Stereoselective Additions to Cyclopropenes

Abstract

This thesis concerns strain-release driven stereoselective addition reactions to cyclopropenes leading to the synthesis of medium-sized 8-membered 1,5-dioxocane ring structures, optically active cyclopropylboronates, and densely functionalized cyclopropane scaffolds via the addition of highly reactive carbon nucleophiles. This thesis is separated into three chapters detailing the background, development, optimization, scope, and limitations of each developed methodology. Chapter one describes a strain-release driven nucleophilic (4+4) cyclodimerization of cyclopropenes providing a fused three ring system possessing a medium-sized eight member ring core. The process is believed to proceed via a face-selective nucleophilic attack of an alkoxide on the strained double bond of cyclopropene followed by highly diastereoselective nucleophilic ring closure. Additionally, a newly developed expedited and cost saving method of accessing prochiral cyclopropenes possessing an unsubstituted double bond via Rh(II)-catalyzed [2+1] cycloaddition is detailed. Chapter two describes the directed rhodium(I)-catalyzed asymmetric hydroboration of cyclopropenes bearing ester and amide functions as directing groups. Hydroboration of esters provided variable results sensitive to the identity of the substituent on the opposing face of cyclopropene. The utilization of a much more Lewis basic amide function as a highly efficient directing group along with the development of a new class of prochiral cyclopropenyl amides is detailed. Chapter three describes the directed copper(I)-catalyzed ring retentive addition of Grignard reagents across the stained double bond of cyclopropenes. The high degree of conformational and configurational stability of the intermediate cyclopropyl Grignard reagent allowed for highly diastereoselective trapping with a variety of electrophiles, providing the possibility of constructing two carbon-carbon bonds and up to four contiguous stereocenters in a single chemical step.