Diazo groups nitrile synthesis

The nitrile group in 82 has been transformed into other versatile functional groups, and the derivatives so obtained have been used in the synthesis of various naturally occurring C-nucleosides and their analogs. Reduction of 82 with lithium aluminum hydride gave the amine 90 which was, in turn, transformed84 into the ureido and N-ni-troso derivatives (91-93) by treatment with nitrourea, followed by benzylation, and nitrosation.85 The diazo derivative 94, obtained by treatment of 93 with alcoholic potassium hydroxide, was a key intermediate in the synthesis of formycin B and oxoformycin B (see Section III,2,a,b). 

There has been continued interest in the synthesis of oxazoles from a-diazo carbonyl compounds and nitriles catalyzed by Lewis acids. The BFa-catalyzed reaction of a-diazoacetophenones or methyl p-nitrophenyldiazoacetate with chloroacetonitrile affords 5-aryl-2-chloromethyloxazoles or 2-chloromethyl-5-methoxy-4-(p-nitrophenyl)oxazole, respectively (Equation (19)) <89BCJ618>. The former products react with primary, secondary, and tertiary amines by nucleophilic displacement of the chloride group. Methyl or ethyl isocyanate may be used as the nitrile component to prepare... 

The major product obtained by alkylation of the carbanion derived from 2-(dimethylamino)ethylmethylphenylphosphine oxide (66) is (67) rather than (68), while alkylation of the carbanion derived from ethylmethylphenylphosphine oxide (70) takes place exclusively at the methyl group.33 The former reaction provides a useful synthesis of appropriately alkylated vinylphosphine oxides (69) which are not otherwise easily prepared (Scheme 12). The N-silylated nitrile imines (72) have been prepared in solution by silylation of carbanions (71) of diazomethylphosphine sulphides.34 At room temperature compounds (72) rearrange to the isomeric diazo compounds (73). 

Methylene compounds activated by cyano or nitro groups (e. g., malonodinitrile, see Keller et al., 1975, and Stadler et al., 1975) exhibit a complex product pattern in classical diazo transfer reactions with tosyl azide. It seems, however, that ben-zothiazolium salts (Balli et al., 1978a), or such salts in combination with NaN3 in CH3OH-H2O (Kolobov et al., 1987) can be used for the synthesis of 2-diazo-nitriles. 

Ducept and Marsden described a general synthesis of 5-ethoxy-2-substituted 4-(triethylsilyl)oxazoles 176 from the rhodium(II)octanoate-catalyzed diazo-transfer reaction of ethyl (triethylsilyl)diazoacetate 175 and nitriles (Scheme 1.48). The reaction conditions tolerate a wide variety of functional groups on the nitrile, including alkyl, aryl, heteroaryl, vinyl, carbonyl, sUyloxy, and dialkylamino. Desilylation of 176 with TBAF afforded the corresponding 2-alkyl(aryl)-5-ethoxy-oxazoles 177, which are normally inaccessible from diazoesters using conventional rhodium-carbene methodology. The authors noted that carbonyl groups in the 2 position of 176 are not compatible with TBAF deprotection. 

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