Pd/Zn Dual Catalysis for Site-,Enantio-,and Diastereo-Divergent 2-(Alkoxycarbonyl)allylation ofα-Hydroxyketones with Morita–Baylis–Hillman Adducts

A synergistic Pd/Zn dual chiral catalyst system has been developed for the stereodivergent transformation of Morita–Baylis–Hillman(MBH)carbonates and unprotectedα-hydroxyketones to afford the corresponding allylation products(>50 examples).These products bearing vicinal stereocenters were obtained in high yields with excellent regio-/diastereo-/enantioselectivities.On cyclization in an acidic medium,the allylation products could transform to the corresponding acyl-functionalizedβ,γ-disubstitutedα-methylene-γ-butyrolactones(AMGBLs).All four stereoisomers of AMGBL were readily accessed using the same starting materials with full control of the stereochemistry of the contiguous stereogenic centers,simply by switching the chiral ligand combination for the Pd/Zn system.A nucleophilic site-divergent reactivity was observed for the allylation of primary and secondaryα-hydroxyketones,suggesting that distinct enolate intermediates might have prevailed in these reactions.

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.