In the Henry reaction

The diastereoselectivity is observed in the Henry reaction using optical active niti o compounds or a-heteroatom substituted aldehydes. Lor example, the reaction of O-benzyl-D-lactal-dehyde with methyl 3-niti opropionate in the presence of neubal alumina leads to a mixture of three niti o-aldol products from which D-ribo isomer is isolated by direct crystallization. D-Ribo... 

The Michael addition of nitroalkanes to election-deficient alkenes provides a powerful synthetic tool in which it is perceived that the nitro group can be transformed into various functionalities. Various kinds of bases have been used for this transformation in homogeneous solutions, or, alternatively, some heterogeneous catalysts have been employed. In general, bases used in the Henry reaction are also effective for these additions (Scheme 4.18).133... 

The C,C-coupling reactions of SENAs with carbonyl compounds were studied in most detail (132, 179, 182, 183, 185, 253, 254, 449, 450). Only aldehydes are involved in the Henry reaction with SENAs and activating additives of ammonium fluorides (or triethylamine (185)) are required for this process (Scheme 3.189). 

Figure 6.54 Structures of guanidine-based thiourea derivatives screened in the Henry reaction of nitromethane with cyclohexane carboxaldehyde under phase-transfer conditions.

Figure 6.55 Uncharged tris-thiourea 190 without guanidinium moiety and charged guanidinium structure 191 without a thiourea group appeared catalytically inactive in the Henry reaction of cyclohexane carboxaldehyde with nitromethane, while guanidine-thiourea 183 gave 99% yield and 95% ee under identical (optimized) conditions.

All the steps in the Henry reaction are completely reversible. The first step of the mechanism is the deprotonation of the nitroalkane by the base at the a-position to form the corresponding resonance stabilized anion. Next, an aldol reaction (C-alkylation of the nitroalkane) takes place with the carbonyl compound to form diastereomeric P-nitro alkoxides. Finally the P-nitro alkoxides are protonated to give the expected p-nitro alcohols. 

Gao, J., Marteii, A. E. Novei chirai N4S2- and NeSs-donor macrocyciic iigands synthesis, protonation constants, metai-ion binding and asymmetric cataiysis in the Henry reaction. Org. Biomol. Chem. 2003, 1, 2801-2806. 

Concerning future work, an improvement might be the extension of the asymmetric catalytic nitroaldol reaction to the field of solid-support synthesis. An interesting contribution concerning the use of dendritic catalysts in the Henry reaction was reported very recently by Cossio et al. [48], who demonstrated that dendrimers based on achiral triethanolamine exhibit catalytic properties. Several nitroalkanols were synthesized with syn/anti ratio up to 2 1 (racemic syn- and anti-products). The design of enantiomerically pure dendrimers and their application to the field of asymmetric catalytic nitroaldol reaction should be of high interest. 

Sterochemical control in the Henry reaction had been essentially neglected until lithionitronates, doubly-lithiated nitronates and silylnitronates methodologies were explored. Treatment of nitropropane with -BuLi furnishes nitronate 57, which then reacts with 4-nitrobenzaldehyde in the presence of Ti(/-OPr)Cl3 in THF to provide nitroalcohol 55 in high erythro anti) selectivity. Silyl nitronates in the presence of fluorides also prefers erythro (anti) products " while dilithiated nitronates reacts with aldehydes to afford 2-nitroalcohols in high threo syn) selectivity. ... 

Figure 6.12 Simplified intermediate structures in the Henry reaction.

While these organocatalysts comprise a considerably broad stractural/functional spectrum, a common requirement for them to work efficiently in the Henry reaction appears to be the presence of (i) a basic unit to generate the nucleophilic nitronate species and (ii) some hydrogen bond donor sites capable of interacting with the acceptor carbonyl group. 

At almost the same time, and based on their earUer studies with cinchona alkaloid organocatalysts bearing both a Br0nsted-base and thiourea residues, Hiemstra and coworkers were able to achieve good enantioselectivities and yields in the Henry reaction between aromatic aldehydes and nitromethane [8]. With unactivated aromatic aldehydes (i.e., R = 4-MeO-Ph) longer reaction times were required (Scheme 29.3). 

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