Enantioselective synthesis of nitroalkanes bearing all-carbon quaternary stereogenic centers through Cu-catalyzed asymmetric conjugate additions

The first examples of catalytic asymmetric conjugate addition (ACA) of alkylzinc reagents to trisubstituted nitroalkenes, leading to the formation of nitroalkanes bearing a quaternary carbon stereogenic center, are reported. Reactions are promoted in the presence of 4 mol % of a readily available amino acid-based phosphine and 2 mol % (CuOTf).C6H6. Cu-catalyzed reactions proceed efficiently in up to 98% ee and can be carried out with a variety of dialkylzinc reagents and trisubstituted nitroolefins. We highlight the synthetic utility of the products obtained by efficient conversion of optically enriched nitroalkanes to the corresponding carboxylic acids.     

Efficient Cu-catalyzed asymmetric conjugate additions of alkylzinc reagents to aromatic and aliphatic acyclic nitroalkenes

An efficient and highly enantioselective (up to 95% ee) Cu-catalyzed method for asymmetric conjugate addition (ACA) of alkylzinc reagents to acyclic disubstituted nitroalkenes is presented. Reactions are typically effected at ambient temperature in the presence of 2 mol % chiral dipeptide phosphine and 1 mol % (CuOTf)(2).C(6)H(6). Nitroalkenes bearing aromatic as well as aliphatic substituents readily undergo asymmetric additions. [reaction: see text]     

Dehydration of ��-nitro alcohols catalyzed by Bu2SnO

??-Nitro alcohols (nitro aldols) in boiling benzene in the presence of Bu2SnO (20?C30 mol.%) under neutral conditions undergo dehydration leading to nitroalkenes.     

Organocatalytic sequential Michael reactions: stereoselective synthesis of multifunctionalized tetrahydroindan derivatives

Multifunctionalized tetrahydroindan derivatives with four stereocenters were constructed via two sequential Michael reactions between cyclic γ,δ-unsaturated-β-ketoester and nitroalkenes initiated with 0.5-2 mol % of cinchona alkaloid based bifunctional organocatalysts and then with 1 equiv of tetramethylguanidine for cyclization. The desired products could be obtained in high yields (up to 99% yield) with excellent enantioselectivities (95-99% ee) as well as diastereoselectivities (up to >99:1 dr) even on a gram scale.     

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.     

Hydroxyalkylation of conjugated nitroalkenes with activated nonenolizable carbonyl compounds

[reaction: see text] The Morita-Baylis-Hillman reaction of a variety of conjugated nitroalkenes with activated nonenolizable carbonyl compounds such as glyoxylate, trifluoropyruvate, pyruvaldehyde, and ninhydrin in the presence of 40-100 mol % of DMAP in acetonitrile or 100 mol % of imidazole in CHCl(3) or THF provided the adducts in decent to good yields. In most cases, the reactions catalyzed by DMAP in acetonitrile were faster and provided the desired MBH adducts in higher yields as compared to the imidazole catalyzed reactions.     

Keto<==>enol, imine<==>enamine, and nitro<==>aci-nitro tautomerism and their interrelationship in substituted nitroethylenes. Keto, imine, nitro, and vinyl substituent effects and the importance of H-bonding

Tautomeric isomers and conformers of 2-nitrovinyl alcohol (1), 2-nitrovinylamine (2), and 1-nitro-propene (3) are reported at the MP2 and B3LYP levels of theory, using the 6-31G* basis set, with energy evaluation at B3LYP/6-311+G** and G2MP2. The nitroalkenes are the global minima on their respective potential energy surfaces. The barriers for the concerted 1,5-H transfer to the corresponding nitronic acids amount to only 5.0 kcal/mol for 1, 13.2 kcal/mol for 2, and a sizable 37.8 kcal/mol for 3. Whereas the aci-nitro tautomer of 2-nitrovinyl alcohol is easily accessible, beta-iminonitronic acid has little kinetic stability. H-bonding is a strong stabilizing factor in these nitroalkenes, estimated at 7.0 and 3.7 kcal/mol for the OH and NH2 derivatives, respectively, while its stabilization in their nitronic acids amounts to as much as 13 kcal/mol. The H-bonds are evident from the very short O...H and N...H distances and are characterized by bond critical points. The NO2 substituent effect of about 11.4 kcal/mol at G2MP2 on both the classical keto <==> enol and imine <==> enamine tautomeric processes stabilizes the nitroethylene derivatives. The keto, imine, and vinyl substituent effects at G2MP2 on the nitro <==> aci-nitro tautomeric process are also determined as are their pi-resonance components. The substituents have a large influence on the ionization energies of the nitroethylene derivatives.     

B(C6F5)3-Catalyzed Conjugate Addition Reactions: Addition of C–H Aromatics as Nucleophiles to Nitroalkenes

Russian Journal of Organic Chemistry - A mild and efficient B(C6F5)3-catalyzed conjugate addition of N, N-dialkylanilines to aromatic nitroalkenes is reported. The catalyst shows excellent...     

Organocatalytic asymmetric Michael addition of 2,4-pentandione to nitroolefins

[reaction: see text] A novel binaphthyl-derived amine thiourea organocatalyst has been developed and demonstrated to efficiently catalyze Michael addition reactions (using as low as 1 mol % loading) of diketones to nitroalkenes with remarkably high enantioselectivities.     

Si2CN: a stable nitrogen-containing radical with cyclic ground state

The structures and isomerization of Si(2)CN species are explored at density functional theory and ab initio levels. Fourteen minimum isomers are located connected by 23 interconversion transition states. At the coupled-cluster single double (CCSD)(T)/6-311+G(2df)//QCISD/6-311G(d) +zero-point vibrational energies level, the thermodynamically most stable isomer is a four-membered ring form cSiSiCN 1 with Si-C cross bonding. Isomer 1 has very strong C-N multiple bonding characters, formally suggestive of a radical adduct between Si(2) and CN. Such a highly pi-electron localization can effectively stabilize isomer 1 to be the ground state. The second low-lying isomer is a linear form SiCNSi 5 (9.8 kcal/mol above 1) with resonating structure among [Si=C-*N=Si], *[Si=C=N=Si], and [Si=C=N-Si*]* with the former two bearing more weight. The species 1 and 5 have very high kinetic stability stabilized by the barriers of at least 25 kcal/mol. Both isomers should be experimentally or astrophysically observable. In light of the fact that no cyclic nitrogen-containing species have been detected in space, the cyclic species 1 could be a very promising candidate. The calculated results are compared to those of the analogous molecules C(3)N, C(3)P, SiC(2)N, and SiC(2)P. Implications of Si(2)CN in interstellar and N-doped SiC vaporization processes are also discussed.     

Silver/ThioClickFerrophos-Catalyzed Enantioselective Conjugate Addition and Cycloaddition of Glycine Imino Ester with Nitroalkenes

We applied the combination of AgOAc with ThioClickFerrophos, the chiral ferrocenyl triazole-based P,S-ligand, to the reaction of glycine imino ester with nitroalkenes. The conjugate addition of the imino methyl ester preferentially produced anti-α-imino-γ-nitrobutyrates in good yields with high enantioselectivities (ee) of up to 99% at -25 °C in THF in the presence of triethylamine. Meanwhile, the pyrrolidine cycloadducts were obtained as major products in good yields with high enantioselectivities (up to 96% ee) using tert-butyl imino ester in the absence of triethylamine at room temperature.     

Ab initio study of hydrogen-bond formation between cyclic ethers and selected amino acid side chains

Binding energies for hydrogen-bonded complexes of six cyclic ethers with five hydrogen-bond donor molecules that mimic selected amino acid side chains have been calculated at the MP2/6-31G*, MP2/6-31+G*, MP2/6-311++G**(single point), and MP2/aug-cc-pvtz levels, using geometries obtained with or without counterpoise corrections throughout the geometry optimization. The calculated basis set superposition error (BSSE) amounts to 10-20% and 5-10% of the uncorrected binding energies for the neutral and ionic species, respectively, at the MP2/aug-cc-pvtz level. The authors conclude that the O...H distances in the hydrogen bonds and binding energies for the studied systems may be determined with uncertainties of up to 0.08 A and 1-2 kcal/mol, respectively, in comparison with the MP2/aug-cc-pvtz values at a reasonable computational cost by performing standard geometry optimization at the MP2/6-31+G* level. Hydrogen-bond formation energies are more negative for cyclic ethers compared to their counterparts with a C=C double bond in the ring next to the oxygen atom. The less negative hydrogen-bonding energy and the increased O...H separation have been attributed to the reduced basicity of the ether oxygen when the lone pairs can enter conjugation with the pi-electrons of the Calpha=Cbeta double bond. The present study is the first step toward the development of an affordable computational level for estimating the binding energies of natural product, fused ring ether systems to the human estrogen receptor.     

Silver complexes of cyclic hexachlorotriphosphazene

The first solid-state structures of complexed P3N3X6 (X = halogen) are reported for X = Cl. The compounds were obtained from P3N3Cl6 and Ag[Al(OR)4] salts in CH2Cl2/CS2 solution. The very weakly coordinating anion with R = C(CF3)3 led to the salt Ag(P3N3Cl6)2+[Al(OR)4]- (1), but the more strongly coordinating anion with R' = C(CH3)(CF3)2 gave the molecular adduct (P3N3Cl6)AgAl(OR')4 (3). Crystals of [Ag(CH2Cl2)(P3N3Cl6)2]+[Al(OR)4]- (2), in which Ag+ is coordinated by two phosphazene and one CH2Cl2 ligands, were isolated from CH2Cl2 solution. The three compounds were characterized by their X-ray structures, and 1 and 3 also by NMR and vibrational spectroscopy. Solution and solid-state 31P NMR investigations in combination with quantum chemically calculated chemical shifts show that the 31P NMR shifts of free and silver-coordinated P3N3Cl6 differ by less than 3 ppm and indicate a very weakly bound P3N3Cl6 ligand in 1. The experimental silver ion affinity (SIA) of the phosphazene ligand was derived from the solid-state structure of 3. The SIA shows that (PNCl2)3 is only a slightly stronger Lewis base than P4 and CH2Cl2, while other ligands such as S8, P4S3, toluene, and 1,2-Cl2C2H4 are far stronger ligands towards the silver cation. The energetics of the complexes were assessed with inclusion of entropic, thermal, and solvation contributions (MP2/TZVPP, COSMO). The formation of the cations in 1, 2, and 3 was calculated to be exergonic by delta(r)G(degrees)(CH2Cl2) = -97, -107, and -27 kJ mol(-1), respectively. All prepared complexes are thermally stable; formation of P3N3Cl5+ and AgCl was not observed, even at 60 degrees C in an ultrasonic bath. Therefore, the formation of P3N3Cl5+ was investigated by quantum chemical calculations. Other possible reaction pathways that could lead to the successful preparation of P3N3X5+ salts were defined.     

Highly enantioselective conjugate addition of fluoromalonates to nitroalkenes using bifunctional organocatalysts

The enantioselective conjugate addition of fluoromalonates to aromatic nitroalkenes catalyzed by chiral amine-thiourea bifunctional organocatalysts generated a stereocenter at the carbon bearing the aromatic group and an adjacent prochiral center from the fluoromalonate. Treatment of fluoromalonates with aromatic nitroalkenes under mild reaction conditions afforded the corresponding 2-fluoro-2-(2-nitro-1-arylethyl)malonates with high yields (72-93%) and excellent enantioselectivities (91-98% ee).     

Cheletropic decomposition of cyclic nitrosoamines revisited: the nature of the transition states and a critical role of the ring strain

The cheletropic decompositions of 1-nitrosoaziridine (1), 1-nitroso-Delta(3)-pyrroline (2), 7-nitroso-7-azabicyclo[2.2. 1]hepta-2,5-diene (3), and 6-nitroso-6-azabicyclo[2.1.1]hexa-4-ene (4) have been studied theoretically using high level ab initio computations. Activation parameters of the decomposition of nitrosoaziridine 1 were obtained experimentally in heptane (DeltaH()(298) = 18.6 kcal mol(-)(1), DeltaS()(298) = -7.6 cal mol(-)(1) K(-)(1)) and methanol (20.3 kcal mol(-)(1), 0.3 cal mol(-)(1) K(-)(1)). Among employed theoretical methods (B3LYP, MP2, CCD, CCSD(T)//CCD), the B3LYP method in conjunction with 6-31+G, 6-311+G, and 6-311++G(3df,2pd) basis sets gives the best agreement with experimental data. It was found that typical N-nitrosoheterocycles 2-4 which have high N-N bond rotation barriers (>16 kcal mol(-)(1)) extrude nitrous oxide via a highly asynchronous transition state with a planar ring nitrogen atom. Nitrosoaziridine 1, with a low rotation barrier (<9 kcal mol(-)(1)) represents a special case. This compound can eliminate N(2)O via a low energy linear synperiplanar transition state (DeltaH()(298) = 20.6 kcal mol(-)(1), DeltaS()(298) = 2.5 cal mol(-)(1) K(-)(1)). Two higher energy transition states are also available. The B3LYP activation barriers of the cheletropic fragmentation of nitrosoheterocycles 2-4 decrease in the series: 2 (58 kcal mol(-)(1)) > 3 (18 kcal mol(-)(1)) > 4 (12) kcal mol(-)(1). The relative strain energies increase in the same order: 2 (0 kcal mol(-)(1)) < 3 (39 kcal mol(-)(1)) < 4 (52 kcal mol(-)(1)). Comparison of the relative energies of 2-4 and their transition states on a common scale where the energy of nitrosopyrroline 2 is assumed as reference indicates that the thermal stability of the cyclic nitrosoamines toward cheletropic decomposition is almost entirely determined by the ring strain.     

Dynamic equilibrium between cyclic oligomers. Thermodynamic and structural characterization of a square and a triangle

A dynamic equilibrium has been found in CDCl3 between a neutral molecular square, [cis-Mo2(DAniF)2]4(O2CC6F4CO2)4 (1) and triangle, [cis-Mo2(DAniF)2]3(O2CC6F4CO2)3 (2) (DAniF = the anion of N,N'-di-p-anisylformamidine). The two components have been crystallographically characterized and solution studies by 1H and 19F NMR spectra of the concentration- and the temperature-dependence of the equilibrium have been performed. The conversion of three moles of molecular squares 1 to four moles of molecular triangles 2 has an equilibrium constant of 1.98(7) x 10(-4) at 23.7 degrees C. At this temperature, the DeltaG(0) for the conversion of three moles of squares to four moles of triangles is 21.0 kJ mol(-1). The conversion is enthalpically disfavored (DeltaH(0) = 23.5 kJ mol(-1)), but entropically favored (DeltaS(0) = 8.2 J K(-1) mol(-1)).     

Beyond-thermal-equilibrium" conversion of methane to acetylene and hydrogen under pulsed corona discharge

At ambient temperature and pressure, C2H2 and H2 are the dominating products from pure methane conversion under pulsed corona discharge (PCD). When the energy density of 194-1788 kJ/mol was applied, 7%-30% of C2H2 yield and 6%-35% of H2 yield per pass have been obtained. These results are higher than the maximum thermodynamic yield of C2H2 (5.1%) and H2 (3.8%) at 100 kPa and 1100 K, respectively. Thereby, pulsed corona discharge is a very effective tool for "beyond-thermal-equilibrium" conversion of methane to C2H2 and H2 at ambient temperature and pressure. In the PCD energy density range of 339-822 kJ/mol, the carbon distribution of the methane conversion products is found to be: C2H2 86%-89%, C2H6 4%-6%, C2H4 4%-6%, C3 -2%, C4 -1%. Through comparison of the product from pure methane, ethane and ethylene conversion at the same discharge conditions, it can be concluded that three pathways may be responsible for the C2H2 formation via CHx radicals produced from the collisions of CH4 molecules with energi     

Platinum-catalyzed intramolecular hydroalkoxylation of gamma- and delta-hydroxy olefins to form cyclic ethers

Reaction of 2,2-diphenyl-4-penten-1-ol with a catalytic mixture of [PtCl2(H2C=CH2)]2 (1 mol %) and P(4-C6H4CF3)3 (2 mol %) at 70 degrees C for 24 h led to the isolation of 2-methyl-4,4-diphenyltetrahydrofuran in 78% yield. The platinum-catalyzed hydroalkoxylation of gamma-hydroxy olefins tolerated substitution at the alpha, beta, and gamma-carbon atoms and at the internal and cis and trans terminal olefinic positions. Platinum-catalyzed hydroalkoxylation tolerated a number of functional groups including pivaloate and acetate esters, amides, silyl and benzyl ethers, and pendant hydroxyl and olefinic groups. Pt-catalyzed olefin hydroalkylation was also applicable to the formation of fused- and spirobicyclic ethers and was effective for the hydroalkoxylation of delta-hydroxy olefins to form tetrahydropyran derivatives.     

Highly enantioselective copper-bisoxazoline-catalyzed allylic oxidation of cyclic olefins with tert-butyl p-nitroperbenzoate

Catalytic asymmetric allylic oxidation of cyclic olefins ocurrs for the first time in very high (94-99% ee) enantioselectivity using copper(I) complexes of malonyl derived bisoxazolines and tert-butyl p-nitroperbenzoate giving allyl benzoates in moderate yield. The copper complex, 15 mol %, was used in acetonitrile at -20 degrees C over an extended period, 5-12 d, with excess olefin together with one equivalent of perester. The S-esters were generated in accord with the model proposed previously for the (S,S)-bisoxazoline ligand. An eta2 intermediate was ruled out using low-temperature 13C NMR with the complex in the presence of olefin.     

Diastereoselective reductive nitro-Mannich reactions

A range of nitroalkenes 1 and imines 3 derived from alkyl, aryl, and heteroaryl aldehydes underwent a tandem 1,4-hydride addition nitro-Mannich reaction to afford anti-rich β-nitroamines 4. The crude anti-β-nitroamines 4 could be converted to the corresponding anti-β-nitroacetamides 5 (33 examples) to allow purification in good yield from the parent nitroalkenes (60-87%), and with a high diastereomeric ratio (90:10 to mostly >95:5). A representative selection of anti-β-nitroacetamides 5 (five examples) were reduced to vicinal diamines 7 with zinc hydrochloride; concomitant acyl migration provided differentially protected vicinal diamines 7 in good yield (80-91%).