Nitromethane Michael reactions

An elegant example of sequence of reactions involving the Henry reaction, the Michael reaction, and elimination of HNO is demonstrated in a short synthesis of anthracyclmones. Nitromethane is used to introduce the ClO-gronp simultaneously v/irh the C9-hydroxy group fEq. 7,136. ... 

The addition of active methylene compounds (ethyl malonate, ethyl aceto-acetate, ethyl plienylacetate, nitromethane, acrylonitrile, etc.) to the ap-double bond of a conjugated unsaturated ketone, ester or nitrile in the presence of a basic cataljst (s ium ethoxide, piperidine, diethylamiue, etc.) is known as the Michael reaction or Michael addition. The reaction may be illustrated by the addition of ethyl malonate to ethyl fumarate in the presence of sodium ethoxide hydrolysis and decarboxylation of the addendum (ethyl propane-1 1 2 3-tetracarboxylate) yields tricarballylic acid ... 

The Michael reaction of benzylidene acetophenone and benzylidene acetone with ethyl acetoacetate, nitromethane, and acetylacetone was studied by Musaliar and co-workers in the presence of a cetyltrimethy-lammonium bromide-containing aqueous micellar medium.50 The Michael reaction of various nitro alkanes with electrophilic alkenes is performed in NaOH (0.025-0.1 M) in the presence of cetyltrimethylam-monium chloride (CTACI) without any organic solvent (Eq. 10.23).51... 

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... 

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... 

The Michael reaction of nitromethane with methyl vinyl ketone and l-decene-3-one followed by reductive cyclization gives two isomeric pyrrolizidines, depending on reduction conditions (Eq. 10.74).117... 

Sods [80] reported novel thiourea catalyst 134 in an efficient Michael reaction between nitromethane and chalcones to access chiral nitrocarbonyls in high enan-tioselectivity (Scheme 30). 

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 ... 

As described in Sections 2.3.1.2 and 2.2.3, Choudary et al. recently revealed nanocrystalline magnesium oxide (NAP-MgO) as a recyclable heterogeneous catalyst [40, 45]. These authors extended the use of this new type of heterogeneous catalyst for the asymmetric Michael reaction of different acyclic enones with nitromethane and 2-nitropropane [69a]. In a Michael reaction of chalcone with nitromethane in THF solvent at -20°C, NAP-MgO/(lR,2R)-(-)-diaminocyclohexane (DAC) was found to be an excellent catalyst system (96% ee, 95% yield) (Scheme 2.32). This Michael reaction proceeds via the dual activation of both substrates (nucleophiles and electrophiles) by NAP-MgO. The Lewis basic site (O /O ) of the NAP-MgO activates the nitroalkanes, while the Lewis acid moiety (Mg /Mg )... 

Arylidenebarbituric and thiobarbituric acids react with compounds containing an active methylene group under Michael reaction conditions.246,247 Compounds 69 (R = H, p-N02, p-Cl X = O, S) have been obtained in the reaction of 5-arylidenebarbituric or thiobarbituric acids with cyclohexanone, benzyl phenyl ketone, camphor, ethyl ester of phenylacetic acid, or nitromethane. The reaction with ethyl cyanoacetate or ethyl... 

Methyl-l-nitro-2-propanol, the product expected from the base-catalyzed addition of nitromethane to acetone, spontaneously loses water to give 2-methyl-1-nitro-l-propene as an intermediate which, with excess nitromethane, undergoes a Michael reaction to yield 2,2-dimethyl-l,3-dinitropropane see Ref. 6(a). 

The pressure kinetic effect on the Michael reaction between methyl vinyl ketone and nitromethane was studied under various conditions including lanthanide catalysis [36] (Scheme 10.8). Table 10.8 shows some kinetic results. 

D-A reactions, comprising st-DNA and the Cn " complex of 4,4 -dimethyl bipyridine. Nitromethane and dimethyl malonate, both of which enolize readily, were employed as the nncleophiles. With 100 equivalents of dimethyl malonate, a clean and quantitative conversion into the Michael addnct was observed after 3 days, with an ee of 91%. The addition of nitromethane was slower nsing 1000 equivalents 97% conversion and an ee of 85% were obtained in the same time. The snbstrate scope proved to be broad a series of derivatives of the snbstrate were tested in the Michael reaction and generally gave high conversions (typically > 75%) and ees (86-99% with dimethylmalonate as the nncleophile, and 82-94% with nitromethane as the nncleophile). Only in the case of the Michael addition to the enone with R = Me instead of aryl, did the ee drop to 60%. Again, it was shown that the reaction conld be performed on a preparative scale (1 mmol), and that the catalyst solution conld be recycled withont loss of activity or enanti-oselectivity over at least two rnns. 

Scheme 3.3 Enantioselective 31a and 31c-catalyzed Michael reaction of nitromethane to 0(,P-unsaturated aldehydes.

Scheme 3.4 Enantioselective Michael reaction of nitromethane and dibenzylmalonate to a,p-unsaturated aldehydes in water.

Scheme 5.7 Enantioselective Michael reaction of nitromethane to chalcones applied to the enantioselective synthesis of baclofen.

Amorphous SA treated with 3-aminopropyltriethoxysilane (tertiary amine) and 3-(diethylamino) propyltrimethoxysilane (primary amine) acts as a heterogeneous catalyst for the one-pot synthesis of 1,3-dinitroalkanes from aldehydes and nitromethane (Scheme 6.21) [133]. Trifunctionality of the catalyst surface has been proposed. Aldehydes are activated by surface acid sites and they react with secondary amino group to form imine intermediates. The proton of nitromethane is abstracted by a tertiary amine group accompanied by nucleophilic attack of the deprotonated nitromethane on the imine, which is also assisted by a surface acid site, resulting in nitroalkenes. Another nitromethane is activated by the tertiary amine group, and the Michael reaction with nitroalkenes occurs to give the 1,3-dinitroalkanes. 

Chiral y-amino acids and y-nitroesters have been prepared, under PTC conditions, from 4-nitro-5-styrylisoxazoles, derivatives efficiently used as cinnamate equivalents in the asymmetric Michael reaction with nitroalkanes[181]. The reaction is catalyzed by Cinchonidine-derived catalyst 122 (2-5 mol%) at low temperatures (-30 to 0°C) affording high selectivities not only with nitromethane but also with secondary and tertiary nitroalkanes as nucleophiles. As seen in Scheme 2.66, the... 

Fig. 4. Effect of pretreatment temperature on the activities of KF/AI2O3 for the isomerization of 1-pentene and Michel reaction between nitromethane and 2-hutanone 43 1-pentene isomerization at 273 K, Q Michael reaction at 273 K.

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