Transition Metal-Mediated Synthesis of Oxazoles

Abstract

Among the synthetic methods for the formation of the oxazole ring, transition metal-mediated protocols are the most attractive in terms of selectivity, efficiency and mildness of reaction conditions. In this review we discuss methods for the preparation of oxazoles using transition metal complexes highlighting the key bonds being formed. This reveals critical gaps in the existing literature for the construction of this biologically significant ring system highlighting exciting opportunities for further research.

(E)-5-[Bromo(phenyl)methylene]-4-phenyl-2-(p-tolyl)-4,5-dihydrooxazole

“…The reaction conditions in the initial propargylic substitution reaction of propargylic alcohol 5 and p-toluamide (6) were those identified in our previous work (5 mol% AuBr3/15 mol% AgOTf in toluene, reflux, 20 min). Various bromine sources (N-bromosuccinimide: NBS, 1,3-dibromo-5,5-dimethylhydantoin, and dibromoisocyanuric acid) were investigated for the cyclization of propargylic amide 7 (Scheme 3).…”

“…When bromocyclization was conducted using either 1,3-dibromo-5,5-dimethylhydantoin or dibromoisocyanuric acid as the bromine source, the yield of product 9 was low in both cases. Finally, treatment of propargylic alcohol 5 with p-toluamide (6) in the presence of AuBr3 (5 mol%) and AgOTf (15 mol%) in toluene refluxing for 20 min gave propargylic amide 7, and then addition of NBS (2 eq) resulted in gold(III)-catalyzed bromocyclization [15] to furnish bromooxazoline 9 in 54% yield in one pot. (When the intermediate propargyl amide 7 was isolated and reacted with NBS at 0 °C in toluene without gold catalyst, the bromocyclization did not proceed.…”

“…Therefore, extensive efforts have been made to develop synthetic methods for these compounds over several decades. Most of them are based on cyclization from propargylic amides 3 to oxazolines 4 in the presence of transition metals [6,7] or other reagents [8,9]. However, there were no reports of oxazoline 4 synthesis by propargylic substitution reaction followed by cyclization from propargylic alcohol 1 with amide 2 (Scheme 1).…”

Ring forming transformations of ynamides via cycloaddition

“…But recent developments in organometallic reagents catalyzed and transition metal-catalyzed bimolecular cycloaddition reactions offer alternative approaches to furnish oxazole derivatives using mild reaction conditions. 53,54…”