Determination of the interconversion energy barrier of three novel pentahelicene derivative enantiomers by dynamic high resolution liquid chromatography.

Dynamic high resolution liquid chromatography (DHPLC) was used to determine the kinetic and thermodynamic activation parameters of interconversion of three novel pentahelicene derivatives {3,5-bis(trifluoromethyl)benzo[i]pentahelicene, naphtho[1,2-i]pentahelicene and 4-methoxybenzo[i]pentahelicene}. DHPLC was performed on a chiral isopropyl - carbamate cyclofructan 6 (LARIHC CF6-P) column under normal phase conditions. Variation of the column temperature and flow rate was used to study the interconversion process. A computer assisted deconvolution method was employed to determine the individual peak areas and the retention times required for the calculation of apparent enantiomerization energy barriers, enthalphy and entropy of the interconvertion of above defined pentahelicene derivative enantiomers. An ab initio quantum chemistry method was used to estimate theoretical kinetic and thermodynamic interconversion parameters and to evaluate experimental data of these three novel pentahelicene derivative enantiomers.

Tetracyclic dihydronaphthalene derivatives via gold-catalyzed aminative homodimerization of ortho-alkynylbenzaldehydes.

Gold(i) catalyzes domino homodimerization of o-alkynylbenzaldehydes via a sequence of 6-endo-dig-cyclization, amine addition, and [4+2] cycloaddition involving two bicyclic intermediates. The resulting products integrate medicinally relevant 1,2-dihydronaphthalene and isochromene moieties into a single amine-substituted tetracyclic framework.

Competing amination and C-H arylation pathways in Pd/xantphos-catalyzed transformations of binaphthyl triflates: switchable routes to chiral amines and helicene derivatives.

A Pd(OAc)2/xantphos catalyst system was found effective for benzylaminations of binaphthyl 2-triflates bearing a variety of alkyl, benzyl, and substituted phenyl substituents at the 2'-position. With 2'-aryl substituents, an intramolecular Pd-catalyzed C-H arylation was observed as a competing side reaction under some conditions. By adjusting the solvent and quantity of the amine, the reaction was optimized to favor either the amination or the C-H arylation pathway, affording two distinct and potentially useful sets of products. The amines represent tunable chiral ligand precursors, while the C-H arylation pathway affords a series of benzofused [5]helicene derivatives. Kinetic studies and activation parameters for the C-H arylation pathway, supported by DFT calculations, are consistent with a concerted metalation-deprotonation (CMD) mechanism involving a Pd-bound carbonate as the base. Xantphos is proposed to facilitate the turnover-limiting inner-sphere CMD step by acting as a hemilabile ligand, while its wide bite angle engenders a low reductive elimination barrier.

"Decarbonization" of an imino-N-heterocyclic carbene ligand via triple benzyl migration from hafnium.

An imino-N-heterocyclic carbene underwent three sequential benzyl migrations upon reaction with tetrabenzylhafnium, resulting in complete removal of the carbene carbon from the ligand. The resulting eneamido-amidinato hafnium complex showed alkene polymerization activity comparable to that of a precatalyst containing the intact iminocarbene ligand.

Ligand- and Brønsted acid/base-switchable reaction pathways in gold(I)-catalyzed cycloisomerizations of allenoic acids.

Gold-promoted cyclizations of 2,2-diaryl substituted γ-allenoic acids were found to give three isomeric lactone products, each of which could be obtained selectively by exploiting Brønsted acid/base and ligand effects. Simple 5-exo-trig cyclization products were favored by strong donor ligands or base additives, whereas weak donor ligands and a Brønsted acid additive gave isomeric enelactones resulting from double bond migration. Further optimization afforded a class of medicinally relevant bridged tricyclic lactones via a tandem hydroacyloxylation/hydroarylation process. Kinetic studies and control experiments indicated that the initial 5-exo-trig cyclization product serves as a branch point for further isomerization to the other lactone products via cooperative gold(I)/Brønsted acid catalysis.

Enantiomeric separation of isochromene derivatives by high-performance liquid chromatography using cyclodextrin based stationary phases and principal component analysis of the separation data.

Isochromene derivatives are very important precursors in the natural products industry. Hence the enantiomeric separations of chiral isochromenes are important in the pharmaceutical industry and for organic asymmetric synthesis. Here we report enantiomeric separations of 21 different chiral isochromene derivatives, which were synthesized using alkynylbenzaldehyde cyclization catalyzed by chiral gold(I) acyclic diaminocarbene complexes. All separations were achieved by high-performance liquid chromatography with cyclodextrin based (Cyclobond) chiral stationary phases. Retention data of 21 chiral compounds and 14 other previously separated isochromene derivatives were analyzed using principal component analysis. The effect of the structure of the substituents on the isochromene ring on enantiomeric resolution as well as the other separation properties was analyzed in detail. Using principal component analysis it can be shown that the structural features that contribute to increased retention are different from those that enhance enantiomeric resolution. In addition, principal component analysis is useful for eliminating redundant factors from consideration when analyzing the effect of various chromatographic parameters. It was found that the chiral recognition mechanism is different for the larger γ-cyclodextrin as compared to the smaller ß-cyclodextrin derivatives. Finally this specific system of chiral analytes and cyclodextrin based chiral selectors provides an effective format to examine the application of principal component analysis to enantiomeric separations using basic retention data and structural features.

Access to 2'-substituted binaphthyl monoalcohols via complementary nickel-catalyzed Kumada coupling reactions under mild conditions: key role of a P,O ligand.

Two complementary Kumada coupling methods for the conversion of monotriflated 1,1'-binaphthalene-2,2'-diol (BINOL) into 2'-substituted binaphthyl monoalcohols under mild conditions are reported. A protocol using NiCl2(dppe), in combination with an improved preparation of the monotriflate, is effective for 1,1'-binaphthalene-2-ols containing unsubstituted or electron-poor aryl or benzyl 2'-substituents. An alternative procedure, using a potentially hemilabile-bidentate phosphinan-4-ol ligand, is superior for products containing neopentyl or electron-rich aryl 2'-substituents. The obtained binaphthyl alcohols represent potentially useful synthons for chiral ligands and auxiliaries.

ß-Lactam synthon-interceded diastereoselective synthesis of functionalized octahydroindole-based molecular scaffolds and their in vitro cytotoxic evaluation.

A convenient and unprecedented synthesis of functionally enriched octahydroindole-based scaffolds has been developed via inter- and intra-molecular amidolysis of C-3 functionalized ß-lactams. The cytotoxic evaluation on oesophageal cancer cell line WHCO1 has revealed 7d as the most potent of the test compounds exhibiting an IC(50) value of 12.97 µM. The developed strategy further assumes significance as it entails the preparation of highly functionalized indoles without the aid of transition metal catalysis or pre-functionalization of substrates.

Interplay of metallophilic interactions, π-π stacking, and ligand substituent effects in the structures and luminescence properties of neutral Pt(II) and Pd(II) aryl isocyanide complexes.

Packing interactions in the crystal structures of a series of cis-M(CNAr)(2)Cl(2) complexes (M = Pt, Pd; Ar = substituted phenyl) were examined and correlated with the luminescence properties of the Pt complexes. The structures of the PhNC and p-tolyl isocyanide complexes exhibit extended chains of metallophilic interactions with M···M distances of 3.24-3.25 and 3.34 Å, respectively, with nearly isostructural Pt and Pd compounds. Both structure types contain void channels running parallel to the M···M chains. The channels are 3-4 Å wide and vacant for the phenyl structures, while those in the p-tolyl structures are up to 7.6 Å wide and contain water. These channeled structures are stabilized by a combination of metallophilic bonding and aryl π-π stacking interactions. The Pt structure with 4-F substituents also features extended Pt···Pt chains, but with longer 3.79 Å distances alternating with shorter 3.37 Å contacts. Structures with 4-CF(3) and 4-OMe substituents exhibit mostly isolated dimers of M···M contacts. In complexes with 2,6-dimethylphenyl isocyanide, steric hindrance precludes any short M···M contacts. The primary effect of aryl substitution is to provide alternative packing motifs, such as CF(3)···π and CH(3)···π interactions, that either augment or disrupt the combination of metallophilic contacts and π-π stacking needed to stabilize extended M···M chains. Differences in the Pt and Pd structures containing 4-F and 4-OMe substituents are consistent with a higher driving force for metallophilic interactions for Pt versus Pd. The M-C and M-Cl bond distances indicate a slightly higher trans influence for aryl isocyanides bound to Pt versus Pd. The three extended Pt···Pt chain structures display luminescence assignable to (dσ*→pσ) excited states, demonstrating the existence of substantial orbital communication along the metal-metal chains. Face-indexing shows that the preferred crystal growth axis is along the metal-metal chains for the luminescent structures. Variable temperature structural studies showed that both M···M and π-π interactions contract upon cooling. Overall, this study suggests that synergy with π-π and other interactions is necessary to stabilize extended M···M chain structures. Thus, efforts to design functional materials based on metallophilic bonding must consider the full array of available packing motifs.

Direct observation of a carbonylation reaction relevant to CO/alkene copolymerization in a methylpalladium carbonyl complex containing a bis(N-heterocyclic carbene) ligand.

Use of a bulky bidentate bis(NHC) ligand allows isolation of a stable cationic methylpalladium carbonyl complex that undergoes clean carbonylation to an acyl complex under excess CO, modeling a key step in CO/alkene copolymerization.

One-step assembly of a chiral palladium bis(acyclic diaminocarbene) complex and its unexpected oxidation to a bis(amidine) complex.

Addition of trans-N,N'-dimethyl-1,2-diaminocyclohexane to a palladium bis(arylisocyanide) complex leads to the one-step formation of the first chiral bis(acyclic diaminocarbene) complex, which is thermally stable under N(2) but undergoes slow oxidation to a bis(amidine) complex under air.

cis-cis-trans-Bis(acetonitrile-κN)dichloridobis(triphenyl-phosphine-κP)ruthenium(II) acetonitrile disolvate.

The title compound, [RuCl(2)(C(2)H(3)N)(2)(C(18)H(15)P)(2)]·2C(2)H(3)N, was obtained upon stirring an acetonitrile/ethanol solution of [RuCl(2)(PPh(3))(3)]. In the crystal structure, each Ru(II) ion is coordinated by two Cl [Ru-Cl = 2.4308 (7) and 2.4139 (7) Å], two N [Ru-N = 2.016 (2) and 2.003 (2) Å], and two P [Ru-P = 2.3688 (7) and 2.3887 (7) Å] atoms in a distorted octa-hedral geometry. Packing inter-actions include typical C-H⋯π contacts involving phenyl groups as well as weak hydrogen bonds between CH(3)CN methyl H atoms and Cl or solvent CH(3)CN N atoms.

Radical autoxidation and autogenous O2 evolution in manganese-porphyrin catalyzed alkane oxidations with chlorite.

A manganese porphyrin catalyst employing chlorite (ClO(2)(-)) as a "shunt" oxidant displays remarkable activity in alkane oxidation, oxidizing cyclohexane to cyclohexanol and cyclohexanone with >800 turnover numbers. The ketone is apparently formed without the intermediacy of alcohol and accounts for an unusually large fraction of the product ( approximately 40%). Radical scavenging experiments indicate that the alkane oxidation mechanism involves both carbon-centered and oxygen-centered radicals. The carbon-radical trap CBrCl(3) completely suppresses cyclohexanone formation and reduces cyclohexanol turnovers, while the oxygen-radical trap Ph(2)NH inhibits all oxidation until it is consumed. These observations are indicative of an autoxidation mechanism, a scenario further supported by TEMPO inhibition and (18)O(2) incorporation into products. However, similar cyclohexane oxidation activity occurs when air is excluded. This is explained by mass spectrometric and volumetric measurements showing catalyst-dependent O(2) evolution from the reaction mixture. The catalytic disproportionation of ClO(2)(-) into Cl(-) and O(2) provides sufficient O(2) to support an autoxidation mechanism. A two-path oxidation scheme is proposed to explain all of the experimental observations. The first pathway involves manganese-porphyrin catalyzed decomposition of ClO(2)(-) into both O(2) and an unidentified radical initiator, leading to classical autoxidation chemistry providing equal amounts of cyclohexanol and cyclohexanone. The second pathway is a "rebound" oxygenation involving a high-valent manganese-oxo intermediate, accounting for the excess of alcohol over ketone. This system highlights the importance of mechanistic studies in catalytic oxidations with highly reactive oxidants, and it is unusual in its ability to sustain autoxidation even under apparent exclusion of O(2).

Symmetry and geometry considerations of atom transfer: deoxygenation of (silox)3WNO and R3PO (R = Me, Ph, (t)Bu) by (silox)3M (M = V, NbL (L = PMe3, 4-picoline), Ta; silox = (t)Bu3SiO).

Deoxygenations of (silox)(3)WNO (12) and R(3)PO (R = Me, Ph, (t)Bu) by M(silox)(3) (1-M; M = V, NbL (L = PMe(3), 4-picoline), Ta; silox = (t)Bu(3)SiO) reflect the consequences of electronic effects enforced by a limiting steric environment. 1-Ta rapidly deoxygenated R(3)PO (23 degrees C; R = Me (DeltaG degrees (rxn)(calcd) = -47 kcal/mol), Ph) but not (t)Bu(3)PO (85 degrees, >2 days), and cyclometalation competed with deoxygenation of 12 to (silox)(3)WN (11) and (silox)(3)TaO (3-Ta; DeltaG degrees (rxn)(calcd) = -100 kcal/mol). 1-V deoxygenated 12 slowly and formed stable adducts (silox)(3)V-OPR(3) (3-OPR(3)) with OPR(3). 1-Nb(4-picoline) (S = 0) and 1-NbPMe(3) (S = 1) deoxygenated R(3)PO (23 degrees C; R = Me (DeltaG degrees (rxn)(calcd from 1-Nb) = -47 kcal/mol), Ph) rapidly and 12 slowly (DeltaG degrees (rxn)(calcd) = -100 kcal/mol), and failed to deoxygenate (t)Bu(3)PO. Access to a triplet state is critical for substrate (EO) binding, and the S --> T barrier of approximately 17 kcal/mol (calcd) hinders deoxygenations by 1-Ta, while 1-V (S = 1) and 1-Nb (S --> T barrier approximately 2 kcal/mol) are competent. Once binding occurs, significant mixing with an (1)A(1) excited state derived from population of a sigma-orbital is needed to ensure a low-energy intersystem crossing of the (3)A(2) (reactant) and (1)A(1) (product) states. Correlation of a reactant sigma-orbital with a product sigma-orbital is required, and the greater the degree of bending in the (silox)(3)M-O-E angle, the more mixing energetically lowers the intersystem crossing point. The inability of substrates EO = 12 and (t)Bu(3)PO to attain a bent 90 degree angle M-O-E due to sterics explains their slow or negligible deoxygenations. Syntheses of relevant compounds and ramifications of the results are discussed. X-ray structural details are provided for 3-OPMe(3) (90 degree angle V-O-P = 157.61(9) degrees), 3-OP(t)Bu(3) ( 90 degree angle V-O-P = 180 degrees ), 1-NbPMe(3), and (silox)(3)ClWO (9).