Palladium-Catalyzed Regioselective Asymmetric Chemodivergent Allylation of Oxazolones with Morita-Baylis-Hillman Adducts

Oxazolones are structural subunits in numerous natural products and designed molecules with substantial pharmacological properties. Here, a palladium-catalyzed chemodivergent regio-and enantioselective allylic alkylation of 4-or 5 -substituted oxazol-2(3H)-ones with Morita-Baylis-Hillman (MBH) adducts has been developed using a spiroketal-based diphosphine as the ligand (50 examples). Interestingly, 4-substituted oxazol-2(3H)-ones acted as a C-nucleophiles in the reaction to afford a range of chiral 4,5-substituted oxazol-2(3H)-ones in high yields (72-99%) with good to excellent chemo-, regio-, and enantioselectivities (C/N 95:5->99:1, b/l 91:9->99:1, 85-98% ee). When a N-nucleophile was used under otherwise identical conditions, 5 -substituted oxazol-2(3H)-ones delivered a range of chiral 3,5-substituted oxazol-2(3H)-ones in high yields (68- 98%) with good regio-and enantioselectivities (b/l 71:29-91:9, 66-94% ee). The synthesis can be readily performed on gram scale under fairly low catalyst loadings, and the utility of the protocol was showcased in the facile transformation of the products into more elaborate chiral molecules.