Oxidation Under Reductive Conditions: From Benzylic Ethers to Acetals with Perfect Atom‐Economy by Titanocene(III) Catalysis

Described here is a titanocene‐catalyzed reaction for the synthesis of acetals and hemiaminals from benzylic ethers and benzylic amines, respectively, with pendant epoxides. The reaction proceeds by catalysis in single‐electron steps. The oxidative addition comprises an epoxide opening. An H‐atom transfer, to generate a benzylic radical, serves as a radical translocation step, and an organometallic oxygen rebound as a reductive elimination. The reaction mechanism was studied by high‐level dispersion corrected hybrid functional DFT with implicit solvation. The low‐energy conformational space was searched by the efficient CREST program. The stereoselectivity was deduced from the lowest lying benzylic radical structures and their conformations are controlled by hyperconjugative interactions and steric interactions between the titanocene catalyst and the aryl groups of the substrate. An interesting mechanistic aspect is that the oxidation of the benzylic center occurs under reducing conditions.