Oxazolones are structural subunits in numerous natural products and designed molecules with substantial pharmacological properties.Here,a palladium-catalyzed chemodivergent regio-and enantioselective allylic alkylatio...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.展开更多
基金financial supports from the National Key R&D Program of China(grant nos.2022YFA1503702 and 2021YFF0701602)NSFC(grant nos.22231011 and 22271303).
文摘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.
