Metal-free, hydroacylation of CC and NN bonds via aerobic C–H activation of aldehydes, and reaction of the products thereof

Abstract

In this report, a thorough evaluation of the use of aerobically initiated, metal-free hydroacylation of various C=C and N=N acceptor molecules with a wide range of aldehydes is presented. The aerobic-activation conditions that have been developed are in sharp contrast to previous conditions for hydroacylation, which tend to use transition metals, peroxides that require thermal or photochemical degradation, or N-heterocyclic carbenes. The mildness of the conditions enables a number of reactions involving sensitive reaction partners and, perhaps most significantly, allows for α-functionalised chiral aldehydes to undergo radical-based hydroacylation with complete retention of optical purity. We also demonstrate how the resulting hydroacylation products can be transformed into other useful intermediates, such as γ-keto-sulfonamides, sultams, sultones, cyclic N-sulfonyl imines and amides.

A facile, one-pot procedure for the conversion of aromatic aldehydes to esters, as well as thioesters and amides, via acyl hydrazide intermediates

“…to form compounds of the form of hydrazide 4). 21 In this case however, when using aromatic aldehydes, and thus in turn aromatic hydrazides, no sharp decrease in yield was observed (ca. 10% reduction).…”

“…Previously we have reported a highly efficient protocol for the conversion of aldehydes to acyl hydrazides using aerobic C-H activation, which proceeded successfully "on water". 21,22 However, in view of the fact that esterification proceeded most efficiently in DMF, we appraised the reaction of an aldehyde with an azodicarboxylate (for the formation of an acyl hydrazide) in this solvent. Gratifyingly, use of DMF as solvent actually improved the yield of the transformation from 75% to 89% (Scheme 1).…”

“…More recently, Chudasama, Caddick and co-workers have shown the formed acyl hydrazides to undergo reaction with Grignard reagents for the efficient synthesis of ketones. 19,21 With the acyl donor ability of acyl hydrazides in mind, we were intrigued by the possibility of using acyl hydrazides for the synthesis of esters. Moreover, with the stability of acyl hydrazides being well documented, we envisioned from the outset that such a development could be adapted to the one-pot conversion of aldehydes to esters via an in situ prepared acyl hydrazide intermediate ( Figure 1c).…”

“…[15][16][17][18][19][20][21][22][23][24][25][26] Moreover, the overall transformation has been shown to proceed under a wide range of reaction conditions, in a variety of solvents and with the aldehyde being employed as the limiting reagent. More recently, Chudasama, Caddick and co-workers have shown the formed acyl hydrazides to undergo reaction with Grignard reagents for the efficient synthesis of ketones.…”

Iron‐Catalyzed Aerobic Oxidation of Aldehydes: Single Component Catalyst and Mechanistic Studies

“…[1] It is well known that some aldehydes may be oxidized to acids very slowly when exposed to air. [2] However, the process of autoxidation was too slow to meet the requirement of industrial manufacture or preparation in academic laboratory. Traditionally, strong and stoichiometric oxidants, such as KMnO 4 , [3] CrO 3 , [4] and hypervalent iodine compounds, [5] have to be used to convert aldehydes to carboxylic acids.…”