Allylation nitroalkanes

Chemoselective C-alkylation of the highly acidic and enolic triacetic acid lactone 104 (pAl, = 4.94) and tetronic acid (pA, = 3.76) is possible by use of DBU[68]. No 0-alkylation takes place. The same compound 105 is obtained by the regioslective allylation of copper-protected methyl 3,5-dioxohexano-ate[69]. It is known that base-catalyzed alkylation of nitro compounds affords 0-alkylation products, and the smooth Pd-catalyzed C-allylation of nitroalkanes[38.39], nitroacetate[70], and phenylstilfonylnitromethane[71] is possible. Chemoselective C-allylation of nitroethane (106) or the nitroacetate 107 has been applied to the synthesis of the skeleton of the ergoline alkaloid 108[70]. 

The Henry reaction of ketones with nitroalkanes in the presence of etbylenediamine gives allylic nitro compounds, which give a,fi-imsanirated carbonyl compounds via the Nef reaction fEq. 6.30. ... 

Monoanions derived from nitroalkanes are more prone to alkylate on oxygen rather than on carbon in reactions with alkyl halides, as discussed in Section 5.1. Methods to circumvent O-alkylation of nitro compounds are presented in Sections 5.1 and 5.4, in which alkylation of the a.a-dianions of primary nitro compounds and radial reactions are described. Palladium-catalyzed alkylation of nitro compounds offers another useful method for C-alkylation of nitro compounds. Tsuj i and Trost have developed the carbon-carbon bond forming reactions using 7t-allyl Pd complexes. Various nucleophiles such as the anions derived from diethyl malonate or ethyl acetoacetate are employed for this transformation, as shown in Scheme 5.7. This process is now one of the most important tools for synthesis of complex compounds.6811-1 Nitro compounds can participate in palladium-catalyzed alkylation, both as alkylating agents (see Section 7.1.2) and nucleophiles. This section summarizes the C-alkylation of nitro compounds using transition metals. 

Asymmetric synthesis of tricyclic nitro ergoline synthon (up to 70% ee) is accomplished by intramolecular cyclization of nitro compound Pd(0)-catalyzed complexes with classical C2 symmetry diphosphanes.94 Palladium complexes of 4,5-dihydrooxazoles are better chiral ligands to promote asymmetric allylic alkylation than classical catalysts. For example, allylic substitution with nitromethane gives enantioselectivity exceeding 99% ee (Eq. 5.62).95 Phosphi-noxazolines can induce very high enatioselectivity in other transition metal-catalyzed reactions.96 Diastereo- and enantioselective allylation of substituted nitroalkanes has also been reported.9513... 

Simple nitroalkanes such as nitroethane, 1-nitropropane, or 2-nitropropane are generally bad electrophiles for the SN2 reactions.14 In contrast, nitro groups at allylic positions are readily displaced by thiolate ions (Eq. 7.13)15 or lithium dialkylcuprates (Eq. 7.14).16... 

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. 

Nitroalkanes react with Jt-deficient alkenes, for example, p-nitro ketones are produced from a,P-unsaturated ketones [41], whereas allylic nitro compounds have been prepared via the Michael-type addition of nitroalkanes with electron-deficient alkynes (Table 6.19). The reaction in either dimethylsulphoxide [42] or dimethyl-formamide [43] is catalysed by potassium fluoride in the presence of benzyltriethyl-ammonium chloride the reaction with dimethyl acetylenedicarboxylate is only successful in dimethylsulphoxide [42], Primary nitroalkanes produce double Michael adducts [42,44], A-Protected a-aminoacetonitriles react with alkynes under catalysed solidiliquid conditions to produce the Michael adducts [45] which, upon treatment with aqueous copper(Il) sulphate, are converted into a,p-unsaturated ketones. 

Nitroalkanes react with allylic carbonates in the presence of iridium catalysts [83]. However, nitroalkanes are prochiral, and products are formed with poor diastereo-selectivity. Nitroalkanes and other prochiral nucleophiles are discussed further in Sect. 6. 

A stereocontrolled synthesis of racemic monomorine I (16a) has been accomplished by Stevens and Lee (438). An allyl alcohol obtained by reaction of acrolein with the Grignard reagent of the chloroacetal (367) was oxidized to yield the enone (368). The Michael addition of 1-nitropentane to 368 was catalyzed by tetramethylguanidine to yield the nitroalkane (369). Reductive cyclization of 369... 

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... 

Fishbein L. 1981. Carcinogenicity and mutagenicity of solvents I. Glycidyl ethers, dioxane, nitroalkanes, dimethylformamide and allyl derivatives. Sci Total Environ 17 97-110. 

This methodology has been used to provide efficient protocols for the asymmetric allylic alkylation of p-keto esters, ketone enolates, barbituric acid derivatives, and nitroalkanes. Several natural products and analogs have been accessed using asymmetric desymmetrization of substrates with carbon nucleophiles. The palladium-catalyzed reaction of a dibenzoate with a sulfonylsuccinimide gave an advanced intermediate in the synthesis of L-showdomycin (eq 3). ... 

Bartoli et al. [31] reported the formation of enantiomerically pure amines and hydroxylamines from optically active nitroalkanes with allylic and benzylic Grignard reagents. The intermediate nitrones (see Table 3, entry 7) were mixtures of E- and Z-isomcrs from the protected nitroalkanes. Although the regiochemistry is complicated, the stereochemistry of the double bond was affected by the nature of the Grignard reagent. The major isomer was always the R-isomer. 

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]. 

In order to treat influenza infections, the development of neuraminidase inhibitors is required. The currently available compounds are not potent enough, and they have a number of side effects. The stereoselective total synthesis of one potent inhibitor, BXC-1812 (RWJ-270201), was achieved by M.J. Muller and co-workers. The key intermediate substituted nitromethane was prepared via a Pd-catalyzed allylation of nitromethane under basic conditions. The transformation of this nitroalkane to the corresponding carboxylic acid methyl ester was carried out in two steps. The Nef reaction was conducted in DMF instead of the usual DMSO because DMSO as the solvent caused extensive epimerization of the product. The initially formed carboxylic acid was then esterified. 

Nitriles. Primary nitroalkanes are converted to nitriles with this reagent combination in the presence of triethylamine. Conjugated nitriles are formed more rapidly from allylic nitroalkenes. 

Intramolecular reactions generally give excellent results. Allylation of the nitroalkane portion of the indole 251 closes the six-membered ring of the ergoline alkaloids such as chanoclavine 253. Genet s study of various ligands revealed that BINAP provided the best results.58... 

Genet investigated the intramolecular reaction of a nitroalkane and an allylic acetate in the indole nucleus and obtained the cyclized product in 65% yield and 66% ee using chiraphos as the hgand. Scheme 36 [52]. 

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