Isocyanides and Arylacetic Acids: Synthesis and Reactivity of 3-Aryl-2-acyloxyacrylamides, an Example of Serendipity-Oriented Synthesis

Abstract

Research progress is often promoted by unexpected results that open the way to new scenarios. In this communication, an unprecedented condensation of arylacetic acids and isocyanides and the unusual base-mediated rearrangement of the resulting products to give two novel classes of polysubstituted pyrrolones and pyrrolidinediones are reported.

Ketene Three‐Component Reaction: A Metal‐Free Multicomponent Approach to Stereodefined Captodative Olefins

“…In a control experiment we reacted equimolar amounts of 2-diazo-1-phenylethanone, cyclohexylisocyanide, and propionic acid at room temperature in the absence of UV light, and observed that no reaction took place. Notably, homo compound 1 f, which decomposed when prepared with our previously developed method, [7] was in this case isolated without problem. Variation of the reaction conditions showed that heptane was a better solvent than toluene, diisopropyl ether, or chloroform, and that when using a shorter wavelength (300 or 254 nm) the reaction was faster but less clean, as a consequence of the partial instability of the captodative olefin upon irradiation.…”

“…[15] However, to our delight, when we irradiated the same components in a quartz test tube at 350 nm, the multicomponent adduct was obtained in 50 % yield. It is worth noting that the previously reported method [7] was unsuccessful with acids other than arylacetic ones, and additionally the reaction illustrated in Scheme 3 did not afford any of the desired captodative olefin when acyl chlorides lacking an aromatic ring in the a-position were employed. The best results were obtained by irradiating the deoxygenated reaction mixture at 350 nm for three hours in the presence of an excess of trans-piperylene (Table 1).…”

“…Comparison between a) the previously reported method [7] and b) the new Passerini-like multicomponent reactions with arylketenes as carbonyl surrogates. General multicomponent approach to captodative olefins 1.…”

“…Comparison between a) the previously reported method [7] and b) the new Passerini-like multicomponent reactions with arylketenes as carbonyl surrogates. Comparison between a) the previously reported method [7] and b) the new Passerini-like multicomponent reactions with arylketenes as carbonyl surrogates.…”

“…[7] The key feature of this reaction is that one molecule of carboxylic acid behaves as an electrophile through formation of an acyl imidate with one molecule of isocyanide. [7] The key feature of this reaction is that one molecule of carboxylic acid behaves as an electrophile through formation of an acyl imidate with one molecule of isocyanide.…”