The Asymmetric Borane Reduction Of Prochiral Imines Catalyzed By Chelated Chiral Borate Esters

Optically active compounds, which possess important significance for the development of life science, material science, information science etc. can merely be acquired by chiral technologies. Asymmetric catalytic synthesis is one of the most attractive chiral technologies.In the early 2002, asymmetric catalytic activity of chelated chiral borate esters, which possess three B-0 bonds and one B←N coordination bond, toward borane reduction of prochiral ketones was first observed by our research group. In the presence of 0.1 equivalent of a chelated chiral borate ester, prochiral ketones were reduced by 0.6 equivalent of borane in THF for 2 h to give chiral secondary alcohols of up to 92% e.e.. Because chelated chiral borate esters generally have high stability to pyrolysis and racemization, and strong resistance to oxidation, hydrolysis and acidolysis as well as simple procedure and lower cost for the preparation, deep investigation on this class of chiral catalysts has important significance for the development and the utilization of the chiral catalysts, which do not contain noble metal and the enrichment of asymmetric synthetic chemistry.The aim of the present thesis is to widen the range of the application of chelated chiral borate esters with a O3BN framework to asymmetric synthesis, to examine asymmetric catalytic activity of them toward borane reduction of prochiral imines and to explore possibility of the application of this class of chiral catalysts to asymmetric synthesis of optically active amines.The thesis is divided into three chapters.In the chapter one, advance in the preparation of optically active amines via the reduction of prochiral imines was reviewed.In the chapter two, application of tetracoordinated chiral boron compounds non-containing B-H bond to catalytic asymmetric synthesis was specially introduced.In the chapter three, study on asymmetric catalysis of chelated chiral borate esters with a O₃BN framework to asymmetric borane reduction of prochiral iminesperformed by author was described. Synthesis of nine chelated chiral borate esters with a O3BN framework and seven prochiral imines as well as some improved preparation for the known compounds were introduced; the relationship between the catalytic activity of the chelated chiral borate esters and the composition was examined; affect of the amount of the catalyst used and the composition of the substrates on the stereoselectivity of the reduction was investigated and a possible catalytic mechanism of chelated chiral borate ester to the borane reduction of prochiral imines was suggested based on the MB NMR spectra of (R,S)-1 and (S,S)-1 and their mixture with a THF solution of borane. It was found that asymmetric catalytic activity of the chelated chiral borate esters toward the borane reduction of prochiral imines was in close relation to the composition of chelated chiral borate esters, chiral induction ability of chelated chiral borate esters to this reduction was principally determined by the chiral moiety in the chelated cycle; all the borate esters with chiral moiety in the chelated cycle possessed asymmetric catalytic activity toward the reduction; the chiral borate esters non-containing chiral moiety in the chelated cycle hardly showed asymmetric catalytic activity toward the reduction; the chiral borate esters derived from enantiopure l,l'-bi-2-naphthol showed higher chiral introduction ability than those derived from tartarate ester. It is similar to the borane reduction of imines catalyzed by chiral oxazaborolidines, the e.e. values of the products were increased with the increase of the used amount of the chiral borate ester; however, upgrading e.e. value was not obvious under more than 1 equivalent of the catalyst. Under the experimental conditions, the stereo- selectivity of the reduction was considerably influenced by the composition of the prochiral imines. It should be specially pointed out that the chiral borate esters derived from enantiopure l,l'-bi-2-naphthol catalyzed the reduction of the prochiral imines derived from unsymmetric dialkyl ketones to give higher stereoselectivity than those derived from alkylaryl ketones. This is clear difference from the reduction of imines catalyzed by chiral oxazaborolidines. This fact forebodes that it is possible to find highly effective chiral catalyst for the borane reduction of prochiral imines derived from unsymmetric dialkyl ketones via molecular modification of chelated chiral borate esters. It appearsthat chelated chiral borate esters and chiral oxazaborolidines were mutually supplementary in chiral induction to the borane reduction of imines.Under the selected conditions, prochiral imines were reduced by 1.25 equivalent of borane in THF in the presence of equivalent of chelated chiral borate ester at ambient temperature to give chiral secondary amines in high yield and up to 74% e.e..