Chelates of fluoroalkyl containing enaminoketones

The structure and areas of practical application of fluoroalkyl containing enaminoketone chelates with d-metals are reviewed. Synthesis of ligands and the routes to the regioisomeric enaminoketones are also considered.     

Probing electronic and regioisomeric control in an asymmetric Henry reaction catalyzed by camphor-imidazoline ligands

Starting from (R)-camphordiamine, 13 new camphor-annulated imidazoline ligands are synthesized in good yields as two regioisomeric series. Yields of up to 94% and good enantioselectivities up to 67% are achieved for the copper(II)-catalyzed Henry reaction giving the product stereoselectively according to the regioisomer used.     

Synthesis of a series of vicinal diamines with potential biological activity

A broad range of vicinal diamines based on styrene oxide are synthesisedvia mixtures of regioisomeric amino alcohols. The ring opening of the intermediate aziridinium ions by primary amines proceeds with high regioselectivity, leading to the target diamines as single regioisomers for all reaction series. The compounds are of potential biological interest as ligands for cisplatin analogues. Anticancer activity tests of both groups of compounds are in progress.     

Chromatographic and spectroscopic methods of identification for the side-chain regioisomers of 3,4-methylenedioxyphenethylamines related to MDEA,MDMMA, and MBDB

Three regioisomeric 3,4-methylenedioxyphenethylamines having the same molecular weight and major mass spectral fragments of equivalent mass have been reported as components of clandestine drug samples in recent years. These drugs of abuse are 3,4-methylenedioxy-N-ethylamphetamine, 3,4-methylenedioxy-N,N-dimethylamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine. These three compounds are a subset of a total of ten regioisomeric 3,4-methylenedioxyphenethylamines of molecular weight 207, yielding regioisomeric fragment ions of equivalent mass (m/z 72 and 135/136) in the electron impact mass spectrum. The specific identification of one of these compounds in a forensic drug sample depends upon the analyst's ability to eliminate the other regioisomers as possible interfering or coeluting substances. This paper reports the synthesis, mass spectral characterization, and chromatographic analysis of these ten unique regioisomers. The ten regioisomeric methylenedioxyphenethylamines are synthesized from commercially available precursor chemicals. The electron impact mass spectra of these regioisomers show some variation in the relative intensity of the major ions with only one or two minor ions that might be considered side-chain specific fragments. Thus, the ultimate identification of any one of these amines with the elimination of the other nine regioisomeric substances depends heavily upon chromatographic methods. Chromatographic separation of these ten uniquely regioisomeric amines is studied using gas chromatographic temperature program optimization.     

The Sharpless asymmetric aminohydroxylation reaction: optimising ligand/substrate control of regioselectivity for the synthesis of 3- and 4-aminosugars

An investigation of the factors responsible for the sense and magnitude of regioselectivity in the Sharpless asymmetric aminohydroxylation (AA) has been conducted. Theoretical investigations of ligand-osmium binding geometry and experimental investigations of the Sharpless AA reaction on a series of functionalized pent-2-enoic acid ester substrates demonstrate that the opposite regioselectivity afforded using PHAL and AQN ligands results from a change in substrate orientation with respect to the catalyst. Two distinct ligand binding domains within the catalyst have been proposed that undergo attractive interactions with the substrates. Selective access to each of the four potential regio- and stereo-isomeric AA products could be achieved through the appropriate choice of ligand and substrate. These results have been applied toward the efficient stereoselective synthesis of naturally occurring and regioisomeric 3- and 4-aminosugar derivatives.     

Regioisomeric differentiation of 2,3- and 3,4-methylenedioxy ring-substituted phenylalkylamines by gas chromatography/tandem mass spectrometry

Numerous abused drugs of the 3,4-methylenedioxymetamphetamine (MDMA; Ecstasy; N-methyl-1-(3,4-methylenedioxyphenyl)-2-propaneamine) type and various alkyl chain- and aromatic ring-substituted isomers give very similar electron ionization (EI) mass spectra. This seriously affects the analysis of especially ring regioisomeric drug variants. Using collision-induced dissociation (CID) (argon) under EI and chemical ionization, the mass spectra of 18 2,3- and 3, 4-methylenedioxy ring-substituted phenylethylamines were recorded. These techniques permitted an unequivocal differentiation of all studied ring regioisomeric methylenedioxyphenylethylamines. CID mass spectrometry therefore appear to be a reliable tool to establish the kind of ring substitution pattern in regioisomeric methylenedioxyphenalkylamines. Copyright 2000 John Wiley & Sons, Ltd.     

Asymmetric peroxidation of prochiral allylic and benzylic compounds with tert-butyl hydroperoxide and chiral bisoxazoline–copper complexes

The first enantioselective peroxidation of prochiral allylic and benzylic C-H compounds by the use of chiral bisoxazoline-copper(I) complexes, generated in situ from the ligands 3 and 4a-d, and t-BuOOH as oxidant is reported. Cyclohexene 1, cyclopentene 5, -angelica lactone 7, allylbenzene 9 and 2-phenylbutane 11 were converted into the optically active allylic and benzylic tert-butyl peroxides 2, 6, 8, 10a and 12 in good yields and ee values of 4-20%. Oxidations of 1-substituted 1-cyclohexenes 13a-c led to mixtures of regioisomeric peroxides 16a-c, 17a-c and 18a-c with different regio- and enantioselectivities, depending on the 1-substituent and the ligand used. The highest ee values (up to 84%) were observed for (S)-3-tert-butylperoxy-1-methyl-1-cyclohexene 17a.     

Novel capsular aggregates from flexible tripodal triureas with C(s) symmetry

Tris(2- and 3-ureidobenzyl)amines with C(s) symmetry self-assemble in solution forming mixtures of regioisomeric capsular aggregates, one of which is chiral and the other centrosymmetric. Under certain conditions, a predominance of the centrosymmetric regioisomer is found before equilibrium, that is, a mixture close to the statistical ratio of the two species is reached. In the solid state, there is a preference for the centrosymmetric capsules. Molecular models of both regioisomeric aggregates have been built and analyzed for comparison. Guests inside capsules formed by self-assembly of desymmetrized tris(3-ureidobenzyl)amines feel different magnetic environments, depending on whether they are inside a chiral or an achiral regioisomeric container. Of special significance are the experiments with a more flexible triurea endowed with an ureidopropylic arm, which self-assembles with the same efficiency as the more rigid tris(ureidobenzyl)amines.     

Novel Capsular Aggregates from Flexible Tripodal Triureas with Cs Symmetry

Tris(2‐ and 3‐ureidobenzyl)amines with C_s symmetry self‐assemble in solution forming mixtures of regioisomeric capsular aggregates, one of which is chiral and the other centrosymmetric. Under certain conditions, a predominance of the centrosymmetric regioisomer is found before equilibrium, that is, a mixture close to the statistical ratio of the two species is reached. In the solid state, there is a preference for the centrosymmetric capsules. Molecular models of both regioisomeric aggregates have been built and analyzed for comparison. Guests inside capsules formed by self‐assembly of desymmetrized tris(3‐ureidobenzyl)amines feel different magnetic environments, depending on whether they are inside a chiral or an achiral regioisomeric container. Of special significance are the experiments with a more flexible triurea endowed with an ureidopropylic arm, which self‐assembles with the same efficiency as the more rigid tris(ureidobenzyl)amines.     

Hexa-Coordinated Silicon Complexes Derived from Regioisomeric Aminotriphenylethanols and Their use as Dopants for Liquid Crystals

Abstract

Tridentate imine ligands that are obtained from the chiral, regioisomeric amino alcohols 2-amino-1,1,2-triphenyethanol and 2-amino-1,2,2-triphenylethanol serve for the formation of bis-chelated silicon complexes. Whereas the complex based on the former amino alcohol is obtained as a diastereomeric mixture, the complex that is derived from 2-amino-1,2,2-triphenylethanol forms in a completely diastereoselective manner, and its configuration is determined as (A,R,R), according to a crystal structure analysis. The new silicon complexes are found to be efficient dopants for the conversion of nematic liquid crystals into cholesteric phases.

GRAPHICAL ABSTRACT     

Tuning haptotropic rearrangements of arene-chromium complexes: steric and electronic effects of phosphorus coligands

(Eta6-arene)tricarbonylchromium 2 was synthesised by [3+2+1] benzannulation of the Fischer carbene complex 1 and converted to the thermodynamically more favorable regioisomer 3 by haptotropic metal migration. Photo-induced ligand-exchange reactions in both regioisomers with triphenylphosphine, triphenylphosphite, trimethylphosphine, and trimethylphosphite afforded dicarbonyl(phosphine or phosphite)arene complexes 4-11. The regioisomers were separated by high-performance liquid chromatography (HPLC), and kinetic analyses of the thermo-induced haptotropic metal shift were performed with regioisomers 4, 6, 8, and 10. The kinetic parameters were compared with those obtained for the parent tricarbonyl complex 2 and were discussed in terms of the steric and electronic properties of the phosphorus ligands by applying a quantitative analysis of ligand effects (QALE). The molecular structures of regioisomeric PPh3 and P(OPh)3 complexes 4/5 and 6/7 as well as of P(OMe)3 complex 10 have been established by single-crystal X-ray analysis.     

Synthesis of chromanyl and dihydrobenzofuranyl piperazines

The synthesis of a series of regioisomeric chromanyl and dihydrobenzofuranyl piperazines is described.     

Mass spectrometric analysis of four regioisomers of F2-isoprostanes formed by free radical oxidation of arachidonic acid

F₂-isoprostanes are complex metabolites of arachidonic acid generated via nonenzymatic free radical oxidation and are isomeric to prostaglandin F_2α, enzymatically produced by prostaglandin H₂ synthase. In theory, four distinct regioisomeric families are possible. These regioisomeric families have a common 1,3-diol cyclopentane structural feature, but differ by the comparative length of two attached alkyl chains and the position of a third hydroxyl group. Eight synthetic PGF_2α isomers were found separable by capillary gas chromatography (GC) and reversed-phase high-performance liquid chromatography (HPLC). Electrospray ionization tandem mass spectrometry was used to detect the elution of these isomers from the HPLC column by monitoring the characteristic loss of 44 u (C₂H₄O) from the 1,3-diol cyclopentane ring. Catalytic reduction, derivatization, and electron ionization mass spectrometric techniques were used to obtain definitive information as to the location of the side chain hydroxyl position in these isomers through abundant α-cleavage ions. Free radical oxidation of arachidonic acid was used to generate a complex mixture of F₂-isoprostanes, which were separated by HPLC and capillary GC. Members of each of the four specific regioisomeric isoprostane families could be identified in this mixture from the predicted α-cleavage ions. Although many epimers within a single family type could be separated, the four regioisomeric families were substantially superimposed in their HPLC and GC elution. The Type I and Type IV regioisomers were the major F₂-isoprostane products, but the complexity of the isomers required more than a simple GC-mass spectrometry assay to precisely identify a particular stereoisomer within a regioisomeric family (e. g., 8-epi-PGF_2α). Type I F₂-isoprostanes are unique noncyclooxygenase products and may be more specific targets to measure lipid peroxidation in vivo.     

A study of the scope and regioselectivity of the ruthenium-catalyzed [3 + 2]-cycloaddition of azides with internal alkynes

[3 + 2]-Cycloadditions of alkyl azides with various unsymmetrical internal alkynes in the presence of CpRuCl(PPh3)2 as catalyst in refluxing benzene have been examined, leading to 1,4,5-trisubstituted-1,2,3-triazoles. Whereas alkyl phenyl and dialkyl acetylenes undergo cycloadditions to afford mixtures of regioisomeric 1,2,3-triazoles, acyl-substituted internal alkynes react with complete regioselectivity. In addition, propargyl alcohols and propargyl amines were found to react with azides to afford single regioisomeric products.     

Acid-catalyzed intramolecular ring-opening reactions of cyclopropanated oxabenzonorbornadienes with alcohol nucleophiles

An investigation of intramolecular ring-opening reactions of various cyclopropanated oxabenzonorbornadienes (CPOBDs) with alcohol nucleophiles is reported, which forms two regioisomeric products in good yields. The effect of various tether lengths was explored, wherein increasing the alcohol tether length to 4 or 5 carbons exclusively generated Type 3 products in good yield, while C-1-hydroxymethyl substituted CPOBD formed a 1,3,5-cycloheptatriene derivative in excellent yield. Electron donating arene and electron withdrawing C-5-bridgehead substituents formed Type 3 major products, whereas electron withdrawing arenes and electron donating C-5 substituents preferentially afforded Type 2 compounds. A mechanism is also proposed for the formation of both regioisomeric products.     

Bis-chelated imine-alkoxytitanium complexes: novel chiral dopants with high helical twisting power in liquid crystals

Enantiomerically and diastereomerically pure bis-chelated imine-alkoxytitanium complexes 6 and 7 have been synthesized and used as chiral dopants for converting nematic into cholesteric phases. The dopants were tested in mainly commercially available nematic liquid crystalline compounds or mixtures: LC1 (BASF), ZLI-1695 and ZLI-1840 (Merck), as well as N-(4-methoxybenzylidene)-4'-butylaniline (MBBA). The values of the helical twisting power (HTP) were determined by the Grandjean-Cano method. Exceptionally high helical twisting powers were obtained. Thus, the titanium complex 6 h displayed a HTP value of 740 microm(-1) in MBBA, the highest HTP value reported. The helical twisting power has been found to depend strongly on the structure of the nematic phase and the substitution pattern of the chiral ligand in the titanium complexes 6 and 7. Crystal structure analysis of 6 f confirmed the A,R,R configuration of the metal complex. The chiral imine ligands 4 and 5 were derived from the regioisomeric amino alcohols 1 and 2.     

Gas chromatography-mass spectrometry analysis of regioisomeric ring substituted methoxy methyl phenylacetones

The methoxy methyl phenylacetones share an isobaric relationship (equivalent mass but different elemental composition) to the controlled precursor substance 3,4-methylenedioxyphenylacetone. The 10 methoxy methyl phenylacetones as well as the methylenedioxyphenylacetones show essentially equivalent mass spectra with major fragment ions at m/z 135 and 43. Those methoxy methyl phenylacetones with the methoxy group substituted ortho to the benzylic cation in the m/z 135 ion show a further fragmentation to lose formaldehyde (CH2O) and yield a significant ion at m/z 105. The loss of formaldehyde from the ortho methoxy benzyl cation was confirmed using commercially available regioisomeric 2-, 3-, and 4-methoxyphenylacetones. The 10 regioisomeric methoxy methyl phenylacetones were prepared from the appropriately substituted benzaldehydes. Complete gas chromatographic resolution of all ten regioisomeric ketones was obtained on a stationary phase containing modified beta-cyclodextrin. Using the cyclodextrin containing phase, the ortho methoxy-substituted ketones (K1-K4) eluted before the meta-methoxy-substituted ketones (K5-K8) and the para-methoxy-substituted ketones (K9-K10) showed the greatest affinity for the stationary liquid phase and eluted last. Complete separation of the 10 ketones was not obtained on Rtx-1 and Rtx-200 columns.     

Approaches to novel AB heteroaromatic polyamides based on cyanoimidazoles

We report the synthesis of several AB monomers based on 2-amino-4,5-dicyanoimidazole. Polymerization of the monomers to poly(imidazoleamide)s, by several methods is described. Amino acids 2-amino-4-cyano-1-methyl-5-imidazolecarboxylic acid and 2-amino-5-cyano-1-methyl-4-imidazolecarboxylic acid were prepared by mono-ethanolysis of 2-amino-4,5-dicyanoimidazole followed by methylation of the 1-nitrogen. The resulting regioisomeric mixture of ethyl esters was separated by fractional crystallization and hydrolyzed to the desired amino acids. The regioisomeric structure was determined by NOE studies of the decarboxylated amino acids. The corresponding acid chlorides were prepared with thionyl chloride and isolated as the HCl salts. Activated esters were prepared by reacting the acid chlorides with alcohols such as 1,1,1-trifluoroethanol and 2-chlorophenol. Model compounds were prepared by the acylation of aminocyanoimidazoles but yields were low. The low nucleophilicity of the aminocyanoimidazolecarboxylic acids was partially overcome by the use of the acylation catalyst 4-dimethylaminopyridine (DMAP) and the activating agent silicon tetrachloride. The acid chlorides were polymerized in amide solvents such as hexamethyl phosphoramide with pyridine and DMAP. A copolyamide consisting of both regioisomers was prepared from a regioisomeric mixture of the acid chlorides. In addition, aminolysis of 2-chlorophenyl 2-amino-4-cyano-1-methyl-5-imidazolecarboxylate resulted in a low yield of poly(imidazoleamide). Poly(imidazoleamide)s were red to tan which suggest conjugation along the polymer backbone. The solubility of the polyamides varied from amide solvents to sulfuric acid depending on the regioisomeric structure and molecular weight. The molecular weight of the heteroaramids was in the range from 1500 to 4000 based on viscosity measurements in sulfuric acid. The poly(imidazoleamide)s were thermally stable in excess of 300°C under air and nitrogen atmosphere. © 1993 John Wiley & Sons, Inc.     

Complex-induced proximity effects. Temperature-dependent regiochemical diversity in lithiation-electrophilic substitution reactions of N-BOC-2-azabicyclo[2.1.1]hexane. 2,4- and 3,5-methanoprolines

[reaction: see text] Azabicycle 4 and sec-butyllithium/TMEDA afford the C(1) bridgehead alpha-lithio anion at 0 degrees C. Anion quenching with carbon dioxide, methyl chloroformate, or DMF provide the bridgehead acid 8a (N-BOC-2,4-methanoproline), ester 8b, or aldehyde 8c, respectively. By contrast, at -78 degrees C these same reagents give a mixture of regioisomeric methylene and bridgehead anions whose quenching leads to mixtures of regioisomeric methylene and bridgehead acids 6a/8a, esters 6b/8b, or aldehydes 6c/8c, respectively. The previously unknown 3,5-methanoproline was prepared as its N-BOC methyl ester 6b.     

New insights on the asymmetric hydroboration of perfluoroalkenes

Enantioselective access to Markovnikov regioisomeric perfluoroalcohols is achieved in the presence of chiral cationic rhodium complexes and specific hydroborating reagents.