Chapter 1 The synthesis of oxazoles from diazocarbonyl compounds

Abstract

This chapter presents a study on the synthesis of oxazoles from diazocarbonyl compounds. The chapter presents a work, summarized in the classic treatise in 1949, is the foundation of modern oxazole chemistry. The subsequent discovery during the 1950's by Kondrat’eva that oxazoles can function as azadienes in the Diels–Alder reaction, and by Huisgen that mesoionic oxazoles participate in 1,3-dipolar cycloaddition reactions prompted further research into the ring system. Recently the oxazole ring system has been found in an ever increasing range of natural products, many of them “peptide alkaloids” in which the heterocyclic ring is most likely formed by a modification of a serine or threonine containing peptide. There are several methods available for the synthesis of oxazoles; this chapter focuses on just one route, which has been used extensively in a laboratory—namely, that involving the reaction of diazocarbonyl compounds with nitriles. Oxazole formation can be envisaged as proceeding by the following three possible pathways: (1) 1,3-dipolar cycloaddition of a free ketocarbene to the nitrile (Path A); (2) the formation and subsequent 1,5-cyclisation of a nitrile ylide (Path B); or (3) the formation and subsequent rearrangement of a 2- acyl-2H-azirine (Path C). The role of Lewis acids in the formation of oxazoles from diazocarbonyl compounds and nitriles has been discussed. The chapter also discusses transition-metal catalyzed reactions, including copper, tungsten, palladium, and rhodium.