Development of palladium-catalyzed methods for the synthesis of substituted pyrrolidines.

This thesis describes the development of two new methods for the synthesis of substituted pyrrolidines. The first method is a palladium-catalyzed carboamination of gamma-amino alkenes with aryl or vinyl halides and accomplishes the formation of both a carbon-carbon and a carbon-nitrogen bond and up to two stereocenters in a single step. The first examples of this reaction involved the coupling of gamma-(N-arylamino) alkenes with aryl bromides and are described herein. The effects of ligand properties and substrate electronics on product structure are discussed in detail, as are the regioselectivity and diastereoselectivity of the reaction. The observed effects of N-substituent and ligand structure on competing beta-hydride elimination and reductive elimination reactions have been applied to a new regioselective synthesis of 5- or 6-substituted octahydrocyclopenta[b]pyrroles from common N-aryl-2-(cyclopent-2-enyl)ethylamine starting materials. In subsequent work, conditions for the carboamination of gamma-( N-arylamino) alkenes with vinyl bromides, aryl chlorides, and aryl iodides have been developed. Additionally, a tandem N-arylation/carboamination reaction is described. This reaction accomplishes the modular synthesis of differentially arylated N-aryl-2-benzyl pyrrolidines in a single step from simple primary gamma-amino alkene precursors. The second method is a palladium-catalyzed insertion of alkenes into aziridines. This method would provide a convergent and atom-economical synthesis of pyrrolidines, while accomplishing the formation of both a carbon-carbon and a carbon-nitrogen bond and up to two stereocenters. The reaction should afford the desired pyrrolidines in a stereospecific fashion, wherein the stereochemistry of the product is determined by the geometry of the starting olefin. Our efforts toward the development of this method are described. This work has resulted in the first synthesis of azapalladacyclobutane complexes bearing an anionic amido group. Additionally, the first example of alkene insertion into an azametallacyclobutane complex is described. This occurs in an intramolecular fashion to provide unusual bridged bicyclic palladacycles in the presence of a catalytic amount of CuI. During our studies of the reactivity of N-sulfonyl aziridines with palladium(0) complexes, we also discovered a new palladium-catalyzed aziridine isomerization reaction, which affords N-sulfonylketimines under mild conditions.Ph.D.Organic chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/126784/2/3276253.pd