Copper‐Catalyzed Rearrangement of Tertiary Amines through Oxidation of Aliphatic CH Bonds in Air or Oxygen: Direct Synthesis of α‐Amino Acetals

Abstract

A surprising turn of events: Mechanistic studies, including trapping, control, and isotope‐labeling experiments, led to the proposal of a rearrangement mechanism involving oxidation of aliphatic CH bonds (see scheme; TMEDA=tetramethylethylenediamine).

Iodine‐Catalyzed Oxidative Rearrangement of Amines to α‐Amino Acetals and α‐Amino Aldehydes

“…On the basis of our experimental results and previous reports, [3,5,16] we propose the mechanism depicted in Scheme 4. Initially, the hydrogen atom at the a-carbon of substrate 1 or 3 is abstracted by 2phenylisopropoxy radical to form a-amino radical 8.…”

“…[1] Therefore, the development of methods for the preparation of these compounds is of considerable interest. In pioneering work, Loh and a co-worker [3] reported Cu-catalyzed oxidative rearrangement of acyclic tertiary amines to afford a-amino acetals (Scheme 1a). In pioneering work, Loh and a co-worker [3] reported Cu-catalyzed oxidative rearrangement of acyclic tertiary amines to afford a-amino acetals (Scheme 1a).…”

Aerobic Copper-Catalyzed Organic Reactions

“…For example, Loh and co-workers reported an elegant copper-catalyzed rearrangement of tertiary amines via oxidation of aliphatic C–H bonds under air or oxygen atmosphere for the synthesis of α-amino acetals Scheme 587. 1123 This more complex reaction is a result of a four electron oxidation, which is proposed to occur via four single electron transfers. Specifically, an amine of an alkyl amine underwent both an oxidation and an oxidative migration from C1 to C2 via an aziridine as outlined in Scheme 588.…”

Transition-Metal-Catalyzed Cleavage of C–N Single Bonds

“…Alternatively, 106 could undergo a direct aldol-type condensation and a Michael addition to give 103. 139 This transformation provides a mild and cheap method for the direct synthesis of a variety of useful α-amino acetals 110. A plausible mechanism for this rearrangement was illustrated on the basis of trapping, control, and isotope-labeling experiments.…”