Nitroaldol addition

As described here, both enantiomers of 3 can be prepared In three steps from commercially available diethyl D- and L-tartrate in up to 70% over-all yield.2 3 5 Procedures to obtain the benzylidene acetal,11 12 with the ensuing reduction step,11. 2 are based on previous literature reports. Both enantiomers of 3 have been used in highly stereoselective nitroaldol additions.3 13 Imines, nitrones, oximes, and nitrile oxides derived therefrom were recently employed in a variety of additions/cycloadditions.14 15 (-)-2-0-Benzyl-L-glyceraldehyde has further been used... 

Aliphatic nitro compounds are highly versatile building blocks in organic synthesis7 8 (see Scheme 1). For example, the nitroaldol addition (Henry reaction)9 leads to the formation of 1,2-nitro alcohols, 2, which are easily transformed into 1,2-amino alcohols, 3, by reduction, and into a-hydroxycarbonyl compounds, 4, by hydrolysis10 (Nef reaction). The former process, mostly using nitromethane, has been widely employed in carbohydrate chemistry.11... 

By examining Scheme 1 it is possible to verify the key role of the base as catalyst for the overall process and to justify the lack of stereoselectivity which, in general, has been observed in nitroaldol additions. In fact, the reversibility of the nitroaldol process, as well as the difficulty of a stereoselective protonation of the stereogenic center of the nitronate intermediates, leads to a mixture of diastereomeric 2-nitro alcohols. 

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. 

A closely related C-C bond-forming process is the LLB-catalyzed Henry -or nitroaldol - addition reaction [106, 108]. The earliest reported enantiose-lective example of this used nitromethane and a broad selection of aldehydes. Shibasaki described asymmetric nitroaldol reactions in the presence of (R)-LLB (213) in the synthesis of the effective /3-blocker (-)-pindolol (221, Scheme 4.25) [109]. 

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