Studies On Asymmetric Carbon-Carbon Bond Formation

Organic compounds of life, such as protein, nucleic acids and amylose are all chiral and their structural units almost keep in a mono-configuration (R or S). The catalytic asymmetric synthesis is the one of the methods to obtain the optically pure compunds which requires a stereoselective control in early synthetic steps and is also most atom economy and challengeable to industrializition. In chemical industry, how to deal the byproduct and upgrade the effeciency have attracted great concern. Over the past two decades, the target of organic chemistry has been to develop the catalytic asymmetric methodology and many successful approaches to convert the prochiral substrate to chiral adducts appeared.Currently, investigation of reaction mechanism, especially chiral origin, still keeps budding. This paper aims at the catalytic asymmetric carbon-carbon bond formation in cyanosilylation of of ketones, Henry reaction of nitrocompound and aldehydes, and Michael addition of ketone to nitroolefins.i) An efficient and optically active bifunctional tetraaza ligand (2S)-N-((1R,2R)-2-((S)-pyrrolidine-2-carboxamido)-1,2-diphenylethyl)pyrrolidine-2-carboxamide has been developed for the addition of trimethylsilyl cyanide (TMSCN) to ketones. The bifunctional catalyst system based on a monometallic titanium complex was found to be a highly enantioselective catalyst to provide O-TMS cyanohydrins with up to 94% ee.ii) A new chiral hydrogenated Salen catalyst has been developed for asymmetric Henry reaction in moderate to high yields (up to 96%) with excellent enantioselectivities (up to 96% ee). A variety of aromatic, heteroaromatic, enal and aliphatic aldehydes were found to be suitable substrates in the presence of hydrogenated Salen 1f (10 mol%), (CuOTf)2.C7H8 (5 mol%) and 4 ? molecular sieves. This protocol possesses fine features of air-tolerant and easy manipulation with readily available reagents and has aslo been successfully extended to the synthesis of (S)-norphenylephrine in 67% overall yield, starting from commercially available m-hydroxybenzaldehyde. Based on experimental investigation and MM+ calculation, a possible catalytic cycle including a transition state was proposed to explain the origin of reactivity and asymmetric inductivity.iii) The chiral functionalized salt catalysis, which differs from the known enzyme- and transition metal-based methods, has been successfully developed to carry out Michael addition of ketone to nitroolefins. Chiral anion salt, chiral cation salt, or chiral anion-chiral cation salt could expect to be remarkably effective catalysts and afford corresponding chemically and optically pure Michael addition adducts. Primary amine group activating the ketone during salt catalysis was their obvious and common property. Based on preliminary experimental investigation and previous report on primary amine catalysis, a reaction pathway via imine, enamine, iminium ion to imine was proposed.