Nine-Membered Ketolactams by Oxidative Cyclization Expansion

Considerable progress has been made over decades in synthetic organic chemistry in order to build up molecular complexity, often through the design of advanced catalytic systems. Yet, simply exposing organic molecules to benchmark oxidants in catalyst free conditions can sometimes lead to surprising and highly valuable products. Thus, a synthetic method for accessing rare 9-membered ketolactams is herein described, under mild oxidative conditions. Key 18 O and 17 O label experiments revealed an unexpected oxygen atom migration event in the ring expansion process. The scope, mechanism, synthetic applications, and 9 to 7 membered ring contraction opportunities are discussed.