Abstract: In this talk, three projects will be discussed that utilize nickel catalysis for C–C bond formation. While the most common coupling reactions employ palladium catalysts, the unique properties and benefits of nickel catalysts enable greater development of this field. Nickel catalysts have multiple attractive features compared to palladium catalysts including low cost, different common oxidation states, ability to activate sluggish electrophiles, and the propensity to do both polar and radical-type oxidative additions. This latter feature is reflected in the three projects described, as both stereospecific and stereoablative processes were found.

First, the synthesis of an arylalkane library will be discussed. This synthesis utilized aryltetrahydropyrans in a stereospecific nickel-catalyzed cross-coupling reaction to form arylalkane products in good yield and high diastereoselectivity. Additionally, the compounds were tested for anti-cancer activity through the NIH Developmental Therapeutics Program (DTP).

Next, the focus will shift on cross-electrophile coupling (XEC) reactions, and the development of an XEC of 1,3-dimesylates for alkylcyclopropane synthesis will be described. This will include reaction optimization, scope development, and the synthesis of enantioenriched cyclopropanes. A key intermediate altered our understanding of the reaction mechanism, and the oxidative addition step was determined to be stereoablative. In a similar vein, the XEC reaction of alkyl mesylates with allylic halides has also been developed. The reaction optimization and initial findings of scope exploration will be presented.