New Copper-Catalyzed Reactions of Organoboron and Organosilicon Compounds

Thesis (Ph.D.)--University of Washington, 2013Copper-catalyzed transformations such as allylic substitution, conjugate addition, and electrophilic amination have proven to be indispensable tools for the formation of carbon-carbon and carbon-heteroatom bonds. Nevertheless, the use of highly reactive organometallic reagents limits functional group compatibility of these reactions and can contribute to poor selectivity in certain cases. Presented herein are four reactions that address the above mentioned limitations by catalytically accessing aryl, alkenyl, and alkyl copper intermediates from mild transmetalation partners. Specifically, the use of organoborane and silane transmetalation partners in copper-catalyzed reactions resulted in high levels of chemoselectivity, stereoselectivity, and regioselectivity thus providing products that are unattainable with the traditional approaches. Chapter 1 will describe the use of arylboronic esters as transmetalation partners in a copper catalyzed allylic substitution reaction. The comparatively low reactivity of the arylboronic esters allowed the preferential formation of monoaryl copper intermediates while avoiding the formation of diaryl cuprates. As a result, high SN2′ selectivity was observed in the allylic arylation, alkenylation, and alkylation reactions. Finally, the development of an enantioselective variant giving up to 70% ee will be described. Detailed in chapter 2 is a formal hydroamination of alkenes using copper catalysis. Complete anti-Markovnikov selectivity for the alkene substrates is achieved in one-pot by hydroboration followed by copper-catalyzed electrophilic amination. This methodology was applied to the synthesis of trialkyl amines in the presence of a variety of functional groups, and was used to alkylate heterocycles. Furthermore, while investigating the reaction mechanism, Unambiguous evidence of a stable alkyl copper intermediate was provided with the first X-ray crystal structure of such a species. An extension of the hydroamination methodology will then be described in chapter 3. Copper-catalyzed coupling of arylboronic esters with electrophilic O-benzoyl hydroxylamines provided access to 32 different N,N-disubstituted anilines and heteroaromatic amines. The products obtained in these reactions have unprecedented levels of steric hindrance, but are nevertheless synthesized under mild conditions and in high yield. Finally, in chapter 4, I will outline a new approach to catalytic hydrofunctionalization that was used to develop a selective semireduction of alkynes. Simply using a silane and an alcohol, both terminal and internal alkynes were reduced to the alkene with surprising chemoselectivity and complete stereoselectivity. Moreover, as little as 0.5 mol % of a copper catalyst can be used and no over-reduction was observed