New nickel compounds for alkylation and fluoroalkylation studies

Abstract

Negishi21 introduced zinc reagents as nucleophiles to couple with electrophiles in the formation of C-C bonds. Negishi cross-coupling reactions allowed higher functional group tolerance than other coupling reactions. Negishi used Pd-catalyzed catalysts, homoallylic and homopropargylic alkylzinc reagents and synthesized 1,5-dienes and 1,5-enynes, which constitute the core structure of terpenoids. Negishi found that primary and secondary alkylzinc reagents were more reactive than corresponding alkylmagnesium reagents for the conditions he used. For a very long time coupling reactions were restricted to alkyl-alkyl couplings and sp2 (alkenyl and aryl derivatives) electrophiles. The classical approaches failed in controlling β-hydrogen eliminations when using alkyl halides and pseudohalides. This meant that only methyl, allyl, and benzyl derivatives couple effectively. The problem of β-hydride elimination in palladium-alkyl intermediates could be stopped when used sterically-strong and highly electron donating trialkyl phosphines.22 In this chapter I will go through the development of nickel catalyzed Negishi cross-coupling reactions, because much of my work is focused on understanding these reactions in detail.