Oxidative Coupling of Diazo and NH₄I: A Route to Primary Oxamates and α-Ketoamides

Abstract

A simple and efficient method has been developed for the preparation of primary oxamates and α-ketoamides through the oxidative coupling of diazo compounds and NH 4 I. Under the optimized reaction conditions, a range of diazoesters and αdiazoketones was explored, and the corresponding products were obtained in moderate to good yields. This protocol is metal-free, is performed under mild conditions, has a wide substrate scope, and offers operational simplicity.

Iodine–TBHP mediated efficient synthesis of α-ketoamides from vinyl azides and amines under mild conditions

“…Significantly, a trace amount of the product was formed under an oxygen atmosphere (Table 1, entry 12). After these fundamental experiments, a short survey on solvents was also performed and notably, CH 3 CN was found to be a worthy solvent among THF, toluene and DMSO for the ketoamide synthesis (Table 1, entries [13][14][15]. By increasing the amount of iodine from 50 mol% to 1 equiv., no significant change in the yield was found (Table 1, entry 16).…”

“…Practically, the amidation of α-oxocarboxylic acids has turned out to be a general approach for obtaining α-ketoamide and its derivatives. Besides, other substrates such as acetophenones, α-ketoaldehydes or keto acids, arylethanols, styrenes, phenylacetylenes, alkylarenes, halides, α-hydroxyketone, 9 arylacetic acid, 10 enaminone, 11 benzoylacetonitrile, 12 α-aminocarbonyl, 13 diazo compounds, 14 benzofuran-3(2 H )-ones, 15 etc. have been introduced to synthesize α-ketoamides (Scheme 1a).…”

Oxamates as 1,2‐Diketone Equivalents: The Effect of Fluorine

“…Furthermore, the synthesis of oxamates through an oxidative double cross‐carbonylation of amines and alcohols in the presence of palladium catalyst under low‐pressure CO/O 2 has been well documented [14–16] . A very recent method for primary oxamates uses the oxidative coupling of diazo group containing precursors and NH 4 I [17] . In a Pd/C‐catalyzed mild, efficient, and ligand‐free synthesis oxamates became available by oxidative cross double carbonylation of amines and alcohols under a basic co‐catalyst [18] .…”

Mg(OtBu)2-catalyzed C–H oxidation of α-azido arylethanones using TBHP as the oxidant and carbonyl oxygen source: facile access to primary α-ketoamides

“…1 For these reasons, considerable efforts have been continuously devoted to the development of efficient and general methods for such ketoamide preparation. 2 Traditional methods have focused on amidation of α-oxocarboxylic acids and their derivatives with nitrogen sources and have been well investigated. 2,3 However, many cases suffer from harsh reaction conditions and discharge of large amounts of unwanted wastes, thus causing a narrow application and substrate scope.…”

“…2 Traditional methods have focused on amidation of α-oxocarboxylic acids and their derivatives with nitrogen sources and have been well investigated. 2,3 However, many cases suffer from harsh reaction conditions and discharge of large amounts of unwanted wastes, thus causing a narrow application and substrate scope. In recent years, the catalytic oxidation of methylene C(sp 3 )–H bonds has been developed, which provided diverse α-ketoamides under milder conditions in an atom- and step-economical manner.…”