Michael additions of nitromethane

The Michael addition of nitromethane to vinylogons esters of iV-protected amino acids proceeds v/ith good yields and v/ith good diastereoselecdvity fEq. 4.135. ... 

In recent years, there has been increased recognition that water is an attractive medium for organic reactions from the environmental point of view. The Michael addition of various nitroalkanes to conjugated enones can be performed in NaOH (0.025 M) and in the presence of cetyltrimethylammonium chloride (CTAC1) as cationic surfactant in the absence of organic solvents (Eq. 4.109).146 The Michael addition of nitromethane to methyl acrylate is carried out in water using NaOH as a base to give the mono adduct (Table 4.2).147... 

The Michael addition of nitromethane to cyclopentenone derivatives is used for synthesis of prostaglandins (Scheme 4.20).158 Here, the anion of nitromethane is used as a formyl anion synthon. 

Newkome and coworkers have developed synthesis of dendritic molecules using the Michael addition of nitromethane to 0t, 3-unsaturated esters as a key reaction (Scheme 4.24).166... 

Barco and coworkers have reported a more elegant synthesis of the nitrocyclohexanone via the double Michael addition of nitromethane with enones. (Eq. 4.130).178... 

The Michael addition of nitromethane to vinylogous esters of / -protected amino acids proceeds with good yields and with good diastereoselectivity (Eq. 4.135).195... 

Matsumoto and coworkers have introduced a new strategy for asymmetric induction under high pressure. The Michael addition of nitromethane to chalcone is performed at 10 kbar in the presence of a catalytic amount of chiral alkaloids. The extent of asymmetric induction reaches up to 50% ee with quinidine in toluene.201... 

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 hydrogenation in the presence of Pd/C is also effective for the conversion of nitro compounds to amines.94 The Michael addition of nitromethane to 2-alkenoic esters followed by catalytic hydrogenation using 10% Pd/C in acetic acid and hydrolysis is a convenient method for the preparation of 3-alkyl-4-aminobutanoic acids, which are important y-amino acids for biological study (Eq. 6.48).94b The reduction can be carried out at room temperature and atmospheric pressure. 

Asymmetric Michael addition of nitromethane to a crotonyl camphorsultam gives access to the enantio-pure 2-oxoesters, which may be converted into the 3-hydroxy-5-methylpiperidin-... 

In 2008, Chakraborty el al. reported that Michael addition of nitromethane to the sugar olefinic derivative 36 provided the sugar-based (I-nitro acid ester 37 (Scheme 14), which was used as starting material for the preparation of a novel type of cyclohexyl amines.36... 

Michael addition of nitromethane to D-glucose based vinyl sulfone 38 to afford nitro sugars 39 and 40 was also recently described (Scheme 15).37... 

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. 

Figure 6.39 Cinchona alkaloid-thioureas prepared from quinine (121), dihydroquinine (122), C9-epi-quinine (123), and quinidine (124) catalytic efficiency evaluated in the Michael addition of nitromethane to tram-chalcone 1,3-diphenyl-propenone at 10mol% loading and rt.

Regioselectivity in the Michael addition of nitromethane to x/i-unsaturatcd esters in the presence of Triton B has been studied both theoretically and experimentally.87... 

Sv -sclcctivc Michael addition of nitromethane and its homologues to enoates derived from (R)-(+)-glyceraldehyde acetonide (Z)-(102) in the presence of B114N F 3H2O or DBU has been reported to produce mainly. s v -(103) with 80-100% de (Scheme 23). 

In 1978, Wynberg and coworkers reported the first example of a chiral quaternary ammonium fluoride-catalyzed Michael addition of nitromethane to chalcone (Scheme 9.1) [3]. The reaction was performed in toluene at 20 °C with 10mol% of chiral ammonium salt 1 or 3a and excess potassium fluoride (KF, 15 equiv.), yielding the y-nitro ketone with 10-23% enantiomeric excess (ee). The requisite chiral... 

Michael addition of nitromethane to chalcones can be catalysed by cinchona alkaloid-derived chiral bifunctional thiourea (142) (0.5-10 mol%) to give the corresponding products at 25-100 °C in high chemical yields and high enantioselectivity ... 

Scheme 6.2 Thiourea-catalyzed Michael additions of nitromethane to chalcones.

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. 

Two large-scale syntheses were reported by Quaedflieg et al. at Tibotec.31 Chiral synthon 20, obtained from ascorbic acid, was converted to a,p-unsaturated ester 21 in 92% yield and E/Z ratio was > 95 5. Michael addition of nitromethane to 21 was carried out with DBU as base to provide 22 in 80% yield and a syn/anti ratio of 5.7 1. A Nef reaction then converted 22 to a mixture of lactone 23 (major, 56%) (a/p = 3.8 1) and ester 24 (minor). The a-23 was obtained via recrystallization in isopropanol (37%), with high enantiomeric purity (> 99%). Isomerization of P-23 followed by recrystallization in isopropyl alcohol gave an additional 9% yield of a-23. It is interesting that most of 24 remained in the aqueous layer. Lithium borohydride reduction of a-23 followed by acid-catalyzed cyclization resulted in (-)-ll. 

Watanabe and coworkers have described some Co -bipyridyl (phenanthroline) catalyzed Michael additions of nitromethane generalized by equation (49) but the catalyzing effect of the complex remains obscure.292... 

Asymmetric Michael Addition of Nitromethane to Enone. N-Methylephedrinium fluoride catalyzes the Michael addition of nitromethane to chalcone to afford the adduct with 23% ee in 50% yield (eq 27). ... 

Michael additions of nitromethane. Italian chemists were able to effect Michael addition of nitromethane to z,/ -unsaturated carboxylic acid esters with catalysis by lelramethylguanidine. Yields of 1 1 adducts (1) are in the range 50-85 % when R or R are alkyl or aryl groups. If R and R are H, I 2 adducts (2) are also formed in substantial amounts. 

Michael addition of nitromethane with this catalyst to the ketone (3) was used to obtain the nitroketone (4) in 84% yield. The reaction was the first step in a synthesis of ( )-ll-desoxyprostagIandin Ei, F, and F,j. 

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) ... 

Condensations. Alumina promotes the formation of a-hydroxyphosphonate esters from aromatic aldehydes and dialkyl phosphonates, and the adducts are converted to a-aminophosphonate esters on reaction with ammonia. A solvent-free synthesis of a-nitro ketones comprises mixing nitroalkanes, aldehydes, and neutral alumina and oxidizing the adducts with wet, alumina-supported CrOj (15 examples, 68-86%). The Knoevenagel reaction, the Michael addition of nitromethane to gcm-diactivated alkenes, and the formation of iminothiazolines from thioureas and a-halo ketones are readily effected with alumina under microwave irradiation. 

In 2009, the Magnus group disclosed the synthesis of racemic codeine [50]. In their synthesis (1) an intramolecular phenol alkylation generating an A-C bicyclic ring system with a quaternary carbon, (2) a stereo-controlled, one-pot formation of a B-ring by way of the combination of Henry reaction and Michael addition of nitromethane with a cyclohexadienone-aldehyde, and (3) an introduction of the requisite functionalities in the C-ring by the epoxide-mediated selenylation followed by oxidation, were employed as the key transformations. 

Scheme 11. Stereoselective functionalization of enone 3 via Michael addition of nitromethane/reduction and thiacetic acid/nitromethane reduction approach.

Scheme 33. Michael addition of nitromethane onto methyl vinyl ketone...

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