Barabash A. Сonsecutive methylenations of carbonyl compounds and oxacycles with dimethylsulfoxonium methylide.

The work extends the dimethylsulfoxonium methylide (DMSM) synthetic potential as a methylene transfer reagent. Methylenation of various sterically congested ketones with DMSM (Corey reaction) was studied experimentally and computationally at the DFT and ab initio levels of theory utilizing the PCM model. The limiting step involves a transformation of intermediate cis-betaine to its trans-conformer. The latter transformation is hampered for highly sterically congested ketones that are inert under the Corey reaction conditions. The excess of base and temperature increase open an alternative reaction channel that leads to corresponding cyclopropyl ketones instead (alpha-dimethylenation). The suggested initial reaction step involves an attack of the reagent onto the ketone enolate followed by the intramolecular cyclization into cyclopropanolate anion. This reaction parallels the well-established C-methylenations of electron-enriched aromatics with DMSM. In the presence of oxygen under high temperatures the reaction selectively gives alpha-hydroxy acetic acids as a result of aerobic oxidation with formal shift of the carbonyl group. New and general method for the regio- and stereospecific preparation of oxolanes through the methylenation of respective oxetanes with DMSM was developed. Computations suggest that further ring expansions of oxolanes to the six-membered oxanes are hampered kinetically.