Synthesis Of New Chiral Squaric Bornylamino Alcohols And Their Application In Asymmetric Catalytic Reductions

Asymmetric synthesis is a hot field in modern organic synthesis. Development of high effective and enantionselective synthesis is a highlight in modern synthetic chemistry. Asymmetric reduction of prochiral ketones using oxazaborolidines has become one of the standard tools for the synthetic chemist, allowing access to enantiomerically enriched secondary alcohols with excellent enantiomeric excess that may seve as the chiral ligands for enantionselectivity synthesis and highly useful intermediates in the synthesis of bioactive compounds,nature products and medication. In this paper, we exploited and inosculated two kinds of derivatives from squaric and camphor and firstly synthesized a series of new chiral squaric bornylamino alcohols derived from (R)-(+)-camphor and squaric acid and subsequent utilized them in the catalytic asymmetric reduction of prochiral ketones. Three series of chiral ligands, including eleven squaric bornylamino alcohols derived from camphor which containing alkoxy and amino groups have been designed and synthesized. The structures of these ligands possess the characteristics of charity, adjusting, rigidity. All the ligands are new compounds and their structures were conformed by elemental and spectral analyses. We in-deeper studied their catalytic capability as chiral ligands for the catalytic asymmetric reduction of prochiral ketones. We found these ligands in the asymmetric reduction of ω-bromoacetophenone were obtained middle to high enantioselective, especially the 3-n-butoxy-4-{(1R,2R,3S,4S)-2-hydroxy-1,7,7-tr imethylbicyclo[2.2.1]heptan-3ylamino}cyclobut-3-ene-1,2-dione gave the secondary alcohol products with e.e. of up to 99%. In the asymmetric reduction, the cis-endo-endo amino alcohol ligands generally gave higher e.e. than the cis-exo-exo amino alcohol ligands. To cis-endo-endo amino alcohol ligands, the ligands with alkoxy groups on the C-3 position showed higher enantioselectivity than the ligands with amino groups on the C-3 position. We used the cis-endo-endo amino alcohols and the cis-exo-exo amino alcohols derived oxazaborolidines as catalysts, the two products with opposite configuration were conveniently obtained. We supposed the possible mechanism for this catalytic reduction, the hetero atoms on the C-3 position might act as Lewis base in the asymmetric process and leaded them to possess the property of bifunctional catalysts.