Oxazoles Diels-Alder reactions

Part A is devoted specifically to the synthesis, reactions, and spectroscopic properties of oxazoles and encompasses four chapters Chapter 1—Synthesis and Reactions of Oxazoles Chapter 2—Spectroscopic Properties of Oxazoles Chapter 3—Oxazole Diels-Alder Reactions and Chapter 4— Mesoionic Oxazoles. 

Oxazoles represent the most widely recognized heteroaromatic azadiene capable of [4 + 2] cycloaddition reactions. The course of the oxazole Diels-Alder reaction and the facility with which it proceeds are dependent upon the dienophile structure (alkene, alkyne), the oxazole and dienophile substitution, and the reaction conditions. Alkene dienophiles provide pyridine products derived from fragmentation of the [4 + 2] cycloadducts which subsequently aromatize through a variety of reaction pathways to provide the substituted pyridines (Scheme 14). In comparison, alkyne dienophiles provide substituted fiirans that arise from the retro Diels-Alder reaction with loss of R CN from the initial [4 + 2] cycloadduct (Scheme 15,206 Representative applications of the [4 + 2] cycloaddition reactions of oxazoles are summarized in Table 14. Selected examples of additional five-membered heteroaromatic azadienes participatiitg in [4 + 2] cycloaddition reactions have been detailed and include the Diels-Alder reactions of thiazoles, - 1,3,4-oxadiazoles, isoxazoles, pyrroles and imidazoles. ... 

Intermolecular Alkyne Oxazole Diels-Alder Reactions... 

The effect of pressure on the rate and product distribution of oxazole Diels-Alder reactions has been studied for 5-methoxy-2-methyl-4-(4-nitrophenyl)oxazole 61, a 5-alkoxyoxazole (Fig. 3.18). " " At atmospheric pressure, 61 gave low yields of cycloaddition products with A -phenyl maleimide and did not react at all with dimethyl maleate or dimethyl fumarate, even when heated at 110°C for 100 h. However, after 10 min at 10 kbar, a benzene solution of 61 and iV-phenyl maleimide provided a 4 1 mixture of endo (62) and exo (63) adducts in quantitative yield. Longer reaction times result in equilibration of 62 and 63, which is postulated to occur via a retro-Diels-Alder reaction, producing a 65 35 ratio after 25 h at 10 kbar. If the reaction is carried out at 10 kbar for 25 h using methanol as the solvent, hydroxypyridine 64 is isolated in quantitative yield. Dimethyl maleate could be induced to react with 61 only at elevated temperature and pressure (10 kbar, 60°C, lOOh, CgHg) to give a 71% yield of hydroxypyridine 65. However, even these... 

Jacobi has used intramolecular oxazole-alkyne Diels-Alder reactions, elegantly and with great success, to prepare a number of natural products containing fruan, lactone, and butenolide rings. These syntheses and the methodology based on the oxazole Diels-Alder reaction, termed bis-heteroannulation, have been reviewed in detaU. ... 

TABLE 3.3. INTRAMOLECULAR OXAZOLE DIELS-ALDER REACTIONS... 

For intramolecular oxazole Diels-Alder reactions see Table 3.3, p. 452. 

Several additional examples of oxazole Diels-Alder reactions applied to the synthesis of natural products have appeared. Using the same synthetic strategy that resulted in the total synthesis of normalindine, " Ohba and co-workers adapted the oxazole-olefin Diels-Alder cycloaddition for the synthesis of the mono-terpene alkaloids plectrodorine and oxerine. The synthesis of (-)-plectrodorine began with the requisite Diels-Alder precursor 262a, prepared from (5)-(-)-malic acid (Fig. 3.78). The intramolecular Diels-Alder reaction of this 2-alkyloxazole... 

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