Comforth rearrangement

Dewar and Turchi described the Comforth rearrangement of 5-alkoxyoxazole-4-thiocarboxylates as a potentially general method for the synthesis of 5-thiooxazole-4-carboxylic esters. Specifically, they found that thiol ester 13 underwent thermal isomerization to the corresponding 5-thiooxazole 14 in 94% yield. 

Williams and McClymont have observed that acylation reactions of the dianion of 2-(5-oxazolyl)-l,3-dithiane (15) lead to formation of 4,5-disubstituted oxazole products through a Comforth rearrangement pathway under base-induced, low-temperature conditions. For example, deprotonation of 15 with LiHMDS (3.0 equivalents) at -78°C, followed by addition of benzoyl chloride or p-chlorobenzoyl chloride and warming to 0°C, provided 16 in 74% and 47% yield, respectively. 

A microwave assisted Comforth rearrangement of oxazole-4-carboxamides 106 efficiently afforded 5-aminooxazole-4-carboxylates 107. This procedure was applied to the formal synthesis of a natural antibiotic derived from pseudomonic acid <06TL4698>. 

Williams, D. R. McClymont, E. L. Carbanion methodology for alkylations and acylations in the synthesis of substituted oxazoles. The formation of Comforth rearrangement products. Tetrahedron Lett. 1993, 34, 7705—7708. 

Cope Elimination Reaction Cope Rearrangement Corey-Bakshi-Shibata Reduction Corev-Kim Oxidation Corey-Winter Olefin Synthesis Comforth Rearrangement Coumarin-Benzofuran Ring Contraction Crafts (see Friedel-Crafts Reaction)... 

Based on tandem Dimroth-Comforth rearrangements, reaction of 1,2,3-thiadiazole-4-carboxaldehyde 64 with l-amino -carbamoyl-l,2,3-triazole-5-oIate 65 afforded the sodium A[-(4-thiocarbonyl-l,2,3-triazol-l-yl)carbamoyl-1,2,3-triazol-5-olate 68 with moderate overall yield (Scheme 21) [61]. 

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