Development of Iridium-Catalyzed Allylation Reactions of Ketones and Imines and Nickel-Catalyzed and Titanium-Mediated Cross-Coupling Reactions of N-Chloroamines

Transition metal catalysts have enabled many synthetically useful transformations to be developed under mild reaction conditions. Often the mild reaction conditions are a consequence of transition metals' ability to access reactive intermediates by lowering transition state energies, and in some situations the transition metal is able to reverse the polarity of a functional group. This latter type of reactivity may be referred to as umpolung reactivity. We sought to develop transition metal-catalyzed umpolung reactions to address two types of bond formations: allylation reactions of carbonyls and carbonyl derivatives and the synthesis of anilines.;The allylation reaction of carbonyl and carbonyl derivatives is a synthetically useful transformation that has been studied by many research groups. Two limitations in allylation methodology that we wanted to address were that most allylation methods require the use of stoichiometric amounts of allylmetal reagents and that there is no general catalytic method for intramolecular allylation reactions. We were interested in addressing these limitations by using nucleophilic allylmetal species as catalytic reaction intermediates that could be generated in situ by oxidative addition of an allyl alcohol derivative. Nucleophilic NHC-ligated palladium complexes as catalysts were examined for the intramolecular allylation reaction of aldehydes. The palladium complexes did not promote the desired umpolung allylation reactions using allyl alcohol derivatives with reductants such as silanes and formates. Diene-ligated allyliridium catalysts were examined for the allylation of aldehydes, ketones, and aldimines. The iridium catalyst was found to be effective for the allylation of ketones and aldimines with allylboronic acid pinacol ester. Expansion of this methodology to include an iridium-catalyzed redox allylation reaction was examined.;The formation of aryl-nitrogen bonds has been an active area of research due to the prevalence of anilines in pharmaceuticals, agrochemicals, and other industrial applications. We sought to develop an aniline synthesis using N-chloroamines as electrophiles, reversing the polarity of the nitrogen atom. Diarylzinc reagents were found to be competent nucleophiles for this reaction in the presence of a nickel catalyst. This reaction was found to be amenable to a one-pot reaction in which the N-chloroamine could be formed in situ. A titanium-mediated reaction between aryl Grignard reagents and N-chloroamines formed in situ was later realized that expanded the functional group tolerance and substrate scope of this transformation.