Nitroolefins

There have been a number of investigations involving the study of nitroolefins as useful intermediates in the synthesis of energetic materials. A characteristic of many of them is a large twist about the double bond. Interest in the structural characteristics that accompany the rotation motivates a discussion of details. As would be expected, the rotation out of the normal planar conformation is associated with spatial crowding. Rgure 14 illustrates some of the largest out-of-plane rotations that have been measured and, in one case, calculated for crowded ethylenes [25j. 

l-dinitro-2,2-di(dimethylamino)ethylene [26J (Fig. 15) there is a torsion of the N1-C1-N2 plane about the C1-C2 double bond of 51.4 relative to the N3-C2-N4 plane. The C1-C2 distance is 1.434(3)A, which is considerably longer than a typical isolated double bond length ( 1.33 A) [27]. 

A quite useful precursor in the synthesis of twisted diaminodinitro olefins is l,l-diiodo-2,2-dinitroethyIene [26] whose structure is shown m 

Telra-t-bulyl ethylene Unknown Torsion calc d to be 45° 

The teactjon that leads to the synthesis of l,l-dinitro-2,2-di(dimethylamino)ethylene is 

To rationalize these results, a conformational study of these peptidomimetics was undertaken. DKP scaffolds can induce a well-defined tridimensional stracture and the importance of this characterishc was proven in several studies [20]. In fact, as a consequence of the absolute configuration of the two a-amino acids forming the cyclic dipephde unit, the two reactive functionalities (amino and carboxylic acid) are locked in a cis- (catalysts 7 and 8) or trans-configuration (catalysts 9 and 10). 

A Monte Carlo/energy minimization (MC/EM) conformational search for the enamine intermediate derivatives revealed conformations where one face of the 

The Morita-Baylis-HiUman (MBH) reaction is described as the coupling between the a-position of an activated double bond and an sp electrophUic carbon (typically an aldehyde, but also an imine) using an appropriate catalyst, normally Lewis bases [21]. Shi and coworkers showed that imidazole and proline formed an efficient co-catalytic system for carrying out the MBH reaction, but with low ee [22]. 

An optimization of the co atalyst was also attempted, using other amino acids as well as several proline derivatives, but with no positive results. 

A closely related transformation was reported by the group of Miller, who used 3-pyridylalanine (Pal) based catalysts for the enantioselective addition of allenoates 

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In Diels-Alder reactions a nitroolefin may function as an electron-deficient ene com-onent or a 1,2-dihydropyridine derivative may be used as a diene component. Both types of iactants often yield cyclic amine precursors in highly stereoselective manner (R.K. Hill, 1962 i. BOchi, 1965, 1966A). 

Nitroolefins also offer the possibilities of 1,2 cycloaddition (37,57) or simple alkylation (57-59) products when they are allowed to react with enamines. The reaction of nitroethylene with the morpholine enamine of cyclohexanone led primarily to a cyclobutane adduct in nonpolar solvents and to a simple alkylated product in polar solvents (57). These products are evidently formed from kinetically controlled reactions since they cannot be converted to the other product under the conditions in which the other... 

The alkylation of enamines with nitroolefins, which gives intermediates for reductive cyclization (6S2), also provided an example of a stable cycliza-tion product derived from attack of the intermediate imonium function by the nitro anion (683). A previously claimed tetrasubstituted enamine, which was obtained from addition of a vinylsulfone to morpholinocyclohexene (314), was shown to be the corresponding cyclobutane (684). Perfluoro-olefins also gave alkylation products with enamines (685). Reactions of enamines with diazodicarboxylate (683,686) have been used diagnostically for 6-substituted cyclohexenamines. In a reaction of 2-penten-4-one with a substituted vinylogous amide, stereochemical direction was seen to depend on solvent polarity (687). 

To a solution of nitroolefin 4 (200 mg) and isocyanide 16 (169 mg) in a 1 1 mixture of THF and isopropanol (5 mL) was added the guanidine base A -t-BuTMG (180 mg). The resulting solution was heated to 50°C for 3 h, poured into water, and extracted with dichloromethane. The organic layer was dried over sodium sulfate and filtered through a short column of silica gel (eluent dichloromethane). Evaporation under vacuum of the solvent gave the desired pyrrole as a pale crystalline solid (272 mg, 90%) mp... 

The regiochemical control of Pd-catalyzed hydnde transfer reacdon is much more effeedve than that of the radical denitradon, as Shown in Eq 7 98 The base-catalyzed reacdon of nitroolefins with aldehydes followed by denitradon provides a new syntbedc method of homoallyl aicohols fEq 7 99 Exomethylene compounds are obtined by denitradon of cyclic allylic nino compounds with PdfO, HGO-,H and Et- N fEq 7 100 ... 

Diels-Alder cycloadditions of enaminothiones with electrophilic die-nophiles (83AHC145, section III,G) have been widely used for the preparation of various thiopyran derivatives. In addition to expected 2H-thiopyrans, 4//-isomers were trapped as intermediates or even as final products. Nitroolefines (90T1951), olefinic carbonyl derivatives [80JH405 85JOC1545 92JCS(P1)2603] allenedicarboxylic esters... 

According to Urbanski (Ref 6), . . Besides adding concentrated HN03 to olefms, true nitration of olefins thru electrophilic substitution can take place to yield nitroolefins.. . In 1878 Haitinger (Ref 1) found that nitration of isobutylene with anhydrous nitric add led to several products, among which was nitroisobutylene (CH3)C2=CHN02, in 10% yield... 

I. The Preparation and Properties of Some Nitroolefine Derivatives..OSRD 1568, Ohio State Univ Res Found, NDRC Contract 9-i22 (July 1943), 9 10... 

Propyl Acrylate (Propylic Acid, Propyl ester). The (theoretical) parent compd for nitroolefin polymers used as propints and expls such as 2,2-Dinitropropylacrylate (DNPA) . See under this title in this Vol, N139-R to N140-L. 

The enantioselective Michael reaction of malonates to nitroolefins catalysed by bifunctional amino-thioureas has recently been reported by Take-moto [161]. Excellent ee (75-93%) were obtained with diethylmalonate after solvent optimisation, toluene being the best solvent both for the activity and for the selectivity. Substituted malonates were then reacted with various nitroolefins under the same conditions. Excellent enantioselectivities were observed (Scheme 45). 

This bifunctionnal amino-thiourea organocatalyst led to high selectivity because it was activating both the nitrone and the malonate, in its enol form, due to the acidic hydrogen atoms of the thiourea. Thus, the amino-thiourea catalyst promoted the Michael reaction of malonates to various nitroolefins... 

By analogy with aromatic nitro compounds, nitroolefins such as yS-nitrostyrene 1032 react with the O-silylketene acetal 1033 at -78 °C, in the presence of the selective Lewis acid MAD, in toluene, to give a 6.3 1 syn/anti mixture of the co-nitro ester 1034 and 94a [98] (Scheme 7.33). 

The diolefin 1064 gives rise to the isoxazoline 1065, which cannot eliminate tri-methylsilanol 4 [122]. Cychzation of the co-nitroolefin 1066 with trimethylchloro-silane (TCS) 14/triethylamine at -35 °C then HCl-induced removal of trimethyl-silanol 4 leads, in 85% yield, to the dimer 1067, which is converted in two more steps into racemic pyrenophorin 1068 [112] (Scheme 7.39). Further cyclizations of co-nitroolefins [109] to monomeric or dimeric isoxazolines have been described. Conjugated dienes such as butadiene afford a mixture of the mono or bis adducts [115-117]. 

Sakai, K, A Nakazawa, K Kondo, and H Ohta (1985) Microbial hydrogenation of nitroolefins. Agric Biol Chem 49 2231-2236. 

Meah Y, V Massey (2000) Old yellow enzyme stepwise reduction of nitroolefins and catalysis of acid-nitro tautomerization. Proc Natl Acad Sci USA 97 10733-10738. 

Some particular features should be mentioned. Instead of Michael additions, a-nitroolefins are reported to yield allyl sulfones under Pd catalysis (equation 21). Halogenated acceptor-olefins can substitute halogen P to the acceptor by ipso-substitution with sulfinate (equation 22 , equation 23 ) or can lose halogen a to the acceptor in the course of a secondary elimination occurring P to the introduced sulfonyl groups (equation 24). On the other hand, the use of hydrated sodium sulfinates can lead to cleavage at the C=C double bond (equation 25). 

Node and Fuji have developed stereoselective nitroolefination of various carbonyl compounds using (3-nitroenamines (Eq. 4.95).118... 

Chiral nitroolefins prepared in Eqs. 4.96 and 4.97 are converted into various natural products as summarized in Scheme 4.16.121-123... 

A total synthesis of (-)-physostigmine is accomplished from a chiral nitroolefin of Eq. 4.101 (Scheme 4.17).128... 

The regiochemical control of Pd-catalyzed hydride transfer reaction is much more effective than that of the radical denitration, as shown in Eq. 7.98. The base-catalyzed reaction of nitroolefins with aldehydes followed by denitration provides a new synthetic method of homoallyl alcohols (Eq. 7.99).140 Exomethylene compounds are obtained by denitration of cyclic allylic nitro compounds with Pd(0), HC02H and Et3N (Eq. 7.100).140b... 

Node and Fuji have developed a new chiral synthesis of various alkaloids using chiral nitroalkene, (S)-(-)-2-methyl-2-(2 -nitrovinyl)-S-valerolactone. Scheme 8.11 shows a total synthesis of (-)-physostigmine, a principal alkaloid of the Calabar bean.53 The key nitroalkene is prepared by asymmetric nitroolefination of a-methyl-8-lactone using a chiral enamine (see... 

The total syntheses of the potent glycosidase inhibitors (+)-castanospermine, (+)-6-epicas-tanosperimine, (+)-australine, and (+)-3-epiaustraline have been reported. These four natural products are derived from a single common intermediate, the nitroso acetal (as shown in Scheme 8.43), which is created in the key step by the asymmetric tandem [4+2]/[3+2] cycloaddition between silaketal nitroolefin and chiral vinyl ether.182 The strategy of the synthesis is outlined in Scheme 8.43. Scheme 8.44 presents a total synthesis of (+)-castanosperimine and (+)-6-epi-castanosperimine from the common intermediate prepared by tandem [4+2]/[3+2] cycloaddition. 

Hydrazones are also useful substrates in the preparation of pyrazoles. Reaction of N-monosubstituted hydrazones with nitroolefins led to a regioselective synthesis of substituted pyrazoles <060L3505>. lf/-3-Ferrocenyl-l-phenylpyrazole-4-carboxaldehyde was achieved by condensation of acetylferrocene with phenylhydrazine followed by intramolecular cyclization of the hydrazone obtained under Vilsmeier-Haack conditions <06SL2581>. A one-pot synthesis of oxime derivatives of l-phenyl-3-arylpyrazole-4-carboxaldehydes has been accomplished by the Vilsmeier-Haack reaction of acetophenone phenylhydrazones <06SC3479>. 

Matthews RD. 1980. Estimated permissible levels, ambient concentrations, and adverse effects of the nitrogenous products of combustion the cyanides, nitroolefins, and nitroparaffins. Journal of Combustion Toxicology 7 157-172. 

Bifunctional thiourea-catalysed enantioselective Michael reaction has been achieved. The thiourea moiety and an amino group of the catalyst activated a nitroolefin and a 1,3-dicarbonyl compound, respectively afford the Michael adduct with high enantioselectivity.177,178 Thioureas work as one of the most effective and general enantioselective nitro-Mannich reaction and carbonyl cyanation catalyst.179,180... 

Paulsen, H. and Greve, W. Synthese von Aminozuckerphosphonaten durch Addition von Dialkyl phosphiten an Nitroolefin-Zucker, Chem. Ber., 106,2114, 1973. 

As follows from above, the rate of [4+ 2]-cycloaddition of nitroolefin (42) is determined by the nature of partner (43) and decreases in the following series of olefines electron-rich > electroneutral > electron-deficient (100). 

Silylation of Products of Conjugated Addition of Nucleophiles to a-Nitroolefins Nitroalkane anions can be generated not only by deprotonation of nitroalkanes (various modifications of these process were considered above) but also by the conjugated addition of nucleophiles 56 to a-nitroalkenes (42) (Scheme 3.56, Table 3.2). 

The use of strongly stabilized nucleophiles, for example, of [(EtO)2P(0)CHX] Li+ 58a-d, where X is a powerful EWG group, such as Me02C, CN, S02Me, or P(O) (OEt)2, in the conjugated addition with a-nitroolefins gives rise to more complex processes (201b) (Scheme 3.58). 

Another synthetic route to boryl nitronates (71k-m), which is, however, poorly developed (231), is based on the reaction of trialkylborons (exemplified by triethylboron) with a-nitroolefins (72a-c) proceeding by the 1,4-addition mechanism (Scheme 3.70, cf. Scheme 3.56). 

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