An Unconventional Reaction of 2,2‐Diazido Acylacetates with Amines

Abstract

We have discovered that 2,2‐diazido acylacetates, a class of compounds with essentially unknown reactivity, can be coupled to amines through a new strategy that does not involve any reagents. 2,2‐Diazido acetate is the unconventional leaving group under carbon–carbon bond cleavage. This reaction leads to the construction of amide bonds, tolerates various functionalities and is performed equally well in numerous solvents under experimentally simple conditions. We also demonstrate that the isolation of the 2,2‐diazido acylacetate compounds can be circumvented: Acylacetates were easily fragmented when treated with (Bu4N)N3 and iodine in the presence of an amine at room temperature. By using this method, a broad range of acylacetates with various structural motifs were directly transformed into amides.

An open-source approach to automation in organic synthesis: The flow chemical formation of benzamides using an inline liquid-liquid extraction system and a homemade 3-axis autosampling/product-collection device

“…C NMR (101 MHz, CDCl 3 ) δ 167.50, 142.00, 134.71, 131.20, 128.40, 128.32, 128.26, 126.80, 125.73, 39.82, 35.42, 29.16, 28.62. The data are consistent with those reported previously in the literature 25. Methyl)benzylbenzamide (4i) was synthesised using the general procedure outlined above, using benzoyl chloride 1 and (4-methyl)benzylamine 2i.…”

2,2‐Diazido‐1,2‐diarylethanones: Synthesis and Reactivity with Primary Amines

“…Our previous studies with 2,2‐diazido carbonyl systems have demonstrated how the neighboring diazido group is capable to ease the amine addition, and thus the carbonyl group may be considered as being highly activated in those systems. [10f], [11a], , From a mechanistic point of view, we assume that the present fragmentation starts with the nucleophilic attack of the amine onto the carbonyl group of diazide A , as outlined in Scheme . Upon addition‐elimination, a diazido leaving group B (or its deprotonated form) may be generated that undergoes further degradation through loss of both dinitrogen and an azide anion under basic conditions.…”

“…This experimental procedure allows for the straightforward installation of diazide units with 1,3‐diketones and, more importantly, 3‐oxo esters. In a number of subsequent studies regarding the reactivity of diazidated compounds 2 , we revealed that treatment with primary amines typically leads to a rapid fragmentation of the carbon core: The diazides are excellent acylation reagents, and amides 3 are easily formed besides a hazardous diazidated leaving group 4 …”

Reactivity of Organic Geminal Diazides at Tetrahedral Carbons

“…In the following paragraph, geminal diazides are presented as surprisingly good acylation agents for nucleophilic amines, a serendipitous finding we reported first in 2017. [ 57 ] As summarized in Scheme 18A, a broad range of 2,2‐diazido acyl acetates 54 reacted smoothly as an acyl group transfer reagent. We observed that, due to the unprecedented activating influence of the two azide groups on adjacent carbonyls, the carbon–carbon bond between C2 and C3 is cleaved with nucleophilic amines: the amide bond formation is then accompanied by the formation of 2,2‐diazido acetate as the somewhat unique leaving group.…”