Reaction of Thioacids with Isocyanates and Isothiocyanates: A Convenient Amide Ligation Process

Abstract

Thiocarboxylates, prepared conveniently by cleavage of 9-fluorenylmethyl or trimethoxybenzyl thioesters, react at room temperature with isocyanates and isothiocyanates to give amide bonds in good to excellent yield. A carboxylate salt is also shown to react with an electron-deficient isocyanate to give the corresponding amide in excellent yield at room temperature.Given the widespread availability of amines and of carboxylic acids, amide bond forming reactions are necessarily some of the most widely applied transformations in parallel synthesis and combinatorial chemistry. The needs for atom ecomony, ever milder conditions, and greater selectivity combine to drive the search for new and improved methods for the formation of amide bonds. 1 The condensation of isocyanides with carboxylic acids has recently received much interest in this regard, 2 and this despite the relatively limited range of commercially available isocyanides and the somewhat forcing reaction conditions. Our attention was caught by a little known reaction 3 involving condensations of the much more widely available isocyanates and isothiocyanates with monothiocarboxylates which result in the formation of amides with loss of a simple, volatile byproduct, carbon oxysulfide or carbon disulfide, respectively. Although this reaction was described in 1973 for use with very simple substrates it has seen very limited application subsequently, 4 perhaps due to the relative paucity of commercially available thioacids. 5 We reasoned that the advent of convenient mild methods for thioacid synthesis 6 would combine with this reaction to afford a convenient and mild method for amide formation, and report here that this is indeed the case. In addition, we report Dcrich@icsn.cnrs-gif.fr.

Synthesis and intramolecular glycosylation of sialyl mono-esters of o-xylylene glycol. The importance of donor configuration and nitrogen protecting groups on cyclization yield and selectivity; isolation and characterization of a N-sialyl acetamide indicative of participation by acetonitrile

“…The configuration of the two isothiocyanates 15α and 15β was established by chemical conversion to the acetamides 13α and 13β by reaction with thioacetic acid. 11,26–31 The X-ray crystal structure of 14α also revealed the cis -conformation about the lactone carboxyl bond indicating this to be the more stable conformation consistent with Huisgen’s original work 16 on the conformation of medium ring lactones.…”

π‐Conjugated Triazenes and Nitriles: Simple Photoinduced Synthesis of Anilides Using Mild and Metal‐Free Conditions

“…2); oxidative coupling of alcohols and amines by using zirconium or ruthenium catalysts (Scheme , eq. 3); the reaction of thioacids with amine surrogates such as isonitriles, isocyanates, azides, and sulphonamides (Scheme , eq. 4); the Buchwald cross‐coupling amidation, and solid‐supported strategies .…”

An Oxidation–Amidation Approach for the Synthesis of Glycuronamides

“…The conventional approach for glycuronamide synthesis involves converting a uronic acid to a reactive intermediate (e.g., an activated ester or acyl halide) and then addition of an amine (Scheme , compounds 1 → 2 → 6 ) 14–20. Recently, Crich and Sasaki have developed an alternate method in which uronic acid thiocarboxylates made in situ react with isocyanates or isothiocyanates to produce glycuronamides ( 1 → 3 → 6 ) 21. In another alternate approach, treatment of 1,6‐ and 3,6‐carbohydrate‐based lactones with amines leads to the corresponding glucuronamides ( 1 → 4 / 5 → 6 ) 22–24.…”