Nitroaldol condensations

Various nitro compounds have been condensed with carbonyl compounds in reactions catalyzed by alkaline earth metal oxides and hydroxides 145). It was found that the reactivities of the nitro compounds were in the order nitro-ethane nitromethane 2-nitropropane, and those of carbonyl compounds were propionaldehyde isobutyraldehyde pivalaldehyde acetone benzaldehyde methyl propionate. Among the catalysts examined, MgO, CaO, Ba(OH)2, and Sr(OH)2, exhibited high activity for nitroaldol reaction of nitromethane with propionaldehyde. In reactions with these catalysts, the yields were between 60% (for MgO) and 26% (for Sr(OH)2) at 313 K after 1 h in a batch reactor. On Mg(OH)2, Ca(OH)2, and BaO, the yields were in the range of 3.8% (for BaO) and 17.5% (for Mg(OH)2). Investigation of the influence of the pre-treatment 

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The nitroaldol condensation reaction involving aldehydes and nitronates, derived from deprotonation of nitroalkanes by bases. 

Table 1. Grafting of 3-aminopropyl groups on mesoporous silica obtained in polar-protic, polar-aprotic and non-polar solvents, surface area and catalytic efficiency for Nitroaldol condensation of 4-hydroxybenzaldehyde and nitromethane [22]. 

A multi-stage synthesis of azocino[4,5,6-cd]indoles has been suggested (03M13519). From 4-bromoindole (84) with the help of successive transformations (among them the Vilsmeier-Haack reaction, Henry nitroaldole condensation, lithium aluminum hydride reduction and insertion of an allyl fragment), indole 85 has been produced in 18% yield. The cyclization of the latter on palladium... 

Interestingly, bis(methylthio)-l-nitroethylene (380) reacts with dimetallic zinc-copper species leading to the corresponding exo-methylene cycloalkenes, such as 381 (Scheme 100) . / -Disubstitutcd nitroolefins are especially difficult to prepare by nitroaldol condensation. The addition of zinc-copper reagents to nitroolefins followed by a reaction with phenylselenyl bromide produces, after IFO, oxidation, EtZ mixtures of -disubstituted nitroalkenes, such as 382 (Scheme 100) . 

The Sowden homologation [21], based on the nitroaldol condensation (Henry reaction) [22] between the aldehydo sugar and nitromethane in basic medium, followed by the Nef decomposition [23] of the resultant nitronate in strongly acidic conditions, has been employed in a more limited number of cases than the cyanohydrin synthesis. A recent example in this area is shown by the stepwise homologation of (V-acetyl-D-mannosamine (11) into /V-acetylneuraminic acid (12) [24] (Scheme 4). Also, this procedure has found... 

Bigi, F., Carloni, S., Maggi, R., Mazzacani, A. and Sartori, G. Nitroaldol condensation promoted by organic bases tethered to amorphous silica and MCM-41-type materials. Stud. Surf. Sci. Catal., 2000, 130D, 3501-3506. 

The ligands in 9.7-9.9 are all based on N,0 or N,N donor-atom-based chelating systems. In contrast, the ligands in 9.10-9.12 are all bidentate alkoxides, with 0,0 donor atoms. The chirality in binapthol, 9.11, arises from the fact that due to steric interactions the molecule does not have a plane of symmetry. The two naphthyl rings lie in different planes. The complex 9.12 has binaphthol as the ligand. Complexes such as 9.12 are used as catalysts in nitroaldol condensation reaction (see Section 9.5.4). 

Figure 9.1 Chiral ligands and metal complexes with hard donor atoms. The complexes of these ligands with metal ions in relatively high oxidation states are used in asymmetric epoxidation, cyclopropanation, and nitroaldol condensation reactions.

Asymmetric nitroaldol condensation, reaction 9.10, has been used to make an intermediate for the drug S-propanolol 9.61. The condensation reaction is catalyzed by the chiral heterobimetallic binaphthol complex 9.12 with high (>90%) enantioselectivity. 

Figure 9.15 Catalytic cycle for asymmetric nitroaldol condensation reaction with 9.12 as the chiral catalyst. The La-O bond marked by an arrow opens up due to protonation of the O atom by nitromethane.

The e.e. of the nitroaldol condensation reaction between PhCHO and CH3N02 catalyzed by 9.12-type complexes with different rare earth metals are <20% for Yb3+, 40% for Y3+, and >70% for Eu3+,Sm3+. Give a plausible explanation. 

As reported in Figure 2.5, nitroolefins (26), easily obtained by nitroaldol condensation between 5-nitro ketones (24) and aldehydes (25), are converted directly into the spiroketals (29) by reduction with sodium boronhydride in methanol. The one-pot reduction-spiroketalization of nitroalkenes (26) probably proceeds via the nitronate (27) that by acidification is converted into carbonyl derivatives, which spontaneously cyclize to emiketals (28). Removal of the tetrahydropyranyl group, by heating the acidic mixture during the workup, affords, in a one-pot reaction from (26), the desired spiroketals in 64-66% overall yields. The spiroketalization of (26)-(29b) proceeds in high ( )-diastereoselectivity. 

The nitroaldol condensation with nitromethane (Henry s reaction), followed by Nef decomposition of the resultant nitronate under strongly acidic conditions, has been used to elongate aldehydes. For instance, A-acetyl-D-mannosamine has been converted into A-acetylneuraminic acid applying this method iteratively [69]. Chikashita and coworkers [70] have reported good levels of anti diastereoselectivity better than 99% in an iterative homologation sequence using 2-lithio-l,3-dithiane [71] with 2,3-O-cyclohexylidene-D-glyceraldehyde R)-62. In the case of the BOM-protected tetrose derivative, the addition of 2-lithio-l,3-dithiane was syn selective (synlanti 82 18) (Scheme 13.30). 

The nitroaldol condensation with nitromethane (Henry s reaction), followed by Nef decomposition of the resultant nitronate under strongly acidic conditions has been used to elongate aldehydes. For instance, A-acetyl-D-mannosamine has been converted into A-acetylneu-... 

Khan, F. A., Dash, J., Satapathy, R., Upadhyay, S. K. Hydrotalcite catalysis in ionic liquid medium a recyclable reaction system for heterogeneous Knoevenagei and nitroaldol condensation. Tetrahedron Lett. 2004,45, 3055-3058. 

As base. Nitroaldol condensation and conjugate addition of dialkyl phosphites to a,p-unsaturated carbonyl compounds are readily catalyzed by tetramethylguanidine at 0°. 

The nitroaldol condensation between nitroalkanes and aromatic aldehydes to give ( )-nitrostyrenes 24 (Scheme 3.8), routinely performed in the presence of a wide range of base catalysts, has been studied in the presence of aliphatic amines supported on MCM-41 silica. 

MSN materials functionalized with AEP and a hydrophobic secondary group such as allyl (AL) and mercaptopropyl (MP) showed a great polarity effect in the nitroaldol condensation of 4-hydroxy- and 4-octyloxybenzaldehyde with nitromethane (Scheme 3.37). ... 

Bellini R, Noe M, Perosa A, Selva M (2008) Selective nitroaldol condensations over heterogeneous catalysts in the presence of supercritical carbon dioxide. J Org Chem 73 8520-8528... 

As bases. The ylides (Me2N)3P=CR2 serve as bases in alkylation reactions, nitroaldol condensation, and the Homer reaction. 

As base. For vicarious substitution of m-dinitrobenzene with carbon nucleophiles under photochemical conditions, TBAF serves as the base. The nitroaldol condensation with a-amino aldehydes constitutes the key step of a stereoselective synthesis of 1,3-diamino-2-alkanols. ... 

The butyrolactone skeleton of precursors for the sugar component of the glycoside antibiotics L-ristosamine and L-daunosamine can be readily assembled by a nitroaldol reaction of 3-nitropropionate (553) with 831, followed by lactonization [229] (Scheme 111). The initial condensation gives 832 in only moderate yield, probably due to the reversible nature of the nitroaldol reaction. If the crude product is treated with pyridinium tosylate, a mixture of lactones 833 and 834 is produced with concomitant loss of the THP group. The ratio of lactones is dependent on the base used in the nitroaldol condensation. Use of potassium tert-butoxide affords a 2 1 mixture of 833 and 834. The ratio can be increased to 5 1 with KF 2H20/tetrabutylammonium chloride, but the overall yield decreases. 

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