With Nitroolefins

An easy and efficient copper-catalyzed reaction for the synthesis of quinoxalines from 1,2-DABs and nitroolefins has been developed (Chen et al. 2013). This reaction could proceed well enough without any additional base and be applied to various available substrates with a one-step synthetic procedure in moderate to good yields. 

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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). 

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>. 

Whereas cyclic secondary enaminones and nitroolefins mainly yield indoles in which the enamine nitrogen is incorporated into the heterocyclus (equation 242), linear tertiary a-ketoenamines are shown to react with nitroolefines at low temperature under kinetic control to give 1,2-oxazine N-oxides as [4 + 2]-cycloadducts, followed by retro-Diels-Alder reaction or rearrangement under thermodynamic control which leads diastereo-selectively to aminocyclopentenes. The reaction is called [3 + 2]-carbocyclization, apparently because the ketoenamine is reacting as a 1,3-dipole. The products are hydrolysable to polysubstituted nitrocyclopentanones with retained configuration325 (equation 243). 

Sharpless bis-cinchona alkaloids such as [DHQD]2PYR (163a) have proved to serve as highly efficient catalysts for the asymmetric vinylogous Michael addition of the electron-deficient vinyl malonitriles 164 as the nucleophilic species to nitroole-fins 124 [50], This process exhibited exclusive y-regioselectivity and high diastereo-and enantioselectivity. Only the anti-products 165 were observed in all reactions (Scheme 9.57). Of note, 1-tetralone did not react with nitroolefins under these... 

Scheme 5.19 Michael addition reactions of carbonyl compounds with nitroolefins.

The combination of titanium-TADDOL 34 mediates the reaction of diethylzinc with nitroolefins to afford the products in relatively high ees (Scheme 18) [77]. 

A number of enantiomerically pure amines catalyse the asymmetric Michael reaction of ketones with nitroolefins. Amongst these some of the most successful... 

The highly efficient enantioselective Friedel-Crafts reaction of pyrroles (203) with nitroolefins (204) catalyzed by the chiral phosphoric acid (154), afforded 2-substituted or 2,5-disubstituted pyrroles (205) in up to 94% ee for a wide range of substrates (Scheme 57). ... 

The roles of the catalytic functions are not necessarily opposite or limited to Lewis acid/base pairs. For example, amine thiourea derivatives like Takemoto s catalyst 4 merge the hydrogen bond donor capability of the thiourea moiety with Bronsted base functionality of the amine function and revealed itself particularly efficient organocatalysts for Michael reactions of various 1,3-dicarbonyl compounds with nitroolefins (Scheme 3) [17-19]. 

Scheme 2.118 Asymmetric Friedel-Ciafts eilkylation of indoles with nitroolefins...

Scheme 3.24 Diels-Alder reactions of cyclohexenones with nitroolefins promoted by catalyst 61 in seawater and brine...

Scheme 3.70 Organocatalytic [3+2] cycloadditions of a-substituted isocyanoesters with nitroolefins...

Sadek and coworkers [29] reported two-component domino reactions of l,l,3-tricyano-2-aminopropionitrile 29 with nitroolefins 30 in 1,4-dioxane under microwave irradiation, efficiently providing poly-substituted diaminobenzonitriles 31 in 70-73% yields (Scheme 12.11). 

When heteronucleophiles react with nitroolefins possessing extended conjuga-ticMi at the p-position, the heteroatoms are appended to a stereogenic allylic or propargylic carlxMi, providing synthetically valuable nitro compounds. For example, aza-Michael addition to nitroenynes under catalysis of the ionic Brpnsted acid, chiral tetraarylaminophosphonium barfate 11, produced the propargylic amine... 

The strong preference of y-butenolides to react at the y-position in conjugate addition was demonstrated in the reaction of y-substituted y-butenolides with nitroolefins (Scheme 25) [43]. Under the catalysis of aminothiourea 25, bond formation occurred at the sterically encumbered y-position with high site- and stereoselectivity. The sense of stereoinduction was dictated by the tert-leucine... 

In a few specialised examples 1,3-dien-2-amines were found to undergo a [4+2] cycloaddition with nitroolefins to form tricyclic derivatives of 4-nitrocyclohexenylamine. 

Dihydroisoquinoline esters undergo an oxidative [3 + 2] cycloaddition with nitroolefines or N-sulfuryl aldimines when treated with a cobalt catalyst (Scheme 69) (130BC6691). This cycloaddition provides a fairly robust approach to dihydropyrrolo[l,2-rj]isoquinolines. Nitroolefins with a number of aryl substituents underwent reaction with the dihydroiso-quinolines.The aryl groups could have either electron-donating (methoxy)... 

After these reports, the same group extended the utility of this catalytic system to asymmetric Michael addition and aldol reactions (212, 213]. Sulfonamide catalysts such as 37-39 have also been developed for the same purpose [214-219]. The behavior of these catalysts, typically exemplified by enantioselec-tive Michael addition reactions of cyclohexanone with nitroolefins, is compiled in Scheme 1.15. 

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