Copper-Catalyzed Oxidation of Hydrazones to Diazo Compounds Using Oxygen as the Terminal Oxidant

Abstract

A mild method for accessing diazo compounds via aerobic oxidation of hydrazones is described. This catalytic transformation employs a Cu­(OAc)2/pyridine catalyst and molecular oxygen from ambient air as the terminal oxidant, generating water as the sole byproduct and affording the desired diazo compounds within minutes at room temperature. A broad array of electronically diverse aryldiazo esters, ketones, and amides can be accessed. Pyridine dramatically enhances the rate of the reaction by solubilizing the copper catalyst and serving as the Brønsted base in the turnover-limiting proton-coupled oxidation of hydrazone by copper­(II). Insights gained from mechanistic studies led to expansion of the scope of this method to include diaryl hydrazones, delivering diaryl diazomethane derivatives, which cannot be accessed via established diazo transfer methods. The products of this method may be employed in rhodium carbene catalysis without isolation of the diazo intermediate to afford cyclopropane products in good yield with high enantioselectivity.

Asymmetric synthesis of pharmaceutically relevant 1-aryl-2-heteroaryl- and 1,2-diheteroarylcyclopropane-1-carboxylates

“…We have recently developed a copper-catalysed method for the synthesis of diazo compounds from hydrazones, in which the only by-product is water. 49 The copper catalysed-reaction is greatly accelerated with N,N 0 -dimethyl aminopyridine (DMAP), but DMAP, a very nucleophilic pyridine, would be expected to poison the catalyst or react with the carbene. 29,36,40 Therefore, we have conducted exploratory studies to determine if the unpuried diazo compound from a copper-catalysed oxidation can be directly used in the rhodium-catalysed reaction.…”

Catalytic Aerobic Oxidation of Hydrazines into 2‐Tetrazenes

“…[26] Besides, copper (i) is effective for the oxidative coupling [27] of amines to hydrazines, [28][29][30] or azo derivatives, [31] as well as that of various N-functions, where at least one of the nitrogen atoms is sp 2 . [32][33][34][35] However, from that perspective hydrazines themselves, particularly the poorly substituted, highly reducing ones are more challenging because of their ability to engage in single electron transfers. [36] We had another reason to select copper, which will be explained later.…”

“…Copper ( ii ) was chosen as the catalytic oxidant of hydrazines because the aerobic oxidation of copper ( i ) complexes to copper ( ii ) ones is generally easy (Figure 1). [26] Besides, copper ( i ) is effective for the oxidative coupling [27] of amines to hydrazines, [28–30] or azo derivatives, [31] as well as that of various N‐functions, where at least one of the nitrogen atoms is sp 2 [32–35] . However, from that perspective hydrazines themselves, particularly the poorly substituted, highly reducing ones are more challenging because of their ability to engage in single electron transfers [36] …”

Autoxidation of 4-Hydrazinylquinolin-2(1H)-one; Synthesis of Pyridazino[4,3-c:5,6-c′]diquinoline-6,7(5H,8H)-diones

“…Accordingly, it supports the steps of transformations of 7′ into 8 and 9 into 3 . Moreover, aerial catalytic oxidation in pyridine transformed hydrazones into diazo compounds [ 48 ].…”