Synthesis of fluorinated pyrrolizidine, indolizidine and quinolizidine derivatives

Abstract

This review provides literature data dealing with the synthesis of fluorinated pyrrolizidines, indolizidines, and quinolizidines. Synthesis of trifluoromethylated derivatives requires to use of commercially available building blocks bearing pre-installed trifluoromethyl group or synthetic trifluoromethylated templates incorporating a chiral auxiliary as starting materials. On the other hand, nucleophilic or radical difluoromethylation followed by cyclization reactions using different types of stable and readily available difluoromethylating agents was established as an efficient approach for the synthesis of difluoromethylenated pyrrolizidines, indolizidines, and quinolizidines. Furthermore, a new possibility to synthesize monofluorinated quinolizidines opens the reaction of α-trifluoromethyl alkenes and dihydroisoquinoline acetic acids using visible light photocatalysis. Generality and limitations of these methods are discussed