Silyl nitro addition, Henry reaction

TBDMSCl-Assisted Reactions. Nitro aldol (Henry) reactions have been reported to be promoted by TBDMSCl. To a THF solution of tetra-n-butylammonium fluoride is added sequentially equimolar amounts of the nitro compound, aldehyde, and EtsN, followed by an excess of TBDMSCl (eq 11). Substitution of TMSCl for TBDMSCl reduces the yield of nitro aldol product. The authors speculate that TBDMSCl is responsible for activation of the aldehyde while n-Bu4NF activates the nitro compound. In a related method, primary and secondary nitro alkanes were treated with LDA in THF followed by addition of TBDMSCl to give the corresponding silyl nitronates. The silyl nitronates reacted with a variety of aliphatic and aromatic aldehydes which gave vicinal nitro TBDMS aldol products. ... 

The basc-eatalyzcd addition of nilroalkancs to carbonyl compounds is a reversible reaction and proceeds under thermodynamic control. Thus low (R, R )/(R, S ) selectivities arc observed in the classical Henry reaction which leads to the silylated x-nitro alcohols 2. 

The classical Henry reaction conditions (base catalyzed addition) have some drawbacks sometimes the nitro alcohols are obtained in low yields and diastereoselectivities are not always high. To improve these results, a number of modifications were introduced. One of them is the Seebach s silyl nitronate method,25 that involves a reaction between an aldehyde with a silyl nitronate prepared by metalation of the corresponding nitro alkane with LDA, followed by reaction of the resulting nitronate with tert-butyldimethylsilyl chloride.26... 

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. 

Classical C,C-coupling reactions of AN anions (Henry, Michael, and Mannich) involve complex systems of equilibria and, consequently, generally not performed in protic solvents. The introduction of the silyl protecting group allows one to perform these reactions in an aprotic medium to prepare or retain products unstable in the presence of active protons. In addition, the use of nucleophiles which are specifically active toward silicon (e.g., the fluoride anion) enables one to design a process in which the effective concentration of a-nitro carbanions is maintained low. 

---