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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.

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%.

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.

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.

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.

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.

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.

New chiral host molecules 1 and 2 involving a bulky terpenoid unit and aromatic ethyne spacer groups were synthesized using Pd-catalyzed cross-coupling reactions of (+)-2α-ethynyl-2β-hydroxybornane (4) or (+)-2α-ethynyl-2β-hydroxyfenchane (5) with 9,10-dibromoanthracene. Host compounds 1 and 2 from crystalline inclusions with 1-methoxy-2-propanol (3) in 1:1 and 1:2 stoichiometry, respectively. In the case of 1, complete enantiomer resolution (ee > 99%) of 3 is effected in one cocrystallization step. However, constitutional isomer 2 failed in the enantiomer separation of 3, which might be explained due to the different crystal lattice buildup of these cocrystals. Chirality 9:203–210, 1997. © 1997 Wiley-Liss, Inc.

Structural models resulting from the x-ray crystal structure determination of small molecules are shown to be closely mimicking some of the protein structure and function features. Crystals of inclusion compounds, a special type of solid molecular associates, lend special support to such a view. They are inherently suited for such modelling purposes due to easily visible association and molecular recognition effects. It is envisaged that combination of the analysis of high-resolution small molecule crystallographic models and those of protein structures will yield to further fruitful analogies.

Preparation of P-amino-3-phosphabicyclo[3.1.0]-hexane 3-oxides either by addition of dichlorocarbene to the double bond of 1-amino-2,5-dihydro-1H-phosphole 1-oxides or by substitution of the P-chloro derivative of the bicyclic system was accomplished. Two different diastereomers are obtained by the two approaches; their 13C NMR spectra were interpreted on the basis of the P-ethoxy isomers, whose structures were confirmed by X-ray analysis. The P-hydroxy adduct was also prepared, and it was found that intermolecular OH … O hydrogen bonding connects the molecules together in the solid phase. This effect eliminates the possibility of diastereoisomerism, as was also observed in the case of P-hydroxy tetrahydrophosphinine oxides. Thermolysis of the P-hydroxy adduct is a better way to synthesize 1-hydroxy-1,2-dihydrophosphinine oxides than by hydrolysis of the phosphinic chlorides.

The four studied semi-rigid fluorenol derivatives differ only in the size of the 9-substituents. All four compounds crystallize with two molecules per asymmetric unit and with relatively low crystallographic symmetry [P1 for the 9-methyl derivative (1) and P21/n for the 9-(1-naphthyl) (3) and 9-(2-biphenylyl) (4) derivatives]. Crystal data: 1, a = 8·779(1), b = 11·570(1), c = 11·747(1), α = 91·197(5), β = 104·345(4), γ = 105·848(6)° 2, a = 8·425(1), b = 13·819(1), c = 23·902(2)A, β = 95·87(1)° 3, a = 15·679(4), b = 8·567(2); c = 23·884(17)A, β = 92·60(6)° 4, a = 7·770(6), b = 33·766(10), c = 13·649(4)A, β = 95·30(1)°. Nevertheless, the packing modes are different. The 9-methylfluoren-9-ol molecules, forming H-bonded tetramers with full H-bond saturation, give rise to the lowest packing coefficient among the four compounds. The crystals of the 9-phenyl derivative are built up of H-bonded dimers, whereas those of the bulky 9-naphthyl and 9-diphenylyl derivatives consist of single molecules only. The latter two compounds, however, have a denser packing than the two that contain H-bonded aggregates. The crystal structures are held together mainly by ordinary Van der Waals forces. In the case of 9-biphenylyfluoren-9-ol, the structure seems to be stabilized also by weak H-bond-type interactions from the alcoholic hydroxyl group to the π-electron cloud of an aromatic ring in the neighbouring molecule the O…centroid distances are 3·182(3) and 3·248(4)A, and in the 9-naphthyl derivative the OH groups are involved in some short (˜3·3A) intermolecular approach, possibly indicating an electrostatically favourable packing for the compound.

The synthesis of some (methyl)glyoxal 1,2-bis(acylhydrazones) (1, 3–6) and their cyclization into the title compounds (7–10) under acetylating conditions are described. The stereostructures of the new bi-heterocyclic diastereomers were studied by 1H- and 13C-NMR measurements as well as by X-ray analysis.

The first crystal structure of a heterocalix[9]arene host molecule created from six benzimidazol-2-one and three p-methylanisole units displays guest binding via a cascade of interactions of the two acetone and two dichloromethane guest molecules with the host and with each other as well.

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.

Seven new hexahelicenes (3−7, 9, 10) containing different functional group substituents have been synthesized and, in three cases (4, 8, 10), optically resolved. Optical rotations were measured and CD spectra are reported. X-ray crystal structures of the helicenes 1, 3, 4, 8, and 9 have been determined, of which 4 represents a 1:1 clathrate with acetone. These show a concerted interplay of C−H···O, C−H···π, and π···π supramolecular interactions in the packings, mostly yielding stacks of molecules (1, 3, 4, 8). Statistical analysis of the molecular dimensions in these and related crystal structures was carried out in order to identify potential parameters relevant to macroscopic phenomena, including optical rotation. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

The chiral monoaza-15-crown-5 type lariat ethers 1 and 2 derived from α- d -glucose and from d -mannitol, respectively, have been applied as phase transfer catalysts in the enantioselective Michael addition of 2-nitropropane to aromatic 3b–c and heteroaromatic 3d–h chalcone analogues. Among the catalysts, the glucose-based 1c with a phosphinoxidobutyl side arm proved to be the most effective, it inducing 34% e.e. for 4b, 59% e.e. for 4c, 80% e.e. for 4d, 64% e.e. for 4e, 17% e.e. for 4f. Catalyst 1a having 3-hydroxypropyl substituent resulted in 81% e.e. for compound 4g. The formation of the (+)-(S)-enantiomer of 4 was preferred using crown ethers 1a–c, while the (−)-(R)-enantiomer was in excess with catalyst 2. The absolute configuration of the Michael adduct 4d was determined by single-crystal X-ray analysis.

Das vollstandige Manuskript dieser Zuschrift erscheint in: Angew. Chem. Suppl. 1982, 1373. DOI: 10.1002/ange.198213730

Bs wird eine neue Methode zur Herstellung der Isomeren A und B der Kronenverbindung 3 in einer Zweiphasenreaktion beschrieben. Aus dem Isomer 3B werden die Derivate 5 unterschiedlicher Loslichkeit und komplexbildender Eigenschaften hergestellt. Synthesis and Formation of Complexes of Crown Ethers from Methyl 4,6-O-Benzylidene-α-D-glucopyranoside A new method for the synthesis of the isomers A and B of the crown ether 3 in a two phase system is described. Starting from 3B the derivatives 5 with different solubility and complex forming characteristics have been prepared.

A strategy has been developed for the design, synthesis, and testing of new clathrate hosts that possess relationship complementarity to specific guest-compounds.