Aminotrifluoromethylation of Olefins via Cyclic Amine Formation: Mechanistic Study and Application to Synthesis of Trifluoromethylated Pyrrolidines

We examined the mechanism of our
previously reported aminotrifluoromethylation
reaction, which proceeds via intramolecular cyclization of alkenylamines
in the presence of the combination of copper catalyst and Togni reagent
(1). Kinetic studies revealed that the initial rate of
the reaction was first order with respect to Togni reagent and CuI,
as well as the substrate. Changes of the 19F NMR chemical
shift of Togni reagent during the reaction suggested the existence
of a dynamic equilibrium involving coordination of not only Togni
reagent, but also the substrate amine and the product aziridine to
copper. ESI-MS analysis provided evidence of involvement of reactive
Cu­(II) intermediates in the catalytic cycle. Overall, our results
indicate that the reaction proceeds at the hypervalent iodine moiety
of Togni reagent, which is activated by Cu­(II) species acting as a
Lewis acid catalyst. On the basis of these mechanistic considerations,
we developed an efficient synthesis of trifluoromethylated pyrrolidine
derivatives. This transformation exhibited a remarkable rate enhancement
upon addition of Et3N.