Diastereoselective synthesis of substituted cyclopentanones via [3 + 2] cycloaddition of sulfoxonium ylides with alkenes.

We report a straightforward one-step, highly diastereoselective [3 + 2] cycloaddition for the synthesis of cyclopentanones incorporating up to four stereogenic centres. Sulfoxonium ylides are readily available, safe-to-use reagents and were utilised as three-carbon synthons to introduce alkyl, aryl, and heteroatom substituents at the α-positions of the cyclopentanone. A variety of terminal and internal alkenes serve as two-carbon synthons for installation of alkyl, alkenyl, and (hetero)aryl substituents at the β-positions. Depending on the reactant combination, the cycloaddition is best performed either in hexafluoroisopropanol as the reaction solvent or with ZnCl2 as a Lewis acid in trifluoroethanol. Stereochemical analyses of the reaction products using trans- and cis-1,2-disubstituted alkenes support a stepwise cyclisation mechanism. The cyclopentanone products are versatile intermediates to other valuable compound classes such as diastereomerically pure δ-lactones and cyclopentanols.