Methyl‐Selective α‐Oxygenation of Tertiary Amines to Formamides by Employing Copper/Moderately Hindered Nitroxyl Radical (DMN‐AZADO or 1‐Me‐AZADO)

Abstract

Methyl‐selective α‐oxygenation of tertiary amines is a highly attractive approach for synthesizing formamides while preserving the amine substrate skeletons. Therefore, the development of efficient catalysts that can advance regioselective α‐oxygenation at the N‐methyl positions using molecular oxygen (O2) as the terminal oxidant is an important subject. In this study, we successfully developed a highly regioselective and efficient aerobic methyl‐selective α‐oxygenation of tertiary amines by employing a Cu/nitroxyl radical catalyst system. The use of moderately hindered nitroxyl radicals, such as 1,5‐dimethyl‐9‐azanoradamantane N‐oxyl (DMN‐AZADO) and 1‐methyl‐2‐azaadamanane N‐oxyl (1‐Me‐AZADO), was very important to promote the oxygenation effectively mainly because these N‐oxyls have longer life‐times than less hindered N‐oxyls. Various types of tertiary N‐methylamines were selectively converted to the corresponding formamides. A plausible reaction mechanism is also discussed on the basis of experimental evidence, together with DFT calculations. The high regioselectivity of this catalyst system stems from steric restriction of the amine‐N‐oxyl interactions.

Anderson-type polyoxometalate-based metal–organic framework as an efficient heterogeneous catalyst for selective oxidation of benzylic C–H bonds

“…[53][54][55][56] Meanwhile, as one of the most utilized transition metals, copper is also extensively applied for synthetic organic chemistry. [57][58][59][60] Very recently, Copper-based catalyst has showed enzymatic activity for C-H oxidation with NHPI as co-catalyst. 61 By integration of Anderson-type {CrMo 6 } cluster and {Cu 4 O 3 } unit in the framework of POMOF-1, we thus intend to use it as a catalyst for the synthesis of aryl carboxylic acids via oxidation of methylarenes.…”