Vinylation nitroalkanes

Three-component tandem cyHzations involving [2 -1- 4] and [2 -1- 3] additions can be performed vdth vinyl nitroalkanes bound to the polymer. In some cases, however, high pressure is necessary to perform the conversions [338, 339], Based on the design of the building blocks, reduction of the N-0 bonds formed in cycloaddition may lead to formal O-contraction, resulting in compact polycyclic amines of defined relative configurations [340]. 

Many of these reactions are reversible, and for the stronger nucleophiles they usually proceed the fastest. Typical examples are the addition of ammonia, amines, phosphines, and bisulfite. Alkaline conditions permit the addition of mercaptans, sulfides, ketones, nitroalkanes, and alcohols to acrylamide. Good examples of alcohol reactions are those involving polymeric alcohols such as poly(vinyl alcohol), cellulose, and starch. The alkaline conditions employed with these reactions result in partial hydrolysis of the amide, yielding mixed carbamojdethyl and carboxyethyl products. 

Nitrodesilyladcn fEq. 2.17 and nitrodeslanyiadon fEq. 2.18 are ef cienl methods for the preparadon of some lands of nitroalkanes from readily available alkylsilanes or ailylslan-nanes. Similar nitradon also lakes place al the vinylic posidons fsee Eq. 2.36 in Secdon 2.1.4. ... 

Nitrodesilylation (Eq. 2.17)36 and nitrodestanylation (Eq. 2.18)37 are efficient methods for the preparation of some kinds of nitroalkanes from readily available alkylsilanes or allylstan-nanes. Similar nitration also takes place at the vinylic positions (see Eq. 2.36 in Section 2.1.4). 

Catalytic enantioselective nucleophilic addition of nitroalkanes to electron-deficient alke-nes is a challenging area in organic synthesis. The use of cinchona alkaloids as chiral catalysts has been studied for many years. Asymmetric induction in the Michael addition of nitroalkanes to enones has been carried out with various chiral bases. Wynberg and coworkers have used various alkaloids and their derivatives, but the enantiomeric excess (ee) is generally low (up to 20%).199 The Michael addition of methyl vinyl ketone to 2-nitrocycloalkanes catalyzed by the cinchona alkaloid cinchonine affords adducts in high yields in up to 60% ee (Eq. 4.137).200... 

The a-arylation of carbonyl compounds (sometimes in enantioselective version) such as ketones,107-115 amides,114 115 lactones,116 azlactones,117 malonates,118 piperidinones,119,120 cyanoesters,121,122 nitriles,125,124 sul-fones, trimethylsilyl enolates, nitroalkanes, esters, amino acids, or acids has been reported using palladium catalysis. The asymmetric vinylation of ketone enolates has been developed with palladium complexes bearing electron-rich chiral monodentate ligands.155... 

Conjugate addition of RN02 to enones. Primary nitroalkanes and a, (3-enones when activated by alumina form conjugate addition products that are oxidized in situ by alkaline hydrogen peroxide to 1,4-diketones. A similar reaction of nitromethane with a vinyl ketone provides 1,4,7-triketones. 

Reduction of nitroalkanes RNO2 with samarium(II) iodide, obtained from samarium and 1,2-diiodoethane, yields either alkylhydroxylamines RNHOH or alkylamines RNH2, depending on the amount of the reagent434. The base-catalysed reaction of nitroalkanes with phenyl(vinyl) sulphoxide (399) yields the conjugate adducts 400, which fragment to allylic nitro compounds 401 on thermolysis435. 

Cyclic alkyl nitronates may be used in tandem [4+2]/[3+2] cycloadditions of nitroalkanes, and this reaction has been extensively studied by Denmark et al. (64,333-335). In recent work, they developed the silicon-tethered heterodiene-alkene 219 (Scheme 12.63). Steric hindrance and the fact that both the nitroalkene and the a,p-unsaturated ester in 219 are electron deficient renders the possibility of self-condensation. Instead, 219 reacts with the electron-rich chiral vinyl ether 220 in the presence of the catalyst 224 to form the intermediate chiral nitronate 221. The tandem reaction proceeds from 221 with an intramolecular 1,3-dipolar cycloaddition to form 222 with 93% de. Further synthetic steps led to the formation of ( )-detoxinine 223 (333). A similar type of tandem reaction has also been applied by Chattopadhyaya and co-workers (336), using 2, 3 -dideoxy-3 -nitro-2, 3 -didehydrothymidine as the starting material (336). 

Synthetically especially valuable is the oxidation of carbonyl compounds and nitroalkanes by manganese(III) salts to form carboxymethyl and nitromethyl radicals, respectively. These radicals can be trapped by olefins like 1,3-butadiene or aromatic compounds to yield synthetically interesting products. In this case it is very advantageous to generate and regenerate the oxidizing species in situ by indirect electrolysis. This was the basis for the development of a process for the synthesis of sorbic acid viay-vinyl-y-butyrolactone Equations (31)—(35) summarize the im-... 

Tertiary nitroalkanes (R3C-N02) are neutral. The most important unsaturated analogues are the vinyl nitro compounds (e.g. R CH=CH-N02). All these nitro compounds have in recent years become of great interest as versatile intermediates in organic synthesis.196 Some of these aspects are noted in Chapter 1, p. 21, in Section 5.7.7, p. 599, and in Section 5.9.3, p. 635, and are further exemplified in the following discussion. 

Michael additions. Michael addition of nitroalkanes to vinyl sulfoxides (equation 1) and to ketene diethyl dithioacetal S-monooxide (equation II) proceeds in high yield when DBU is used as base. The adducts can be converted into a,/J-enals.1... 

Substitutions by the SRn 1 mechanism (substitution, radical-nucleophilic, unimolecular) are a well-studied group of reactions which involve SET steps and radical anion intermediates (see Scheme 10.4). They have been elucidated for a range of precursors which include aryl, vinyl and bridgehead halides (i.e. halides which cannot undergo SN1 or SN2 mechanisms), and substituted nitro compounds. Studies of aryl halide reactions are discussed in Chapter 2. The methods used to determine the mechanisms of these reactions include inhibition and trapping studies, ESR spectroscopy, variation of the functional group and nucleophile reactivity coupled with product analysis, and the effect of solvent. We exemplify SRN1 mechanistic studies with the reactions of o -substituted nitroalkanes (Scheme 10.29) [23,24]. 

Michael-aldol reaction as an alternative to the Morita-Baylis-Hillman reaction 14 recent results in conjugate addition of nitroalkanes to electron-poor alkenes 15 asymmetric cyclopropanation of chiral (l-phosphoryl)vinyl sulfoxides 16 synthetic methodology using tertiary phosphines as nucleophilic catalysts in combination with allenoates or 2-alkynoates 17 recent advances in the transition metal-catalysed asymmetric hydrosilylation of ketones, imines, and electrophilic C=C bonds 18 Michael additions catalysed by transition metals and lanthanide species 19 recent progress in asymmetric organocatalysis, including the aldol reaction, Mannich reaction, Michael addition, cycloadditions, allylation, epoxidation, and phase-transfer catalysis 20 and nucleophilic phosphine organocatalysis.21... 

Reduction of nitroalkenes. Vinyl nitro compounds are reduced to saturated ketones or aldehydes by Raney nickel and an aqueous solution of sodium hypophosphite. Ester groups, C=C bonds, and aryl NO, and halo groups are not reduced. Under these conditions nitroalkanes arc reduced to amines, and oximes are converted into carbonyl compounds in high yield. 

Both the above mechanisms are proposed in the literature with Mannich bases of nitroalkanes the substitution is clearly favored by the steric hindrance of the amine moiety, thus suggesting path 1, - whereas NMR studies on the reaction of P-amino-ketones with hydroxy coumarins do not reveal the presence of vinyl ketone intermediates. lodomethylated phenolic Mannich bases arc also claimed to react according to path 2, although the formation as by-products of dimers and methylene-bis-derivatives accounts for the participation of methylenequinone intermediates in the process. "... 

The resulting derivatives were applied with success in the standard asymmetric allylic alkylation (up to 97 % ee) [134, 136] or in transformations involving either specific allylic substrates (2-cycloalkenyl derivatives, up to >99% ee) [135, 137], unsymmetrical substrates (monosubstituted allyl acetate, up to 83% ee) [140], or especial nucleophiles (nitroalkanes [141], iminoesters [138 a], or diketones [139, 140, 142]). Such ligands were also effective in the formation of quaternary chiral carbon through allylic substitution (eq. (6)) [138, 143], deracemiza-tion of vinyl epoxides (up to 99% ee) [144], or alkylation of ketone enolates [138 b], and deracemization of allylic derivatives [145]. 

Aryllead, vinyllead, and alk-l-ynyllead tricarboxylates behave as aryl, vinyl and alkynyl cation equivalents to react with a variety of nucleophiles, especially soft carbon nucleophiles such as T -dicarbonyl compounds, phenols, and nitroalkanes. In these reactions, unique regioselectivity is obtained in which there is a preference for the generation of quaternary carbon centers. This aspect of reactivity has been put to use in a number of natural product syntheses and can result in the formation of highly hindered structures. 

However, during the addition of -keto esters onto enals, ytterbium triflate proved to be an efficient catalyst [171] as in the Michael additions of a-nitro esters [172]. Several water-soluble phosphines gave the corresponding phos-phonium salts in good yields when added to a,j9-unsaturated acids [173] or activated alkynes [174]. With alkynes, vinyl phosphine oxides or alkenes were formed depending on the pH of the aqueous solution. Significantly, the reaction of nitroalkanes with buten-2-one is considerably accelerated when going from... 

The yields in these reactions are not wonderful and most syntheses planned with acyl anion or d1 synthons are realised with one of the reagents we are about to describe rather than with acyl-lithiums. Things may change as understanding of these rather reactive intermediates develops. There are three main types of acyl anion equivalent reagents which can be considered as modified acetals, that is protected aldehydes, masked carbonyl compounds such a nitroalkanes, and substituted vinyl-lithiums. The rest of this chapter will be devoted to these reagents. 

A huge acceleration of the Michael reaction of nitroalkanes with methyl vinyl ketone was mentioned when going from non-polar organic solvents to water. The hydrophobic effect could be at least to some extent involved, since additives, such as glucose or saccharose, accelerate the reaction even more [72]. Cetyltrimethylam-monium chloride as an amphiphilic species which can influence the hydrophobic interactions was found to promote the Michael reaction of various nitroalkanes with conjugated enones in dilute aqueous solutions of sodium hydroxide [73],... 

The double deprotonation of 2-arylnitroethanes followed by treatment wiA electrophiles led to 2-sub-stituted-2-arylnitroethanes. This fact suggested that the strong base sequentially abstracted a- and then (3-protons of these substrates giving a,(3-dianions (57). The same behavior has been observed with primary nitroalkanes having a vinyl or carbonyl group on the 3-carbon. If there is only one a-nitro CH as in open-chain and cyclic secondary nitroalkanes, bis(lithioxy)enamines (58) and (59) (dianion derivatives of a-nitroalkenes, also called super enamines) are generate and exclusively those with a terminal double bond in the case of 2-nitroalkanes (equations 22 and 23). These dianion derivatives react with aromatic and aliphatic aldehydes as well as ketones to give 1,3-difunctional derivatives. In contrast to the lack of... 

N,N DIPROP YL-4-TRIFLUORO-METHYL-2,6-DINITROANILINE (1582-09-8) Ci3HjsF3N304 Combustible solid (flash point >185 F/>85°C oc Fire rating 1). May react violently with barium, potassium, sodium. Incompatible with organic anhydrides, acrylates, alcohols, aldehydes, alkylene oxides, substituted allyls, cellulose nitrate, cresols, caprolactam solution, epichlorohydrin, ethylene dichloride, isocyanates, ketones, glycols, nitrates, phenols, vinyl acetate. Exothermic decomposition with maleic anhydride. May increase the explosive sensitivity of nitromethane. Reacts with nitroalkanes, forming explosive products. As a dinitroaniline derivative, the extremes of heat (do not store above 90°F/32°C), mechanical shock, and fnction might be... 

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