Chiral Primary Amine Catalyzed Michael Addition For Construction Of Spirocyclic Compounds

Over the last few yeas, organocatalytic enantioselective methodologies for the synthesis of spirooxindoles have attracted much attention. In this thesis, firstly the development of Michael reaction for installation of quaternary carbon center and the cascade reactions for enantioselective synthesis of spirocyclic compounds relative to oxindole backbone in recent years were successively reviewed. Secondly, the systematic Michael/reduction/cyclization sequence of isatylidenemalononitriles with ketones was studied for the construction of enantiomerically enriched spiro[2H-pyran-3,4-indoline] derivatives. Thirdly, the enantioselective conjugate addition reactions of diethyl phosphite to the isatylidenemalononitriles were preliminarily examed, which catalyzed by a primary amine and benzoic acid as a concerted catalyst.1. Based on a cinchona-derived chiral primary amine as catalyst, different chiral and achiral Br(?)nsted acids as additives were screened, hoping that the introduction of a chiral counteranion to the catalytic system would enable the asymmetric reactions of isatylidenemalononitriles with ketones. The catalytic reactions were conducted under the following optimal conditions:ketones (20equiv.), catalyst (10mol%) with L-CSA (20mol%) as the additive in CH2Cl2at room temperature, furnishing multifunctional, optically active Michael adducts in high yields (81-99%) with excellent enantioselectivities (95to99%ee). Subsequently, the Michael adducts were converted into spiro[2H-pyran-3,4-indoline] derivatives in52-93%yields with1.5:1to20:1diastereomeric ratio and90-99%ee by utilizing NaBH4as a cascade reduction/cyclization reagent. 2. Michael reactions between the diethyl phosphite and isatylidenemalononitriles were preliminarily examed to afford a quaternary stereocenters with a phosphorus atom at C3position of oxindoles. We find that the solvent has no great influence on the yield of the reaction. With the optimized reaction conditions:the Michael addition reaction proceeds smoothly in the presence of9-amino(9-deoxy)epi-quinidine with benzoic acid as cocatalyst, which provide the desired products in99%yield and77%ee in1,2-xylene at room temperature.