A-Nitroenamines

Nitroenamines are affected by the isomerism204 shown in equilibrium 22. Compounds with primary (R1 = R2 = H) or secondary amino (R1 = H, R2 = alkyl) groups exist as mixtures of the intramolecularly hydrogen bonded Z and E forms, in an equilibrium (equation 22) depending on the solvent properties. The E form of a nitroenamine with a tertiary amino group is the more populated form. 

The reaction of dibromocarbene with A-nitroenamines, cyclic enamides or enamines ... 

Thermolysis of A -nitroenamines 80a leads to a-nitroimines 81 by [l,3]-rearrangement, or while 80b is converted to the thermodynamically more stable nitroenamine isomer 82 (equation 16) ,... 

Nitroenamines and related compottnds have been used for synthesis of a variety of heterocyclic compottnds. Rajappahassummaiized the chemistry of nltroenamines fseeSecdon4.2. Anga and coworkers have developed the synthesis of heterocycles based on the reacdon of nltropytidones or nltropyrimldmone v/ith nucleophiles. For example, 2-subsdntted 3-nltro-pyridmes are obtained by the reacdon of l-methyl-3,5-dinitro-2-pyridones wiih ketones in the presence of ammonia fEq. 10.82. ... 

The addition-elimination reaction of hetero-atom-substituted nitroalkenes provides functionalized derivatives of unsaturated nitro compounds.26 Nitroenamines are generally prepared from a-nitro ketones and amines (see Chapter 5 regarding acylation of nitro compounds).26... 

A new synthesis of [i-nitroenamines by amination of nitroalkenes with methoxyamine in the presence of base is reported (Eq. 4.23).29... 

Nitroalkenes with potential leaving groups in (3-position such as a dialkylamino, an alkylthio, or a phenylsulfonyl group undergo addition-elimination reactions with nucleophiles. The chemistry of nitroenamines has been extensively investigated, and their potential utility in organic synthesis has been well established.2613 116 Severin and coworkers have developed the addition of elimination reactions of nitroenamines with carbon nucleophiles in 1960-1970, as exemplified in Eq. 4.94.117... 

They have developed direct asymmetric synthesis of quaternary carbon centers via addition-elimination process. The reactions of chiral nitroenamines with zinc enolates of a-substituted-8-lactones afford a,a-disubstituted-6-lactones with a high ee through addition-elimination process, in which (5)-(+)-2-(methoxy methy l)pyrrolidine (SMP) is used as a chiral leaving group (Eq. 4.96).119 Application of this method to other substrates such as a-substituted ketones, esters, and amides has failed to yield high ee. 

Complex 1 1 is considered the only complex present, but the hydrogen bond may be either two (76) or three center (77). Nitroenamines are more prone to complex with 4-fluorophenol than the nitroanilines and they form the strongest hydrogen bond presently known for nitro-bases. In particular, l-piperidino-2-nitroethylene (78) and 1-dimethylamino-2-nitroethylene (79) (both in E form) present a hydrogen bond basicity comparable to that of tributylamine. 

The (—)-sparteine-lithium compounds 409 undergo a facile conjugate addition to 1-nitroalkenes 410 with high enantio- and diastereoselectivity (equation n 1)289,295,296 (lZ)-3,4-5yw-diastereomers 411 are produced. A manifold of synthetically useful transformations of nitroenamines 411 has been worked out. Equation 112 presents a few of them utilizing the diphenyl derivatives 411a . The enantiomers ent-412-ent-416 are available via inversion of 409 by stannylation/lithiodestannylation with slightly decreased overall selectivities . 

The addition of Grignard reagents or organolithiums (alkenyl, alkyl, alkynyl, allyl or aryl) to nitroenamines (281)213 was reported by Severin to afford P-substituted-a-nitroalkenes.214 b Similarly, ketone enolates (sodium or potassium), ester enolates (lithium) and lactone enolates (lithium) react to afford acr-nitroethylidene salts (294) which, on hydrolysis with either silica gel or dilute acid, afford 7-keto-a,(3-unsaturated esters or ketones (295)2l4c-d or acylidene lactones (296).214 Alternatively, the salts (294, X s CH2) can be converted to -y-ketoketones (297) with ascorbic acid and copper catalyst. 

In contrast, a-nitroalkenation adducts (298) are obtained with thermodynamic enolates of a-sub-stituted ketones or esters in addition, Fuji reports that enantioselective addition of a-subsdtuted lactone enolates to chiral nitroenamines is cation dependent with zinc affording maximum enantioselectivity.213... 

The 3-( 7-butylamino)-2-nitroacrylaldehyde is a synthetic equivalent to nitromalonaldehyde that reacts with substituted ethylenediamines in MeOH at 25 °C to provide the first examples of 6-nitro-2,3,4,5-tetrahydro-l//-l,4-diazepines in excellent yield (Scheme 54) <2004JOC8382, 2002H(56)425>. The slow addition of a solution of the diamine to the nitroenamine was required in order to minimize oligomer formation. 

When azadienamines 6 is charged on a silica gel column at room temperature, formylated nitroenamine 10 is effectively produced by half hydrolysis [25] (Scheme 7). Formylnitroenamine 10 can be used as the building block for built-in method to afford versatile nitro azaheterocyclic compounds [26] and nitrophenols [27] in reactions with dinucleophilic reagents. 

Nitropyrimidinone 3 has also electrophilic sites, the 2-and the 6-positions, which are attacked by amines to yield nitro enamines having a carbamoyl group 11 in good yields [28]. Nitroenamine 11 is converted to polyfunc-tionalized pyridone 12a upon treatment with sodium enolate of ethyl 3-oxobutanoate 13a [29]. 

Nitroenamine derivatives are typical push-pull alkenes, and have been widely used in organic syntheses [3,30,31]. Although their synthetic utility is quite high, functionalized ones are not often employed because of their difficult preparation. Hence, the aminolysis of pyrimidinones 2 and 3 is regarded as a new preparative method for functionalized nitroenamines 10 and 11. 

All of the RTF reactions mentioned so far involve a combination of dielec-trophilic substrates and dinucleophilic reagents, namely dinitropyridone 1 and nitropyrimidinone 3 cause RTF reactions upon treatment with dinucleophilic reagents. Meanwhile, nitropyrimidinones 2 and 3 readily react with primary amines to afford functionalized nitroenamines as shown in Sect. 4. Since the nitroenamines 10 and 11 have both nucleophilic and electrophilic sites, this structural feature is applicable to development of the new type of RTF reaction by use of regents having both electrophilic and a nucleophilic sites. 

A new approach to 6-nitro-l//-[l,4]-diazepines 192 based on reaction of the formylated nitroenamine 190 with the 1,2-diamines 191 has been reported yields were generally good in... 

I -Organyl -4-ni tr< tpyra/olcs have been prepared by the reaction of /3-nitroenamines having a formyl group at the /(-position and hydrazines in methanol [496] (Scheme 71). 

Important classes of enamines are those having electron-withdrawing substituents, R2 and/or R3, at C(2), particularly when the substituent(s) act(s) by a +R effect, as in aminoenones and nitroenamines. The stronger and more extensive electron delocalization and the concomitant changes in bond orders of the resulting push-pull systems is well reflected in the NMR spectra and have been extensively investigated in this way. 

The 13C-, 15N- and -NMR spectral data for a series of simple l-amino-2-nitroalkenes are collected in Table 30. The greater electron-withdrawing character of the nitro group as compared with carbonyl results in downfield shifts of the resonances of C(2) ( + 10 to +14 ppm), the enaminic nitrogen ( + 23.2 to + 27.4 ppm) and the olefinic protons [ + 0.8 to +1.0 ppm for H(l) +1.5 to = 1.8 ppm for H(2)] of 2-nitroenamines with respect to enaminones. This deshielding does not affect C(l), which has in fact a lower chemical shift ( — 5.5 to — 10.2 ppm) in 2-nitroenamines. The NMR spectra show that 2-nitroenamines with a primary or a secondary amino groups exist in solution as solvent-dependent equilibrium mixtures of E- and Z-isomers. The... 

---