Robinson —Gabriel cyclodehydration

The Robinson-Gabriel cyclodehydration of 2-acylamidoketones 1 is one of the oldest yet most versatile synthesis of 2,5-di- and 2,4,5-trialkyl, aryl, heteroaryl-, and aralkyloxazoles 2. ... 

Nicolaou and co-workers established the severely strained A-ring oxazole (21) in their total synthesis of antitumor agent diazonamide A through initial oxidation of the hindered alcohol of intermediate 20 with TPAP and subsequent Robinson-Gabriel cyclodehydration of the resultant ketoamide with a mixture of POCI3 and pyridine (1 2) at 70°C. ... 

Workers at Lilly prepared the oxazole-containing, dual PPAR ot/y agonist 23, through Robinson-Gabriel cyclodehydration of ketone 22 with acetic anhydride and sulfuric acid in refluxing ethyl acetate. ... 

Robinson-Gabriel Cyclodehydration, Robinson-Gabriel Synthesis)... 

Wipf and Miller have reported side-chain oxidation of 3-hydroxy amides with the Dess-Martin periodinane, followed by immediate cyclodehydration with triphenylphosphine-iodine, which provides a versatile extension of the Robinson-Gabriel method to substituted oxazoles. Application of this method was used to prepare the oxazole fragment 10 in 55% overall yield from 3-hydroxy amide 8. 

Oxazoles may be similarly prepared in good yields. Thus, 5-ethoxy-4-methyloxazole (173) was obtained by treating ethyl 2-formamide propionate (172) with phosphorus pentoxide in chloroform at 55°C (72JCS(P1)909,914). Known collectively as the Robinson-Gabriel synthesis, these cyclodehydrations can be effected by sulfuric acid or anhydrous hydrogen fluoride (cf CHEC 4.18). 

One of the most reliable methods for constructing the oxazole ring is the cyclodehydration of a-acylamino ketones, the Robinson-Gabriel synthesis (1909/1910) (equation 93). The reaction is usually conducted in the presence of sulfuric add or phosphorus pentachloride and more recently polyphosphoric add, phosgene or anhydrous hydrogen fluoride have... 

A convenient route to polysubstituted oxazoles was developed through a variation on the Robinson-Gabriel synthesis in which the key 1,4-dicarbonyl compounds were obtained by a rhodium carbene N-H insertion reaction. Dirhodium tetraacetate catalysed reaction of primary amides 103 and diazocarbonyl compounds 107 gave a-acylaminoketones 108, which were converted into 109 by cyclodehydration using the Wipf and Miller protocol <04T3967>. 

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