Nitromethanes addition reactions

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. 

The title Diels-Alder (DA) addition reaction shown in equation 81195 has been reinvestigated recently196 by labelling 223 with 14C successively at C(i) and at C(2). The [2-14C]-l-nitro-2-phenylethene has been obtained in the reaction of [7-14C]benzaldehyde with nitromethane (equation 82). 

When the thiole derivatives are converted into the corresponding sulfenyl chloride such as 56, an addition reaction to styrene or /3-methylstyrene in nitromethane gives regioisomeric mixtures of adducts 57 and 58 (Scheme 11) <2001CHE702> as well as the cyclization products 59 which are generated in 47% (R = H) and 52% (R = OI I () yield, respectively. 

For the cyclization of dialdehydes, however, its utility seems limited. Being a nitromethane addition product, it can readily undergo retro-nitromethane addition with alkali to give formaldehyde and nitromethane. Thus, it is not surprising that reaction of glutaraldehyde with 2-nitroethanol under the usual conditions (i.e. 1 molar equivalent of sodium hydroxide in aqueous ethanol) should yield 2-nitrocyclohexane-1,3-diol 5), a nitromethane cyclization product With catal5dic amounts of sodium hydroxide (pH 8—9), however, 1-hydroxymethyl-l-nitro-cyclohexane-2-6-diol (80) can be isolated in yields of 24—29%... 

A second approach (472) to 512 started with trans-2-buitnc epoxide (524) (Scheme 67). Opening of the epoxide ring of 524 with lithium acetylide gave an acetylenic alcohol, which was converted to the acetylenic acid (525) by carbox-ylation with gaseous carbon dioxide. Partial hydrogenation of 525 followed by lactonization afforded the a,3-unsaturated lactone (526) which was transformed to the nitrolactone (527) by a Michael addition reaction of nitromethane. The Nef reaction of 527 gave the tetrahydrofuranyl acetal (528) which was converted to... 

Shibasaki made several improvements in the asymmetric Michael addition reaction using the previously developed BINOL-based (R)-ALB, (R)-6, and (R)-LPB, (R)-7 [1]. The former is prepared from (R)-BINOL, diisobutylaluminum hydride, and butyllithium, while the latter is from (R)-BINOL, La(Oz -Pr)3, and potassium f-butoxide. Only 0.1 mol % of (R)-6 and 0.09 mol % of potassium f-butoxide were needed to catalyze the addition of dimethyl malonate to 2-cy-clohexenone on a kilogram scale in >99% ee, when 4-A molecular sieves were added [15,16]. (R)-6 in the presence of sodium f-butoxide catalyzes the asymmetric 1,4-addition of the Horner-Wadsworth-Emmons reagent [17]. (R)-7 catalyzes the addition of nitromethane to chalcone [18]. Feringa prepared another aluminum complex from BINOL and lithium aluminum hydride and used this in the addition of nitroacetate to methyl vinyl ketone [19]. Later, Shibasaki developed a linked lanthanum reagent (R,R)-8 for the same asymmetric addition, in which two BINOLs were connected at the 3-positions with a 2-oxapropylene... 

The polarisation produced by co-ordination to the metal may be transmitted through a conjugated system. Michael addition reactions of nucleophiles to TV-bonded acrylonitrile are known, and provide a convenient method for the preparation of derivatives. A wide range of nucleophiles may be used in these conjugate additions. For example, the anion of nitromethane (generated in situ) reacts with the ruthenium(m) complex [Ru(NH3)5N=CCH=CH2)]3+, 4.6, to yield a complex of 4-nitrobutyronitrile (Fig. 4-18). 

Nitro compounds are also useful starting materials, because a nitro group can be readily converted to a carbonyl group or to amino functionality. Addition reactions of nitroalkane have been reported by Yamaguchi [13b], Shibasald [6a], Bako and Toke, Corey, Hanessian, and Kanemasa [21]. For example, Kanemasa used their chiral Lewis acid complex 35 for the reaction of 36 with nitromethane (Scheme 18). The reaction proceeded with the aid of the amine co-catalyst, affording the product 37 with high enantioselectivity. This system was also applicable to the reaction of malononitrile [2 le]. 

Many annellated 3-nitropyrroles have been prepared by the reaction of ylids, generated from a variety of heterocycles, with nitromethane.1 The sequence of steps involves protonation of the ylid by nitromethane, addition of the anion CH2N02 to the iminium system, cyclization on the carbonyl, dehydration, and finally dehydrogenation. Thus, the isoquinolinium ylids 8 react with nitromethane in the presence of base to give 1-nitropyrrolo-[2,l-fl]isoquinolines (9) in about 20% yield (Scheme 4). A side reaction is the loss of nitrous acid from the intermediate, to give 10. 

Electrolysis of pure nitromethane with an Ni cathode and a sacrificial Mg anode produces the anion of nitromethane, which may be useful in many addition reactions. If nitromethane in MeCN is reduced, the yield of addition products is low [20]. 

Michael addition. Ostaszynski and Wielgat 58] used potassium (luoride as j talysi for the Michael addition of nitromethane to a double bond. (Alkali lorides were originally suggested by Yasuda ct al. [59] as catalysts foi the chael addition reactions.) The work of addition of nitroalkanes was continued J]- Various acceptors, for example, methylacrylate and acrylonitrile, were fd. Among nitroalkanes gem-dinitroalkancs were applied as donors. Nitro-ICS readily formed double salts with KHFj, RbHFj and CsHFj. The yield Ihe adducts of such salts with compounds containing a double bond varied reen 60 and 90%, viz. (5) ... 

Lower yields were obtained in acetonitrile or nitromethane the reaction of trimethylcyclo-propene with molecular chlorine under various conditions also resulted in ring opening, although addition of iodobenzene dichloride gave a 1,2-dichlorocyclopropane. 

The enone 3 was further functionalized via tandem reaction by Michael addition of methanol to the conjugate system at C-5, followed by base catalyzed nitromethane addition to the keto function at C-2 and base catalyzed (TMG -tetramethylguanidine) mesylation/elimination with the formation of new a-nitroenone as depicted in Scheme 7. The intermediate a-nitroenone functionalized at C-2 as a conjugate system is indeed an excellent Michael acceptor of reactive nucleophiles, including 1-thio-P-D-glucose. The conjugate addition of this reactive thiol was performed in the same fashion as before (2, 3) with the stereoselective formation of the first representative example of highly functionalized and previously unknown class of C-nitro-5-thiodisaccharide derivatives. 

Deoxy-6-nitro-D-glucose (90) and 6-deoxy-6-nitro-L-idose (91) were the first reducing nitro sugars to be synthesized.98 Nitromethane addition to 1,2-O-isopropylidene-a-D-xy/o-pentodialdo-1,4-furanose (87) produced a mixture of 6-deoxy-l,2-0-isopropylidene-6-nitro-a-D-glucofuranose (88) and -j8-L-idofuranose (89). These C-5 epimers could be separated by reaction with acetone, whereby 89 gave a l,2 3,5-di-isopropylidene acetal more readily than did 88. Acid hydrolysis of the acetone groups then afforded 90 and 91. 

Because of their kinship to syntheses of nitro sugars, some syntheses of simpler, cyclic, aliphatic nitro compounds will be mentioned. Tetrahydropyran-2-ol, which is in tautomeric equilibrium with 5-hydroxypentanal (126), was found to undergo nitromethane addition catalyzed by sodium hydroxide to give120 tetrahydro-2-(nitromethyl)-pyran (128). Undoubtedly, the first reaction-product is the diol ni-tronate (127), which, under the conditions of processing (acidification and steam distillation), forms the cyclic ether 128. 

Itoh, K. and Kanemasa, S. (2002) Enantioselective Michael additions of nitromethane by a catal3ftic double activation method using chiral Lewis acid and chiral atitine catalysts. Journal of the American Chemical Society, 124, 13394—13395 Itoh, K., Oderaotoshi, Y. and Kanemasa, S. (2003) Enantioselective Michael addition reactions of malononitrile catalysed by chiral Lewis acid and achiral antine catalysts. Tetrahedron Asymmetry, 14, 635 39. 

In summary, most of the known synthetic routes to azaadamantanes depend on condensation of an amine or ammonia with a carbonyl compound or equivalent (aldehyde, ketone, ortho ester, acetal) or other active methylene compound, such as nitromethane. The syntheses of 10 and 13 employed bromo intermediates in displacement or addition reactions. 

In the addition of nitromethane with group containing a double bond, hydrogen atoms of nitroalkane are usually added to the atom of double bonds with less hydrogen atoms, but the opposite results will be obtained with the presence of unsaturated ethers. In the addition reaction between an unsaturated compound with conjugated double bonds and an nitroalkane, double bonds will be isomerized. 

---