Copper Boryl Heterobimetallic Complexes in the Copper-Catalyzed Hydrofunctionalization of Alkynes and Alkenyl Boronate Esters

Abstract

Transition metal-catalyzed reactions are widely used in organic synthesis due in part to their ability to form carbon-carbon and carbon-heteroatom bonds selectively and efficiently from readily available starting materials. The key to the success of many of these complex transformations is the ability to access highly reactive and versatile organometallic intermediates that can facilitate the formation of these new bonds. Studying and understanding the role of said intermediates in elementary steps can further accelerate the development of important synthetic transformations. Presented herein are two reactions that explore the catalytic generation and further transformation of alkyl 1,1-boryl copper heterobimetallic complexes in the context of the hydrofunctionalization of unsaturated starting materials. Chapter 1 describes the differential dihydrofunctionalization of terminal alkynes towards the synthesis of allylic boronate esters through the reductive three-component coupling of terminal alkynes, alkenyl bromides, and pinacolborane. This transformation is promoted by the cooperative action of a copper/palladium catalyst system and results in the hydrofunctionalization of both π-bonds of an alkyne. The synthesis of allylic boronate esters, using the present method, can be accomplished in the presence of a wide range of functional groups. Finally, the importance of subtle ligand effects on the performance of the palladium co-catalyst was explored by taking advantage of an isolated 1,1-copper boryl heterobimetallic complex. Chapter 2 explores the use of transition metal catalysis to form ylide equivalents from readily available starting materials with the goal of using these intermediates to develop a catalytic Wittig-type olefination of carbonyls and imines. The key Wittig-type intermediate, a 1,1-copper boryl heterobimetallic complex, was obtained by hydrocupration of alkenyl boronate esters. Using imines as coupling partners, this methodology was applied to the synthesis of highly E-selective styrenes and sterically hindered aliphatic alkenes in the presence of a variety of functional groups. Mechanistic investigations revealed the source of the alkene diastereoselectivity as well as the role of the key heterobimetallic complex.