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Rapid and Scalable Halosulfonylation of Strain-Release Reagents.

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.

SUBMITTER: Pickford HD

PROVIDER: S-EPMC10100009 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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Rapid and Scalable Halosulfonylation of Strain-Release Reagents.

Pickford Helena D HD Ripenko Vasyl V McNamee Ryan E RE Holovchuk Serhii S Thompson Amber L AL Smith Russell C RC Mykhailiuk Pavel K PK Anderson Edward A EA

Angewandte Chemie (International ed. in English) 20221110 3

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 ...[more]

PMID: 36226350

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