Studies On Asymmetric Cyanation Of Aldehydes Catalyzed By Self-Assembled Catalyst Based On BINOL

Cyanohydrin is versatile intermediate in the context of organic chemistry, especially, in asymmetric synthesis. The addition of cyanide to carbonyl compounds is the most direct, efficient and popular strategy. In this dissertation, the efforts were focused on asymmetric cyanation of aldehydes using EtOCOCN as cyanid sourc to afford a series of useful and creative results.Three self-assembled catalyst systems were designed and successfully applied to the cyanation of aldehydes using EtOCOCN as cyanide source. Impact factors on the enantioselectivity and reactivity of this reaction were systematically studied. At the same time, excellent results were obtained.Amongst of the self-assembled multicomponet titanium catalyst, which is consisted of (S)-6,6'-dibromo-1,1'-bi-2-naphthol, cinchonine, (1R,2S)-(-)-N-methyl -ephedrine and tetra-isopropyl titanate, ratio of each component, solvent, temperature, concentration of substrates, loading of catalyst and others were investigated systematically. Under the optimized conditions, most of the aromatic,α,β-unsaturated, aliphatic and steric hindrance aldehydes could be converted into the corresponding cyanohydrin carbonates with 45-94% ee in the presence of 10 mol% the self-assembled catalyst.Triggered by Shibasaki`s method, the heterometallic (S)-aluminum lithium bis(binaphthoxide) was prepared using Al(OiPr)₃, n-BuLi and BINOL, bearing high stability and reactivity. Under the optimized conditions, most of the aromatic,α,β-unsaturated, aliphatic and steric hindrance aldehydes could be converted into the corresponding cyanohydrin carbonates with 74-95% ee in the presence of 10 mol% the self-assembled catalyst. Especially, the aliphatic aldehydes afforded excellent results.Compared with the first self-assembled catalyst system, the bifunctional self-assembled system has following features: lower amount of catalyst loading, more effective for aliphatic aldehydes, the milder reaction conditions and provide a different enantiomer of the cyanohydrin ethyl carbonates with 62-92% ee.According to the experiment results, possible catalytic cycle were proposed to illustrate the experimental observations for the cyano-ethoxycarbonylation of aldehydes. All of these results offer some important reference to asymmetric cyanation of carbonyl compounds investigated in the future.