Sustainable Approach to Azaheterocyclic Acetamides by Decarboxylative Aminoformylation

Abstract

A green and efficient synthesis of azaheterocyclic acetamides has been developed that significantly reduces the consumption of nitrogen-containing reagents from more than 20 equiv in previously reported methods to 1.5 equiv. This reduction decreased both the pollution potential and cost, especially if the nitrogencontaining reagent is expensive and difficult to recycle. Therefore, this strategy is environmentally friendly and sustainable. Moreover, this process uses economical inorganic peroxysulfate as an oxidant to initiate the difunctionalization of alkenes via aminoformyl radicals and aryl C(sp 2 )−H bonds, providing efficient and sustainable access to a broad substrate scope and promising functional group tolerance. Notably, a series of unreported dioxoisoquinolines and oxindole derivatives were synthesized by applying this green method, which highlights its potential utility in medicine-related clinical research.

Oxamic acids: useful precursors of carbamoyl radicals

“…The same authors generalized the approach to the addition of carbamoyl radical II to acrylimides 34 (Scheme 19). 41 In this Scheme 16 Intramolecular decarboxylative Heck-type reactions of oxamic acids.…”

“…Interestingly, when acrylamide 30 does not bear an ortho CN substituent as in 32 , radical intermediate i was shown by Ma and co-workers 41 to directly cyclize onto the aromatic ring providing the 5-membered ring lactam 33 in generally high yields whatever the substitution on the aromatic ring (Scheme 18). N -Protected acrylamide 32 was however compulsory as the reaction with the N–H analogue did not afford the desired lactam.…”

“…The same authors generalized the approach to the addition of carbamoyl radical II to acrylimides 34 (Scheme 19). 41 In this case, the addition was followed by a 6- exo cyclization of the radical i , onto the aromatic ring, affording the corresponding cyclohexadienyl radical ii . Oxidation of the latter led to the corresponding cation iii , giving to the 6-membered ring imide 35 after rearomatization.…”

Metal-Free Synthesis of Carbamoylated Chroman-4-Ones via Cascade Radical Annulation of 2-(Allyloxy)arylaldehydes with Oxamic Acids

“…On the basis of the above control experiment and the recent literature [ 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ], a plausible reaction pathway for this carbamoylation reaction is proposed. As shown in Scheme 6 , initially, the radical anion SO 4 −• generates via the decomposition of (NH 4 ) 2 S 2 O 8 in DMSO.…”

Microwave Irradiation and Formamide: A Perfect Match for Ultrafast Carbamoylation via Radical Reactions

“…Later, the photogeneration of the simplest carbamoyl radical ( • CONH 2 ) from formamide for direct amidation of unsaturated compounds was described in the literature. − Additionally, the generation of carbamoyl radicals through a redox system was developed by Minisci et al , for the carbamoylation of heteroaromatic bases using Fenton’s reagents in formamide. Since then, other Minisci-type reactions and tandem carboxamidation/cyclization processes employing formamides have been reported. − …”