Nitro-substituted olefins

In several recent studies, nitro-substituted olefins have been shown to exhibit high electrophilic reactivities in superacid-promoted reactions.29 NMR studies have been used to identify some of the superelectrophilic intermediates in these reactions. For example, it was found that nitroethy-lene reacts with benzene in the presence of 10 equivalents of CF3SO3H to give deoxybenzoin oxime in 96% yield (eq 29). Since the reaction does not occur with only one equivalent of TfOH, it was proposed that the N,N-dihydroxy-iminium-methylium dication (51) is generated. In spectroscopic studies, l-nitro-2-methyl-l-propene (52) was dissolved in CF3SO3H, and at —5°C the stable dication (53) could be directly observed by and 13 C NMR spectroscopy (eq 30). 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

Primary nitroparaffins react with two moles of formaldehyde and two moles of amines to yield 2-nitro-l,3-propanediamines. With excess formaldehyde, Mannich bases from primary nitroparaffins and primary amines can react further to give nitro-substituted cycHc derivatives, such as tetrahydro-l,3-oxa2iaes or hexahydropyrimidines (38,39). Pyrolysis of salts of Mannich bases, particularly of the boron trifluoride complex (40), yields nitro olefins by loss of the amine moiety. Closely related to the Mannich reaction is the formation of sodium 2-nitrobutane-1-sulfonate [76794-27-9] by warming 1-nitropropane with formaldehyde and sodium sulfite (41). 

The chemical entrainment method was used by Ono et al. (1979) to eliminate the nitro group in nitroalkene derivatives. On simple mixing with thiophenol and sodium sulfide in DMF, nitro aryl olefins substitute hydrogen for the nitro group (Scheme 5.9). 

ESR measurements. The presence of the intermediate organic radical anion was confirmed by comparison with a similar intermediate obtained from the SET of the nitro-substituted aldehyde with an electron-rich olefin (Scheme 40197, equation 187197, Figures 15 and 16). 

Tosylmethyl isocyanide can react i.a. with fluoro- and perfluoroalkyl-substituted olefins, e.g., tert-butyl (E)-4,4,4-trifluoro-2-butenoate [9IJFC(53)61] and )8-perfluoroalkyl-substituted a,/3-unsaturated ketones (88CL1891) to provide 3-trifiuoromethylpyrroles. The latter are also accessible from isocyanoacetates and 3-nitro-2-hydroxy-l,l,l-trifluoroalkanes, which in situ are transformed into olefins on treatment with acetic anhy-dride/DBU (89BCJ3386) (Scheme 31). 

Kuster GJT, Steeghs RHJ, Scheeren HW. Novel five/five-and six/five-membered bicyclic nitroso acetals from high-pressure-promoted cyclisation reactions of p-methoxybenzyl vinyl ether, l-nitro-2-heteroaryl ethenes, and mono- and di-substituted olefins. Eur. J. Org. Chem. 2001 553-560. 

CM involving a diene partner can be difficult when the other olefin is hindered. Morita and Kuwahara had to employ an allylic pivalate as a diene precursor for the preparation of the dienoic fragment of elaiolide [35], Koide and coworkers resorted to the use of the nitro-substituted [Ru]-VII [36] for the metathesis of a diene leading to FR901464, which is a potent anticancer product isolated from Pseudomonas sp. No. 2663 [37]. However, the CM of diene 66 with 2 equiv. of allylic alcohol 65 performed by Crimmins et al. led to diene 67 in 63% yield along with 31% of recovered 66 and the homodimer of 65, which could be recycled (Scheme 10.21) [38]. The T-selectivity on the other hand was total. Compound 67 was then transformed into apoptolidinone, the aglycone of apoptolidine, which induces cell death by inhibiting the mitochondrial FoFi-ATPase. 

Michael condensations are catalyzed by alkaU alkoxides, tertiary amines, and quaternary bases and salts. Active methylene compounds and aUphatic nitro compounds add to form P-substituted propionates. These addition reactions are frequendy reversible at high temperatures. Exceptions are the tertiary nitro adducts which are converted to olefins at elevated temperatures (24). 

In the examples, a nitro group is substituted for a hydrogen atom, and water is a by-product. Nitro groups may, however, be substituted for other atoms or groups of atoms. In Victor Meyer reactions which use silver nitrite, the nitro group replaces a hahde atom, eg, I or Br. In a modification of this method, sodium nitrite dissolved in dimethyl formamide or other suitable solvent is used instead of silver nitrite (1). Nitro compounds can also be produced by addition reactions, eg, the reaction of nitric acid or nitrogen dioxide with unsaturated compounds such as olefins or acetylenes. 

Ozonation of Aromatics. Aromatic ring unsaturation is attacked much slower than olefinic double bonds, but behaves as if the double bonds in the classical Kekule stmctures really do exist. Thus, benzene yields three moles of glyoxal, which can be oxidized further to glyoxyUc acid and then to oxahc acid. Substituted aromatics give mixtures of aUphatic acids. Ring substituents such as amino, nitro, and sulfonate are cleaved during ozonation. 

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). 

Epoxidation of substituted spiro[cyclopentane-l,9 -fluorene]-2-enes 68 with a peroxidic reagent was studied [98], The spiro olefins react with m-chloroperbenzoic acid (mCPBA) in chloroform at 3 °C to give a mixture of the epoxides. In all cases (2-nitro (68b), 4-nitro (68c), 2-fluoro (68d) and 2-methoxyl (68e) groups), the iyn-epoxides, i.e., the syn addition of the peroxidic reagent with respect to the substituent, is favored. For example, for 6 nsyn anti = 63 31 for 68c syn anti = 65 35. Thus, a similar bias is observed in both the reduction of the carbonyl derivatives of 30 and the epoxidation of the derivatives of 68. 

ISOC reaction was employed to synthesize substituted tetrahydrofurans 172 fused to isoxazolines (Scheme 21) [44b]. The silyl nitronates 170 resulted via the nitro ethers 169 from base-mediated Michael addition of allyl alcohols 168 to nitro olefins 167. Cycloaddition of 170 followed by elimination of silanol provided 172. Reactions were conducted in stepwise and one-pot tandem fashion (see Table 16). A terminal olefinic Me substituent increased the rate of cycloaddition (Entry 3), while an internal olefinic Me substituent decreased it (Entry 4). 

Recently, it has been demonstrated (495) that the [3+ 2]-cycloaddition reactions of 3-bromo-substituted six-membered cyclic nitronates (400), which are constructed from olefins (401) and l-bromo-l-nitro-2,4/-methoxyphenylethylene, with olefins (402) produce 3-vinylisoxazolines (403) or five-membered cyclic nitronates (404) in good yields (Scheme 3.221). 

Another type of Cinchona alkaloid catalyzed reactions that employs azodicarbo-xylates includes enantioselective allylic amination. Jprgensen [51-53] investigated the enantioselective electrophilic addition to aUyhc C-H bonds activated by a chiral Brpnsted base. Using Cinchona alkaloids, the first enantioselective, metal-free aUyhc amination was reported using alkylidene cyanoacetates with dialkyl azodi-carboxylates (Scheme 12). The product was further functionalized and used in subsequent tandem reactions to generate useful chiral building blocks (52, 53). Subsequent work was applied to other types of allylic nitriles in the addition to a,P-unsaturated aldehydes and P-substituted nitro-olefins (Scheme 13). 

Wang and co-workers [57,58] reported several Michael-type enantioselective additions with nitro-olefins. Under neat conditions, 1,3-dinitro compounds were generated in the 74 addition of nitroalkanes 75 to various P-substituted nitro-olefins (Scheme 15). Other Michael-type involving nitro-olefins reactions were illustrated using triazole donors 77 to offer good yields and high enantioselectivities (Scheme 16). 

The conjugate addition of nitro olefins under chiral Cmc/mna-thiourea catalysis has shown promising results with a variety of Michael donors. Dixon conducted a screen of various chiral thioureas and identified catalyst 117 as a versatile catalyst that works well with p-substituted nitro-olefms (78) [74]. Aromatic, heteroaromatic... 

Chen and co-workers utilized the chiral bifunctional catalysts to directly access vinylogous carbon-carbon bonds via the asymmetric Michael addition of a,a-dicy-ano-olefms to nitro-olefms [102]. The scope of the reaction was explored with a variety of substituted a,a-dicyano-olefins and P-substituted nitro-olefms (Scheme 50). The authors propose the catalysf s tertiary amine functionality depro-tonates the cyano-olefm, activating the nucleophile to add to the -face of the pre-coordinated nitro-olefm. 

Terada and co-workers reported a novel guanidine catalyst with a chiral binaphthol backbone for the asymmetric addition of dicarbonyl compounds to nitro-olefins [126]. Substitution on the binaphthol backbone dramatically increased enantioselectivity. 

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