P -nitroketones

Rovis and co-workers have also extended the intermolecular Stetter reaction to inclnde nitroaUcenes as the electrophilic component. Fluorinated triazolinm precatalyst 155 was effective in catalysing the reaction of a variety of heteroaromatic aldehydes 153 with nitroalkenes 154 to generate P-nitroketones in excellent yields and enantioselectivities. The authors propose that stereoelectronically induced conformational effects on the catalyst skeleton are key to the high selectivities observed with flnorinated catalyst 155 (Scheme 12.33) [69],... 

Several derivatives of this type have been produced by treatment of conjugated azoalkenes with CH-substituted -diketones, p-ketoesters, p-ketolactones, p-ketonitriles or p-nitroketones containing an activated methinic group (89G631,92JCS(P1)3099, 93T7027). 

Recently, the Rovis group reported the asymmetric intermolecular Stetter reactions of unactivated aliphatic aldehydes and nitrostyrenes. Using fluorinated triazolium salt II as precatalyst, both straight-chain aliphatic substitution and a-branched aldehydes worked well and provided p-nitroketones 52 in good yields and with excellent enantioselectivities (Scheme 20.25). 

Since the early example of a proline-catalyzed asymmetric domino Michael-aldol reaction reported by Bui and Barbas in 2000 [57], a number of these reactions have been successfully developed by several groups. For example, Wang et al. have reported the synthesis of chiral densely functionalized cyclopentenes on the basis of a domino Michael-aldol reaction followed by dehydration between aromatic enals and dimethyl 2-oxoethylmalonate [67]. High yields (63-89%) and enanhose-lectivities (91-97% ee) were obtained by using (S)-diphenylprolinol sUyl ethers as catalysts. On the other hand, the condensation of P-nitroketones 36 onto enals in the presence of 8 was shown by Hong et al. to afford the corresponding domino Michael-aldol products 37 through the iminium-enamine activation mode [68]. 

The Michael addition of nitroalkanes to a, P-unsaturated ketones gives y-nitroketones, which are converted into pyrroles by reduction of the nitro group with Bu3P and PhSSPh (Eq. 10.2).4... 

Giorgi G, Miranda S, Lopez-Alvarado P, Avendano C, Rodriguez J, Menendez JC (2005) Unique Michael addition-initiated domino reaction for the stereoselective synthesis of functionalized macrolactones from alpha-nitroketones in water. Org Lett 7 2197-2200... 

Formation of the d bond by the reductive cyclization of a,oj- nitroketones (68CRV747, p. 778), -cyanoketones and -cyanoesters (74MIP51800) has been used in the preparation of both 1,4- and 1,5-benzodiazepines. 

The synthesis of unsymmetrical 1,4-diketones results from the conjugate addition of the nitronate anion (as the acyl anion equivalent) to an a,fi-unsaturated ketone [Method (6)].l47a The intermediate nitroketone is converted into the diketone by reduction with titanium(m) chloride at pH 1, or by ozono-lysis of the nitronate anion147b (cf. Section 5.7.7, p. 599). 

Reduction of nitroketones with titanium(m) chloride at pH 1. The foregoing nitroketone may be converted into the diketone by means of the following general procedure. The nitroketone in solution in tetrahydrofuran (0.2 m) is treated with 4 equivalents of titanium(m) chloride (1) (20% aqueous hydrochloric acid solution) and stirred under nitrogen at room temperature for 24 hours. The reaction mixture is then poured into ether and the phases separated. The aqueous phase is extracted several times with ether the organic extracts are combined, washed with 5 per cent sodium hydrogen carbonate and with brine, and then dried over anhydrous sodium sulphate, concentrated and distilled. The yield of heptane-2,5-dione is 66 per cent p.m.r. spectrum (CC14, TMS) 8 1.00 (t, 3H), 2.10 (s, 3H), 2.60 (s, 4H) and 3.41 (q, 2H). 

In the reduction of aromatic nitroketones in concentrated sulphuric acid the normal reaction, i.e., the formation of p-amidophenol derivatives, occurs (Gattermann ). 

P, P] Seebach and Brock reported the dichlorodiisopropoxytitanium-mediated addition of the trimethylsilyl enol ether of cyclohexanone to /3-nitrostyrenes (83). The initial products generated are nitronic esters 39.1-39.3. Separation followed by fluoride-induced desilylation of these intermediates yields the corresponding syn and anti nitroketones. The results of this study are summarized in Scheme 39 and Table 12. Anti isomers are obtained in moderate diastereomeric excess. Moreover, the method is complementary to the additions of similar substrates by way of their lithium enolates (2) or enamines (vide supra), which provide the syn diastereomers. Further reactions of the intermediate nitronic esters were briefly explored. For example, addition of aldehydes and activated olefins provides stereoselectively the products from nitroaldol and [3 + 2] cycloadditions. 

In addition, it has been shown that the catalytic use of PS-N3PAPT (10 mol%) was very effective for Michael addition reactions of a variety of Michael donors such as p-ketoesters, ot-nitroketones and nitroalkanes with activated olefins such as methyl acrylate and methyl vinyl ketone [41] (Scheme 6.9). The recyclability of the catalyst was established after it had been used 12 times. When diethyl malonate or ethyl cyanoacetate was used as the Michael donor substrate, the expected disubstituted adducts were obtained in moderate to good yields. 

Chiral cyclohexene derivatives were also constructed by an asymmetric four-component quadruple domino reaction initiated by oxa-Michael addition of alcohols to acrolein. The other two components were another equivalent of acrolein and a nitroalkene. Enders has shown that cyclohexene derivatives can also be assembled by a domino reaction of y-nitroketones and enals. Domino Michael/aldol condensation of 5-oxoalkanals and a,p-unsaturated aldehydes afforded densely functionalised cyclohexenes. Combination of unsaturated aldehydes with unsaturated p-ketoesters resulted in the formation of chiral cyclohexene derivatives via a Michael/ Morita-Baylis-Hillman sequence (Scheme 8.21). ... 

Silyl enol ethers of P-amido substituted cyclohexanone give [2+2] cyclisadons to form N-heterocycles, fluoroalkyl amides convert cyclohexanones to the enol ether, C N02)4 witii benzocyclohexanone gives a-nitroketones, and with diazoesters give optically active siloxycyclopropanes. Pb(OAc)4 gives acetoxy derivatives, deracemisation by enantioselective protonation demonstrated, methyl vinyl ketones added to give a,e-diones, and... 

In the mid-2000s, Griengl and coworkers reasoned that a small molecule with a similar pK as HCN, for example, nitromethane, could act as nucleophile for addition to carbonyl compounds (nitroaldol or Henry reaction Scheme 25.3) [111]. The Henry reaction is a classical name reaction in organic chemistry for the formation of C—C bonds. The resulting p-nitro alcohols can be transformed to nitroalkenes, 2-nitroketones, a-hydroxycarboxylic acids, and 1,2-amino alcohols. Although several other enzymes and proteins such as hydrolases and lipases [112], transglutaminase... 

This approach also allows a very efficient synthesis of different y-nitroketones containing quaternary stereogenic centers starting from cyclic as weU as selected acyclic P,P-disubstituted enones and cinchonine-based primary amine catalyst (Figure 21.4). The reaction is also possible with more demanding 2-nitropropane and nitroethane. In most cases, under lOkbar pressure and in the presence of 1-5 mol% of the simple chiral primary amine catalyst, good yields and good to excellent enantioselectivities were obtained. 

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