Catalytic Hydroamination Using Aminium Radical Cations

Abstract

Aminium radical cations are classical intermediates that are known to perform rapid anti-Markovnikov selective olefin additions. Despite their desirable reactivity, catalytic methods that utilize this reactive intermediate to accomplish C-N bond formation from simple amine and olefin precursors do not exist. This thesis describes the successful development of a catalytic hydroamination protocol enabled by the use of aminium radical cations.

First, through the use of photoredox catalysis, amine oxidation to an aminum radical cation was achieved allowing for intramolecular C-N bond formation. Subsequent reduction and proton transfer afforded the hydroamination product in a catalytic fashion. A mechanistic investigation supported the proposed sequential electron transfer events as the active hydroamination mechanism with C-N bond formation being the turnover-limiting step of the catalytic cycle. Next, the scope of the hydroamination protocol was expanded to include alkyl amines and alkyl olefins through the successful use of a hydrogen atom donor to turn the catalytic cycle over. This method was then extended to intermolecular hydroaminations in which the rate of aminium radical cation olefin addition is essential for reactivity. This insight allowed for the development of both secondary and primary amine selective reactions providing access to a wide variety of amine products from simple amine and olefin starting materials. Finally, an asymmetric variant of our initial hydroamination reaction was achieved through use of a chiral phosphate. The phosphate was found to form a very strong interaction with the aminium radical cation, allowing for an enantioselective radical addition to the olefin.