A Closed-Shell Mechanism Alternative for Sibi’s α-Oxyamination of Aldehydes

Significance

In 2007, independent reports by the groups of Sibi (J. Am. Chem. Soc. 2007, 129, 4124) and MacMillan (Science 2007, 316, 582) demonstrated that a catalytic amount of a secondary amine is able to activate aldehydes via the formation of a radical cation in the presence of a single electron oxidant, thus avoiding the previous necessity for preformed enamines (e.g., K. Narasaka et al. Chem. Lett. 1992, 2099). Now, mechanistic investigations of Sibi’s α-oxyamination of aldehydes (2 → 3 catalyzed by 1) by the MacMillan group challenges the mechanism via enamine-derived radical cation B proposed by ­Sibi. Instead, a mechanism involving an activation of TEMPO by the complexation with FeCl₃ (D) is proposed as an alternative.