Nitroso acetals alkyl nitronates

Silylation of 3-alkyl-substituted five-membered cyclic nitronates remains virtually unknown, although one example of the successful synthesis of the corresponding nitroso acetal was documented (Scheme 3.203) 475. 

However, C,C-coupling reactions of sterically less hindered alkyl nitronates derived from secondary AN with silyl ketene acetal were successfully performed (Eq. 3). These reactions produced the target mixed nitroso acetals in moderate yields. 

Aside from the relatively trivial conversions of nitronates to the corresponding oxime and carbonyl compounds (10,11), the chemistry of nitronates remained relatively unexplored for much of the early 1900s. However, in 1964, Tartakovskii et al. (12) demonstrated that alkyl nitronate esters were competent partners in the newly discovered class of dipolar cycloadditions with alkenes (Scheme 2.1). Both cyclic and acyclic nitronates participated, thus providing a new functional group were the nitrogen atom existed at the center of an acetal (13). These compounds were subsequently referred to as nitroso acetals (14) or nitrosals (15). 

The nitroso acetals that result from the [3 + 2] cycloaddition of alkyl nitronates with dipolarophiles typically provide several characteristic spectroscopic signals for identification. As in the silyl counterparts, the O—N—O stretch in the alkyl nitroso acetals is observed in the IR ranges between 1000 and 1030 cm (Tables 2.22 and 2.23) (57,75-77). However, this resonance is usually not strong, and can be obscured by other functional group resonances with more substituted nitroso acetals. 

The number of investigations on the enantioselective dipolar cycloaddition of nitronates is still rather limited. In the case of simple alkyl nitronates, the facial selectivity is controlled solely by the steric environment about the two faces of the chiral unit. For example, the reaction of steroid dipolarophile 270 proceeds with the nitronate approaching the Re face of the alkene (Eq. 2.23) (234). The facial selectivity is controlled by the C(19) methyl group, which blocks the Si face of the dipolarophile. Similarly, exposure of 279 to ethyl acrylate at 40 °C for 24 h, provides a single nitroso acetal (Scheme 2.21) (242). The facial selectivity is presumed to arise from steric shielding by the menthol group, however the full stereostructure has not been established. 

A very similar strategy has been used for the synthesis of (—)-7-epiaustraIine 272 (Scheme 16.57) and (—)-l-epicas-tanospermine (271) [142]. An important feature of the synthesis of (—)-l-epicastanospermine is that the alkylation has been used to constmct not the five-, but the six-membered ring of this indohzidine alkaloid. In this reaction sequence the [3 + 2] cycloaddition between the nitronate 248 (prepared as shown in Scheme 16.54) and dipolarophile 110 provides nitroso acetal 266 with very high yield and selectivity. L-Selectride reduction provides the common intermediate 267, which can be mesylated and used for the synthesis... 

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