Rapid and Scalable Halosulfonylation of Strain‐Release Reagents. (10th November 2022)

• Record Type: Journal Article
• Authors: Pickford, Helena D.; Ripenko, Vasyl; McNamee, Ryan E.; Holovchuk, Serhii; Thompson, Amber L.; Smith, Russell C.; Mykhailiuk, Pavel K.; Anderson, Edward A.
• Is Part Of: Angewandte Chemie. Volume 135:Number 3(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-10
• Subjects: Bicyclic Compounds -- Bioisosteres -- Small-Ring Systems -- Strained Molecules -- Sulfonylation; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.202213508
• Languages: English
• ISSNs: 0044-8249

Abstract

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. Abstract : A one‐pot halosulfonylation of strained hydrocarbons is described that proceeds under practical, scalable and mild conditions. Sulfonyl halides featuring aryl, heteroaryl and alkyl substituents are generated in situ from sulfinate salts and convenient halogen atom sources. This chemistry enables the synthesis of an array of halogen/sulfonyl‐substituted bioisosteres and cyclobutanes, on up to multidecagram scale. Hal=Halogen.