Nitro compounds Nitroaldols

Due to the reversibility of this nitroaldol reaction, the easy epimerization at the nitro-sub-stituted carbon, and the often low yields in reactions with nitro compounds other than ni-tromethane, few stereoselective additions have been reported. Highly stereoselective reactions are known for the synthesis of cyclic systems (see Section 1.3.5.6.6.). 

Nitroalkanols are intermediate compounds that are used extensively in many important syntheses 142). They can be converted by hydrogenation into / -aminoalcohols, which are intermediates for pharmacologically important chemicals such as chloroamphenicol and ephedrine. They are obtained by Henry s reaction by the condensation of nitroalkanes with aldehydes. The classical method for this transformation involves the use of bases such as alkali metal hydroxides, alkoxides, Ba(OH)2, amines, etc. 142-144). However, these catalysts give predominantly dehydrated products—nitroalkenes— which are susceptible to polymerization (Scheme 16). The reaction proceeds by the nucleophilic addition of the carbanion formed by the abstraction of a proton from the nitro compound to the carbon atom of the carbonyl group, finally forming the nitroaldol by abstraction of a proton from the catalyst. 

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... 

The stable hemiacetal tetrahydropyranol 94 was used in a Wittig reaction to give the unsaturated ester 95 mostly as the E-isomer. Oxidation, nitroaldol and elimination gave the unsaturated nitro-compound 98. It turns out that the aryl-lithium does conjugate addition without any copper and that it reacts exclusively with the nitroalkene to give 99. 

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... 

Nitroalkanes having an a-hydrogen atom undergo aldol-type condensation with aldehydes and ketones in the presence of a base to give p-hydroxy nitro compounds or nitroethylene compounds. The reaction is known as the Henry reaction " or nitroaldol reaction. 

Nitroaldol Reaction (The Henry Reaction). The nitroaldol reactions (or Henry reaction) is an aldol type reaction between a nitro compound and a carbonyl compound. The primary aldol products may be dehydrated to the corresponding alkenes. 

In the mid-2000s, Griengl and coworkers reasoned that a small molecule with a similar pK as HCN, for example, nitromethane, could act as nucleophile for addition to carbonyl compounds (nitroaldol or Henry reaction Scheme 25.3) [111]. The Henry reaction is a classical name reaction in organic chemistry for the formation of C—C bonds. The resulting p-nitro alcohols can be transformed to nitroalkenes, 2-nitroketones, a-hydroxycarboxylic acids, and 1,2-amino alcohols. Although several other enzymes and proteins such as hydrolases and lipases [112], transglutaminase... 

Sequential radical cyclizations are also featured in an efficient and clever synthesis of the cedrane framework 83 (see Scheme 15).30 Compound 81, the product of a regioselective Diels-Alder reaction between isoprene (79) and nitroethylene (80), participates in a nitroaldol reaction (Henry reaction) with 5-methyl-4-hexenal in the presence of a basic resin to give 82. Because the nitro group in... 

Another recent example supporting the influence of the nature of the base in intramolecular Henry reactions in nitro sugars is depicted in Scheme 23. The intramolecular nitroaldol cyclization of compound 67 using alkoxides, hydroxides or carbonates gave unsatisfactory results, but when this compound and DABCO (3 eq.) were refluxed in benzene, surprisingly, only... 

The compound 3 can be easily prepared, in one pot, through a solvent-free procedure by nitroaldol reaction of nitroalkane 1 (2.2 mmol) and aldehyde 2 (2.2 mmol, freshly distilled), on activated neutral alumina (0.6 g, the alumina was added to a mechanically stirred solution of 1 and 2, at 0°C, then at room temperature for 20 h). Then, in situ addition (0°C) of wet-alumina supported chro-mium(VI) oxide (0.88 g (8.8 mmol) of C1O3 and 2.64 g of wet alumina). After standing for additional 20 h, the product was extracted with diethyl ether and passed through a bed of alumina. Evaporation of the organic solvent and flash chromatographic purification afforded the pure a-nitro ketone 3 in good yields (68-86%). 

Nitroaldol reactions of enantiomerically pure a-amino aldehydes with nitromethane using a catalytic amount of LLB were found to proceed in a highly diastereoselective manner.35 The adducts (3-amino-2-hydroxy-l-nitro derivatives) are attractive intermediates for the synthesis of unnatural erythro-amino-2-hydroxy acids, which are important components of several biologically active compounds. As an example, the promising HIV-protease inhibitor KNI-272 (65)36 37... 

The Henry reaction or the nitroaldol is a classical reaction where the a-anion of an alkyinitro compound reacts with an aldehyde or ketone to form a p-nitroalcohol adduct. Over the decades, the Henry reaction has been used to synthesize natural products and pharmaceutical intermediates. In addition, asyimnetric catalysis has allowed this venerable reaction to contribute to a plethora of stereoselective aldol condensations. Reviews (a) Ballini, R. Bosica, G. Fiorini, D. Palmieri, A. Front. Nat. Prod. Chem. 2005, 1, 37-41. (b) Ono, N. In The Nitro Group in Organic Synthesis Wiley-VCH Weinheim, 2001 Chapter 3 The Nitro-Aldol (Henry) Reaction, pp. 30-69. (c) Luzzio, F. A. Tetrahedron 2001, 57, 915-945. 

Intramolecular nitroaldol reactions of 6-nitro- 1,3-dicarbonyl compounds (46) have been the focus of attention for their peculiar aspects. Seebach et al.69>7° reported the cyclization of these (equation 17), yielding highly functionalized and substituted six-membered rings in diastereomerically pure form. Cyclization of the corresponding 5-nitro-1,3-dicarbonyl compounds (equation 18) has been performed by adding a tetrahydrofuran solution of them and diisopropylamine to hydrochloric acid/borate buffer solution. Compounds (47) and (48), certainly formed as intermediates in all these reactions as one stereoisomer, were not very stable and an easy elimination of nitrous acid from (47) gave (48), which completely rearranged to the more stable isomer (49). 

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