Dipolarophiles silyl nitronates

Other Types of Nitronates in [3 + 2]-Cycloaddition Reactions with Olefins As mentioned above, of all known types of nitronates, only alkyl and silyl nitronates can be involved in [3 + 2]-cycloaddition reactions with olefins. However, furoxans (161), which can also be considered as cyclic nitronates, can react with active dipolarophiles under extreme conditions to give nitrosoacetals (162) (Scheme 3.131, Eq. 1). 

Silyl nitronates containing chiral inductors have not been as yet used in intermolecular [3 + 2]-cycloaddition reactions. In this case, the facial discrimination was generally created by introducing chiral nonracemic fragments into dipolarophiles (see review 433). 

The primary cycloadduct from combination of a dipolarophile with a silyl nitronate is an isoxazolidine. The and NMR spectra are highly informative for the structural determination of these products. Tables 2.7 and 2.8 (21,25,34,35). Both the and NMR data show that HC(5) are shifted downfield relative to HC(3). An expected downheld shift is also observed with electron-withdrawing or conjugating groups. In the absence of functionalization at C(3), there is a significant upfield shift of the corresponding resonance. The IR data is less reliable. The O—N—O stretch is reported to be 1055 cm (Fig. 2.8), however, this stretching... 

A more common method for the preparation of silyl nitronates is the use of trimethylsilyl chloride (TMSCl) in the presence of a base. With triethylamine, silyl nitronates are prepared from primary nitroalkanes in moderate yields however, it is necessary to conduct the silylation in acetonitrile for good yields with secondary nitroalkanes (18,101). In several cases, this silylation has been done in the presence of the dipolarophile for both inter- and intramolecular processes, or the nitronate has been used in subsequent reactions without purification (18,22). Employment of l,8-diazabicyclo(5.4.0)undec-7-ene (DBU) as the base allows this procedure to be general for most nitroalkanes (19). 

The steric and electronic properties of the dipolarophile have a large impact on the rate and yield of the cycloaddition. In the case of simple monosubstituted silyl nitronates, the [3 + 2] cycloaddition proceeds smoothly with dipolarophiles bearing electron-withdrawing or conjugating groups (Table 2.34) (20,101,108,109). 

Only a few attempts to control the facial selectivity of this [3+2] process are on record, all dealing with the use of chiral, non-racemic dipolarophiles (117). The reactions of a vinyl substituted cephem (121) with the silyl nitronates derived from nitromethane, nitroethane, and nitropropane proceed over 3 days at room temperature to provide a single stereoisomer in moderate yields, Eq. 2.8 (118,119). Approach of the simple nitronate to the dipolarophile is believed to be from the less hindered a-face, however, the configuration of the newly created stereocenter could not be unambiguously assigned. 

In a second report on the use of chiral dipolarophiles, the cycloadditions of silyl nitronates with 123 and 124 provide modest facial selectivity (Table 2.37) (35). Unfortunately, the yields of the cycloadducts are only moderate because of the steric bulk of the dipolarophile. 

A second strategy to control facial selectivity involves the use of chiral sultams and lactams as auxiliaries for the dipolarophile (120-123). Cycloaddition of 132 with a variety of substituted nitronates provides up to 9 1 selectivity of the major diastereomer (Table 2.38). However, substitution at the a-position of the dipolarophile leads to a reduction in stereoselectivity (entry 5). Assuming an s-cis conformation of the dipolarophile, it is proposed that the major isomer arises from an endo approach of the nitronate to the Re face of the dipolarophile (Fig. 2.13). This is supported by X-ray crystallographic analysis of one of the cycloadducts, which resides in a conformation similar to the proposed transition state. However, this analysis assumes that the silyl nitronate is only reacting through the... 

E) configuration. The dipolar cycloaddition of 141 with a silyl nitronate shows a slight increase of facial selectivity over 132 (Eq. 2.9). Because the cycloadducts are converted directly to the corresponding isoxazolines, only the facial selectivity can be determined. It is believed that the cycloaddition proceeds on the Re face of the dipolarophile due to shielding of the Si face by the auxihary. Both chiral auxiliaries can be liberated from the cycloadduct upon reduction with L-Selectride. 

The intramolecular cycloaddition of a silyl nitronate bearing a dipolarophilic appendage provides easy access to fused, bicyclic isoxazolidines (22). This process, in general, is very facile, and has allowed the use of unfunctionalized alkenes as dipolarophiles (Table 2.39) (106,124). Thus, a silyl nitronate bearing an allyl group will undergo the [3 + 2] cycloaddition at room temperature over 15 h to provide the corresponding isoxazoline upon acidic workup in moderate yield. 

Several diastereomers may result from the [3 + 2] cycloaddition of silyl nitronates. In the case of the trifluoroisoxazolidine, the major isomers are epimers at nitrogen due to the high inversion barrier (24). Diastereomers from different modes of approach of the dipolarophile are observed in less significant amounts. Equilibration of the nitrogen epimers is accomplished upon heating in toluene at 110°C for several hours. 

Heteroatomic dipolarophiles are competent in the dipolar cycloaddition of nitronates. The in situ generated thioaldehydes and thioketones react with silyl nitronate 120 to afford the 1,4,2-oxathiazolidine in good yield (Table 2.36) (113-116). 

Silyl nitronate dipoles - reaction with auxiliary-bearing C=C dipolarophiles... 

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. 

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