From alpha to beta: a two-step strategy for stereoinversion of C16 glucocorticoids.

C16-Methylcorticoids are important anti-inflammatory agents whose activity depends on the C16 methyl configuration. However, access to C16β analogues remains challenging. Herein, we report the first concise two-step stereoinversion of C16α-methylcorticoids to C16β diastereomers through C17 hydroxyl elimination followed by Mn-catalyzed Mukaiyama hydration. Betamethasone, beclomethasone, clobetasol, clobetamethasone, and difluorolaxone were obtained in useful yields with high diastereoselectivities (19 : 1 to >99 : 1 dr).