N‐Silylaminotitanium Chlorides — Synthesis,Structures, Multinuclear Magnetic Resonance,and some Applications

N‐Silylaminotitanium trichlorides, Me₃S(R)N‐TiCl₃ ( 18 ) [R = ^tBu ( a ), SiMe₃ ( b ), 9‐borabicyclo[3.3.1]nonyl (9‐BBN)( c )], and (CH₂SiMe₂)₂N‐TiCl₃ ( 18d ) were obtained in high yield and high purity from the reaction of the respective bis(silylamino)plumbylene with an excess of titanium tetrachloride. The crystal structure of 18a was determined by X‐ray analysis. The reactions of the analogous stannylenes with an excess of TiCl₄ did not lead to 18 . N‐Lithio‐trimethylsilyl[9‐(9‐borabicyclo[3.3.1]nonyl)]amine ( 8 ) was prepared, structurally characterized and used for the synthesis of a new bis(amino)stannylene 10 and a plumbylene 11 . The compounds 18a—d served as ideal starting materials for the synthesis of bis(silylamino)titanium dichlorides, where the silylamino groups can be identical ( 19 ) or different ( 20 ). This was achieved either by the reaction of 18 again with bis(amino)plumbylenes or with lithium N‐silylamides. In contrast to the direct synthesis starting from titanium tetrachloride and two equivalents of the respective lithium amide, which in general affords 19 with identical amino groups only in low yield, the procedure starting from 18 is much more versatile and gave the pure compounds 19 or 20 in almost quantitative yield. Further treatment of the dichlorides 19 or 20 with lithium amides led to tris(amino)titanium chlorides 21 . The dichlorides 19 or 20 reacted with two equivalents of alkynyllithium reagents to give the first well characterized examples of di(alkyn‐1‐yl)bis(N‐silylamino)titanium compounds 22 — 27 . These compounds reacted with trialkylboranes (triethyl or tripropylborane) by 1, 1‐organoboration. In some cases, the extremely reactive reaction products could be identified as novel 1, 1‐bis(silylamino)titana‐2, 4‐cyclopentadienes 28 — 31 bearing a dialkylboryl group in 3‐position. In solution, the proposed structures of all products were deduced from a consistent set of data derived from multinuclear magnetic resonance spectroscopy (¹H, ¹¹B, ¹³C, ¹⁴N, ¹⁵N, ²⁹Si, ³⁵Cl NMR).     

Convenient Synthesis of 14‐Aryl‐14‐H‐dibenzo[a,j]xanthenes Catalyzed by Acyclic Brønsted Acidic Ionic Liquid [H—NMP]+[HSO4]− under Microwave Irradiation

Efficient method for direct preparation of 14‐aryl‐14‐H‐dibenzo[a,j]xanthenes through condensation of β‐naphthol with various aromatic aldehydes in the presence of the catalytic amount of [H—NMP]⁺[HSO₄]^? under microwave irradiation was described. This method has the advantages such as; very easy reaction workup, absolute separation of catalyst from the reaction mixture and smooth recyclability of catalyst. In this reaction 14‐aryl‐14‐H‐dibenzo[a,j]xanthenes were obtained as desired products in excellent yields and short reaction times via green and one‐pot procedure.     

Quantification of chlordesmethyldiazepam by liquid chromatography–tandem mass spectrometry: application to a cloxazolam bioequivalence study

A rapid, sensitive and specific LC‐MS/MS method was developed and validated for quantifying chlordesmethyldiazepam (CDDZ or delorazepam), the active metabolite of cloxazolam, in human plasma. In the analytical assay, bromazepam (internal standard) and CDDZ were extracted using a liquid‐liquid extraction (diethyl‐ether/hexane, 80/20, v/v) procedure. The LC‐MS/MS method on a RP‐C18 column had an overall run time of 5.0 min and was linear (1/x weighted) over the range 0.5–50 ng/mL (R > 0.999). The between‐run precision was 8.0% (1.5 ng/mL), 7.6% (9 ng/mL), 7.4% (40 ng/mL), and 10.9% at the low limit of quantification—LLOQ (0.500 ng/mL). The between‐run accuracies were 0.1, –1.5, –2.7 and 8.7% for the above mentioned concentrations, respectively. All current bioanalytical method validation requirements (FDA and ANVISA) were achieved and it was applied to the bioequivalence study (Cloxazolam—test, Eurofarma Lab. Ltda and Olcadil®— reference, Novartis Biociências S/A). The relative bioavailability between both formulations was assessed by calculating individual test/reference ratios for Cmax, AUClast and AUC0‐inf. The pharmacokinetic profiles indicated bioequivalence since all ratios were as proposed by FDA and ANVISA. Copyright © 2009 John Wiley & Sons, Ltd.     

Ab Initio Molecular Dynamics with Explicit Solvent Reveals a Two‐Step Pathway in the Frustrated Lewis Pair Reaction

The role solvent plays in reactions involving frustrated Lewis pairs (FLPs)—for example, the stoichiometric mixture of a bulky Lewis acid and a bulky Lewis base—still remains largely unexplored at the molecular level. For a reaction of the phosphorus/boron FLP and dissolved CO₂ gas, first principles (Born–Oppenheimer) molecular dynamics with explicit solvent reveals a hitherto unknown two‐step reaction pathway—one that complements the concerted (one‐step) mechanism known from the minimum‐energy‐path calculations. The rationalization of the discovered reaction pathway—that is, the stepwise formation of P?C and O?B bonds—is that the environment (typical organic solvents) stabilizes an intermediate which results from nucleophilic attack of the phosphorus Lewis base on CO₂. This finding is significant because presently the concerted reaction‐path paradigm predominates in the rationalization of FLP reactivity. Herein we point out how to attain experimental proof of our results.     

Autocatalytic Enantiomerisation at the Crystal Surface in Deracemisation of Scalemic Conglomerates

Deracemisation of racemic or scalemic conglomerates of intrinsically chiral compounds appears to be a promising method of chiral resolution. By combining the established methods of asymmetric synthesis and the physical process of crystal growth, we were able to achieve a complete deracemisation (with 100 % ee) of an asymmetric Mannich product conglomerate—vigorously stirred in its saturated solution—from a starting enantiomeric excess value of 15.8 % in the presence of pyrrolidine (8 mol %) as an achiral catalyst for the CC bond‐forming reaction. Strong activation of this deracemisation process was observed on mild isothermal heating to only 40 °C, resulting in dramatic acceleration by a factor of about 20 with respect to the results obtained at room temperature. Despite the fact that the racemisation half‐life time of the nearly enantiopure Mannich product (with 99 % ee) in the homogenous solution at the reaction temperature is eight days, the deracemisation process took only hours in a small‐scale experiment. This apparent paradox is explained by a proposed rapid enantiomerisation at the crystal/solution interface, which was corroborated by a ¹³C labelling experiment that confirmed the involvement of rapid enantiomerisation. Frequent monitoring of the solution‐phase ee of the slowly racemising compound further revealed that the minor enantiomer dominated in solution, supporting an explanation based on a kinetic model. A generalisation of the process of “aymmetric autocatalysis” (resulting in automultiplication of chiral products in homogenous media) to encompass heterogeneous systems is also suggested.     

Ir‐Catalyzed Asymmetric Hydrogenation of α‐Alkylidene β‐Lactams and Cyclobutanones

Chiral β‐lactams and cyclobutanones are present in numerous natural and pharmaceutical products. The stereoselective construction of chiral four‐membered cyclic compounds is an ongoing challenge for the chemical community. Herein, we report a highly stereocontrolled construction of four‐membered ring (mini‐sized) β‐lactams and cyclobutanones via an Ir/ In‐BiphPHOX ‐catalyzed asymmetric hydrogenation, providing the corresponding optically active four‐membered ring carbonyl products bearing an α‐chiral carbon center with excellent yields (up to 99%) and enantioselectivities (up to 98%) under mild reaction conditions (1.0—2.5 bar H₂ for 1.0—10 h). The reaction presents wide substrate scope. Diverse transformations of the catalyzed products were also conducted to show the potential utility of this protocol.     

Chiral Frustrated Lewis Pairs Catalyzed Highly Enantioselective Hydrosilylations of Ketones

A highly enantioselective Piers‐type hydrosilylation of simple ketones was successfully realized using a chiral frustrated Lewis pair of tri‐tert‐butylphosphine and chiral diene‐derived borane as catalyst. A wide range of optically active secondary alcohols were furnished in 80%—99% yields with 81%—97% ee's under mild reaction conditions.     

ChemInform Abstract: Anosovite‐Type V3O5: A New Binary Oxide of Vanadium.

The new anosovite‐type polymorph of the title compound is synthesized by reaction of either V₂F₆·4H₂O or a mixture of 60 wt.% VF₂·4H₂O and 40 wt.% VF₃·3H₂O with a flowing water‐saturated gaseous mixture of 15—20 vol% H₂ in argon (588 K, 14—18 h).     

Diastereo‐ and Enantioselective Intramolecular [2+2] Photocycloaddition Reactions of 3‐(ω′‐Alkenyl)‐ and 3‐(ω′‐Alkenyloxy)‐Substituted 5,6‐Dihydro‐1H‐pyridin‐2‐ones

3‐(ω′‐Alkenyl)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 2 – 4 were prepared as photocycloaddition precursors either by cross‐coupling from 3‐iodo‐5,6‐dihydro‐1H‐pyridin‐2‐one ( 8 ) or—more favorably—from the corresponding α‐(ω′‐alkenyl)‐substituted δ‐valerolactams 9 – 11 by a selenylation/elimination sequence (56–62 % overall yield). 3‐(ω′‐Alkenyloxy)‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones 5 and 6 were accessible in 43 and 37 % overall yield from 3‐diazopiperidin‐2‐one ( 15 ) by an α,α‐chloroselenylation reaction at the 3‐position followed by nucleophilic displacement of a chloride ion with an ω‐alkenolate and oxidative elimination of selenoxide. Upon irradiation at λ=254 nm, the precursor compounds underwent a clean intramolecular [2+2] photocycloaddition reaction. Substrates 2 and 5 , tethered by a two‐atom chain, exclusively delivered the respective crossed products 19 and 20 , and substrates 3 , 5 , and 6 , tethered by longer chains, gave the straight products 21 – 23 . The completely regio‐ and diastereoselective photocycloaddition reactions proceeded in 63–83 % yield. Irradiation in the presence of the chiral templates (?)‐ 1 and (+)‐ 31 at ?75 °C in toluene rendered the reactions enantioselective with selectivities varying between 40 and 85 % ee. Truncated template rac‐ 31 was prepared as a noranalogue of the well‐established template 1 in eight steps and 56 % yield from the Kemp triacid ( 24 ). Subsequent resolution delivered the enantiomerically pure templates (?)‐ 31 and (+)‐ 31 . The outcome of the reactions is compared to the results achieved with 4‐substituted 5,6‐dihydro‐1H‐pyridin‐2‐ones and quinolones.     

Electrochemical Intramolecular C—H/O—H Cross‐Coupling of 2‐Arylbenzoic Acids

A synthetic protocol to lactones by electro‐oxidative induced C—H activation of 2‐arylbenzoic acids has been developed. By using Na₂SO₄ aqueous solution as a cheap and green supporting electrolyte, different 2‐arylbenzoic acids could provide the corresponding lactones in 30%—90% yields. This reaction could be conducted on a gram scale with a good efficiency as well as a high utility for natural product synthesis.     

Photocuring kinetics of UV‐initiated free‐radical photopolymerizations with and without silica nanoparticles

We used photodifferential scanning calorimetry to investigate the photocuring kinetics of UV‐initiated free‐radical photopolymerizations of acrylate systems with and without silica nanoparticles. Two kinetics parameters—the rate constant (k) and the order of the initiation reaction (m)—were determined for hybrid organic–inorganic nanocomposite systems containing different amounts of added silica nanoparticles (0–20 wt %) and at different isothermal temperatures (30–100 °C) using an autocatalytic kinetics model. The kinetic analysis revealed that the silica nanoparticles apparently accelerate the cure reaction and cure rate of the UV‐curable acrylate system, most probably due to the synergistic effect of silica nanoparticles during the photopolymerization process. However, a slight decrease in polymerization reactivity that occurred when the silica content increased beyond 15 wt % was attributed to aggregation between silica nanoparticles. We also observed that the addition of silica nanoparticles lowered the activation energy for the UV‐curable acrylate system, and that the collision factor for the system with silica nanoparticles was higher than that obtained for the system without silica nanoparticles, indicating that the reactivity of the former was greater than that of the latter. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 658–670, 2005     

One‐Pot Organocatalytic Enantioselective Michael/Povarov Domino Strategy for the Construction of Spirooctahydroacridine‐3,3′‐oxindole Scaffolds

An asymmetric organocatalytic one‐pot strategy for the construction of spirooctahydroacridine‐3,3′‐oxindole scaffolds has been successfully developed by means of a domino Michael/Povarov reaction sequence. The one‐pot protocol affords the chiral spirocyclohexaneoxindoles bearing an octahydroacridine motif with five stereocenters in good to high yields (up to 89 % yield) with excellent to perfect diastereoselectivities (up to >20:1 d.r.) and enantioselectivities (up to >99 % ee). This highly efficient one‐pot domino procedure will allow diversity‐oriented syntheses of this intriguing class of compounds with potential biological activities.     

溴化镁催化的1,2,3,4-四氢吡啶酮无溶剂合成研究

An efficient and environmentally friendly procedure for the one-pot synthesis of tetrahydropyrimidinones from aldehydes, β-diketones and urea/thiourea by using magnesium bromide as an inexpensive and easily available catalyst under solvent-free conditions was described. Compared with the classical Biginelli reaction conditions, this new method has the advantage of good to excellent yields (74%-94%) and short reaction time (45-90 min). The structure of the Biginelli reaction product from β-diketone, salicylaldehyde and urea has been proposed to possess an oxygen-bridge by cyclization (intramolecular Michael-addition).     

Consecutive Reaction of Bis [2,2,2－trifluoroethyl] phosphite. One－pot Synthesis of Substituted 3－Cyano－β, γ－unsaturated Nitriles with Exclusive or Predominant E－Selectivity

The consecutive reaction of bis [ 2, 2, 2-trifluoroethyl] phosphite and its application to the one-pot synthesis of 3-cyano-β, γ-unsaturated nitriles with exdusive or predominant E-selectivity (E: Z = 100-85: 0-15) and excellent yields (94%-99%) are described.     

One‐Pot Process to Carborano‐Coumarin via Catalytic CascadeDehydrogenative Cross‐Coupling

Ir‐catalyzed cascade dehydrogenative CH/BH and BH/OH cross‐coupling of carboranyl carboxylic acid with readily available benzoic acid has been achieved, leading to the facile synthesis of previously unavailable carborano‐coumarin in a simple one‐pot process. Two cage B—H, one aryl C—H and one O—H bonds are activated to construct efficiently new B—C and B—O bonds. The cascade cyclization can stop at the first B—H/C—H cross‐coupling step by tuning the reaction conditions, resulting in a series of α‐carboranyl benzoic acid and aryl carborane derivatives. Control experiments indicate that B—H/C—H dehydrocoupling proceeds preferentially over B—H/O—H dehydrocoupling, and both directing groups and oxidants are crucial for this reaction. An iridium(V) intermediate is proposed to be involved in the catalytic cycle.     

The Atmospheric Oxidation Mechanism of Benzyl Alcohol Initiated by OH Radicals: The Addition Channels

Benzyl alcohol (BA) is present in indoor atmospheres, where it reacts with OH radicals and undergoes further oxidation. A theoretical study is carried out to elucidate the reaction mechanism and to identify the main products of the oxidation of BA that is initiated by OH radicals. The reaction is found to proceed by H‐abstraction from the CH₂ group (25 %) and addition to the ipso (60 %) and ortho (15 %) positions of the aromatic ring. The BA–OH adducts react further with O₂ via the bicyclic radical intermediates—the same way as for benzene—forming mainly 3‐hydroxy‐2‐oxopropanal and butenedial. If NO_x is low, the bicyclic peroxy radicals undergo intramolecular H‐migration, forming products containing OH, OOH, and CH₂OH/CHO functional groups, and contribute to secondary organic aerosol (SOA) formation.     

Synthesis of Tetrasubstituted Alkenes through a Palladium‐Catalyzed Domino Carbopalladation/C?H‐Activation Reaction

Helical tetrasubstituted alkenes ( 7 ) were obtained in a highly efficient way through a palladium‐catalyzed domino‐carbopalladation/CH‐activation reaction of propargylic alcohols 6 in good to excellent yields. Electron‐withdrawing‐ and electron‐donating substituents can be introduced onto the upper and lower aromatic rings. The substrates ( 6 ) for the domino process were synthesized by addition of the lithiated alkyne ( 20 ) to various aldehydes ( 19 ); moreover, the substrates were accessible enantioselectively (in 95 % ee) by reduction of the corresponding ketone using the Noyori procedure.     

Synthesis of Novel Alkyl Amide Functionalized Trifluoromethyl Substituted Furo/thieno Pyridine Derivatives: Their Anticancer Activity and CoMFA and CoMSIA Studies

A series of novel alkyl amide functionalized trifluoromethyl substituted furo/thieno pyridine derivatives 4a–h , 5a–d , and 6a–h were prepared starting from 2‐oxo/thioxo‐6‐phenyl/thien‐2‐yl‐4‐(trifluoromethyl)‐1,2‐dihydropyridine‐3‐carbonitrile 1 on reaction with bromoethylacetate followed by reaction with different primary aliphatic amines, cyclic secondary amines, or l ‐amino acids under different set of conditions. All the synthesized compounds 4a–h , 5a–d , and 6a–h were screened for anticancer activity against four cancer cell lines such as HeLa—cervical cancer (CCL‐2), COLO205—colon cancer (CCL‐222), HepG2—liver cancer (HB‐8065), and MCF7—breast cancer (HTB‐22). Compounds 4g and 4h are found to have promising anticancer activity at micromolar concentration. CoMFA and CoMSIA methods were applied to derive 3D‐QSAR models for alkyl amide tagged furo/thieno pyridine derivatives as potential anticancer inhibitors. 3D‐QSAR models provided a strong basis for future rational design of more active and selective HeLa, COLO205, HepG2, and MCF‐7 cell line inhibitors.     

Facile,one‐pot synthesis of aromatic diamine‐based phosphinated benzoxazines and their flame‐retardant thermosets

Three aromatic diamine‐based, phosphinated benzoxazines ( 7–9 ) were prepared from three typical aromatic diamines—4,4′‐diamino diphenyl methane ( 1 ), 4,4′‐diamino diphenyl sulfone ( 2 ), and 4,4′‐diamino diphenyl ether ( 3 ) by a one‐pot procedure. To clarify the reaction mechanism, a two‐pot procedure was applied, in which the reaction intermediates ( 4–6 ) were isolated for characterization. The structures of intermediates and benzoxazines were confirmed by high resolution mass, IR, and 1D and 2D‐NMR spectra. In addition to self‐polymerization, ( 7–9 ) were copolymerized with cresol novolac epoxy (CNE). After curing, the homopolymers of P( 7–9 ) are brittle while the copolymers of ( 7–9 )/CNE are tough. Dynamic mechanical analysis shows the T_gs of ( 7–9 )/CNE copolymers are 187, 190, and 171 °C, respectively. Thermal mechanical analysis shows the CTEs of ( 7–9 )/CNE copolymers are 46, 38, and 46 ppm, respectively. All the ( 7–9 )/CNE copolymers belong to an UL‐94 V‐0 grade, demonstrating good flame retardancy. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2010     

Chemometric analysis for optimizing derivatization in gas chromatography‐based procedures

This paper focuses on the application of principal component analysis (PCA) to facilitate the optimization of the derivatization of oestrogenic steroids—estrone, 17β‐estradiol, estriol, 17α‐ethinylestradiol and diethylstilbestrol—in order to achieve (1) the complete derivatization of all the hydroxyl groups contained in the structure of the compounds and (2) the greatest effectiveness of this reaction. Six different derivatization reagents were used in this study, whereas 2‐methyl‐anthracene was applied as the internal standard to evaluate the effectiveness of the reactions. The experimental data were subjected to PCA. With PCA, the dimensionality of the original multivariable data set could be reduced and the selection of optimum conditions for derivatization facilitated. The mixture of 99% N,O‐bis(trimethylsilyl)trifluoroacetamide + 1% trimethylchlorosilane and pyridine (1:1, v/v) at 60 °C for 30 min has been established as the most convenient and efficient means of derivatizing the aforementioned oestrogenic steroids and diethylstilbestrol; the N‐methyl‐N‐(trimethylsilyl)trifluoroacetamide + pyridine (1:1, v/v) mixture seems to be a promising alternative. The application of PCA for optimizing the derivatization procedure, proposed for the first time in this study, is particularly useful in the development of multicomponent methods across several chemical classes of compounds. Copyright © 2011 John Wiley & Sons, Ltd.