Straightforward Synthesis of 1,2‐Dicyanoalkanes from Nitroalkenes and Silyl Cyanide Mediated by Tetrabutylammonium Fluoride

A straightforward synthesis of 1,2‐dicyanoalkanes by reacting nitroalkenes with trimethylsilyl cyanide in the presence of tetrabutylammonium fluoride is described. The reaction proceeds through a tandem double Michael addition under mild conditions. Employing the hypervalent silicate generated from trimethylsilyl cyanide and tetrabutylammonium fluoride is essential for achieving this transformation. Mechanistic studies suggest that a small amount of water included in the reaction media plays a key role. This protocol is applicable to various types of substrates including electron‐rich and electron‐deficient aromatic nitroalkenes, and aliphatic nitroalkenes. Moreover, vinyl sulfones were found to be good alternatives, particularly for electron‐deficient nitroalkenes. The broad substrate scope and functional group tolerance of the reaction makes this approach a practical method for the synthesis of valuable 1,2‐dicyanoalkanes.     

Mukaiyama-Michael vinylogous additions to nitroalkenes under solvent-free conditions

The first Mukaiyama-Michael vinylogous reaction of a dioxinone-derived silyl ether to nitroalkenes is reported. The conjugate addition is performed in absence of any catalyst under solvent-free conditions, proceeding with satisfactory efficiency with variously substituted nitroalkenes.     

Synthesis and anticancer activity studies of alpha-aminoalkylated conjugated nitroalkenes

Novel alpha-aminoalkylated conjugated nitroalkenes which inhibit human cervical cancer (HeLa) cell proliferation by binding to tubulin were synthesized by imidazole/LiCl-mediated reaction of conjugated nitroalkenes with N-tosylimines.     

Asymmetric reduction of nitroalkenes with baker's yeast

Various α,β-disubstituted and trisubstituted nitroalkenes were chemoselectively reduced with baker's yeast to the corresponding nitroalkanes. Stereoselectivities of the reduction of α,β-disubstituted nitroalkenes were modest to low, and e.e.s up to 52% were obtained. Trisubstituted nitroalkenes could be reduced to the corresponding nitroalkanes with excellent enantioselectivities, moderate diastereoselectivities and in good yield.     

Organocatalytic synthesis of quaternary stereocenter bearing a fluorine atom: enantioselective conjugate addition of α-fluoro-β-ketoesters to nitroalkenes

The catalytic enantioselective conjugate addition reaction of α-fluoro-β-ketoesters to nitroalkenes promoted by chiral bifunctional organocatalysts is described. The treatment of α-fluoro-β-ketoesters with nitroalkenes under mild reaction conditions afforded the corresponding Michael adducts containing a fluorinated quaternary stereogenic center with excellent enantioselectivity (up to >99% ee).     

An efficient synthesis of nitroalkenes by alkene cross metathesis: facile access to small ring systems

A synthesis of highly functionalized nitroalkenes is reported that utilizes a cross metathesis (CM) reaction between simple aliphatic nitro compounds and a range of substituted alkenes. This chemistry offers a simple and attractive route to nitroalkenes that would otherwise be difficult to prepare, and that have a very useful application as precursors to a variety of heterocyclic entities.     

Ni(II)-Bis[(R,R)-N,N'-dibenzylcyclohexane-1,2-diamine]Br2 catalyzed enantioselective Michael additions of 1,3-dicarbonyl compounds to conjugated nitroalkenes

A highly enantioselective Michael addition of 1,3-dicarbonyl compounds to nitroalkenes has been developed that employs a newly developed Ni(II)-(bis)diamine based catalyst. The reaction scope includes substituted and unsubstituted malonates, beta-ketoesters, and nitroalkenes bearing aromatic and aliphatic residues. Ease of synthesis of this complex is noteworthy.     

Asymmetric Friedel-Crafts alkylation of methoxyfuran with nitroalkenes catalyzed by diphenylamine-tethered bis(oxazoline)-Zn(II) complexes

The first catalytic asymmetric Friedel-Crafts reaction of 2-methoxyfuran with nitroalkenes was developed under the catalysis of diphenylamine-tethered bis(oxazoline)-Zn(OTf)2 complexes. The reaction conditions and ligands were optimized, and the scope of the reaction was tested by varying the nitroalkenes. For most of aromatic and heteroaromatic nitroalkenes, good yields and high enantioselectivities (86-96% ee) were obtained. The methoxyfuran group in the product can be transformed to carboxylic acid via oxidative fragmentation with full retention of the configuration.     

NCC Pincer Ni (II) Complexes Catalyzed Hydrophosphination of Nitroalkenes with Diphenylphosphine

An efficient NCC pincer Ni (II)-catalyzed hydrophosphination of nitroalkenes with diphenylphosphine has been developed. Under the optimized conditions, both (hetero)aromatic and aliphatic nitroalkenes were well tolerated, irrespective of electronic effect, to provide the corresponding products in up to 99% yield.     

Catalytic Enantioselective Addition of Thioacids to Trisubstituted Nitroalkenes

The first example of a catalytic enantioselective addition to and nitronate protonation of trisubstituted nitroalkenes to produce highly enantioenriched products with a tetrasubstituted carbon is reported. Thioacids added in excellent yields and with high enantioselectivities to both activated and unactivated nitroalkenes. The 1,2‐nitrothioacetate products can be readily converted in two steps to biomedically relevant 1,2‐aminosulfonic acids without loss of enantiopurity.     

Chiral cobalt(II)-salen-catalyzed Michael addition of amines to β-substituted nitroalkenes

Optically active cobalt(II) salen complexes were found to be effective Lewis acid catalysts for the enantioselective Michael addition of O-alkylhydroxylamines to nitroalkenes to afford the corresponding N-alkylhydroxyl-1,2-nitroamines in high yields and with good to high enantioselectivities. This study represents the first example of a transition-metal-catalyzed asymmetric Michael addition of amines to nitroalkenes.     

Highly efficient hydrazination of conjugated nitroalkenes via imidazole or DMAP mediated Morita-Baylis-Hillman reaction

Novel alpha-hydrazino-alpha,beta-unsaturated nitroalkenes, which exhibit dynamic phenomenon on the NMR time scale, were synthesized in excellent yields via imidazole or DMAP mediated Morita-Baylis-Hillman (MBH) type reaction of nitroalkenes with azodicarboxylates.     

Applications of Helical‐Chiral Pyridines as Organocatalysts in Asymmetric Synthesis

A new family of chiral pyridines has been designed and synthesized for use in asymmetric organocatalysis. Thus, helical‐chiral pyridines induce high enantioselectivity in a range of mechanistically unrelated, synthetically significant transformations, including Friedel‐Crafts alkylation with nitroalkenes, periselective Diels‐Alder reactions with nitroalkenes, the ring‐opening of epoxides with a chloride nucleophile, and the propargylation of aldehydes.     

A novel synthesis of γ-nitro ketones via detrifluoroacetylative Michael addition of 1-trifluoromethyl-1,3-diketones to conjugated nitroalkenes

A novel synthesis of γ-nitro ketones via detrifluoroacetylative Michael addition of 1-trifluoromethyl-1,3-diketones to conjugated nitroalkenes in the presence of sodium acetate in ethanol at room temperature is developed. A series of trifluoromethylated 1,3-diones and nitroalkenes are surveyed to determine the scope of this high-yielding reaction.     

Asymmetric conjugate addition of carbonyl compounds to nitroalkenes catalyzed by chiral bifunctional thioureas

Readily available chiral thioureas derived from cyclohexane-1,2-diamine were prepared and found to be highly effective organocatalysts for the conjugate addition of aldehydes and ketones to nitroalkenes. Excellent enantioselectivities and yields were obtained for a variety of aryl and heteroaryl nitroalkenes. The base additives are essential for good yields and excellent enantioselectivities in this transformation. Based on new experimental evidence, a modified catalytic mechanism was proposed to rationalize the important role of the base additives.     

Highly enantioselective direct conjugate addition of ketones to nitroalkenes promoted by a chiral primary amine-thiourea catalyst

Primary amine-thiourea derivative 1 is an active and highly enantioselective catalyst for the conjugate addition of ketones to nitroalkenes. Broad substrate scope is described, with nitroalkenes bearing either aromatic or aliphatic substituents and a wide variety of ketones shown to be useful reacting partners. Ethyl ketones react preferentially, generating anti products with methyl-bearing stereocenters with good-to-excellent diastereoselectivity. An enamine mechanism is indicated, with cooperative activation of the electrophile by the thiourea and of the ketone by the primary amine.     

Regioselective synthesis of sulfonylpyrazoles via base mediated reaction of diazosulfones with nitroalkenes and a facile entry into Withasomnine

A base mediated reaction of α-diazo-β-ketosulfone with nitroalkenes affords sulfonylpyrazoles as single regioisomers in excellent yield in a one-pot room temperature reaction. Aryl, heteroaryl, styrenyl, alkyl, hydroxymethyl, and hydrazinyl groups could be introduced on the pyrazole ring by the appropriate choice of nitroalkenes. Synthesis of sulfonylpyrazole fused to other heterocycles and application of the methodology to an expedient synthesis of a pyrazole alkaloid, Withasomnine, are also reported.     

Stereoselective synthesis of azepines through the conjugate addition of formamides to nitroalkenes and subsequent intramolecular nitrile oxide cycloaddition reaction

A concise and stereoselective formation of azepines is achieved through the conjugate addition of formamides to nitroalkenes and the subsequent intramolecular nitrile oxide cycloaddition (INOC) reaction. High cis-selectivity was observed. The one-pot modification of the two reactions provides direct preparation of azepines from nitroalkenes and formamides in moderate yields. The formyl group was readily removed by an acidic treatment without significant epimerization.     

Acid–base organocatalysts for the aza-Morita–Baylis–Hillman reaction of nitroalkenes

A new class of acid–base chiral organocatalysts 1a and 2 for aza-Morita–Baylis–Hillman (aza-MBH) reaction of conjugated nitroalkenes is described. The acidic phenolic hydroxy groups and basic imidazole unit cooperatively activate nitroalkenes to promote the aza-MBH reaction in good yields with moderate enantioselectivities.     

Fast diastereoselective Baylis-Hillman reaction by nitroalkenes: synthesis of di- and triene derivatives

The Baylis-Hillman reaction is performed using nitroalkenes as activated alkenes, ethyl-2-bromomethylacrylate as electrophilic acceptor and DBU as catalyst base. Nitro dienes are obtained in good yields and very short reaction times. Moreover, starting from appropriate nitroalkenes it is possible to realize one pot the synthesis of trienic systems.