Possesses C2 Symmetry Research Articles

Catalytic Asymmetric Synthesis of 2,6‐Disubstituted Cuneanes through Enantioselective Constitutional Isomerization of 1,4‐Disubstituted Cubanes

Abstract2,6‐Disubstituted cuneane has potential as a p‐disubstituted benzene bioisostere and a novel chiral scaffold. It is a constitutional isomer of a 1,4‐disubstituted cubane obtained via a metal‐catalyzed skeletal rearrangement. Unlike the highly symmetrical 1,4‐disubstituted cubane, the isomerized 2,6‐disubstituted cuneane is a chiral molecule possessing C2 symmetry. Examining various chiral catalysts revealed that the Pd‐pincer catalyst provides a good asymmetric induction.

Sequential condensation-6π-electrocyclization reaction of a chiral 1,3-Diketone possessing C2 symmetry

The sequential Knoevenagel condensation-6π-electrocyclization reaction of the novel chiral 1,3-cyclohexanedione derivative possessing C2 symmetry developed by our group was demonstrated. Chiral 6,8-dihydroxy-7,8-dihydro-2H-chromen-5-one derivatives were obtained in good to excellent yields.

Investigating the conformers of 1, 2, 3, 4-tetrahydroquinoxaline: A combined theoretical and experimental investigation through potential energy surface studies, FT-IR and UV–Vis absorption measurements

1, 2, 3, 4-tetrahydroquinoxaline (THQX) show two inequivalent conformers at various levels of quantum chemical computations along with the variation of basis sets in S0 and S1 states. They are separated by 450 ± 100 cm−1 and 55 cm−1 in S0 and S1 states respectively. The twisted conformer with the equatorial orientation of hydrogen atom of both the NH groups and bearing C2 symmetry is computed to be the most stable conformer (C1) in S0. The global minima in S1 state do not differ considerably although C2 symmetry is lost. Two potential energy surfaces (PES) are plotted with respect to i) N–C–C–N dihedral angle and the NH orientation and ii) two different orientations of the H atoms of the NH groups. Four transitions states are found in S0. Three of them are bent structures and out of them two possesses C2 symmetry. Corresponding surfaces in S1 yield two transition states. The twisting angle for the optimised conformer is 310±1.50 in S0 and 280± 10 in S1. The characteristic low frequency vibrations appear at 107 cm−1 and 160 cm−1 in S0. Apart from some weak lines most of the observed vibrational frequencies in FT-IR spectra corroborate well with the computed ones. Calculation of molecular electrostatic potential indicates the sights of electrophilic interactions. Frontier molecular orbitals are calculated. The peaks in the observed UV–Vis absorption spectra are explained corresponding to the associated molecular orbitals. These spectra corroborate well with the calculated ones. The calculations predict that the dominant character of these transitions would be π-π∗ in nature.

Asymmetric Synthesis and Structure Revision of Guignardone H and I: Development of a Chiral 1,3-Diketone Possessing C2 Symmetry.

A novel chiral 1,3-diketone possessing C2 symmetry was synthesized and utilized in the asymmetric synthesis of guignardone H and I by employing sequential condensation-6π-electrocyclization reactions with the novel 1,3-diketone followed by stereoselective hydrogenation as key steps. Although the synthetic compounds differed from natural guignardone H and I, we realized that the C4-epimers of the proposed structures for guignardone H and I were the actual structures.

Isomorphous rare-earth bis[bis(2,6-diisopropylphenyl)phosphate] complexes and their self-assembly into two-dimensional frameworks by intramolecular hydrogen bonds.

The crystal structures of rare-earth diaryl- or dialkylphosphate derivatives are poorly explored. Crystals of bis[bis(2,6-diisopropylphenyl)phosphato-κO]chloridotetrakis(methanol-κO)neodymium methanol disolvate, [Nd(C24H34O4P)Cl(CH4O)4]·2CH3OH, (1), and of the lutetium, [Lu(C24H34O4P)Cl(CH4O)4]·2CH3OH, (2), and yttrium, [Y(C24H34O4P)Cl(CH4O)4]·2CH3OH, (3), analogues have been obtained by reactions between lithium bis(2,6-diisopropylphenyl)phosphate and LnCl3(H2O)6 (in a 2:1 ratio) in methanol. Compounds (1)-(3) crystallize in the C2/c space group. Their crystal structures are isomorphous. The molecule possesses C2 symmetry with a twofold crystallographic axis passing through the Ln and Cl atoms. The bis(2,6-diisopropylphenyl)phosphate ligands all display a κ1O-monodentate coordination mode. The coordination polyhedron for the metal atom [coordination number (CN) = 7] is a distorted pentagonal bipyramid. Each [Ln{O2P(O-2,6-iPr2C6H3)2}2Cl(CH3OH)4] molecular unit exhibits two intramolecular O-H...O hydrogen bonds, forming six-membered rings, and two intramolecular O-H...Cl interactions, forming four-membered rings. Intermolecular O-H...O hydrogen bonds connect each unit via four noncoordinating methanol molecules with four other units, forming a two-dimensional hydrogen-bond network. Crystals of bis[bis(2,6-diisopropylphenyl)phosphato-κO]tetrakis(methanol-κO)(nitrato-κ2O,O')neodymium methanol disolvate, [Nd(C24H34O4P)(NO3)(CH4O)4]·2CH3OH, (4), have been obtained in an analogous manner from NdCl3(H2O)6. Compound (4) also crystalizes in the C2/c space group. Its crystal structure is similar to those of (1)-(3). The κ2O,O'-bidentate nitrate anion is disordered over a twofold axis, being located nearly on it. Half of the molecule is crystallographically unique (CNNd = 8). Unlike (1)-(3), complex (4) exhibits disorder of all three methanol molecules, one isopropyl group of the phosphate ligand and the NO3- ligand. The structure of (4) displays intra- and intermolecular O-H...O hydrogen bonds similar to those in (1)-(3). Compounds (1)-(4) represent the first reported mononuclear bis[bis(diaryl/dialkyl)phosphate] rare-earth complexes.

Human βB2-Crystallin Forms a Face-en-Face Dimer in Solution: An Integrated NMR and SAXS Study

βγ-Crystallins are long-lived eye lens proteins that are crucial for lens transparency and refractive power. Each βγ-crystallin comprises two homologous domains, which are connected by a short linker. γ-Crystallins are monomeric, while β-crystallins crystallize as dimers and multimers. In the crystal, human βB2-crystallin is a domain-swapped dimer while the N-terminally truncated βB1-crystallin forms a face-en-face dimer. Combining and integrating data from multi-angle light scattering, nuclear magnetic resonance, and small-angle X-ray scattering of full-length and terminally truncated human βB2-crystallin in solution, we show that both these βB2-crystallin proteins are dimeric, possess C2 symmetry, and are more compact than domain-swapped dimers. Importantly, no inter-molecular paramagnetic relaxation enhancement effects compatible with domain swapping were detected. Our collective experimental results unambiguously demonstrate that, in solution, human βB2-crystallin is not domain swapped and exhibits a face-en-face dimer structure similar to the crystal structure of truncated βB1-crystallin.

Searching for Practically Useful P-Chirogenic Phosphine Ligands.

In this account, the design, synthesis, and application of P-chirogenic phosphine ligands that have been mainly carried out in our laboratory over the last three decades are described. Various enantiopure P-chirogenic phosphine ligands have been efficiently prepared by using phosphine boranes as intermediates. Conformationally rigid and electron-rich P-chirogenic phosphine ligands possessing C2 symmetry as well as a bulky alkyl group and a small group at the phosphorus atoms exhibit excellent enantioselectivities and catalytic efficiency in a variety of transition-metal-catalyzed asymmetric reactions. Enantiopure 2,3-bis(tert-butylmethylphosphino)quinoxaline (QuinoxP*) is an air-stable crystalline solid that shows superior enantioinduction ability in catalytic asymmetric syntheses. Mechanistic studies of Rh-catalyzed asymmetric hydrogenation using structurally simple P-chirogenic phosphine ligands, such as tBu-BisP*, are briefly described.

Solid- and gas-phase structures and spectroscopic and chemical properties of tris(pentafluorosulfanyl)amine, N(SF5)3, and bis(pentafluorosufanyl)aminyl radical, [rad]N(SF5)2

Tris(pentafluorosulfanyl)amine, N(SF5)3, and the bis(pentafluorosulfanyl)aminyl radical, N(SF5)2, have been synthesized and characterized by gas electron diffraction, single crystal XRD, NMR, EPR, FT-IR, Raman, and UV–vis spectroscopy, and by their thermal decompositions. The amine possesses a planar molecular structure of D3 symmetry with an unusually long NS bond of 1.829(6) Å. The long NS bonds are in accordance with the small Arrhenius activation barrier for the decay into N(SF5)2 and SF5 radicals of 6.9 kcal mol−1, and its half-life at room temperature is only 50 min. The aminyl radical possesses C2 symmetry with NS = 1.692(4) Å and SNS = 135.1(5)°, and its structure is similar to that of FN(SF5)2. This radical is much more stable than the amine (half-life at room temperature is 130 min). Dimerization and formation of the corresponding hydrazine, (SF5)2NN(SF5)2, was not observed, nor was the nitrene:NSF5 or its isomer FNSF4.

Hydroxyethylamine Based Phthalimides as New Class of Plasmepsin Hits: Design, Synthesis and Antimalarial Evaluation.

A novel class of phthalimides functionalized with privileged scaffolds was designed, synthesized and evaluated as potential inhibitors of plasmepsin 2 (Ki: 0.99 ± 0.1 μM for 6u) and plasmepsin 4 (Ki: 3.3 ± 0.3 μM for 6t), enzymes found in the digestive vacuole of the plasmodium parasite and considered as crucial drug targets. Three compounds were identified as potential candidates for further development. The listed compounds were also assayed for their antimalarial efficacy against chloroquine (CQ) sensitive strain (3D7) of Plasmodium falciparum. Assay of twenty seven hydroxyethylamine derivatives revealed four (5e, 6j, 6o and 6s) as strongly active, which were further evaluated against CQ resistant strain (7GB) of P. falciparum. Compound 5e possessing the piperidinopiperidine moiety exhibited promising antimalarial activity with an IC50 of 1.16 ± 0.04 μM. Further, compounds 5e, 6j, 6o and 6s exhibited low cytotoxic effect on MCF-7 cell line. Compound 6s possessing C 2 symmetry was identified as the least cytotoxic with significant antimalarial activity (IC50: 1.30 ± 0.03 μM). The combined presence of hydroxyethylamine and cyclic amines (piperazines and piperidines) was observed as crucial for the activity. The current studies suggest that hydroxyethylamine based molecules act as potent antimalarial agent and may be helpful in drug development.

Bimetallic Complexes Supported by a Redox-Active Ligand with Fused Pincer-Type Coordination Sites.

The remarkable chemistry of mononuclear complexes featuring tridentate, meridionally chelating "pincer" ligands has stimulated the development of ligand frameworks containing multiple pincer sites. Here, the coordination chemistry of a novel pentadentate ligand (L(N3O2)) that provides two closely spaced NNO pincer-type compartments fused together at a central diarylamido unit is described. The trianionic L(N3O2) chelate supports homobimetallic structures in which each M(II) ion (M = Co, Cu, Zn) is bound in a meridional fashion by the bridging diarylamido N atom and O,N-donors of the salicyaldimine arms. The metal centers are also coordinated by a mono- or bidentate auxiliary ligand (L(aux)), resulting in complexes with the general form [M2(L(N3O2))(L(aux))2](+) (where L(aux) = 1-methyl-benzimidazole (1MeBI), 2,2'-bipyridine (bpy), 4,4'-dibromo-2,2'-bipyridine (bpy(Br2)), or (S)-2-(4-isopropyl-4,5-dihydrooxazolyl)pyridine (S-(iPr)OxPy)). The fused nature of the NNO pincer sites results in short metal-metal distances ranging from 2.70 Å for [Co2(L(N3O2)) (bpy)2](+) to 3.28 Å for [Zn2(L(N3O2)) (bpy)2](+), as revealed by X-ray crystallography. The complexes possess C2 symmetry due to the twisting of the aryl rings of the μ-NAr2 core; spectroscopic studies indicate that chiral L(aux) ligands, such as S-(iPr)OxPy, are capable of controlling the helical sense of the L(N3O2) scaffold. Since the four- or five-coordinate M(II) centers are linked solely by the amido moiety, each features an open coordination site in the intermetallic region, allowing for the possibility of metal-metal cooperativity in small-molecule activation. Indeed, the dicobalt(II) complex [Co2(L(N3O2)) (bpy(Br2))2](+) reacts with O2 to yield a dicobalt(III) species with a μ-1,2-peroxo ligand. The bpy-containing complexes exhibit rich electrochemical properties due to multiple metal- and ligand-based redox events across a wide (3.0 V) potential window. Using electron paramagnetic resonance (EPR) spectroscopy and density functional theory (DFT), it was determined that one-electron oxidation of [Co2(L(N3O2)) (bpy)2](+) results in formation of a S = 1/2 species with a L(N3O2)-based radical coupled to low-spin Co(II) centers.

Conformations of the semifluorinated n-alkane H–(CF2)8–H investigated using Fourier transform microwave spectroscopy and quantum chemical calculations

The three lowest energy conformations of the title compound have been investigated using quantum chemical calculations and the lowest energy conformer has been observed using pure rotational spectroscopy. The lowest energy conformer possesses C2 symmetry, a helical CF2 backbone, with the hydrogens nearly eclipsing one another when looking down the long axis of the molecule. The technique of Fourier transform microwave spectroscopy in conjunction with quantum chemical calculations is demonstrated as a complimentary method to X-ray diffraction for structural determinations of small oligomers for which the location of hydrogen atoms may be important.

Tautomeric properties and gas-phase structure of acetylacetone.

The tautomeric and structural properties of acetylacetone, CH3C(O)CH2C(O)CH3, have been studied by gas-phase electron diffraction (GED) and quantum chemical calculations (B3LYP and MP2 approximation with different basis sets up to aug-cc-pVTZ). The analysis of GED intensities resulted in the presence of 100(3)% of the enol tautomer at 300(5) K and 64(5)% of the enol at 671(7) K. The enol tautomer possesses Cs symmetry with a planar ring and strongly asymmetric hydrogen bond. The diketo form possesses C2 symmetry. The experimental geometric parameters of both tautomeric forms are reproduced very closely by B3LYP/aug-cc-pVTZ and MP2/cc-pVTZ methods.

Accurate theoretical predictions for carbonyl diazide molecules: A coupled-cluster study of the potential energy surface and thermochemical properties

Enthalpies of formation (ΔHf°) of syn-syn (C2v), anti-syn (Cs), and the newly proposed C2 isomer of carbonyl diazide, OC(N3)2, at 298K have been predicted using CCSD(T) theory in conjunction with a systematic basis set expansion that has been extrapolated to the complete basis set (CBS) limit. The ΔHf° has been calculated via three independent pathways and ‘chemical accuracy’ has been obtained. The predicted CCSD(T)/CBS values are (kJmol−1): syn-syn (C2v), 471.5; anti-syn (Cs), 479.5; C2, 517.4. These values deviate by 14.5kJmol−1 compared to prior G4 approximations. CCSD(T) torsional potential energy scan reveals a previously undiscovered conformer of OC(N3)2 possessing C2 symmetry.

Conformational Landscape of Diisopropyl Ketone: Quantum Chemical Calculations Validated by Microwave Spectroscopy

We report on the gas-phase structure of the most abundant conformer of diisopropyl ketone, (CH(3))(2)HC-CO-CH(CH(3))(2), as observed by molecular beam Fourier transform microwave spectroscopy. The gas-phase structures of five conformers of diisopropyl ketone were optimized using ab initio calculations at the MP2/6-311++G(d,p) level of theory. The natures of the stationary points were verified using harmonic frequency calculations. The only conformer observed in the supersonic jet possesses C(2) symmetry and appears as an enantiomeric pair. From the microwave spectrum, a set of three highly accurate rotational constants, five centrifugal distortion constants, and three sextic centrifugal distortion constants were determined. The structure of the observed conformer was optimized again at different levels of theory using the HF, MP2, and B3LYP methods. The theoretical constants of the C(2) conformer were subsequently validated using the experimental constants. To understand the transitions of one conformer to the others, the isopropyl groups were rotated against each other. The resulting two-dimensional potential energy surface shows nicely the symmetry of the conformational landscape and also indicates the enantiomeric pairs of the conformers. The barriers to internal rotation of the methyl groups were determined to be 1052 and 905 cm(-1) at the MP2/6-311++G(d,p) and the B3LYP/6-311++G(d,p) levels, respectively. In agreement with the theoretical predictions, no internal rotation patterns could be observed in the microwave spectrum.

Synthesis and X-ray Structure of Zn(II) Complex of N,N'-Bis(2-fluorobenzyl)-(R,R)-1,2-diaminocyclohexane and Application to Nitroaldol Reaction

Chiral ligands possessing C2 symmetry derived from (R,R)-1,2-diaminocyclohexane are particularly attractive auxiliaries to serve as powerful stereodirecting reagents or ligands in asymmetric synthesis, as chiral stationary phases in chromatographic separation and molecular recognition, and as chelating agents for many metals. Trans-1,2-diaminocyclohexane is commercially available at relatively low cost today. It is easily resolved in aqueous medium using Lor D-tartaric acid to obtain the (R,R)-1,2 or the (S,S)-1,2-enantiomer respectively in enantiopure forms. Beside outstanding chiral 1,2-diaminocyclohexane derivatives were synthesized and used as chiral ligands effectively in asymmetric synthesis such as chiral diimines, chiral salens, β-amino alcohols, tetradentate chiral Schiff base ligands, recently the synthesis and application of chiral amines including in N-monosubstituted; N,N'-disubstituted; N,N'-trisubtituted and N,N'-tetrasubstituted have great progress. Some chiral 1,2-diaminocyclohexane derivatives of novel chiral N4S2and N4S3-donor macrocyclic ligands, 10

Molecular structure of diphenyl sulfide in the gas phase

Gas-phase electron diffraction and quantum-chemical calculations were used to study the molecular structure of diphenyl sulfide. It is shown that the diphenyl sulfide molecule (PhS2) possesses C2 symmetry. The main geometrical parameters are as follows: ra(C-S) 1.774(2) A, ra(C-C)av 1.401 A, ∠CSC 103.4(11)°, ∠SCC 122.5 and 117.9(6)°, and ∠CCCav 120.0°. The torsion angles about C-S bonds τ(CSCC) are −49.6(1.4)°.

Bis(tetraphenylphosphonium) tris(2-thioxo-1,3-dithiole-4,5-dithiolato)stannate(IV) at 293 K

The title compound, (C24H20P)2[Sn(C3S5)3], whose structure has been previously reported in the space group P\overline{1} at 120 K [de Assis, Chohan, Howie, Khan, Low, Spencer, Wardell & Wardell (1999), Polyhedron, 18, 3533–3544], has been crystallized in the space group C2/c and its structure has been determined at 293 K. The [Sn(C3S5)3]2− anion possesses C2 symmetry, with the SnIV atom and one C=S group lying on the twofold rotation axis. The crystal packing is stabilized by C—H⋯S hydrogen bonds.

Synthesis of Pseudopeptides Derived from (R,R)-Tartaric Acid as Potential Inhibitors of HIV-Protease

New pseudopeptides possessing C2 symmetry and dihydroxyethylene core derived from (R,R)- tartaric acid and amino esters have been synthesized as potential inhibitors of HIV protease. The amino esters were chosen in order to interact with P1/P1 and P2/P2 subsites of the enzyme. The products were obtained in good yields without noticeable racemization.

Bis(tetraphenylphosphonium) bis(2-thioxo-1,3-dithiole-4,5-dithiolato)cuprate(II)

In the title complex, (C24H20P)2[Cu(C3S5)2], the CuII ion is coordinated by four S atoms from two 2-thioxo-1,3-dithiole-4,5-dithiol­ate ligands in a distorted planar geometry. The anion possesses C2 symmetry with the metal ion lying on a twofold axis.

1,2-Bis(3-thienyloxy)ethane: a thiophene-based precursor for thiophene-based azacryptand Mannich bases

The title compound, C10H12O2S2, is composed of two thio­phene rings bridged by an –O(CH2)2O– chain in a trans arrangement. The mol­ecule possesses C2 symmetry with the twofold axis bis­ecting the central C—C bond. In the crystal structure, mol­ecules related by a centre of symmetry are bridged by C—H⋯O hydrogen bonds, forming a zigzag one-dimensional chain extending in the c-axis direction.