Organocatalytic Strategies Towards Chiral Fluorinated Molecules as Precursors of Bioactive Compounds

Abstract

Fluorination has significant and fairly predictable influence on properties of compounds and is therefore more and more often used as a tool in the design of bioactive compounds and drug candidates. However, access to chiral, fluorinated molecules is very limited. This thesis presents our contribution towards organocatalytic, enantioselective synthesis of fluorinated compounds equipped with functional groups rendering them possibly bioactive or convenient precursors of such molecules. Prochiral, fluorine-containing substrates such as nitro-benzyls, nitroacetates, 1,3 dicarbonyls and ketophosphonates were developed as donors for organocatalytic, enantioselective C-C bond forming reactions, under simple and practical conditions. Synthetic utility of thus synthesised molecules was demonstrated by performing basic functional group transformations on representative products, leading efficiently to potentially valuable chiral, fluorinated compounds such as fluorinated amines, pyrimidine, alpha-fluoro-alpha-amino and alpha-fluoro-beta-amino esters, fluorophosphonate analogue of endothelin-A receptor antagonist, beta-lactam, beta-lactone and others.