For nitro-aldol

Proazaphosphao-ane, PrRNCH-,CH-j,N, is an efficient catalyst for the Henty reacdon, and arious ketones give nitro-aldols by the reacdon with nitromethane and other nitroalkanes fEq. 

The nitro-aldol reacdon followed by dehydradon gives 3-rutto- 1,3-dienes, which are usefid reagents for cycloaddidon fEq. 3.45. ... 

Several approaches based on nitro-aldol for the synthesis of amino sugars have been reported Alumina-catalyzed reaction of methyl 3- nitropropanoate with O-benzyl-o-lactaldehyde gives the o-ribo-nitro-aldol fanti, and isomeri in 63% yield, which is converted into L-dannosamine fsee Secdon 3 3 Jager and coworkers have reported a short synthesis of L-acosamine based on the stereoselective nitro-aldol reaction of 2-O-benzyl-L-lactaldehyde with 3-nitropropanal dimethyl acetal as shovm in Scheme 3 10 The stereoselecdve nitro-aldol reacdon is carried ont by the silyl nitronate approach as discussed in Secdon 3 3... 

A syn-selective asymmetiic nih o-aldol reaction has been reported for structurally simple aldehydes using a new catalyst generated from 6,6-bis[(tiiethylsilyl)ethynyl]BINOL (g in Scheme 3.18). The syn selectivity in the nitro-aldol reaction can be explained by steric hindrance in the bicyclic transition state as can be seen in Newman projection. In the favored h ansition state, the catalyst acts as a Lewis acid and as a Lewis base at different sites. In conbast, the nonchelation-controlled transition state affords anti product with lower ee. This stereoselective nitro-aldol reaction has been applied to simple synthesis of t/ireo-dihydrosphingosine by the reduction of the nitro-aldol product with H2 and Pd-C (Eq. 3.79). 

The LLB catalysts requires at least 3.3 mol% of asymmehic catalyst for efficient nitro-aldol reactions, and the reactions are rather slow (first generation). Second-generation LLB catalysts are prepared by addition of 1 equiv of H2O and 0.9 equiv of n-BuLi. The second-generation-catalysts are more reactive than the first generation LLB as shown in Eq. 3.80. The proposed mechanism of asymmetiic niti o-aldol reaction using these catalysts is presented in Scheme 3.20. ... 

In d sumldf way, a-nitroselenides are prepared via the reacdon of nitronates with phenylse-lenyl bromide, which gives a new synthedc method of 1-nitroalkenes from nitroalkanes The sequence of ct-selenadon, nitro-aldol reacdon, and oxidadon provides a nsefid method for the preparadon of nitroalkenes with a hydroxymethyl group fEq 5 81 ... 

Magnus and coworker have presented a new strategy for the preparadon of taxane diterpenes by using nitro-aldol reacdon and denitradon as key steps fsee Scheme 11 ... 

The present tandem nitro aldol-cyclizadon process is used for the preparadon of the enandomerically pure 4-hydroxy-3-isoxa2olme-3-ones They are prepared starting from chiral ct-mesyloxy aldehydes and ethyl nitroacetate under rruld reacdon conthdons fEq 8 85 ... 

A trifold anionic/pericyclic domino reaction was used for the synthesis of the dioxapyrrolizidine 2-655 combining a nitro aldol condensation, SN-type cyclization, SN-type etherification, and an intramolecular 1,3-dipolar cyclization as described by Rosini and coworkers (Scheme 2.148) [339]. 

Thus, various kinds of bases are effective in inducing the Henry reaction. The choice of base and solvent is not crucial to carry out the Henry reaction of simple nitroalkanes with aldehydes, as summarized in Table 3.1. In general, sterically hindered carbonyl or nitro compounds are less reactive not to give the desired nitro-aldol products in good yield. In such cases, self-condensation of the carbonyl compound is a serious side-reaction. Several modified procedures for the Henry reaction have been developed. 

The nitro-aldol reaction can also be carried out in water using NaOH in the presence of cetyltrimethylammonium chloride (CTAC1) as a cationic surfactant. CTAC1 (5 mmol) is added to a mixture of nitroalkane (50 mmol) and aldehyde (50 mmol) in NaOH 0.025 M (150 mL) at room temperature. The mixture is stirred for 2-3 h and worked up to give the product in 70-90% yield. Compared with the classical methods, this procedure has economical and environmental advantages (Eq. 3.16).27... 

The nitro-aldol reaction followed by dehydration gives 2-nitro-l,3-dienes, which are useful reagents for cycloaddition (Eq. 3.45).70... 

The nitro-aldol approach is impractical for the synthesis of 2,2-disubstituted 1-nitroalkenes due to the reversibility of the reaction when ketones are employed as substrates. Addition-elimination reactions are used for the preparation of such nitroalkenes (see Chapter 4). 

The heterobimetallic asymmetric catalyst, Sm-Li-(/ )-BINOL, catalyzes the nitro-aldol reaction of ot,ot-difluoroaldehydes with nitromethane in a good enantioselective manner, as shown in Eq. 3.78. In general, catalytic asymmetric syntheses of fluorine containing compounds have been rather difficult. The S configuration of the nitro-aldol adduct of Eq. 3.78 shows that the nitronate reacts preferentially on the Si face of aldehydes in the presence of (R)-LLB. In general, (R)-LLB causes attack on the Re face. Thus, enantiotopic face selection for a,a-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. The stereoselectivity for a,a-difluoroaldehydes is identical to that of (3-alkoxyaldehydes, as shown in Scheme 3.19, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

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

Jager and coworkers have used the TBAF catalyzed-stereoselective nitro-aldol reaction for the synthesis of cyclic amino alcohols such as iminopolyols, imino sugars, and cyclic amino acids. They are important classes of compounds and have the potential utility as anti-diabetic,... 

The nitro-aldol reaction using l,l-diethoxy-2-nitroethane is useful for lengthening of the carbon chain of carbohydrates. The reaction of Eq. 3.86 proceeds in a stereoselective way (ds 75%) to give the syw-nitro alcohol in 58% isolated yield.135 The product is converted into 2-amino-2-deoxyaldoses by reaction with H2/Raney Ni. 

Ono and Kamimura have found a very simple method for the stereo-control of the Michael addition of thiols, selenols, or alcohols. The Michael addition of thiolate anions to nitroalkenes followed by protonation at -78 °C gives anti-(J-nitro sulfides (Eq. 4.8).11 This procedure can be extended to the preparation of a/jti-(3-nitro selenides (Eq. 4.9)12 and a/jti-(3-nitro ethers (Eq. 4.10).13 The addition products of benzyl alcohol are converted into P-amino alcohols with the retention of the configuration, which is a useful method for anri-P-amino alcohols. This is an alternative method of stereoselective nitro-aldol reactions (Section 3.3). The anti selectivity of these reactions is explained on the basis of stereoselective protonation to nitronate anion intermediates. The high stereoselectivity requires heteroatom substituents on the P-position of the nitro group. The computational calculation exhibits that the heteroatom covers one site of the plane of the nitronate anion.14... 

Combining, in tandem, the nitro-aldol reaction with the Michael addition using thiophenol is a good method for the preparation of P-nitro sulfides as shown in Eqs. 4.2 and 4.3. This reaction is applied to a total synthesis of tuberine. Tuberine is a simple enamide isolated from Streptomyces amakusaensis and has some structural resemblance to erbastatin, an enamide which has received much attention in recent years as an inhibitor of tyrosine-specific kinases. The reaction of p-anisaldehyde and nitromethane in the presence of thiophenol yields the requisite P-nitro sulfide, which is converted into tuberine via reduction, formylation, oxidation, and thermal elimination of... 

Heterobimetallic asymmetric complexes contain both Bronsted basic and Lewis acidic functionalities. These complexes have been developed by Shibasaki and coworkers and have proved to be highly efficient catalysts for many types of asymmetric reactions, including catalytic asymmetric nitro-aldol reaction (see Section 3.3) and Michael reaction. They have reported that the multifunctional catalyst (f )-LPB [LaK3tris(f )-binaphthoxide] controls the Michael addition of nitromethane to chalcones with >95% ee (Eq. 4.140).205... 

Nitroacetaldehyde diethyl acetal is prepared by the reaction of nitromethane with triethyl orthoformate in the presence of ZnCl2 (Eq. 5.8).17 Jager and coworkers have used this reagent for the synthesis of amino sugars via nitro-aldol reaction.18 Preparation of this useful reagent is now described in volume 74 of Organic Synthesis.19... 

Ono and coworkers have extended the radical elimination of v/c-dinitro compounds to P-nitro sulfones151 and P-nitro sulfides.138,152 As P-nitro sulfides are readily prepared by the Michael addition of thiols to nitroalkenes, radical elimination of P-nitrosulfides provides a useful method for olefin synthesis. For example, cyclohexanone is converted into allyl alcohol by the reaction shown in Eq. 7.110. Treatment of cyclohexanone with a mixture of nitromethane, PhSH, 35%-HCHO, TMG (0.1 equiv) in acetonitrile gives ahydroxymethylated-P-nitro sulfide in 68% yield, which is converted into the corresponding allyl alcohol in 86% yield by the reaction with Bu3SnH.138 Nitro-aldol and the Michael addition reactions take place sequentially to give the required P-nitro sulfides in one pot. 

Nitro-aldols, which are readily available (see Henry reaction Section 3.1), are converted into olefins via conversion of the hydroxyl group to the corresponding phenyl thiocarbonate ester and treatment with tin radical.158 The yield was not reported. Because the radical deoxygenation via thiocarbonate (Barton reaction) proceeds in good yield, the elimination of Eq. 7.115 might be good choice for olefin synthesis.159... 

Another approach to cyclic nitronates has been developed by Rosini et al. in which nitro-aldol and subsequent cyclization is used as a key step. For example, 2,3-epoxy aldehydes react with ethyl nitroacetate on alumina surface in the absence of solvent to give 4-hydroxyisoxazoline 2-oxides in good yields (Eq. 8.80).130... 

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