Carbonyl, addition nitromethane

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

Zard and coworkers have developed a synthesis of substituted dienes by reductive elimination of allylic nitroacetates (equation 33)66. Allylic nitroacetates can be prepared by condensation of nitromethane with the carbonyl compound followed by addition of formaldehyde and acetylation67. Reductive elimination can be carried out by employing either chromous acetate or samarium iodide. 

A salient example regarding a Michael addition of nitronates to a,(5-unsaturated carbonyl compounds is the stereoselective addition of glucosyl nitromethane 93 to levoglucosenone (94) in the presence of tetramethylguanidine (TMG) (Scheme 30).70... 

The same authors (77) also investigated the Michael addition of nitromethane to a,/l-unsaturated carbonyl compounds such as methyl crotonate, 3-buten-2-one, 2-cyclohexen-l-one, and crotonaldehyde in the presence of various solid base catalysts (alumina-supported potassium fluoride and hydroxide, alkaline earth metal oxides, and lanthanum oxide). The reactions were carried out at 273 or 323 K the results show that SrO, BaO, and La203 exhibited practically no activity for any Michael additions, whereas MgO and CaO exhibited no activity for the reaction of methyl crotonate and 3-buten-2-one, but low activities for 2-cyclohexen-l-one and crotonaldehyde. The most active catalysts were KF/alumina and KOH/alumina for all of the Michael additions tested. 

Scheme 6.147 visualizes two proposals for the mechanism of the 131-catalyzed Henry addition of nitromethane to benzaldehyde. In (A), benzaldehyde is achvated by the thiourea moiety through double hydrogen bonding to the carbonyl funchon, while the nitromethane is deprotonated and activated by the basic quinuclidine nitrogen [298] proposal (B), however, based on detailed DFT computations... 

Exercise 17-1 Other groups in addition to carbonyl groups enhance the acidities of adjacent C-H bonds. For instance, nitromethane, CH3N02, has pKa = 10 ethane-nitrile, CH3CN, has a pKa = 25. Explain why these compounds behave as weak acids. Why is CH3COCH3 a stronger acid than CH3C02CH3 ... 

In chapter 21 we mentioned nitro compounds as promoters of conjugate addition they also stabilise anions strongly but do not usually act as electrophiles so that self-condensation is not found with nitro compounds. The nitro group is more than twice as good as a carbonyl group at stabilising an enolate anion. Nitromethane (p/ a 10) 1 has a lower pKa than malonates 4 (pKa 13). In fact it dissolves in aqueous NaOH as the enolate anion 3 formed in a way 2 that looks like enolate anion formation. 

Nitro compounds can be alkylated and are good at conjugate addition (chapter 21) so the products of these reactions can be used to make aldehydes, ketones and amines. A simple synthesis of octanal5 shows that these methods can work very well indeed. Alkylation of nitromethane with bromoheptane gives the nitro-compound 11. Formation of the anion 12 and oxidation with KMnC>4 gives octanal in 89% yield. This chemistry gives us the disconnection to an alkyl halide and a carbonyl anion. The anion 12 is an acyl anion equivalent and we shall need these in the next chapter. 

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]. 

Kabashima, H., Tsuji, H., Shibuya, T. and Hattori, H. Michael addition of nitromethane to a,/ -unsaturated carbonyl compounds over solid base catalysts, J. Mol. Catal., A, 2000, 155, 23-29. 

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. 

Owing to this dichotomy, a, -unsaturated aldehydes, ketones, or esters can undergo a nucleophilic attack at either the carbonyl carbon or the )S-carbon atom (Scheme 2.29). The first of these reactions is a familiar addition to the carbonyl group (1,2-addition) which leads, in this case, to the valuable allylic alcohols. Even more intriguing synthetic options, however, are offered by the alternative pathway, the 1,4-addition generally known as the Michael reaction. The classic version of this reaction employed stable carbanions such as those generated in situ from malonic ester or nitromethane under the action of bases and in the presence of Michael acceptors, e.g. methyl vinyl ketone 90 ... 

In the base-catalyzed addition of nitromethane to aldehydes (the Henry reaction5,8), the methanenitronate anion attacks the electron-deficient carbonyl carbon atom. Such derivatives of aldehydes as the hydrates and hemiacetals react readily, owing to the presence of the carbonyl compound in mobile equilibrium, and consequently, aldoses are amenable to the reaction, which generally proceeds rapidly, giving good yields at or below room temperature. Usually, the stoichiometric amount of an alkali is employed for promoting the reactior. and the nitro alcohols are then obtained as nitronate salts and may... 

With 4-methoxyacetophenone 2, a similar experiment in nitromethane shows any modification of the chemical shift of the 13C-carbonyl signal after introduction of BiCl3. Addition of MeCOCl to this mixture causes the appearance of the characteristic signals of MeCOCl-BiCl3 interaction. 

More recently, the use of high pressure with tetra-n-butylammonium fluoride as catalyst allowed these reactions to be accomplished with cyclic ketones. Thus, the Henry reaction of nitroalkanes with 3- and 4-methylcyclohexanones in THF at 30 C and 9 kbar (1 bar = 100 kPa) afforded fair to high yields (60-90% after 4 d) of the corresponding nitro alcohols, while with 2-methyIcyclohexanones it was possible to obtain addition products, although in moderate yields. These facts explain the modest utility of the Henry reaction as a chain-lengthening reaction when the carbonyl component is a ketone, but also show the difference in reactivity of aldehyde and ketone C==0 groups with respect to nitromethane, primary and secondary nitroalkanes in the presence of a base as catalyst. Such a difference in reactivity can be considered as the most evident chemoselectivity of this reaction. 

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. 

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