Conformational change induced by hydration: trans‐dichloro­bis­[(1R,2R,3R,5S)‐(–)‐isopinocampheylamine]palladium(II) and trans‐dichloro­bis[(1S,2S,3S,5R)‐(+)‐isopinocampheylamine]palladium(II) hemihydrate

The title compounds, trans‐dichloro­bis[(1R,2R,3R,5S)‐(−)‐2,6,6‐trimethyl­bicyclo­[3.1.1]heptan‐3‐amine]palladium(II), [PdCl₂(C₁₀H₁₉N)₂], and trans‐dichloro­bis[(1S,2S,3S,5R)‐(+)‐2,6,6‐trimethyl­bicyclo­[3.1.1]heptan‐3‐amine]palladium(II) hemihydrate, [PdCl₂(C₁₀H₁₉N)₂]·0.5H₂O, present different arrangements of the amine ligands coordinated to Pd^II, viz. antiperiplanar in the former case and (−)anticlinal in the latter. The hemihydrate is an inclusion compound, with a Pd coordination complex and disordered water mol­ecules residing on crystallographic twofold axes. The crystal structure for the hemihydrate includes a short Pd⋯Pd separation of 3.4133 (13) Å.     

The diastereoisomers methyl 5‐(S)‐[2‐(R)/(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate

The title diastereoisomers, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate and methyl 5‐(S)‐[2‐(R)‐methoxycarbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxylate, both C₁₉H₂₃N₃O₅, have been studied in two crystalline forms. The first form, methyl 5‐(S)‐[2‐(S)‐methoxy­carbonyl)‐2,3,4,5‐tetrahydropyrrol‐1‐ylcarbonyl]‐1‐(4‐methylphenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate–methyl 5‐(S)‐[2‐(R)‐methoxy­carbonyl)‐2,3,4,5‐tetra­hydro­pyrrol‐1‐yl­carbonyl]‐1‐(4‐methylphenyl)‐4,5‐dihydropyrazole‐3‐carboxylate (1/1), 2(S),5(S)‐C₁₉H₂₃N₃O₅·2(R),5(S)‐C₁₉H₂₃N₃O₅, contains both S,S and S,R isomers, while the second, methyl 5‐(S)‐[2‐(S)‐methoxycarbonyl)‐2,3,4,5‐tetrahydro­pyrrol‐1‐ylcarbonyl]‐1‐(4‐methyl­phenyl)‐4,5‐di­hydro­pyrazole‐3‐carboxyl­ate, 2(S),5(S)‐C₁₉H₂₃N₃O₅, is the pure S,S isomer. The S,S isomers in the two structures show very similar geometries, the maximum difference being about 15° on one torsion angle. The differences between the S,S and S,R isomers, apart from those due to the inversion of one chiral centre, are more remarkable, and are partially due to a possible rotational disorder of the 2‐­(methoxycarbonyl)tetrahydropyrrole group.     

New electron‐deficient chiral phosphines: (4R,5R)‐1,3‐bis(trifluoromethanesulfonyl)perhydro‐1,3,2‐benzodiazaphosphol‐2‐yl] substituted amines

Three chiral electron‐deficient phosphine ligands, [(4R,15R)‐,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodiazaphosphol‐2‐yl]­diethyl­amine, C₁₂H₂₀F₆N₃O₄PS₂, (IIIa), [(4R,5R)‐1,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodi­aza­phosphol‐2‐yl]­di­methyl­amine, C₁₀H₁₆F₆N₃O₄PS₂, (IIIb), and bis­[(4R,5R)‐1,3‐bis­(tri­fluoro­methane­sulfonyl)­per­hydro‐1,3,2‐benzodi­aza­phosphol‐2‐yl]­methyl­amine, (IV), as the chloroform solvate, C₁₇H₂₃F₁₂N₅O₈P₂S₄·0.98CHCl₃, have been prepared from (1R,2R)‐N,N′‐bis­(tri­fluoro­methane­sulfonyl)‐1,2‐cyclo­hexane­di­amine and diethyl phosphor­amido­us dichloride, dimethyl phosphoramidous dichloride or methyl imidodi­phosphorus tetrachloride. The π‐acceptor abilities of these new types of ligands have been evaluated by X‐ray determination of the P—N bond lengths; it has been found that the most promising ligand is the bis­(phosphine) (IV).     

(1R,2R)‐2‐(4‐Methylenecyclohex‐2‐enyl)propyl (1R,4S)‐camphanate

Esterification of a single diastereomer of 2‐(4‐methylene­cyclohex‐2‐enyl)propanol, (II), with (1R,4S)‐(+)‐camphanic acid [(1R,4S)‐4,7,7‐trimethyl‐3‐oxo‐2‐oxabicyclo[2.2.1]heptane‐1‐carboxylic acid] leads to the crystalline title compound, C₂₀H₂₈O₄. The relative configuration of the camphanate was determined by X‐ray diffraction analysis. The outcome clarifies the relative and absolute stereochemistry of the naturally occurring bisabolane sesquiterpenes β‐turmerone and β‐sesquiphellandrene, since we have converted (II) into both natural products via a stereospecific route.     

The diastereoisomers 2‐[(S/R)‐2‐chloro‐3‐quinolyl]‐2‐[(R)‐1‐(4‐methoxyphenyl)ethylamino]acetonitrile at 100 K

In the structures of the two enantiopure diastereoisomers of the title compound, C₂₀H₁₈ClN₃O, which crystallize in different space groups, the molecules are very similar as far as bond distances and angles are concerned, but more substantial differences are observed in some torsion angles. The crystal structures of both molecules can be described as zigzag layers along the c axis. The packing is stabilized by hydrogen‐bond interactions of N—H...O, C—H...Cl and C—H...π types for 2‐[(R)‐2‐chloro‐3‐quinolyl]‐2‐[(R)‐1‐(4‐methoxyphenyl)ethylamino]acetonitrile, and of N—H...N, C—H...O and C—H...π types for 2‐[(S)‐2‐chloro‐3‐quinolyl]‐2‐[(R)‐1‐(4‐methoxyphenyl)ethylamino]acetonitrile, resulting in the formation of two‐ and three‐dimensional networks.     

Precursor of a β‐lactamase inhibitor: allyl (4S,8S,9R)‐10‐[(E)‐ethyl­idene]‐4‐methoxy‐11‐oxo‐1‐aza­tri­cyclo­[7.2.0.03,8]­undec‐2‐ene‐2‐carboxyl­ate

The molecular structure of the title tricyclic compound, C₁₇H₂₁NO₄, which is the immediate precursor of a potent synthetic inhibitor {Lek157: sodium (8S,9R)‐10‐[(E)‐ethyl­idene]‐4‐methoxy‐11‐oxo‐1‐aza­tri­cyclo­[7.2.0.0^3,8]­undec‐2‐ene‐2‐carboxyl­ate} with remarkable potency, provides experimental evidence for the previously modelled relative position of the fused cyclo­hexyl ring and the carbonyl group of the β‐lactam ring, which takes part in the formation of the initial tetrahedral acyl–enzyme complex. In this hydro­phobic mol­ecule, the overall geometry is influenced by C—H?O intramolecular hydrogen bonds [3.046 (4) and 3.538 (6) Å, with corresponding normalized H?O distances of 2.30 and 2.46 Å], whereas the mol­ecules are interconnected through intermolecular C—H?O hydrogen bonds [3.335 (4)–3.575 (5) Å].     

The absolute configuration of (2S,4S)‐ and (2R,4R)‐2‐tert‐butyl‐4‐methyl‐3‐(4‐tolyl­sulfon­yl)‐1,3‐oxazolidine‐4‐carbaldehyde

The title enanti­omorphic compounds, C₁₆H₂₃NO₄S, have been obtained in an enanti­omerically pure form by crystallization from a diastereomeric mixture either of (2S,4S)‐ and (2R,4S)‐ or of (2R,4R)‐ and (2S,4R)‐2‐tert‐butyl‐4‐methyl‐3‐(4‐tolyl­sulfon­yl)‐1,3‐oxazolidine‐4‐carbaldehyde. These mixtures were prepared by an aziridination rearrangement process starting with (S)‐ or (R)‐2‐tert‐butyl‐5‐methyl‐4H‐1,3‐dioxine. The crystal structures indicate an envelope conformation of the oxazolidine moiety for both compounds.     

Racemic and chiral 1‐[N‐(chloro­acetyl)carbamoylamino]‐2,3‐dihydro‐1H‐inden‐2‐yl chloroacetate

In the racemic crystals of (1S,2R)‐ or (1R,2S)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (I), the enantiomeric mol­ecules form a dimeric structure via the N—H?O cyclic hydrogen bond of the carbamoyl moieties. In the chiral crystals of (—)‐(1S,2R)‐1‐[N‐(chloro­acetyl)­carbamoyl­amino]‐2,3‐di­hydro‐1H‐inden‐2‐yl chloro­acetate, C₁₄H₁₄Cl₂N₂O₄, (II), the N—­H?O intermolecular hydrogen bond forms a zigzag chain around the twofold screw axis. The melting points and calculated densities of (I) and (II) are 446 and 396 K, and 1.481 and 1.445 Mg m^?3, respectively.     

A new optically pure half‐sandwich Cp–Ru diphosphine complex with a chiral metal centre, (S)‐Ru(η5‐C5H5)(EPHOS)Cl {EPHOS is (+)‐(1R,2S)‐2‐[(diphenylphosphino)methylamino]‐1‐phenylpropyl diphenylphosphinite}

The crystal structure of the title compound, chloro(η⁵‐cyclopenta­dienyl){(1R,2S)‐2‐[(di­phenyl­phosphino)­methyl­amino]‐1‐phenyl­propyl di­phenyl­phosphinite‐κ²P,P′}ruthenium(II), [Ru(C₅H₅)Cl(C₃₄H₃₃NOP₂)], is reported. The pseudo‐octa­hedral complex is chiral and the configuration at the Ru atom is S. The seven‐membered metallacycle adopts a boat‐like conformation.     

2(S)‐Amino‐3‐[1H‐imidazol‐4(5)‐yl]­propyl cyclo­hexylmethyl ether di­hydro­chloride and 2(S)‐amino‐3‐[1H‐imidazol‐4(5)‐yl]­propyl 4‐bromo­benzyl ether di­hydro­chloride

(Cyclo­hexyl­methyl­oxy­methyl)(1H‐imidazol‐4‐io­methyl)‐(S)‐ammonium dichloride, C₁₃H₂₅N₃O⁺·2Cl^?, and (4‐bromo­benzyl)(1H‐imidazol‐4‐io­methyl)‐(S)‐ammonium dichloride, C₁₃H₁₈BrN₃O⁺·2Cl^?, are model compounds with different biological activities for evaluation of the hist­amine H3‐receptor activation mechanism. Both title compounds occur in almost similar extended conformations.     

An intermediate in a new synthesis approach to β‐substituted β‐hydroxy­aspartame

The crystal and molecular structure of 1‐tert‐butyl 4‐ethyl (2′R,3′R,5′R,2S,3S)‐3‐bromo­methyl‐3‐hydroxy‐2‐[(2′‐hydroxy‐2′,6′,6′‐tri­methyl­bi­cyclo­[3.1.1]­hept‐3′‐yl­idene)­amino]­succinate, C₂₁H₃₄BrNO₆, is presented. This compound is an intermediate in the new synthetic route to β‐substituted β‐hydroxy­aspartates, which are blockers of glutamate transport.     

Resolution of (S,S)‐4‐(2,2,4‐tri­methyl­chroman‐4‐yl)­phenyl camphanate and its 4‐chromanyl epimer by crystallization

Dianin's compound (4‐p‐hydroxy­phenyl‐2,2,4‐tri­methyl­chroman) has been resolved by crystallization of the (S)‐(−)‐camphanic esters (S,S)‐ and (R,S)‐4‐(2,2,4‐tri­methyl­chroman‐4‐yl)­phenyl 4,7,7‐tri­methyl‐3‐oxo‐2‐oxabi­cyclo[2.2.1]heptane‐1‐carboxyl­ate, both C₂₈H₃₂O₅, from 2‐methoxy­ethanol, yielding the pure S,S diastereomer. The relative stereochemistry of both diastereomers has been determined by X‐ray crystallography, from which the absolute stereochemistry could be deduced from the known configuration of the camphanate moiety. The crystallographic conformations have been analysed, including the 1:1 disorder of the R,S diastereomer.     

(4R,4aR,6S,7S,7aS)‐6‐Hydro­xy‐7‐hy­droxy­methyl‐4‐methyl­per­hydro­cyclo­penta­[c]­pyran‐1‐one chloro­form solvate from Valeriana laxiflora

The structure of an iridolactone isolated from Valeriana laxiflora was established as (4R,4aR,6S,7S,7aS)‐6‐hydroxy‐7‐hydroxy­methyl‐4‐methyl­per­hydro­cyclo­penta­[c]­pyran‐1‐one chloro­form solvate, C₁₀H₁₆O₄·CHCl₃. The two rings are cis‐fused. The δ‐lactone ring adopts a slightly twisted half‐chair conformation with approximate planarity of the lactone group and the cyclo­pentane ring adopts an envelope conformation. The hydroxy group, the hydroxymethyl group and the methyl group all have β orientations. The absolute configuration was determined using anomalous dispersion data enhanced by the adventitious inclusion of a chloro­form solvent mol­ecule. Hydro­gen bonding, crystal packing and ring conformations are discussed in detail.     

(3R*,4R*)‐3‐Iso­propyl‐4‐phenyl­azetidin‐2‐one at 150 K

The title compound, C₁₂H₁₅NO, crystallized in the centrosymmetric space group C2/c with one mol­ecule as the asymmetric unit. There is a single conventional N—H?O hydrogen bond, with a donor–acceptor distance of 2.912 (1) Å, which forms an R(8) cyclic dimer about a center of symmetry. There is a single significant intermolecular C—H?O interaction, which also forms an R(8) cyclic dimer about a center of symmetry. Taken together, these interactions form chains propagating along [110]. Structural comparisons are made with another β‐­lactam, (1′R*,3R*,4S*)‐3‐(1′‐hydroxy­ethyl)‐4‐phenylazet­id­in‐2‐one.     

Two (+)‐α,4‐dimethyl‐2‐oxocyclo­hexaneacetic acids: hydrogen bonding in a terpenoid γ‐keto acid and in a diastereomeric lactol

The (+)‐(αS,1S,4R)‐diastereomer of the title structure, C₁₀H₁₆O₃, aggregates in the solid as non‐symmetric dimers with disorder in both carboxyl groups [O·O = 2.710 (5) and 2.638 (5) Å]. The two mol­ecules constituting the asymmetric unit pair around a pseudo‐twofold rotational axis and differ only slightly in their distances and angles, but one methyl group displays rotational disorder absent in the other mol­ecule. Five inter­molecular C—H·O close contacts exist, involving both ketone groups. The (+)‐(αR,1R,4R)‐diastereomer exists in the crystal in its closed‐ring lactol form, (3R,3aR,6R,7aR)‐2,3,3a,4,5,6,7,7a‐octa­hydro‐7a‐hydroxy‐3,6‐dimethyl­benzo[b]furan‐2‐one, C₁₀H₁₆O₃, and aggregates as hydrogen‐bonded catemers that extend from the hydroxyl group of one mol­ecule to the carbonyl group of a neighbor screw‐related along b [O·O = 2.830 (3) Å and O—H·O = 169°]. One close inter­molecular C—H·O contact exists involving the carbonyl group.     

3,6‐Di­chloro‐4‐[2‐(4‐thia­morpholino)­ethanesulfanyl]­pyridazine and 3,6‐bis­(pyrazol‐1‐yl)‐4‐[2‐(4‐thia­mor­pho­lino)­ethanesulfanyl]­pyridazine

The trans–trans conformations adopted by the derivatized bis­(bidentate) chelating N₄‐donor ligand 3,6‐bis­(pyrazol‐1‐yl)‐4‐[2‐(4‐thia­morpholino)­ethanesulfanyl]­pyridazine, C₁₆H₁₉N₇S₂, and an intermediate in its formation, 3,6‐di­chloro‐4‐[2‐(4‐thia­morpholino)­ethanesulfanyl]­pyridazine, C₁₀H₁₃Cl₂N₃S₂, con­trast with the cis–cis conformation found previously for 3,6‐bis­(thio­phen‐2‐yl)­pyridazine [Ackers, Blake, Hill & Hubberstey (2002). Acta Cryst. C 58 , o640–o641], which places all four heteroatoms on the same side of the mol­ecule.     

Three (E)‐2‐[(bromo­phen­yl)imino­meth­yl]‐4‐methoxy­phenols

The title compounds, (E)‐2‐[(2‐bromo­phenyl)imino­methyl]‐4‐methoxy­phenol, C₁₄H₁₂BrNO₂, (I), (E)‐2‐[(3‐bromo­phenyl)­imino­methyl]‐4‐methoxy­phenol, C₁₄H₁₂BrNO₂, (II), and (E)‐2‐[(4‐bromo­phenyl)imino­methyl]‐4‐methoxy­phenol, C₁₄H₁₂BrNO₂, (III), adopt the phenol–imine tautomeric form. In all three structures, there are strong intra­molecular O—H⋯N hydrogen bonds. Compound (I) has strong inter­molecular hydrogen bonds, while compound (III) has weak inter­molecular hydrogen bonds. In addition to these inter­molecular inter­actions, C—H⋯π inter­actions in (I) and (III), and π–π inter­actions in (I), play roles in the crystal packing. The dihedral angles between the aromatic rings are 15.34 (12), 6.1 (3) and 39.2 (14)° for (I), (II) and (III), respectively.     

Identification of (6R)‐5,6,7,8‐Tetrahydro‐D‐monapterin (=(6R)‐2‐Amino‐5,6,7,8‐tetrahydro‐6‐[(1R,2R)‐1,2,3 ‐trihydroxypropyl]pteridin‐4(3H)‐one) as the Native Pteridine in Tetrahymena pyriformis

The structure of the native pteridine in Tetrahymena pyriformis was determined as (6R)‐5,6,7,8‐tetrahydro‐D ‐monapterin (=(6R)‐2‐amino‐5,6,7,8‐tetrahydro‐6‐[(1R,2R)‐1,2,3‐trihydroxypropyl]pteridin‐4(3H)‐one; 4 ). First, the configuration of the 1,2,3‐trihydroxypropyl side chain was confirmed as D ‐threo by the fluorescence‐detected circular dichroism (FDCD) spectrum of its aromatic pterin derivative 2 obtained by I₂ oxidation (Fig. 1). The configuration at the 6‐position of 4 was determined as (R) by comparison of its hexaacetyl derivative 6 with authentic (6R)‐ and (6S)‐hexaacetyl‐5,6,7,8‐tetrahydro‐D ‐monapterins 6 and 7 , respectively, in the HPLC, LC/MS, and LC‐MS/MS (Figs. 3 – 6). (6R)‐5,6,7,8‐Tetrahydro‐D ‐monapterin ( 4 ) is a newly discovered natural tetrahydropterin.     

Self‐association promoted conformational transition of (3R,4S,8R,9R)‐9‐[(3,5‐bis(trifluoromethyl)phenyl))‐thiourea](9‐deoxy)‐epi‐cinchonine

The conformational diversity of the (3R,4S,8R,9R)‐9‐[(3,5‐bis(trifluoromethyl)phenyl))‐thiourea](9‐deoxy)‐epi‐cinchonine organocatalyst is discussed. Low‐temperature NMR experiments confirmed a self‐association process, which promotes the quinoline rotation between two intramolecularly hydrogen‐bonded monomeric conformers of the catalyst. The balanced population of the coexisting monomeric and dimeric species allowed us to conduct a structural study of a rather complex conformational dynamics of the pure catalyst. The study is extended by a comparison with other members of the bifunctional amine‐thiourea organocatalyst family. Changes in the molecular structure of the catalysts influence the interplay between intra‐ and intermolecular hydrogen bonding, and yield different extent of catalyst self‐association. By assessing the conformation of the individual states, we established the thermodynamic model of a self‐association promoted conformational transition. Copyright © 2009 John Wiley & Sons, Ltd.     

(1R,8R,11R)‐3,3,11‐Tri­methyl‐6,6‐ethyl­ene­dioxy­bi­cyclo­[6.3.0]­undecan‐2‐one and (1R,2R,8R,11R)‐3,3,11‐tri­methyl‐6,6‐ethylenedioxybicyclo[6.3.0]undecan‐2‐ol

The reduction of (1R,8R,11R)‐3,3,11‐tri­methyl‐6,6‐ethyl­ene­dioxy­bi­cyclo­[6.3.0]­undecan‐2‐one, C₁₆H₂₆O₃, (I), gave exclusively an alcohol, C₁₆H₂₈O₃, (II). The stereochemistry of the hydroxyl group in (II) was shown as R. The conformation around the eight‐membered carbocycle in (I) differs markedly from that in (II).