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Four polymorphs of 2-(perfluorophenyl)-2-(phenylamino)acetonitrile have been crystallized and structurally analyzed: in addition to three racemic crystals, a rare kryptoracemate has been obtained. The central single bonds allow for conformational flexibility: the kryptoracemate as well as two of the remaining polymorphs contain several independent molecules with different conformation. In contrast to these uncommon packing modes, the fourth phase is unexceptional and crystallizes with a single molecule in the asymmetric unit. Individual crystallization batches may contain several crystal forms concomitantly. [ABSTRACT FROM AUTHOR]

The terpenols L(-)-borneol, (1S2S3S5R)-3-pinanol, (-)-menthol, and (-)-myrtenol are easily available chiral alcohols for the preparation of enantiomerically pure catechol esters 1-4-H2. Those ligands are used for the hierarchical assembly of triple lithium-bridged dinuclear titanium(IV) triscatecholate helicates Li[Li3(1-4)6Ti2]. In solution, the dimeric species are in a solvent dependent equilibrium with the monomer Li2[(1-4)3Ti]. The equilibrium is studied by ¹H NMR. CD spectroscopy indicates that the configuration at the complex units of the enantiomerically pure dimeric α-chiral derivatives Li[Li3(1-3)6Ti2] is opposite to the configuration of the monomers Li2[(1-3)3Ti]. For the γ-chiral complex Li2[(4)3Ti] only a de of 25% is observed and in this case no interpretation of the mechanism of stereocontrol is possible. [ABSTRACT FROM AUTHOR]

The SAMPL9 blind challenge aims to predict the toluene/water partition coefficient of 16 active pharmaceutical ingredients. In this work, the transfer free energy between the solvation in water and toluene is predicted by molecular dynamics simulations using the MBAR method [M. R. Shirts and J. D. Chodera, J. Chem. Phys. , 2008, 129 , 123105] with replica exchange molecular dynamics [Y. Sugita, A. Kitao and Y. Okamoto, J. Chem. Phys. , 2000, 113 , 6042-6051]. Thereby, simulation results using the force field GAFF/IPolQ-Mod + LJ-fit [A. Mecklenfeld and G. Raabe, ADMET and DMPK , 2020, 8 , 274-296] are compared to simulations with the standard GAFF/RESP model [J. Wang, R. M. Wolf, J. W. Caldwell, P. A. Kollman and D. A. Case, J. Comput. Chem. , 2004, 25 , 1157-1174]. By statistical evaluation of RMSD and R 2 , we compare the results with other participants of the blind challenge. Furthermore, we provide a detailed analysis of solvation structures using the combined distribution function for simulations in water and the plane projection analysis for simulations in toluene, and we work out differences and similarities of the two force fields. These studies allow to gain important insights to increase the understanding of the mechanism of interactions between the drugs and the solvent.

The enantioselective oxidative N-heterocyclic carbene-catalyzed [4+2] annulation reaction of β-methyl enals and cyclic trifluoromethyl ketimines has been developed. A series of biologically interesting dihydroquinazolinone derivatives bearing a trifluoromethyl group and a tetrasubstituted stereocenter are efficiently prepared with very good yields and excellent stereoselectivities.

An N-heterocyclic carbene catalyzed activation of α,β-unsaturated N-acyltriazoles is described. The in situ generated α,β-unsaturated acylazolium intermediates allowed an enantioselective formal [3+3] cycloaddition with 1,3-dicarbonyl compounds. The resulting dihydropyranones are formed in good to excellent yields and with high enantioselectivities.

A one-pot asymmetric Michael addition/hydroalkoxylation sequence, catalyzed by a sequential catalytic system consisting of a squaramide and a silver salt, provides a new series of chiral pyrano-annulated pyrazole derivatives in excellent yields (up to 95%) and high enantioselectivities (up to 97% ee).

An unprecedented stereoselective organocatalytic one-pot 1,4-/1,6-/1,2-addition sequence between β-dicarbonyl compounds, β-nitroalkenes and 4-nitro-5-styrylisoxazoles sequentially catalyzed by low loading of a squaramide catalyst and an achiral base has been developed. The protocol opens an efficient entry to isoxazole bearing cyclohexanes with six consecutive stereogenic centers including one tetrasubstituted carbon in good yields and excellent diastereo- and enantioselectivities.

An NHC-catalyzed regio- and stereoselective Mannich/lactamization domino reaction of N-(benzothiazolyl)imines with α-chloroaldehydes has been developed. This new protocol provides a facile approach for the asymmetric synthesis of benzothiazolo-pyrimidinones and a pyrrolo[1,2-a]indolone in moderate to good yields (34-78%) and excellent stereoselectivities (87-99% ee, up to >20 : 1 d.r.).

A highly stereoselective one-pot procedure involving an enantioselective Michael addition promoted by low loading of an amino-squaramide catalyst followed by an achiral base catalyzed domino Michael-Knoevenagel-type 1,2-addition sequence provides efficient access to fully substituted cyclohexanes bearing five contiguous stereogenic centers in good yields (68-86%) and excellent stereoselectivities (>30 : 1 dr and 96-99% ee).

A rare anion-π complex between bromide and a neutral receptor is reported and related receptor systems are studied with a series of anions. The interaction is observed in the solid state and in solution, and further evidence for it is obtained by a computational study.

Triangular triscatechol ligands are prepared in facile reaction sequences. The catechol units are either bound to the triangular backbone through their 3- or 4-position. With titanium(IV) ions, the ligands form metallosupramolecular M(4)L(4) tetrahedra which are characterized by ESI MS and proton NMR. Quantum-chemical calculations reveal that connectivity at the catechol in the 3-position results in highly condensed structures while attachment in the 4-position affords container molecules providing huge internal cavities.

Anion-π interactions in crystals of fluorobenzyl ammonium salts depend on the degree of fluorination at the aromatics., (This journal is © The Royal Society of Chemistry 2011)

Allyl and 2-methylallyl indium compounds were prepared by salt metathesis starting from indium trichloride and a Grignard reagent. They are highly fluxional in solution and reveal coordination numbers of the indium atoms of four and five in the solid state., (© The Royal Society of Chemistry 2011)

A new triazolium salt derived N-heterocyclic carbene catalyses an asymmetric cross-benzoin-type reaction of heteroaromatic aldehydes and various trifluoromethyl ketones in good to excellent yields (69-96%) and moderate to good enantioselectivities (ee = 39-85%). Up to 99% ee can be achieved by recrystallisation.

Chemical investigation of the marine fungus Ascochyta salicorniae led to the isolation of two new epimeric compounds, ascolactones A (1) and B (2), in addition to the structurally-related polyketides hyalopyrone (3), ascochitine (4), ascochital (5) and ascosalipyrone (6). The absolute configurations of the epimeric compounds 1 and 2 were assigned as (1R,9R) and (1S,9R), respectively, through simulation of the chiroptical properties using quantum-chemical CD calculations, and chiral GC-MS subsequent to oxidative cleavage (Baeyer-Villiger oxidation) of the side chain. In silico screening using the PASS software identified some of the A. salicorniae compounds (1-6) as potential inhibitors of protein phosphatases. Compound was found to inhibit the enzymatic activity of MPtpB with an IC(50) value of 11.5 microM.

The tartaric acid derived bis(beta-diketonate) ligand L affords either 2:3 or 3:2 ligand:metal complexes with nickel(II) ions depending on the stoichiometry of the components; the two complexes possess different electronic and geometric properties.

Quinoline-based C1-symmetric sulfoximines have been used as chiral ligands in copper-catalyzed asymmetric hetero Diels-Alder reactions leading to cycloadducts with up to 96% ee.