A general and practical route to 4,5-disubstituted oxazoles using acid chlorides and isocyanides

Abstract

An efficient and mild method for the synthesis of 4,5-di-substituted oxazolesvia[3 + 2] cycloaddition reaction of isocyanides and acid chlorides is reported.

A simple and efficient method for the synthesis of 4-tosyloxazoles from tosylmethyl isocyanide with α-ketoimidoyl chlorides

“…49 NIS-mediated iodocyclization of N-sulfonyl propargylamides is developed for the synthesis of various oxazolidines and iodoalkylidenedihydrooxazoles via a 5-exo-dig process. 46 According to this investigation and literature reports 50,29 reactions directly arising from acid chlorides are useful and high yielding methods for synthesis of functionalized oxazoles.…”

“…[22][23][24][25][26] Sasaki prepared bisoxazole derivatives which were substituted at the 4-position and dioxazolo metacyclophane derivatives using TosMIC. 27 Oxazole derivatives with substitution at the 5-position were synthesized by cyclocondensation of aldehydes with monosubstituted tosylmethyl isocyanide in moderate yield [28][29][30][31][32][33][34][35][36][37][38][39] and by reaction of aryl aldehydes with TosMIC and also metalated methyl isocyanides. [40][41][42][43][44] Although there are many methods for the synthesis of oxazoles, [45][46][47][48] few approaches are available for the preparation of 4,5-disubstituted oxazoles.…”

“…[40][41][42][43][44] Although there are many methods for the synthesis of oxazoles, [45][46][47][48] few approaches are available for the preparation of 4,5-disubstituted oxazoles. [28][29][30][31][32][33][34][35][36][37][38][39] Reaction of α-diazo-β-keto-carboxylates and -phosphonates with arene carboxamides gives 2-aryloxazole-4carboxylates and 4-phosphonates by carbene N-H insertion, followed by cyclodehydration results in the formation of oxazole-5-carboxylates and 5-phosphonates. 49 NIS-mediated iodocyclization of N-sulfonyl propargylamides is developed for the synthesis of various oxazolidines and iodoalkylidenedihydrooxazoles via a 5-exo-dig process.…”

A computer algorithm to discover iterative sequences of organic reactions

“…In Fig. 3b, the condensation of isocyanide with acyl chloride 29 leads to the formation of an oxazole while subsequent hydrolysis and treatment with thionyl chloride regenerates the acyl chloride needed for the next iteration. The third sequence (Fig.…”

Recent Advances in the Chemistry of Isocyanides with Activated Methylene Group

“…Tiwari and colleagues presented an efficient and mild method for the synthesis of 4,5‐disubstituted oxazoles 105 via [3+2] cycloaddition reaction of acid chlorides 104 and isocyanides 1 in the presence of base. [ 64 ] The resulting 4,5‐disubstituted oxazoles 105 could in turn be functionalized at C5 position. The following reaction mechanism is proposed by two pathways: in pathway I, initially anionic form of isocyanide A undergoes addition on acid chloride with generation of B .…”