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A series of N-benzhydryl protected α-aminophosphonates with α-phenyl, α-(1-naphtyl), α-(9-anthryl) or α-(1-pyrenyl) substituents was synthesized by the Kabachnik–Fields condensation of diphenylmethylamine (benzhydrylamine), the corresponding aryl aldehyde and a dialkyl phosphite under MW irradiation. X-ray studies performed at low temperatures for a few of these α-aminophosphonates confirmed the presence of unusually short intramolecular Cα–Hδ+ ··· δ+H–Cperi contacts.

(S)-α-Phenylethylamine was used in the microwave-assisted Kabachnik-Fields condensation with paraformaldehyde and >P(O)H species, such as dialkyl phosphites, ethyl phenyl-H-phosphinate and diphenylphosphine oxide to provide optically active α-aminophosphonates, α-aminophosphinate and α-aminophosphine oxide, or using a two equivalent quantity of paraformaldehyde and (RO)2P(O)H or Ph2P(O)H, bis(phosphonomethyl)amines and bis(phosphinoylmethyl)amine, respectively. The bis(phosphinoylmethyl)amine served as a precursor for an optically active bidentate P-ligand in the synthesis of a chiral platinum complex.

A family of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides was synthesized by the microwave-assisted solvent-free addition of dialkyl phosphites and diphenylphosphine oxide, respectively, to imines formed from benzaldehyde derivatives and primary amines. After optimization, the reactivity was mapped, and the fine mechanism was evaluated by DFT calculations. Two α-aminophosphonates were subjected to an X-ray study revealing a racemic dimer formation made through a N–H···O=P intermolecular hydrogen bridges pair.

Two dimethyl α-hydroxy-arylmethylphosphonates (aryl = Ph and 2-MeOPh) were subjected to optical resolution via diastereomer complex formation applying the acidic calcium salt of O,O′-dibenzoyl-(2R,3R)-tartaric acid as the resolving agent. The dominating diastereomer complexes, whose structure was determined by single crystal X-ray measurements, were obtained in 96% and 68% diastereomer excess values, respectively. After decomposing the diastereomer formations by extraction, and after recrystallizations, the major enantiomer (S and R, respectively) of the α-hydroxyphosphonates were prepared in enantiomeric excess values of 96% and 68%, respectively. The stereostructure of the two α-hydroxy-arylmethylphosphonates was again established by X-ray measurements. Detailed study on the X-ray data allowed valuable conclusions on the nature of the coordination in the complexes (intermolecular interactions), and on the H-bonding.

The crystal structures of seven α-aryl-α-hydroxyphosphonates synthesized by the Pudovik reaction of substituted benzaldehydes and dialkyl phosphites, namely dimethyl [(hydroxy)(phenyl)methyl]phosphonate, C9H13O4P, dimethyl [(3,4-dimethoxyphenyl)(hydroxy)methyl]phosphonate, C11H17O6P, dimethyl (1-hydroxy-1-phenylethyl)phosphonate, C10H15O4P, dimethyl [1-hydroxy-1-(4-nitrophenyl)ethyl]phosphonate, C10H14NO6P, dibenzyl [hydroxy(2-nitrophenyl)methyl]phosphonate, C21H20NO6P, dibenzyl [(3-chlorophenyl)(hydroxy)methyl]phosphonate, C21H20ClO4P, and dibenzyl [hydroxy(4-methylphenyl)methyl]phosphonate, C22H23O4P, were studied to gain a better understanding of the organization in this type of molecule in the solid state. The crystals obtained for this series of compounds show a balance between C—OH...O=P chain-linked packing and the dimeric types of hydrogen-bond bridges of intermolecular pairs of such functions. The description is based on primary graph-set descriptors. Using graph-set descriptors one level deeper (i.e. secondary graph sets of the C—H...O type) revealed a similarity in the graph-set descriptors, suggesting a fine interplay of substituent- and shape-dependent effects on strong–weak interactions. It seems that the formation of chains or dimers is governed not only by the presence of a tertiary Cα atom, but also by the nature and crowding of the ortho substituents of the α-aryl group.

An efficient resolution method was elaborated for the preparation of (+)-4-chloro-5-methyl-1-phenyl-1,2,3,6-tetrahydrophosphinine oxide using the acidic Ca2+ salt of (-)-O,O-di-p-toluoyl-(2R,3R)-tartaric acid. Crystal structure of the diastereomeric complex was evaluated by single crystal X-ray analysis. Beside this, the absolute P-configuration was also determined by a circular dichroism (CD) spectroscopic study including theoretical calculations. The tetrahydrophosphinine oxide was then converted to the corresponding platinum complex whose stereostructure was investigated by high-level quantum chemical calculations. The Pt complex was tested as a catalyst in the hydroformylation of styrene.

The Kabachnik-Fields condensation was extended using secondary phosphine oxides, such as dibenzylphosphine oxide and bis(4-methylphenyl) phosphine oxide as the P-reactant in reaction with formaldehyde and different primary amines. Besides the alpha-aminophosphine oxides, the corresponding bisproducts, N,N-bis(phosphinoylmethyl)amines were also synthesized under appropriate conditions. The bis(phosphinoyl)amines were then converted to ring platinum complexes after double deoxygenation. The substituent dependence of the energetics of the complexation reaction using bidentate P-ligands, and the stereostructure of a few complexes were evaluated by B3LYP/6-31G(d,p) calculations using the effective core potential (ECP) basis set (SDD). The crystal structure of a few ring Pt species was studied by X-ray analysis. Catalytic activity of the complexes synthesized was investigated in hydroformylation. (C) 2015 Published by Elsevier B.V.

Bannucine is an Aspidosperma alkaloid isolated from the dried leaves of Catharanthus roseus. The molecule is a derivative of vindoline bearing a C10 substituent, a pattern common to the antineoplastic dimeric indole alkaloids of C. roseus. In bannucine, a 2-pyrrolidone moiety is attached at C5′ to the aromatic ring of the vindoline core at C10. In the present work we report the synthesis of bannucine and its 5′-epimer from natural (−)-vindoline using a cyclic N-acyliminium ion intermediate whose N-acylaminocarbinol precursor is synthesized by the partial reduction of succinimide. We also describe the separation and the structural analysis of the two epimers, using among others, single crystal X-ray diffraction methods, in order to clarify the orientation of the proton attached to the C5′ carbon. The in vitro antineoplastic activity of the pure epimers was also investigated, but none of the two substances showed significant activity on the examined tumour cell lines.

A 1-isopropyl-3-phospholene 1-oxide was prepared and the two enantiomers were isolated from the racemate by resolution using optically active TADDOL derivatives or the acidic Ca2+ salts of (−)-O,O-diaroyl-(2R,3R)-tartaric acids. The single crystal X-ray structure of the 1-isopropyl-3-phospholene oxide – spiro-TADDOL 1:2 associate revealed the mode of binding between the host and guest molecules. The role of the interactions between the three molecules was supported not only by the contact data, but also force field and semiempirical calculations. Beside X-ray analysis, the absolute configuration of the P-stereogenic center was also determined on the basis of CD spectroscopy and high level quantum chemical calculations. The racemic and optically active 1-isopropyl-3-phospholenes obtained after deoxygenation were converted to the corresponding borane complexes and Pt(II) complexes. Stereostructure of the latter species was evaluated by high level quantum chemical calculations and the Pt complexes were tested as catalysts in the hydroformylation of styrene.

A series of 1-alkyl-3-methyl-2,5-dihydro-1H-phosphole oxides were converted to the corresponding phosphole oxides that, by the Diels–Alder reaction with N-maleimide derivatives or with another unit of phosphole oxide, yielded trapped phosphole oxides or phosphole oxide dimers, respectively, as new 7-phosphanorbornene 7-oxides. The stereostructures of three derivatives were evaluated by single crystal X-ray analysis. The regio- and stereospecific dimerization was studied by B3LYP/6-31G(d,p) quantum chemical calculations, whose results were in accord with syntheses. Novel mechanistic features were explored. The geometrical data obtained by single crystal X-ray analysis validated the results of quantum chemical calculations, as the deviation was less than 3%.

As an example of acyclic P-chiral phosphine oxides, the resolution of ethyl-(2-methylphenyl)-phenylphosphine oxide was elaborated with TADDOL derivatives, or with calcium salts of the tartaric acid derivatives. Besides the study on the resolving agents, several purification methods were developed in order to prepare enantiopure ethyl-(2-methylphenyl)-phenylphosphine oxide. It was found that the title phosphine oxide is a racemic crystal-forming compound, and the recrystallization of the enantiomeric mixtures could be used for the preparation of pure enantiomers. According to our best method, the (R)-ethyl-(2-methylphenyl)-phenylphosphine oxide could be obtained with an enantiomeric excess of 99% and in a yield of 47%. Complete racemization of the enantiomerically enriched phosphine oxide could be accomplished via the formation of a chlorophosphonium salt. Characterization of the crystal structures of the enantiopure phosphine oxide was complemented with that of the diastereomeric intermediate. X-ray analysis revealed the main nonbonding interactions responsible for enantiomeric recognition.

Efficient synthesis of several new atropisomeric amino alcohols having 1-phenyl-1H-pyrrole skeleton are reported. Steric arrangements of the products were confirmed by a single-crystal X-ray measurement. The consequences of the size of the N-substituents on enantioinduction were examined by employing the enantioselective catalytic addition of diethylzinc to a series of substituted benzaldehydes (yields 91–97%, up to 85% enantiomeric excess). The special effect of the ortho methoxy group of the substrate on the enantioinduction is also interpreted. Chirality 27:216–222, 2015. © 2014 Wiley Periodicals, Inc.

The resolution of 1-i-butyl-3-methyl-3-phospholene 1-oxide was studied applying TADDOL [(−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane], spiro-TADDOL [(−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol], or the acidic and neutral Ca2+ salts of (−)-O,O′-dibenzoyl- and (−)-O,O′-di-p-toluoyl-(2R,3R)-tartaric acid as the resolving agent. The absolute configuration of the P-asymmetric center was determined by circular dichroism spectroscopy and related quantum chemical calculations. In one instance, the single crystal of the diastereomeric complex incorporating i-butyl-3-phospholene oxide and spiro-TADDOL was subjected to X-ray analysis, which suggested a feasible hypothesis for the efficiency of the resolution process under discussion that may be an example for the “solvent-inhibited” resolution.

The resolution methods applying (−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane (“TADDOL”), (−)-(2R,3R)-α,α,α',α'-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol (“spiro-TADDOL”), as well as the acidic and neutral Ca2+ salts of (−)-O,O'-dibenzoyl- and (−)-O,O'-di-p-toluoyl-(2R,3R)-tartaric acid were extended for the preparation of 1-n-butyl-3-methyl-3-phospholene 1-oxide in optically active form. In one case, the intermediate diastereomeric complex could be identified by single-crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by comparing the experimentally obtained and calculated CD spectra. Chirality 26:174–182, 2014. © 2014 Wiley Periodicals, Inc.

1-n-Propoxy-3-methyl-3-phospholene 1-oxide was prepared in optically active form by extending resolution methods applying (−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane (‘TADDOL’) and (−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol (‘spiro-TADDOL’), as well as the acidic and neutral Ca2+ salts of (−)-O,O′-dibenzoyl- and (−)-O,O′-di-p-toluoyl-(2R,3R)-tartaric acid. In one case, the diastereomeric complex could be identified by single crystal X-ray analysis. The absolute P-configuration of the enantiomers of the phospholene oxide was also determined by CD spectroscopy.

The first enzyme-catalyzed kinetic resolution of tert-butyl-3-hydroxy-4-phenylpyrrolidine-1-carboxylate is presented. Enzyme, solvent and temperature optimization resulted in a new resolution method with E = 40 enantioselectivity. The acetate derivative of the (+)-(3S,4R) enantiomer formed while the (−)-(3R,4S) isomer remained intact. Very good enantioselectivities (E > 200) were achieved in the enzyme-catalyzed alcoholysis of the racemic acetate in i-propanol and t-butanol where the (+)-(3S,4R) enantiomer was prepared in pure form (ee > 99.7%). Absolute configuration of the (−)-(3R,4S)-enantiomer was determined by single crystal X-ray diffraction method.

Synthesis, structure determination and in vitro antiproliferative assay of a series of novel ferrocenenyl hydrazones containing 4-halopyridazin-3(2H)-one fragment(s) and three representative N-aryl-substituted (S-p)-ferroceno[d]pyridazinones are presented. The model compounds can be considered as different assemblies of the potential binding sites capable of establishing interactions including hydrogen bonds and pi-pi interactions with the relevant residues of biomolecules. Their in vitro antiproliferative effect was investigated against four tumorous cell lines by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-assay. Our data indicate that bis-hydrazone of 1,1'-diformylferrocene carrying N-benzyl substituents and a chloropyridazinyl-substituted ferroceno[d]pyridazinone display significant activity on each cell lines investigated. The efficiency of the latter drug candidate and one N-benzyl mono-hydrazone on A2870 cell line is comparable to that of cisplatin. The constitution and relative configuration of the model compounds were established by H-1, C-13 and N-15 NMR methods. The structures of a mono-and bis-ferrocenylhydrazone containing 4-bromopyridazinone unit(s) were confirmed by single crystal X-ray diffraction. (C) 2013 Elsevier B.V. All rights reserved.

A series of 2-arylmethylideneferroceno[e]cyclohexanone was prepared by base-catalysed condensation of ferroceno[b]cyclohexanone with a variety of aryl aldehydes including formylferrocene. The decreased reactivity of these novel chalcones towards nucleophic reagents was interpreted by the comparison of DFT reactivity indices calculated for a selection of appropriate models. The conversion of five representative chalcones into ferroceno[g]indazoles of potential biological interest could be achieved by thiosemicarbazide-mediated cyclisation catalysed by hydrochloric acid in ethanol at reflux. The relative configurations of the novel chalcones and ferrocenoindazoles with the elements of planar-, helical- and central chirality were established by NMR methods and single-crystal X-ray diffraction.

TADDOL derivatives and the Ca(2+)-salts of tartaric acid derivatives were found to be versatile and generally applicable resolving agents for the preparation of the enantiomers of P-stereogenic heterocyclic phosphine oxides and phosphinates via the formation of the corresponding diastereomeric molecular and coordination complexes. A few of the diastereomeric intermediates were characterized by single crystal X-ray crystallography to gain insights into the binding mode of the corresponding heterocyclic phosphine oxide ("guest") and the resolving agent ("host") and to study the underlying phenomenon of enantiomeric recognition.

A novel, superbase induced diastereoselective transformation of benzylamino groups containing oxiranes has provided a series of trans-1,2,3-trisubstituted azetidines in good yields. The reaction of the corresponding optically active cis-2,3-disubstituted oxirane yielded the azetidine derivative as a single enantiomer. The structures of the new azetidines were confirmed by NMR spectroscopic methods and, in one case, by single crystal diffraction measurements.

The microwave-assisted double Kabachnik–Fields (phospha-Mannich) reaction of benzylamine and arylamines, two equivalents of paraformaldehyde and the P(O)H reagent, such as dialkyl phosphites, ethyl phenyl-H-phosphinate and diphenylphosphine oxide gave the bis( P(O)CH2)amine derivatives in good yields. The bis(diphenylphosphinoxido) derivatives were converted to the corresponding ring platinum complexes after deoxygenation whose catalytic activity was tested in the hydroformylation of styrene. Crystal structure analysis of one of the complexes reveals interesting correlations between complex structure and solvent inclusion.

Chiral salen complexes with C2-symmetry were prepared by the complexation of a selection of transition metal salts with a novel ligand obtained via controlled diastereoselective diaza-Cope rearrangement of a diimine which was resulted from the condensation 2,2′-[(1R,2R)-1,2-diaminoethane-1,2-diyl]diphenol with formylferrocene. On the effect of air the iron(II)-complex dissolved in DCM underwent oxidation affording a square pyramidal iron(III)-complex with coordinated chlorine atom in the apical position. It was also found that the two ferrocenyl groups present in the cobalt(II)-complex remained intact in the course of iodine-mediated oxidation leading a diamagnetic cobalt(III)-complex. The structures of the new compounds were established by single crystal x-ray diffraction as well as IR 1H-, 13C- and 15N NMR spectroscopy.

An efficient synthetic method has been developed for the preparation of a new family of atropisomeric amino alcohols with 1-phenylpyrrole backbone. The synthesis is based on the different reactivities of the two carboxylic groups in optically active 1-[2-carboxy-6-(trifluoromethyl)phenyl]-1H-pyrrole-2-carboxylic acid (1). The chemical structures of the key intermediates were confirmed by spectroscopic methods and single crystal X-ray diffraction measurements. The very first application of a new optically active amino alcohol as catalyst for the enantioselective addition of diethylzinc to benzaldehyde demonstrated the practical usefulness of atropisomeric compounds in which there are six-atom chains between the two functional groups. Chirality 24:532–542, 2012. © 2012 Wiley Periodicals, Inc.

A novel, highly efficient method has been developed for the separation of the optical isomers of 1-[2-carboxy-6-(trifluoromethyl)phenyl]-1 H -pyrrole-2-carboxylic acid with methyl ( R )-2-phenylglycinate. The structural aspects of chiral discrimination have been discussed via comparison of the molecular structures and the packing energies of the diastereoisomeric salts determined by single crystal X-ray diffraction measurements. Reciprocal resolution and a new, highly efficient second order asymmetric transformation of racemic methyl 2-phenylglycinate with the pure enantiomer of the previously resolved atropisomeric carboxylic acid are also reported.

The importance and reactivity consequences of the double diastereocontrol in noncovalent bifunctional organocatalysis were studied. The results suggest that the bifunctional thioureas can have synthetic limitations in multicomponent domino or autotandem catalysis. Nevertheless, we provided a means to exploit this behavior and used the configuration of the chiral catalyst as a control element in organo-sequential reactions.

Site selective mono- and dimetalation methods have been developed for the functionalization of 1-[(1,1′-biphenyl)-2-yl]-1H-pyrrole. Optical resolution of the prepared 1-[(3-carboxy-1,1′-biphenyl)-2-yl]pyrrole-2-carboxylic acid provided new atropisomeric 1-arylpyrrole derivatives. The absolute configuration of the pure dicarboxylic acid enantiomers was determined by single crystal X-ray diffraction and CD spectroscopy. Chirality 2009. © 2009 Wiley-Liss, Inc.

Cyclization of 1,5-bis(ferrocenylmethylidene)thiocarbonohydrazide with DMAD afforded diastereomeric dimethyl-thiazole-4,5-dicarboxylates. The cis -isomer undergoes ring opening and recyclization to a thiazolone derivative. A further thiazolone was obtained from this precursor with ethyl chloroacetate employing a bifunctional organocatalyst. Due to its propensity to dehydrogenation evidenced by DFT calculations, the studied thiocarbonohydrazide underwent oxidative cyclizations under different conditions to yield a 1,3,4-thiadiazole and a 1,2,4-triazole derivative, respectively. Thermal isomerisation of 1,3,4-thiadiazole into 1,2,4-triazole was also observed. The DMAD-mediated cyclizations of the S-metylated thiocarbonohydrazide and the 1,5-bis(ferrocenylmethylideneamino)guanidine gave 1,2,4-triazole derivatives and a 4-pyrimidone, respectively. The structure of the new compounds was established by IR and NMR spectroscopy, including HMQC, HMBC and DEPT measurements. The solid state structure of a triazole was revealed by single crystal X-ray analysis.

An efficient synthesis and resolution of (±)-1-(2-carboxymethyl-6-ethylphenyl)- 1H -pyrrole-2-carboxylic acid has been developed for the preparation of novel optically active atropisomers. The ee values were measured by a 1 H NMR spectroscopic method using quinidine as the chiral complexing agent. Absolute configurations of the separated enantiomers were determined using single crystal X-ray diffraction measurements of both the disodium salt and the ( R )-1-phenylethylamine salt of the enantiomerically pure dicarboxylic acid, separately. The analysis of the CD spectra with the aid of TD-DFT quantum chemical calculations confirmed the assignment of configurations.

The inhibition of cyclooxygenase enzymes plays an important role in the treatment of inflammatory diseases. N-Hydroxy-4-(5-methyl-3-phenylisoxazol-4-yl)benzenesulfonamide (3)-a primary metabolite of the highly selective COX-2 inhibitor valdecoxib-was synthesized and stabilized as its monohydrate (3a.H(2)O). The anti-inflammatory properties of 3a.H(2)O were investigated in carrageenan-induced edema and in acute and chronic pain models. Based on our biological investigation, we conclude that N-hydroxy-valdecoxib 3a is an active metabolite of valdecoxib.

A new and general synthesis of the linearly fused [1,2,4]triazolo[1,5-b]isoquinoline ring system starting from 2,3-diaminoisoquinolinium salts has been elaborated. Starting compounds bearing an alkyl group in position 4 easily reacted with aldehydes to yield the cyclized products. In the case of a lack of electron donating group in position 4 (e.g., unsubstituted or 4-cyano substituted diamino derivatives) a Dimroth rearrangement took place under the same reaction conditions to yield 3-isoquinolylhydrazones. The mechanism of this unexpected transformation has been verified by isotope labelling experiments. Clarification of the reaction mechanism allowed finding proper reaction conditions to eliminate the rearrangement route, and thus, to perfect successful ring closure to the fused triazoles.

The enantiomers of 1-aryl-, 1-alkyl- and 1-alkoxy-3-methyl-3-phospholene 1-oxides were separated in good yields and in high enantiomeric excesses (up to > 99% ee) by resolution via formation of diastereomeric complexes with (–)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane (TADDOL) or (–)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol.

The antipodes of 1-aryl-, 1-alkyl- and 1-alkoxy-3-methyl-3-phospholene 1-oxides 1a–h and 1-phenyl-3-methyl-3-phospholene 1-sulfide 1i were separated in good yields and high enantiomeric excesses (up to >99% ee) by resolution via formation of diastereomeric complexes with either (−)-(4R,5R)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane 2 (TADDOL) or (−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol 3. The stereostructure of the supramolecular formations and the absolute configurations of the 3-phospholene oxides 1a, 1e and 1f were elucidated by single crystal X-ray crystallography. CD spectroscopy was also useful in determining the absolute configurations of some phospholene oxides 1b, 1c, 1g and 1h.

Single crystal X-ray structure analysis of 3-diphenylphosphinoxido-1-phenyl-4-chloro-1,2,3,6-tetrahydrophosphinine oxide (1)·H2O provided experimental proof for a transannular PO⋯HC type interaction. The embedded water molecule bridges two PO groups of the P-heterocycle via intra-associate hydrogen bonds. Theoretical calculations showed that the conformation of the hetero-ring alters only slightly due to the presence of the water molecule. Thus 1 behaves as a preorganized host molecule for water, presenting a minimum ring-size molecular environment for water binding.

TADDOL derivatives and the Ca(2+)-salts of tartaric acid derivatives were found to be versatile and generally applicable resolving agents for the preparation of the enantiomers of P-stereogenic heterocyclic phosphine oxides and phosphinates via the formation of the corresponding diastereomeric molecular and coordination complexes. A few of the diastereomeric intermediates were characterized by single crystal X-ray crystallography to gain insights into the binding mode of the corresponding heterocyclic phosphine oxide ("guest") and the resolving agent ("host") and to study the underlying phenomenon of enantiomeric recognition.

The antipodes of 1-phenyl-3-methyl-3-phospholene 1-oxide 1a were separated in good yield and in high enantiomeric excess (∼99% ee) by resolution via formation of diastereomeric complexes with (4R,5R)-(−)- and (4S,5S)-(+)-4,5-bis(diphenylhydroxymethyl)-2,2-dimethyldioxolane 2 (TADDOL) or (−)-(2R,3R)-α,α,α′,α′-tetraphenyl-1,4-dioxaspiro[4.5]decan-2,3-dimethanol 3. The method was also suitable for the resolution of the 1-ethoxy-3-phospholene derivative 1b, suggesting that our novel procedure may be of general value, both for the resolution of chiral phosphine oxides and phosphinates.

New host molecules, 1(a, b) and 2(a, b), each containing two bulky borneol or fenchol terminal groups attached to ethynylene central units of different lengths, have been synthesized. Their properties of crystalline inclusion with a variety of organic guests, including alcohols, amines and dipolar aprotic compounds, are reported (26 examples of inclusion compounds). The crystal structures of four selected inclusion compounds have been determined by X-ray diffraction, showing varied modes of supramolecular interaction dependent on the host and guest constitutions. Varying stoichiometries, host–guest compositions and appearance of disorder all indicate match/mismatch phenomena in the molecular recognition process under the build-up of macroscopic crystals. All these crystalline associations are organized through the hydrogen bonding capability of the host hydroxyl groups, thus corresponding to coordinato-clathrate scenery.

The N,N-dimethylbenzyl ammonium maleate salt (1) undergoes chiral crystallization while its oxalate counterpart (2) yields to a centrosymmetric crystal. The difference is related to the motif formation in the chiral vs. the centrosymmetric crystal. The X-ray treatment is complemented by a CSD data bank search of the C–H⋯O geometry of –CH2–N moieties.

Starting from acridono-18-crown-6 ligand 1 ( Fig. 1 ) seven new proton-ionizable chromogenic and fluorogenic ionophores 2–8 ( Fig. 1 ) containing NO2 group(s) and/or Br or Cl atom(s) in the aromatic rings were prepared by electrophilic substitution. The precursor macrocycle 1 was obtained by a modification of the reported procedure which made chromatography unnecessary in purification and gave higher yield. X-ray crystallographic studies of the complexes of acridono-18-crown-6 type ligands 1 , 2 , 3 , 6 and 8 show that the proton-ionizable units are in the acridone tautomeric form and that the ligands invariably bind a water molecule in their cavities by multipodal hydrogen bonding. In two cases ( 6 and 8 ) an additional DMF solvent molecule is also bound at the crown perimeter in the solid state.

Highly lipophilic enantiomerically pure pyridino- and pyridono-18-crown-6 type ligands containing four stereogenic centers to which butyl or butoxymethyl groups are attached have been synthesized. X-Ray analysis of the (R)-1-phenylethylammonium and benzylammonium perchlorate complexes of the unsubstituted pyridono ligand revealed, that, in contrast to the free ligand, in the complex the hydroxypyridine tautomer is present.

Facile chemical synthesis of the natural chiral-pool-derived host 1 and its subsequent crystallization ("supramolecular synthesis") from different solvents yielded crystalline assemblies. Crystal structure determinations of five of the so formed solvent-inclusion compounds (1 a-1 e) reveal hexagonal symmetries in four cases. The structural characteristics of these chiral host-guest ensembles with varying stoichiometries can be best described as assemblies formed through intra-pair hydrogen bridges of host molecules into Piedfort pairs of differing complexity. Hitherto undescribed, these Piedfort pairs also form even larger regular assemblies that we designate "Big Mac"-like shapes. In the only nonhexagonal case, six independent host molecules form a huge supramolecular analogue of [6]benzocyclophane, also known as [6]chochin, extending this giant supermolecule through intermolecular hydrogen bonds into macroscopic (mm-size) dimensions. As all these crystals are inherently chiral, and new model systems for solid-state applications can be envisaged.

Examples of a new type of cryptophane molecule incorporating aromatic groups in the bridges (1 - 4) and for the first time, being also supplied with three endo-positional ionizable carboxylic acid function (1) have been synthesized and characterized. The cryptophane triester 2 yielded a solvate (channel inclusion compound) with trichloromethane and water, the X-ray crystal structure of which is reported. The complexation of 1 with low-molecular-weight alcohols in solution was studied, and the liquid-liquid extraction of different metal ions including alkali (Na+, Cs+), alkaline earth (Mg2+, Ca2+, Sr2+, Ba2+), and the lanthanide metal ions Eu3+ and Yb3+ in an extraction system containing metal nitrate buffer/H2O/1/CHCl3 was examined. Molecular modeling calculations of the cryptophanes 1 and 2, and of the Eu3+ complex of 1 were carried out contributing to the discussion.

The chiral monoaza-15-crown-5 lariat ethers anellated to methyl-4,6-O-benzylidene-α- d -glucopyranoside 1a–c showed significant asymmetric induction as phase transfer catalysts in the Michael addition of 2-nitropropane to substituted chalcones. Among the catalysts bearing different side arms at the nitrogen atom, the compound with a phosphinoxidoalkyl side chain 1c proved to be the most effective (max. 78% e.e.). The type of substituent on the chalcone was found to have a very significant influence on both the chemical yield and the enantioselectivity of the reaction. The absolute configuration of the Michael adducts 3b and 3i was determined by chemical methods, while that of 3d was assigned by X-ray crystal structure determination.

1-(4′-Carboxyphenyl)-2-methyl-3-(piperidine-1-yl)-propan-1-one M3 , erythro -1-(4′-carboxyphenyl)-2-methyl-3-(piperidine-1-yl)-propan-1-ol M4 and threo -1-(4′-carboxyphenyl)-2-methyl-3-(piperidine-1-yl)-propan-1-ol M5 , metabolites of the muscle relaxant tolperisone were synthesized in racemic and optically active forms.