Abstract  Retention factors on a minimum of eight stationary phases at various temperatures by gas-liquid chromatography and in acetonitrile-water and methanol-water mobile phases by reversed-phase liquid chromatography on a Synergi Polar-RP column were combined with further values taken from the literature and liquid-liquid partition coefficients for up to eight totally organic biphasic systems to estimate descriptors for 24 esters (phthalate, oleate, stearate, arbietate, adipate, succinate, sebacate, and diethylmalonate) widely used as plasticizers and solvents in industry. The descriptors facilitated the estimation of several properties of environmental interest (octanol-water, air-octanol, and air-water partition coefficients, and soil-water distribution coefficients, vapor pressure, and water solubility). The descriptors are suitable for use in the solvation parameter model and facilitate the estimation of a wide range of physicochemical, chromatographic, biological, and environmental properties using existing models.

Abstract  Fentanyl, sufentanil and alfentanil are clinically widely used anaesthetics and are structurally related to drugs with entirely different pharmacological activity such as droperidol, loperamide and lorcainide, etc. Therefore, in order to test their pharmacological activity, lactam analogues of fentanyl, a novel class of compounds, have been synthesized. In the first step, various primary amines have been selectively added to 1 equiv, of alpha,beta-unsaturated esters, to afford the beta-amino esters. N-Acylation of these intermediates with dimethyl malonate yields the amido esters, which have been further subjected to Dieckmann-type cyclization, to produce the corresponding 3-methoxycarbonylpiperidine-2,4-diones. The cyclization has been effected under phase-transfer conditions, utilizing potassium carbonate as base and 18-crown-6 as catalyst, This eliminates the need for strong and hazardous bases such as molten sodium or NaH, In the next step, acid hydrolysis and decarboxylation furnish the substituted piperidine-2,4-diones in good yields, as pure products. Alkylation of the N-phenethylpiperidine-2,4-dione with methyl iodide and potassium carbonate in DMSO gives the 3,3-dimethyl derivative, The alkylation procedure is also applicable to other alkylating agents. Reductive amination of the prepared piperidine-2,4-diones with aniline and NaBH3CN in buffered methanol gives the corresponding pure 4-anilino-2-piperidones. The lactam function can be readily reduced (NaBH4-BF3 . Et(2)O), as exemplified with the 3,3-dimethyl derivative, thus providing access to additional fentanyl analogues, not readily accessible by other routes. The synthesis is completed by N-acylation of the anilines with propionyl chloride using triethylamine as base. The prepared 4-propionanilido-2-piperidones and 4-propionanilidopiperidines are expected to provide useful structure-activity relationship data in the pharmacological studies.

Abstract  We describe the development and application of efficient bifunctional acidbase mesoporous silica catalysts, denoted hereafter as Ext-SBA-15-NMe2, comprising tertiary amine and silanol (weak acid) groups for the Michael addition reaction. The catalysts were synthesized by grafting tertiary amine containing organosilane into the mesoporous channel pores of SBA-15 mesoporous silica in polar protic solvent (isopropyl alcohol) or nonpolar solvent (toluene). The resulting materials, Ext-SBA-15-NMe2-IPA or Ext-SBA-15-NMe2-Tol, respectively, were used as catalysts for the Michael addition reactions between trans-- nitrostyrene(s) and active methylene compounds, such as malononitrile, acetylacetone, and diethylmalonate, at different temperatures. A variable-temperature NMR-array technique was used to monitor the reactant conversion and the reaction progress. Among the active methylene compounds tested with trans--nitrostyrene, malononitrile gave the highest conversion of 90% in 0.3h at 0 degrees C if catalyzed by the catalyst Ext-SBA-15-NMe2-IPA, the silanol groups of which were not passivated by trimethysilyl (SiMe3) groups. Compared with Ext-SBA-15-NMe2-Tol, the Ext- SBA-15-NMe2-IPA material (whose the amine groups were grafted in polar-protic solvents), in particular, demonstrated an effective cooperative bifunctional catalysis because of its optimized proportions of tertiary amine groups and a significant number of surface silanol groups that were judiciously left behind on the material with this optimized synthetic strategy. The catalytic activity of this material was found to be significantly higher than that of the corresponding material that was grafted in toluene and that contained less optimized proportions of these two catalytic groups (i.e., amine and silanol groups). The bifunctional catalysts also showed good recyclability upon washing with acetone, which offered an effective way of regenerating the catalyst free from any undesired product/substrate bound on the surface of the catalysts.

Abstract  The oxirane ring opening of 3-[(benzyloxy)methyl]-7-oxabicyclo[4.1.0]heptane with sodium salt of diethyl malonate followed by treatment with TsOH gave (3aR*, 6R*, 7aS*)-6-[(benzyloxy) methyl]hexahydro-1-benzofuran-2(3H)-one (3a) and (3aR*, 5R*, 7aS*)-5-[(benzyloxy) methyl] hexahydro-1-benzofuran-2(3H)-one (3b). Lactones 3a and 3b were formylated and then treated with thiourea or guanidine to give, after deprotection, racemic 5-[2-hydroxy-4- and 2-hydroxy-5-(hydroxymethyl)cyclohexyl]-2-thiouracil (5a and 5b) or -isocytosine (12a and 12b). Simple transformations of the 2-thiouracil derivative led to uracil (7a and 7b), 4-thiouracil (9a and 9b), and cytosine derivatives (10a and 10b).

Abstract  The acceleration effect of various agents on the rate of styrene bulk polymerization in 2,2,6,6-tetramethylpiperidinyloxy (TEMPO) mediated polymerization was investigated, including dimethyl malonate (DMM), diethyl methyl malonate (DEMM), diethyl tert-butylmalonate (DEBM), diethyl diethylmalonate (DEDEM), 3-methyl-2,4-pentanedione (MPD), acetyl malononitrile (Ac-MN), and dimethyl malononitrile (DM-MN). Polymerization with the additive proceeded in a living manner, as indicated by keeping a low polydispersity and increasing the molecular weight with the reaction time and conversion. The structure of the styrene polymerization did not change in the presence of these additives. The monomer conversion efficiency was approximately 99% and maintained a relatively narrow polydispersity of 1.29 with the optimal [Ac-MN]/[TEMPO] molar ratios of 4 in 1.5 h. With the accelerator, dipole/dipole interactions led to a weakening of the C-ON bond and an acceleration of the reaction. There is a trend for a higher polymerization rate with more electron-withdrawing substituents.

Abstract  Vapors of four chemical warfare agent (CWA) stimulants, 2-chloroethyl ethyl sulfide (CEES), diethyl malonate (DEM), dimethyl methylphosphonate (DMMP), and methyl salicylate (MeS), were detected, identified, and quantitated using a fully automated, field-deployable, miniature mass spectrometer. Samples were ionized using a glow discharge electron ionization (GDEI) source, and ions were mass analyzed with a cylindrical ion trap (CIT) mass analyzer. A dual-tube thermal desorption system was used to trap compounds on 50:50 Tenax TA/Carboxen 569 sorbent before their thermal release. The sample concentrations ranged from low parts per billion [ppb] to two parts per million [ppm]. Limits of detection (LODs) ranged from 0.26 to 5.0 ppb. Receiver operating characteristic (ROC) curves are presented for each analyte. A sample of CEES at low ppb concentration was combined separately with two interferents, bleach (saturated vapor) and diesel fuel exhaust (1%), as a way to explore the capability of detecting the simulant in an environmental matrix. Also investigated was a mixture of the four CWA simulants (at concentrations in air ranging from 270 to 380 ppb). Tandem mass (MS/MS) spectral data were used to identify and quantify the individual components.

Abstract  NetState I of the communication-catalysis protocol is defined by a 1 : 1 mixture of the nanoswitches [Cu(1)]+ and 2. Upon one-electron oxidation at the ferrocenyl unit of the switch [Cu(1)]+, copper(i) ions are released that after translocation toggle nanoswitch 2 → [Cu(2)]+ (NetState II) within 4 min. NetState I was fully reset within 1 min by reduction of 1+ → 1. Running this redox-triggered switching protocol in the presence of 4-nitrobenzaldehyde, diethyl malonate and piperidine (catalyst) allows toggling of a catalyzed Knoevenagel addition from ON to OFF and back to ON.

Abstract  Solvatochromic mixed ligand complexes of copper(II) with malonate and diamine derivatives, Cu(n)(RMal)(diam)(n)X(m) (where n=1 or 2, m=1-4, RMal, malonic acid (H(2)Mal), diethylmalonate (HDEtMal) or diethylethoxyethylenemalonate (DEtEMal), and diam, ethylenediamine (en), 1,3-propylenediamine (1,3-pn), N,N,N'-trimethylethylenediamine (Me(3)en), N,N,N'-triethylethylenediamine (Et(3)en), N,N,N',N'-tetramethylethylenediamine (Me(4)en), N,N,N',N'-tetramethylpropylenediamine (Me(4)pn), or N-methyl-1,4-diazacycloheptane (medach); and X=ClO(4)(-) or Cl(-)), has been synthesized and characterized by spectroscopic, magnetic, molar conductance and electrochemical measurements. The mass spectra along with the analytical data of the complexes show peaks with m/e corresponding to a bridged binuclear structure for the chloride complexes, while perchlorate complexes showed either mononuclear structure for DEtMal and DEtEMal or bridged binuclear structure for Mal complexes. These results correspond to IR spectral data, which indicated that the modes of ester and carboxylato coordination sites are mono- and/or bidentate. The d-d absorption bands in weak donor solvents suggest square-planar and distorted square pyramidal-trigonal bipyramid geometries for the perchlorate and chloride complexes; respectively. On the other hand, an octahedral structure is identified for complexes in strong donor solvents. Perchlorate complexes show a drastic color change from violet to green as the donation ability of solvent increases, whereas chloride complexes are highly affected by the acceptor properties of the solvent. Cyclic voltammetric measurements on the complexes, proposed a quasi-reversible or irreversible and mainly diffusion controlled reduction process. Such behavior has been explained according to the ECE mechanism. A linear correlation has been found between the Cu(II) reduction potential and the spectral data. Molecular orbital calculations were performed for the ligands on the bases of PM3 level and the results corresponded to the experimental data. The data are discussed in terms of chromotropic concept and its applications as a Lewis acid-base color indicator.

Abstract  C-2-Methylene O- and C-glycosides are readily synthesized from C-2-acetoxymethyl glycals using Nafion-H(R), montmorillonite K-10, LiClO4 (0.07 M) in dichloromethane and Pd(PPh3)(4) as catalysts. Exclusive alpha or beta selectivities have been observed with various primary, secondary and tertiary alcohols, phenols and diethyl malonate. Further, C-2-acetoxymethyl glycals are also converted into corresponding alpha -methylene-delta -valerolactones in good yields in one step using m-CPBA in the presence of BF3. Et2O. (C) 2000 Elsevier Science Ltd. All rights reserved.

Abstract  In this account we present the synthesis, characterization and catalytic activity in the polymerization of propylene of a bis(dimethyl malonate) titanium bis(diethylamine) complex (1). The complex exhibits in solution a dynamical isomerization following an internal Bailar twist. The activation of complex 1 was obtained by its reaction with methylalumoxane (MAO). The activated complex in solution shows a different dynamic process involving an equilibrium between a monodentate eta(1) and bidentate eta(2) binding of the dimethylmalonate ligand to the metal center. This equilibrium is responsible for the formation of, at least, two active species for the polymerization reaction bearing major symmetry differences. The monodentate coordination (opened form) of the ligand was found to be the major form of the active species of the complex when activated with MAO, most probably due to a strong interaction of the oxygen atoms in the ligand with the strong Lewis acid co-catalyst. The active species in the polymerization were studied by NMR and ESR spectroscopies. The resulting polypropylene showed elastomeric properties with low tacticites. (c) 2006 Elsevier B.V. All rights reserved.

Abstract  Polystyrene incorporating carboxylate group as a-end was synthesized by using initiator 4-chloromethyl benzoic acid via atom transfer radical polymerization. Its omega-chlorine end-group was transformed by cumic acid, diethyl malonate, and thiol, respectively, to form end-functionalized telechelic polystyrenes. These PSts with different functionalized omega-end group (PSt1, PSt2, and PSt3) were obtained and characterized by H NMR and TGA. This type of end-functionalized telechelic polymers can further act as polymeric ligands to form polymeric metal complexes. In this study, PSt1 with carboxylate group at each end was allowed to react with Eu(DBM)(2)Cl center dot 2H(2)O to afford a new polymeric complex PSt1-Eu(III) showing significant red-light emission. Moreover, the film of PSt1-Eu shows similar emission pattern with its DMF solution. (C) 2008 Wiley Periodicals, Inc.

Abstract  An ecofriendly, microwave (MW) promoted and solventless method is described for the alkylation of diethyl malonate, ethyl acetoacetate and ethyl cyanoacetate by a variety of alkyl halides in the presence of K2CO3. In the solid-liquid phase alkylation of active methylene containing substrates, it seems to be of general value that the phase-transfer catalyst, that is an onium salt in the present case, can be omitted and substituted by MW irradiation promoting the formation of the potassium salt of the substrate and its transfer to the organic phase. In certain cases, the use of triethylbenzyl-ammonium chloride led to the formation of by-products under the conditions (similar to 160 degrees C/similar to 12 bar) applied.

Abstract  The kinetics of the monoalkylation reaction of malonic ester with allyl chloride in two-phase systems containing a potassium hydroxide aqueous solution or the solid alkali in the presence of phase transfer catalysts of different nature was studied. The reaction mechanism under phase transfer catalysis conditions was proposed, which includes substrate deprotonation at the interface, transfer of the deprotonated substrate anion into the organic phase, and its alkylation in the organic phase. It was found that the mechanism of the action of phase transfer catalysts in two-phase systems of various types is similar in character and the effectiveness of their action is primarily determined by their ability to transfer or displace the deprotonated substrate anion from the interface to the organic phase.

Abstract  A new unsymmetrical diethyl malonate appended porphyrin and its Yb3+, Er3+ and Nd3+ complexes were prepared and characterized by elemental analysis, NMR, IR, UV-visible and mass spectral methods. The results revealed that the porphyrinate behaved as a tri-deprotonated hexadentate ligand with the appended diethyl malonate group coordinated to the lanthanide ion as an anion. Photoluminescent studies showed that the porphyrin ring transferred the absorbed visible light to the metal ions, which led to emission characteristic of the lanthanide ions in the near-infrared region. The factors affecting the emission intensity were also investigated.

Abstract  A benzofurane type lactone 4 incorporating an alpha-methylene-gamma-butyrolactone moiety has been synthesized. The key steps involved are the Michael condensation of 4-dichloromethyl-4-methyl-2,5-cyclohexadienone 1 with dimethyl malonate and acetoxylation of 4-dichloromethyl-5-carboxymethyl-4-methyl-2-cyclohexenone 2 with lead (IV) acetate in BF3-etherate which are indicative of the general route to gamma-lactone. Microbial degradations of the synthetic benzofurane type lactone 4 have also been studied using Aspergillus niger, Saccharomyces cerevisiae, Bacillus mycoides, Agrobacterium tumefaciens, Pseudomonas glicinea and Pseudomonas fluorescens. The lactone acts both as an additive for the nutrient substrate and as a source of organic carbon.

Abstract  The mechanism and enantioselectivity of the asymmetric conjugate addition of dimethyl malonate to -nitrostyrene catalyzed by cinchona alkaloid QD-4 as organic catalyst are investigated using density function theory and ab initio methods. Six different reaction pathways, corresponding to the different approach modes of -nitrostyrene to dimethyl malonate are considered. Calculations indicate that the reaction process through a dual-activation mechanism, in which the tertiary amine of cinchona alkaloid QD-4 first works as a BrOnsted base to promote the activation of the dimethyl malonate by deprotonation, and then, the hydroxyl group of QD-4 acts as BrOnsted acid to activate the -nitrostyrene. The rate-determining step is the proton transfer process from the tertiary amine of QD-4 to -carbon of -nitrostyrene. The comparison of the mechanisms and energies of the six reaction channels enable us to learn the fact that QD-4 has good catalytic activities for the system, and implies C9OH in QD-4 may not be involved in the activation. These calculation results account well for the observations in experiments. (c) 2014 Wiley Periodicals, Inc.

Abstract  Titanosilicate molecular sieves (TS-1, Ti-MCM-41 and amorphous TiO2-SiO2) catalyze transesterification reactions. Acidity measurements (pyridine adsorption-IR and NH3-TPD) reveal the presence of only weak Lewis acid sites. Catalytic activity parallels the acid strength and increases in the order: TS-1 < Ti-MCM-41 < amorphous TiO2-SiO2. TS-1 efficiently catalyzes the transesterification of only linear esters (ethylacetoacetate and diethylmalonate), but fails for cyclic esters like propylene carbonate. Ti-MCM-41 and amorphous TiO2-SiO2 are superior for the latter. The catalysts could be recycled without any loss in activity/selectivity. (C) 2004 Elsevier B.V. All rights reserved.

Abstract  Enantiomerically enriched, deuterated branched carbonates (Z)-(S)-PhCH(OCO(2)Me)-CH = CHD (1-D), (Z)-(R)-PhCH(OCO(2)Me)CH = CHD (2-D), and linear carbonate (E)-(S)-PhCH = CHCHD(OCO(2)Me) (3-D) were used as probes in the Mo-catalyzed asymmetric allylic alkylation with sodium dimethyl malonate, catalyzed by ligand-complex 11 derived from the mixed benzamide/picolinamide of (S,S)-transdiaminocyclohexane and (norbornadiene)Mo(CO)(4). The results of these studies, along with x-ray crystallography and solution NMR structural analysis of the pi-allyl intermediate, conclusively established the reaction proceeded by a retention-retention pathway. This mechanism contrasts with that defined for Pd-catalyzed allylic alkylations, which proceed by an inversion-inversion pathway. A proposed rationale for the retention pathway for nucleophilic substitution involves CO-coordination to form a tri-CO intermediate, followed by complexation with the anion of dimethyl malonate to produce a seven-coordinate intermediate, which reductively eliminates to afford product with retention of configuration.

Abstract  1-[(2,4-Di-1-pyrrolidinyl-9H-pyrimido[4,5-b]indol-9-yl)-acetyl]pyrrolidine monohydrochloride, PNU-142731A, is under investigation as a potential orally active antioxidant for the treatment of asthma. Stable isotope and radioisotope forms of this compound were needed for drug adsorption, distribution, excretion, and metabolism studies. The synthesis of carbon-14 PNU-142731A, labeled at the C-2 position of the pyrimidine ring was accomplished in 6 steps. [(2,6-Di-1-pyrrolidinyl-4-[2-C-14]pyrimidinyl)amino]acetyl pyrrolidine, [C-14]PNU-145325 was synthesized in 4 steps from 300 mCi (nominally 55 mCi/mmol) of carbon-14 labeled urea and unlabeled diethyl malonate. The synthesis was completed by the cyclization of [C-14]PNU-145325 with 2-bromocyclohexanone, followed by dehydrohalogenation to afford 31 mCi (10.3% overall yield) of [C-14]PNU-142731A as the monohydrochloride salt. The specific activity was 112.02 mu Ci/mg (51 mCi/mmol) with a radiochemical purity of 99% as determined by HPLC and TLC. In a similar manner. [C-13.N-15(2)]urea and [1,3-C-13]diethyl malonate were used to prepare 379 mg of [C-13(3), N-15(2)]PNU-142731A with excellent purity and 99% atom incorporation.

Abstract  Background: Clobazam (CLB) has been used as an anxiolytic, anticonvulsant and antiepileptic drug under the trade names, Frisium, Urbanol, Onfi and Tapclob. Impurity profiling in the pharmaceutical industries is a central task in the manufacturing of drug product. The quantification of impurities in active pharmaceutical ingredients (APIs) is also receiving considerable importance from the regulatory authorities in the point of stringent quality requirement. Thus, the provision of substantial quantity of impurities as standards, which are accomplished either by isolation from crude reaction mass or the synthesis of material with proposed structure using new synthetic route, to analytical method development and validation is a good demand. Therefore, easily accessible synthetic routes to the preparation of impurities with the lowest cost are sought after. To date, no synthetic specifics were found on the synthesis and characterization of CLB Imp-B, -C, -D and -F, and the synthesis of CLB Imp-E. Therefore, the comprehensive study was undertaken on the synthesis and characterization of CLB related impurities and this study might be useful to prepare CLB impurities in the required quantity with purity to use as a reference standard of analytical method development in pharmaceutical industry.

Methods: The synthetic routes were developed for the synthesis of CLB impurities such CLB Imp-B to Imp-F and isolated them using purification techniques with purity in the required quantity. The commercially available key starting materials, reagents and solvents were used in the course of synthesis of impurities. The analytical techniques such as NMR, IR and mass were used to characterize the structure of synthesized CLB related impurities.

Results: The easy accessible synthetic methods were developed for the synthesis of clobazam related impurities, CLB Imp-B to F in good to excellent yields with purity as well as described the cause to formation of these impurities. The KSM related impurity, 2-chloro-1-nitrobenzene and the active methylene hydrogens in clobazam are caused to the formation of CLB Imp-B and CLB Imp-C&-D, respectively. CLB Imp-E and -F are formed due to the degradation of drug molecule, CLB in the presence of base (NaOH). CLB Imp-B was prepared from 2-chloro-1-nitrobenzene by following similar process of CLB reported in the synthetic specific. CLB Imp-F was prepared from 5-chloro-N'-phenylbenzene-1,2-diamine by coupling with mono-methyl malonate followed by N-methylation using dimethyl sulfate. The rest of all impurities were planned to prepare by taking CLB as starting material. CLB Imp-C and -D were synthesized by treating CLB with methyl iodide in the presence of inorganic base. The mixture of aqueous NaOH and CLB was agitated vigorously at 75-80 degrees C to obtain CLB Imp-E. All the synthesized compounds were purified using purification techniques such as crystallization and column chromatography, and well characterized by IR, ESI-mass, H-1 NMR, C-13 NMR and DEPT analyses.

Conclusion: The immaculate discussion about synthetic approaches and structural elucidation using analytical applications such as IR, NMR (H-1, C-13 and DEPT) of CLB Imp-B to F, which are listed in the European pharmacopoeia monograph of clobazam, has been described. All the impurities were obtained with stringent purity (>98%) in the described synthetic routes and the same impurities have been used in analytical method development in our pharmaceutical industry. Also, the plausible mechanistic path ways to the formation of impurities, keeping in view the regulatory importance of clobazam, were discussed in detail.

Abstract  The synthesis of racemic (S)-(+)- or (R)-(-)-[methyl-C-11]amphetamine (3) is reported. The alkylation of dimethyl 2-benzylmalonate with [C-11]methyl iodide yielded dimethyl 2-benzyl-2-([C-11]methyl)malonate (1) which was used as an intermediate in the synthesis of 3. Hydrolysis of 1 with NaOH and subsequent decarboxylation using glacial acetic acid and heating produced 2-benzyl-[3-C-11]propionic acid (2). Conversion of 2 into 3 was achieved via the intermediate isocyanate using diphenyl-phosphoryl azide (DPPA), and subsequently into the amine using conc. HCl. After purification by solid-phase extraction and preparative LC, (+/-)-3 was obtained with a radiochemical purity greater than 98 %. Starting with 3 GBq (81 mCi) [C-11]carbon dioxide, 145 MBq (3.9 mCi) (+/-)-[methyl-C-11]amphetamine was obtained in 45 min with a 22 % decay-corrected radiochemical yield. Enantiomerically pure 3 was obtained by the preparative LC separation of the (+)- or (-)-10-camphorsulfonamide derivatives of the racemate with a total decay-corrected radiochemical yield of 7 % (counted from the start of methyl iodide synthesis). In a typical synthesis, 27 MBq (0.7 mCi) enantiomerically pure (S)-(+)- or (R)-(-)-[methyl-C-11]amphetamine were obtained starting from 3 GBq (81 mCi) [C-11]carbon dioxide. The position of labelling was confirmed by a C-13 synthesis using the same reaction pathway, and analysis by C-13 NMR spectroscopy.

Abstract  A novel family of triazolium salt enantiomers has been efficiently synthesized by combining chemical and biocatalytic methods. The stereoselective action shown by hydrolytic enzymes led to the design of simple and general chemoenzymatic routes in which tunable vectors, such as ring size, substituent stereochemistry, oxygen substitution, anion nature, or N4-triazole alkylating chain, were considered to produce 30 enantiopure triazolium salts in very high overall yields. Finally, selected triazolium salts were tested as phase-transfer catalysts in the asymmetric Michael addition of diethyl malonate to trans-chalcone to rationalize their activity and stereopreference. Low to complete conversion values were achieved in the formation of the Michael addition adduct, which mainly gave low levels of stereoselectivity depending on the different structural patterns considered in this systematic study.

Abstract  Chiral vinylogous sulfonamidopeptides (vs-peptides) were synthesized on TentaGel resin employing (S)- and (R)-N-Boc-vinyIogous sulfonyl chlorides 2a-i as building blocks. Glycine and two different photocleavable molecules were used as linkers, and the corresponding cleavage conditions were optimized. According to preliminary studies in solution and on solid phase. three libraries were synthesized with the "split-mix synthesis" method. Taking advantage of the acidic character of the sulfonamides (RSO2-NHR: pK(a) = 10-11), mild conditions were developed to alkylate the sulfonamide nitrogen atom so as to reduce the acidity of the monomers and of the oligomers and increase their in vivo bioavailability. This synthetic methodology was employed to increase the diversity in a library of di-N-alkylated vs-dipeptides 26. The electron-withdrawing capability of the sulfonamido group pointed to the use of vinylogous sulfonamidopeptides as Michael accepters. The sodium enolate of dimethyl malonate was used as nucleophile to obtain N-Boc-gamma-lactams 35 in moderate yields and good diastereoselectivity.

Abstract  Chiral ferrocene-containing iminoarylphosphite ligands based on 4,4'-dimethoxy-6,6'-di-tertbutyl-biphenyidiol-2,2' and their chelate complexes with Rh(I) and Pd(II) were synthesized for the first time. They were shown to be perspective reagents in the reactions of asymmetric allyl substitution. The Pd-catalyzed alkylation of 1,3-diphenylailylacetate with dimethyl malonate results in a 87% enantiomer excess (ee), while in sulfonylation of 1,3-diphenylallylacetate with sodium para-toluenesulfinite, this figure amounts to 67%. The results obtained were compared with coordination and catalytic efficiency of a less sterically hindered ferrocenyliminophosphite based on pyrocatechol. The compositions and structures of new compounds were determined by the H-1, C-13, P-31 NMR, IR, mass spectrometry (EI, FAB, and electrospray techniques), and elemental analysis.

Abstract  Pyridinium and isoquinolinium ylides (7 and 12) derived from malonic ester react in an unusual manner with isocyanates giving the new pyridinium glide (9) and the new isoquinolinium glide (14). C --> N Migration of the COOEt group takes place at room temperature, but, at an elevated temperature, reverse N --> C migration of the COOEt group proceeds and ylides 9 and 14 are reconverted into the starting ylides 7 and 12, respectively. (C) 2002 John Wiley Sons, Inc.