A sulfoxide reagent for one-pot, three-component syntheses of sulfoxides and sulfinamides Fumito Saito Ludwig Maximilian University Munich, Germany Synthetic methods to access organic S(IV) compounds such as sulfoxides and sulfinamides typically rely on substrates bearing preinstalled sulfur functional groups such as thiols, 1 disulfides, 2 and sulfinates. 3 These protocols, however, suffer from limited structural modularity, as only one of the two substituents can be varied in a critical C–S or N–S bond-forming step. To rapidly prepare a variety of sulfoxides and sulfinamides with different substitution patterns, a three-component coupling to install two substituents onto the central SO unit in a single operation would be an ideal approach. Herein is presented the application of a readily prepared sulfoxide reagent, benzyl 2-pyridyl sulfoxide, 4 for one-pot, three-component syntheses of sulfoxides and sulfinamides via the generation of sulfenate anions (RSO – ) with various Grignard reagents (RMgX). While sulfoxides can be formed by trapping the sulfenate anions with carbon electrophiles such as activated alkyl bromides and hypervalent iodine reagents, all types of sulfinamides – tertiary, secondary, and primary – can also be readily prepared by reactions of the sulfenate anions with electrophilic amine reagents. The syntheses of sulfinamide analogs of known amide- and sulfonamide-containing drug molecules illustrate the utility of the developed method for the preparation of medicinally relevant molecules.
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