Rh-Catalyzed Synthesis of Benzoxapinones and Benzothiapinones

Significance

Reported is the Rh-catalyzed synthesis of medium-ring heterocycles 2 and 4 via an intramolecular olefin hydroacylation of salicylaldehyde derivatives 1 and 3. Using (R,R)-Me-DuPHOS as the ligand leads preferentially to the 7-membered α-substituted products (>15:1 selectivity). However, 8-membered thioether 5 may be formed selectively in 91% yield using (S,S)-BDDP as ligand. The reaction tolerates electron-rich and electron-deficient substrates with equal efficiency, with excellent yields and enantioselectivities obtained in all cases. The authors also report mechanistic and deuterium-labeling studies, which confirm that heteroatom (O, S) coordination is crucial for the reaction to proceed (no product was observed when S was replaced by CH₂), and that, in contrast to a previous report, reductive elimination is unlikely to be turnover-limiting (see: M. Brookhart and co-workers J. Am. Chem. Soc. 2007, 129, 2082).