Studies Directed Toward the Synthesis of Amphibian Alkaloids via Iridium Catalyzed N-Heterocyclization Reactions

The main focus of the research was on the selective conversion of terminal dienes to primary diols. This conversion has always had problems with regioselectivity and low yields due to polymer formation with carbon chains having more than seven carbon atoms. An improvement in the yield and regioselectivity was observed with disiamylborane prepared in situ using 2-methyl- 2-butene and BH3•DMS. The scope of this method with seven, eight and nine carbon chains and different alcohol protecting groups for synthesis of various triols is presented.;With a variety of diol and triol deivatives in hand the study focused on the synthesis of pyrrolidine and piperidine ring systems that are present in a variety of different classes of amphibian alkaloids. We have found the iridium catalyzed Nheterocylization reaction of diols with amines to be very useful for the construction of novel pyrrolidine, piperidine and piperazine derivatives. The scope and utility of the iridium catalyzed N-heterocyclization reaction for the construction of novel anuran scaffolds using amino diols and triols are presented. Studies directed towards the total synthesis of 4,6-disubstituted quinolizidine and (+/-)-epiquinamide are also discussed.