Organocatalytic Asymmetric Michael Addition Of α-Alkyl-β-Keto Esters, 2(5H)-furanone To Enones

Of those common methods for construction of valuable compounds in modern organic synthesis, the Michael addition has been the most fascinating and powerful one. In this paper, new approachs for the Michael additions of a-alkyl-p-keto esters,2(5H)-furanone to enone have been developed.An efficient approach for the enantioselective Michael additions ofα-alkyl-β-keto esters toβ-substituted a,β-unsaturated ketones have been developed, using natural cinchona alkaloid as multifunctional catalyst. The catalyst consists of primary amine, secondary amine and thiourea. The reaction activating by the catalyst is carried out in high reactivity and efficiency. The effects of chiral catalyst, temperature, solvent, concentration of the reaction on the Michael addition were investigated. Under the optimized conditions, we next explored the scope of the asymmetric Michael addition ofα-alkyl-β-keto esters toβ-substituted a,β-unsaturated ketones and obtained in good to excellent yields (up to 75-98%) and high diastereoselectivities (up to>99:1) with excellent ee values (up to 96% ee). The chairl compounds of an all-carbon chiral center and a simultaneous construction of a vicinal chiral tertiary carbon center could easily be transformed into synthetically useful hexahydrophenanthrene structure under mild conditions in good yield.Based on primary-thiourea catalyst, an organocatalytic tandem Michael-Michael reaction has been developed for the first time. The tandem Michael-Michael reaction has been developed to easily prepare stereo complex, multicyclic compounds from simple reactants in satisfactory yields (up to 90%) and almost complete diastereoselectives (>30:1 dr). This approach also realized the first conjugate addition of a,β-unsaturated ester under mild conditions with simple organic catalysis.