Photocatalytic Ring-Opening Sulfinylation of Strained Cycloalkanols with Sulfinates

Abstract

Sulfoxides are structural motifs widely found in natural products and bioactive molecules, while also serving as linchpins for organosulfur compound preparation and as ligands or directing groups for transition-metal-catalyzed transformations. This makes their synthesis a long-standing focus of research. Over the past five years, sulfinylation using readily available sulfinates has proven to be a promising strategy for introducing sulfinyl groups into molecules. In this context, alkyl alcohols have been commonly employed as nucleophiles to react with sulfinates and acylating reagents, enabling the synthesis of sulfinate esters and their chiral variants. However, the potential of alkyl alcohols to act directly as radical precursors in sulfinylation remains unexplored. Herein, we report the first photocatalytic ring-opening sulfinylation of strained cycloalkanols, offering a direct route to sulfoxides with a remote carbonyl group that were traditionally accessed via sequential thioether synthesis and mono-oxidation. In this protocol, with an appropriate acylating reagent, both aryl and alkyl sulfinates are competent substrates. Mechanistically, organic photocatalysis promotes the generation of alkoxy radicals from cyclopropanols and cyclobutanols. The high ring strain of these alkoxy radicals drives a fast β-scission process, furnishing transient alkyl radicals. Subsequent radical substitution with in situ generated sulfinyl sulfones (from sulfinates and acylating reagent) delivers γ- and δ-keto sulfoxides. This one-pot method is characterized by mild reaction conditions, readily available sulfinyl sources and good chemoselectivity. The carbonyl and sulfinyl moieties in the products proved amenable to further derivatization, as shown by a series of well-established transformations.

Keywords

Sulfinylation / Sulfoxides / Cycloalkanols / Sulfinates / Sulfinyl sulfones / Sulfinyl radicals / Photocatalysis / Alkoxy radicals

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