Dimedone, reaction with nitriles

Gogonas and Hadjiarapgolu described the synthesis of oxazoles via a Rh2(OAc)4-catalyzed [3 + 2]-cycloaddition reaction of phenyliodonium salts with nitriles (Scheme 1.46). The starting phenyliodonium salt 167 was prepared from dimedone and diacetoxyiodobenzene in 95% yield. Reaction of 167 with nitriles in the presence of Rh2(OAc)4 gave fused 2-alkyl-, 2-aralkyl-, or 2-aryloxazoles 168 in modest yields. It is noteworthy that the reaction conditions do not require an inert atmosphere. The mechanistic details of this reaction are not yet clear. Selected examples are shown in Table 1.10. 

A similar reaction is probably involved in the reaction of 4-nitrophthalodi-nitrile (27) with dimedone (28), which provided under milder condition compound 29 and at a higher temperature tricyclic compound 30 (87ZOR2629). Similarly as in the vicarious nucleophilic reactions, intermediate 29 is formed by nucleophilic displacement of the ort/io-hydrogen atom in 27 (Scheme 3). 

The only known example of 2-monoalkylaminopyran 123 in the series of tetrahydrochromenes was obtained by the less common three-component reaction of alkylisonitriles 124, acetylenedicarbonic esters 125, and dimedone or 1,3-cyclohexanedione 103 (03M1585) (Scheme 42). This example illustrates how the isonitrile —N =C group can be involved in the formation of a 2-aminopyran ring, similar to the other groups with triple bonds - nitrile C=N and alkynyl C=C. 

The Knoevenagel reaction between benzaldehydes 22 and malononitrile or ethyl cyanoacetate 74 followed by condensation of the resulting ot,p-unsatu-rated nitriles 75 with dimedone (76) was performed in the presence of SiO2-(CH2)3-NEt2 (Scheme 3.22). ... 

The one-pot three-component reaction of isatines, methylene-active nitriles, and a series of reagents, such as dimedone, barbituric acid, and 4-hydroxycoumarin in PEG 400 resulted in the formation of spiro-fused compounds 110-112 with good yield (Scheme 62) [93]. Contrarily, it was reported [94] that this type of reaction did not give appreciable yield of the product (110, R =R =H, R =CN, 24%) in the absence of catalysts under similar conditions (70°C, lOh). The best yields (84-96%) were obtained when gold(lll) chloride (HAuCl4-3H20) was applied as a catalyst. PEG 200, PEG 400, and PEG 600 gave better results than conventional solvents and were equally efficient for this reaction. When PEG 400 was recycled in three runs, the yield of the product (110, R = R =H, R =CN) decreased from 96% to 90%. 

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