New technology for the preparation of chiral compounds in organic chemistry is an area of intense developments, due to the concern that many chiral drugs are consumed as racemic mixtures with the potential toxic effects caused by the other enantiomer. Chiral amines, amino alcohols and amino acids are important organic compounds used as building blocks for the synthesis of many pharmaceutical products, and auxiliaries in a variety of enantioselective organic preparations. The design of new methodologies for the enantioselective synthesis of enantiopure compounds with biological activity will be the main purpose of this project. Through our previous research work, we have developed new procedures for primary phenylalkylamine synthesis with modest to good optical purity via the reduction of N-substituted organometallic imino derivatives using known chiral organoborane reagents. Presently, we envision the application of the developed methodology for the preparation of amines and amino alcohols. Besides, the synthesis of novel chiral aminoborohydrides generated by the alpha-deprotonation of chiral aimine-borane complexes with n-BuLi or LDA for the reduction of imine and/or carbonyl groups, will be proposed. These reagents offer higher reactivity and a better stereochemical control since other competing reducing species are not present. Representative prochiral imines and aromatic ketoimines will be reduced with the proposed chiral agents and their enantioselectivity studied under various reaction conditions. Based on the results of the alpha-alkylation of O-TBS acetophenone oximes, asymmetric induction for the preparation of non-racemic products will be attempted using chiral amides as bases, or chiral catalysts, such as, 1,3,2-oxazaborolidines. The proposed synthetic strategies will be focused on the development of new methods for the preparation of homochiral compounds used as intermediaries or reagents for the synthesis of important pharmacological products.
|Ortiz-Marciales, Margarita; De Jesus, Melvin; Gonzalez, Eduvigis et al. (2004) A 1,3,2-oxazaborolidine dimer derived from (S)-alpha,alpha-diphenylprolinol. Acta Crystallogr C 60:o173-5|
|Ortiz-Marciales, Margarita; Gonzalez, Eduvigis; De Jesus, Melvin et al. (2003) Efficient synthesis of B-alkylated oxazaborolidines derived from ephedrine and norephedrine. Org Lett 5:3447-9|