Silyl nitronates applications

A series of 3-substituted-2-isoxazoles are prepared by the following simple procedure in situ conversion of nitroalkane to the silyl nitronate is followed by 1,3-dipolar cycloaddition to produce the adduct, which undergoes thermal elimination during distillation to furnish the isoxazole (Eq. 8.74). 5 Isoxazoles are useful synthetic intermediates (discussed in the chapter on nitrile oxides Section 8.2.2). Furthermore, the nucleophilic addition to the C=N bond leads to new heterocyclic systems. For example, the addition of diallyl zinc to 5-aryl-4,5-dihydroi-soxazole occurs with high diastereoselectivity (Eq. 8.75).126 Numerous synthetic applications of 1,3-dipolar cycloaddition of nitronates are summarized in work by Torssell and coworker.63a... 

This chapter is divided into four major sections. The first (Section 2.1) will deal with the structure of both alkoxy and silyl nitronates. Specifically, this section will include physical, structural, and spectroscopic properties of nitronates. The next section (Section 2.2) describes the mechanistic aspects of the dipolar cycloaddition including both experimental and theoretical investigations. Also discussed in this section are the regio- and stereochemical features of the process. Finally, the remaining sections will cover the preparation, reaction, and subsequent functionalization of silyl nitronates (Section 2.3) and alkyl nitronates (Section 2.4), respectively. This will include discussion of facial selectivity in the case of chiral nitronates and the application of this process to combinatorial and natural product synthesis. 

There are also several variations on this procedure. The use of trimethylsilyl triflate (TMSOTQ provides the silyl nitronate of methyl nitroacetate in good yield. However, for primary nitroalkanes, a second silylation occurs at the a-position of the nitronate (Eq. 2.5) (102). The use of TMSCl in the presence of lithium sulfide provides good yields of silyl nitronates from secondary nitroalkanes (103,104). Unfortunately, the number of examples is limited and this procedure is not applicable to primary nitroalkanes. 

Less well-established cycloaddition chemistry has also found application in the synthesis of heterocyclic compounds in recent years. An example is the intramolecular cycloaddition of silyl nitronates that has been employed by Ishikawa and Saito to afford 136 in their synthesis of amino polyols (Scheme 14) <2003OL3875>. 

Further applications of the chiral ammonium bifluoride-catalyzed enantioselective Michael addition of silyl nitronates has been shown in the reactions with nitroalkenes as a Michael acceptor (Scheme 9.17). These studies were started by examining the reaction of nitropropane-derived silyl nitronate 23b with P-nitrostyrene, using the chiral quaternary ammonium bifluoride (R,.R)-6d. When P-nitrostyrene was treated with 23b (1.2 equiv.) in the presence of (K,f )-6d (2mol%) in THF at — 78 °C, the... 

Ishikawa T, Shimizu Y, Kudoh T, Saito S (2003) Conversion of D-glucose to cychtol with hydroxymethyl substituent via intramolecular silyl nitronate cycloaddition reaction application to total synthesis of (+)-cyclophelhtol. Org Lett 5 3879-3882... 

Nitro compounds are versatile synthetic intermediates which have found widespread utility in industrial applications. Aromatic nitro compounds are the usual starting materials for commercial applications, but aliphatic compounds exhibit a greater diversity of chemical behavior under reducing conditions. " Nitroso compounds, hydroxylamines, oximes, amines, nitrones, ketones and silyl nitronates are frequently encountered during the reduction of nitro compounds. Several specialized reviews have appeared which highlight the versatility of the nitro group in organic chemistry. ... 

Silyl nitronates, the preactivated nucleophiles of nitroalkanes, are also applicable in the asymmetric conjugated addition reaction with a,(S-unsaturated aldehydes, ketones, and nitroalkenes. Maruoka and co-workers [115] found that AT-spiro... 

The second most important synthetic application of silyl nitronates in C-C bond-forming reactions is their fluoride-mediated addition to aldehydes. Silyl nitronates from secondary nitroalkanes lead to free nitro aldols such as (4), while those from primary nitro alkanes give silylated products. In contrast to the classical Henry reaction, the silyl variant is highly diastereose-lective with aldehydes, furnishing e yfAro-0-silylated nitro aldols (e.g. 5). It is important that the reaction temperature does not rise above 0 °C, otherwise threo/erythro equilibration takes place. The same erythro-nitio aldol derivatives are available by diastere-oselective protonation of silyloxy nitronates (eq 3) (usually the dr is >20 1), while the nonsilylated fAreo-epimers (R = H, dr = 7 3-20 1) are formed by kinetic protonation of lithioxy lithio nitronates in THF/DMPU (eq 4). Other recent modifications of the nitroaldol addition using titanium nitronates or ClSiRs in situ are less selective. It should also be mentioned that there are recent reports about the enantioselective addition of nitromethane to aldehydes in the presence of rare earth binaphthol complexes. 

Evidently, this approach is not limited to the formation of nitronates, nitroso acetals or enoximes. The rearrangements of these compounds by elimination reactions, the trapping of intermediates and finally their reactions with various reagents are of equal importance. It should be emphasized that silylation of AN as a process in organic chemistry is characterized by an unrivalled completeness and diversity of transformations. Hence, the silylation can be considered as a separate field of application of AN in organic synthesis. 

Silyl enol ethers and ketene silyl acetals add to aromatic nitro compounds in the presence of TASF(Me) to give intermediate dihydro aromatic nitronates which can be oxidized with bromine or 2,3-dichloro-5,6-dicyano-l,4-benzoquinone to give a-nitroaryl carbonyl compounds the latter are precursors for indoles and oxindoles. The reaction is widely applicable to alkyl-, halo-, and alkoxy-substituted aromatic nitro confounds, including heterocyclic and polynuclear derivatives (eq 7). 

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