available sulfinate salts and halogen atom sources. This methodology enables the synthesis of an array of pharmaceutically and agrochemically relevant halogen/sulfonyl-substituted bioisosteres and cyclobutanes, on up to multidecagram scale.

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