Development of Transition-Metal Catalyzed Carbon-Carbon Bond Forming Reactions

Chapter One discusses our efforts towards a Rhodium-catalyzed [4 + 2 + 2] cycloaddition of diene-allenes with exogenous allenes. Our efforts began with the development of a racemic reaction achieving high yields through the use of Rh-phosphoramidite and Rh-phosphite catalyst systems. Further, we discuss the challenging development of an enantioselective variant and the methods we used to avoid the problematic [4 + 2] side reaction. We demonstrate that in these reactions, a Rh-H8-monophos complex can produce highly enantioenriched cyclooctanoid products in decent yield. The chapter finishes with a discussion of the potential reaction mechanisms and the evidence thereof. Chapter Two describes the initial efforts towards three Pd-catalyzed C-C bond forming reactions of alkyl halides: 1) The improvement of the alkyl-Heck type cyclization of alkyl iodides; 2) The development of the alkyl-Heck type cyclization of primary alkyl bromides; 3) Efforts towards the enantioselective carbonylation of alkyl iodides using both steric selectivity and directing group based selectivity.Doctor of Philosoph

Enantioselective Synthesis of cis-Fused Cyclooctanoids via Rhodium(I)-Catalyzed [4 + 2 + 2] Cycloadditions

Catalytic multicomponent [<i>m</i> + <i>n</i> + <i>o</i>]-type cycloadditions offer efficient, atom-economical routes to diverse complex carbocycles. Recently, such transformations have emerged as unique strategies for medium ring carbocycle synthesis. Despite the important developments in this area, however, highly enantioselective [<i>m</i> + <i>n</i> + <i>o</i>]-type processes accessing medium ring carbocycles have yet to be developed. Herein, a rhodium-catalyzed [4 + 2 + 2] cycloaddition of allenedienes with allenes enabling the direct stereoselective synthesis of cis-fused cyclooctanoids is reported. These cycloadditions are successful with a diverse range of π-components and demonstrate the potential for high levels of enantioselectivity in a [4 + 2 + 2] process

Synthesis of Nitrogen-Substituted Methylenecyclopropanes by Strain-Driven Overman Rearrangement of Cyclopropenylmethyl Trichloroacetimidates

Nitrogen-substituted methylenecyclopropanes have been prepared by a strain-driven Overman rearrangement of cyclopropenylmethyl trichloroacetimidates. The reaction proceeds at room temperature and without the need of a transition-metal catalyst. Furthermore, it has been shown that C-3-substituted cyclopropenylmethyl trichloroacetimidates undergo a hydrolytic ring-opening reaction to form allenylcarbinols

Palladium-Catalyzed Carbocyclizations of Unactivated Alkyl Bromides with Alkenes Involving Auto-tandem Catalysis

The development of a general catalytic system for the palladium-catalyzed carbocyclization of unactivated alkyl bromides with alkenes is described. This approach uses a commercially available bisphosphine ligand and avoids the use of carbon monoxide atmosphere present in prior studies involving alkyl iodides. Detailed mechanistic studies of the transformation are performed, which are consistent with auto-tandem catalysis involving atom-transfer radical cyclization followed by catalytic dehydrohalogenation. These studies also suggest that reactions involving alkyl iodides may proceed through a metal-initiated, rather than metal-catalyzed, radical chain process

Synthesis of nitrogen-substituted methylenecyclopropanes by strain-driven overman rearrangement of cyclopropenylmethyl trichloroacetimidates

Nitrogen-substituted methylenecyclopropanes have been prepared by a strain-driven Overman rearrangement of cyclopropenylmethyl trichloroacetimidates. The reaction proceeds at room temperature and without the need of a transition-metal catalyst. Furthermore, it has been shown that C-3-substituted cyclopropenylmethyl trichloroacetimidates undergo a hydrolytic ring-opening reaction to form allenylcarbinols