Enantio-, Diastereo- and Regioselective Synthesis of Chiral Cyclic and Acyclic gem-Difluoromethylenes by Palladium-Catalyzed [4+2] Cycloaddition.

gem-Difluoromethylene moieties are attractive in medicinal chemistry due to their ability to mimic other more ubiquitous functional groups. Thus, effective asymmetric methods for their construction are highly desirable, especially for the industrial production of chiral drugs. Using a Pd-catalyzed asymmetric [4+2] cycloaddition between substituted-2-alkylidenetrimethylene carbonates and gem-difluoroalkyl ketones, we were able to easily access chiral 1,3-dioxanes that contain a tetrasubstituted difluoroalkyl stereogenic center in cyclic and acyclic skeletons.

Benchtop-Stable Hypervalent Bromine(III) Compounds: Versatile Strategy and Platform for Air- and Moisture-Stable λ-Bromanes.

We present the first synthesis of air/moisture-stable λ-bromanes ( and ) by using a cyclic 1,2-benzbromoxol-3-one (BBX) strategy. X-ray crystallography and NMR and IR spectroscopy of -triflylimino-λ-bromane () revealed that the bromine(III) center is effectively stabilized by intramolecular R-Br-O hypervalent bonding. This strategy enables the synthesis of a variety of air-, moisture-, and benchtop-stable Br-hydroxy, -acetoxy, -alkynyl, -aryl, and bis[(trifluoromethyl)sulfonyl]methylide λ-bromane derivatives.

Design and Synthesis of a Chiral Halogen-Bond Donor with a Sp-Hybridized Carbon-Iodine Moiety in a Chiral Fluorobissulfonyl Scaffold.

The first example of a chiral halogen-bond donor with a sp-hybridized carbon-iodine moiety in a fluorobissulfonyl scaffold is described. The binaphthyl backbone was designed as a chiral source and the chiral halogen-bond donor (R)-1 was synthesized from (R)-1,1'-binaphthol in 11 steps. An NMR titration experiment demonstrated that (R)-1 worked as a halogen-bond donor.

Synthesis of Both Enantiomers of Nine-Membered CF -Substituted Heterocycles Using a Single Chiral Ligand: Palladium-Catalyzed Decarboxylative Ring Expansion with Kinetic Resolution.

The two enantiomers of trifluoromethyl-benzo[c][1,5]oxazonines, (R)-4 and (S)-4, can be selectively accessed with high enantiopurity by the Pd-catalyzed ring-expansion reaction of trifluoromethyl-benzo[d][1,3]oxazinones (1) with vinyl ethylene carbonates (3) using one antipode of a chiral ligand. Initially, the reaction proceeds by a double decarboxylative ring-expansion with kinetic resolution of 1 in the presence of a Pd-catalyst/chiral ligand to provide (R)-4 with high enantiopurity. At the same time, the nonreactive antipode of 1, (S)-1, which was recovered with an impeccable s factor of up to 713 and an ideal chemical yield, was transferred into the antipode of the products, (S)-4, with high enantiopurity by a second run of the Pd-catalyzed double decarboxylation reaction, but this time without any chiral auxiliary.

Synthesis of Chiral Nonracemic α-Difluoromethylthio Compounds with Tetrasubstituted Stereogenic Centers via a Palladium-Catalyzed Decarboxylative Asymmetric Allylic Alkylation.

The synthesis of chiral, nonracemic difluoromethylthio (SCFH) compounds that contain a tetrasubstituted stereogenic center is reported. Racemic α-SCFH-β-ketoallylesters 5 were initially prepared by an electrophilic difluoromethylthiolation of β-ketoallylesters 6, followed by a Pd-catalyzed Tsuji decarboxylative asymmetric allylic alkylation (DAAA) to provide a wide variety of chiral, nonracemic α-allyl-α-SCFH-ketones (4) with high enantiopurity. This strategy can be extended to the enantioselective synthesis of chiral, nonracemic α-allyl-α-trifluoromethylthio(SCF)-ketones (7).

Trifluoroethoxy-Coated Subphthalocyanines Attract Small Arenes in Their π-Concave Cavity.

Invited for this month's cover is the group of Prof. Norio Shibata based at the Nagoya Institute of Technology, Japan. The cover picture shows the crystal structures of trifluoroethoxy-substituted subphthalocyanines which form crystalline clathrates with one small aromatic molecule, such as toluene or benzene, in their concave cavity.

Trifluoroethoxy-Coated Subphthalocyanines Attract Small Arenes in Their π-Concave Cavity.

X-ray crystallographic analyses of a series of trifluoroethoxy-substituted subphthalocyanines disclosed that a molecule of toluene is clasped at the center of the molecular concave cavity. Twelve trifluoroethoxy substituents, which flexibly surround the toluene molecule to hold it on the 14 π-electron-conjugated surface of the subphthalocyanines, can also catch a molecule of benzene. In contrast, a nonsubstituted subphthalocyanine does not show the same phenomena, and two subphthalocyanine units are required to maintain a small aromatic compound in their concave cavity.

Walking and rolling of crystals induced thermally by phase transition.

The mechanical motion of materials has been increasingly explored in terms of bending and expansion/contraction. However, the locomotion of materials has been limited. Here, we report walking and rolling locomotion of chiral azobenzene crystals, induced thermally by a reversible single-crystal-to-single-crystal phase transition.

A Circularly Arranged Sextuple Triptycene Gear Molecule.

Herein we report the synthesis of a circularly arranged sextuple triptycene gear molecule, hexakis(10-dodecyloxy-9-triptycyl)ethynylbenzene, via the trimerization of the corresponding triyne with a cobalt catalyst. The six triptycene gears are closely engaged with each other as confirmed by single crystal X-ray structure analysis, and their motion in solution was established by NMR spectroscopy. Notably, when one bulky RuCp* complex was attached to one triptycene gear, the whole movement of the six gears was highly restricted via their mechanical engagement.

Voltammetric and Spectroscopic Studies of α- and β-[PWO] Polyoxometalates in Neutral and Acidic Media: Structural Characterization as Their [(n-BuN)][PWO] Salts.

The structure of the Keggin-type β-[PWO] (PW) polyoxometalate, with n-BuN as the countercation, has been determined for the first time by single-crystal X-ray analysis and compared to data obtained from a new determination of the structure of the α-PW isomer, having the same countercation. Analysis of cyclic voltammograms obtained in CHCN (0.1 M [n-BuN][PF]) reveals that the reversible potential for the β-PW isomer always remains ca.

Corrigendum: Sterically Demanding Unsymmetrical Diaryl-λ(3)-iodanes for Electrophilic Pentafluorophenylation and an Approach to α-Pentafluorophenyl Carbonyl Compounds with an All-Carbon Stereocenter.

[This corrects the article DOI: 10.1002/open.201402045.

Difluoromethanesulfonyl hypervalent iodonium ylides for electrophilic difluoromethylthiolation reactions under copper catalysis.

Difluoromethanesulfonyl hypervalent iodonium ylides 2 were developed as electrophilic difluoromethylthiolation reagents for a wide range of nucleophiles. Enamines, indoles, β-keto esters, silyl enol ethers and pyrroles were effectively reacted with 2 affording desired difluoromethylthio (SCF2H)-substituted compounds in good to high yields under copper catalysis. The reaction of allyl alcohols with 2 under the same conditions provided difluoromethylsulfinyl (S(O)CF2H) products in good yields.

Mechanical Motion of Chiral Azobenzene Crystals with Twisting upon Photoirradiation.

The photomechanical motion of chiral crystals of trans-azobenzene derivatives with an (S)- and (R)-phenylethylamide group was investigated and compared with a racemic crystal. Changes in the UV/Vis absorption spectra of the powdered crystals before and after UV irradiation were measured by using an optical waveguide spectrometer, showing that the lifetime of the cis-to-trans thermal back-isomerization of the chiral crystals was faster than that of the racemic crystals. Upon UV irradiation, a long plate-like chiral microcrystal bent away from the light source with a twisting motion.

Cyclodextrin-Isolated Alkynylpyrenes as UV-Stable and Blue-Light-Emitting Molecules Even in Condensed States.

Encapsulation of highly emissive alkynylpyrenes with permethylated α-cyclodextrin (PM-α-CD) followed by capping reaction yielded alkynylpyrene-based [3]rotaxanes. The [3]rotaxane emitted only blue light of monomeric pyrene under various circumstances such as lipophilic, hydrophilic, and even condensed states and exhibited extremely high stability for UV irradiation. These properties would result because PM-α-CD, like bulletproof glass, protected the alkynylpyrene core from the attack of another excited alkynylpyrene and singlet oxygen generated by the energy transfer from the excited alkynylpyrene.

Three New Chlorinated Cyclopentenols, Palmaenols A and B and Palmaetriol, from the Discomycete Lachnum palmae.

The new chlorinated cyclopentenols, palmaenol A (1) and palmaetriol (3), were isolated from the culture broth of the discomycete Lachnum palmae (NBRC- 106495). In addition, a new chlorinated cyclopentenol, palmaenol B (2), a geometric isomer of 1, was also obtained from the culture broth containing KCl. The structures of 1-3 were elucidated from spectroscopic data.

Dehydration of raffinose pentahydrate: structures of raffinose 5-, 4.433-, 4.289- and 4.127-hydrate at 93 K.

Raffinose [or O-α-D-galactopyranosyl-(1→6)-α-D-glucopyranosyl-(1→2)-β-D-fructofuranoside] pentahydrate, C18H32O16·5H2O, (I), and three lower hydrates, namely the 4.433-, (II), 4.289-, (III), and 4.

Enantioselective Trichloromethylation of MBH-Fluorides with Chloroform Based on Silicon-assisted C-F Activation and Carbanion Exchange Induced by a Ruppert-Prakash Reagent.

Enantioselective trichloromethylation of Morita-Baylis-Hillman (MBH)-type allylic fluorides with chloroform (HCCl3 ) under organocatalysis was achieved with high to excellent enantioselectivities. Silicon-assisted CF bond activation by a Ruppert-Prakash reagent and direct activation of HCCl3 by a carbanion exchange process with trifluoromethyl (CF3 ) carbanion generated in situ from the Ruppert-Prakash reagent realized the direct asymmetric trichloromethylation at a stereogenic allylic positon, without any help from transition metal catalysis, and under very mild conditions. Pre-activation of HCCl3 was not required.

Synthesis of Diaryliodonium Salts Having Pentafluorosulfanylarenes and Their Application to Electrophilic Pentafluorosulfanylarylation of C-, O-, N-, and S-Nucleophiles.

Novel reagents for the electrophilic introduction of pentafluorosulfanyl (SF5) arenes into target molecules are disclosed. Unsymmetrical diaryliodonium salts 1 having SF5-arenes were synthesized by a one-pot process from iodo-SF5-benzenes 2 in good yields. The SF5-aryliodonium salts 1 were found to be efficient for the electrophilic SF5-arylation of carbon and heterocentered nucleophiles to furnish the corresponding substituted SF5-arenes in good to high yields.

Crystal structure of (S)-4-carbamoyl-4-(1,3-dioxo-isoindolin-2-yl)butanoic acid.

In the title compound, C13H12N2O5, the phthalimide ring system is essentially planar, with a maximum deviation of 0.0479 (14) Å. In the crystal, each mol-ecule is linked via six neighbouring mol-ecules into a three-dimensional network through N-H⋯O and O-H⋯O hydrogen bonds, which form an R 3 (2)(8) ring motif.

Self-disproportionation of enantiomers of thalidomide and its fluorinated analogue gravity-driven achiral chromatography: mechanistic rationale and implications.

We report on the self-disproportionation of enantiomers (SDE) of non-racemic thalidomide () and 3'-fluorothalidomide () under the conditions of gravity-driven achiral silica-gel chromatography. The presence of a fluorine atom on the chiral center dramatically alters the structure and polarity of and , resulting in the opposite SDE profile on silica-gel.

Sterically Demanding Unsymmetrical Diaryl-λ(3)-iodanes for Electrophilic Pentafluorophenylation and an Approach to α-Pentafluorophenyl Carbonyl Compounds with an All-Carbon Stereocenter.

A sterically demanding unsymmetrical pentafluorophenyl-triisopropylphenyl-λ(3)-iodane was developed as an effective reagent for the electrophilic pentafluorophenylation of various β-keto esters and a β-keto amide. 17 examples of α-pentafluorophenylated 1,3-dicarbonyl compounds 3 having a quaternary carbon center are provided. The resulting compounds were nicely transformed into chiral α-pentafluorophenyl ketones with an all-carbon stereogenic center in high yields and high enantioselectivities using asymmetric organocatalysis (up to 98 % ee) or asymmetric metal catalysis (up to 82 % ee).

In situ X-ray snapshot analysis of transient molecular adsorption in a crystalline channel.

Molecular adsorption is a fundamental phenomenon in porous materials and is usually characterized by the efficiency and selectivity of molecular separations and reactions. However, for functional porous materials, analysis of the dynamic behaviour of molecular adsorbents is a major challenge. Here, we use in situ single-crystal X-ray diffraction to analyse multi-step molecular adsorption in a crystalline nanochannel of a metal-macrocycle framework.

Supramolecular phosphatases formed by the self-assembly of the bis(Zn²⁺-cyclen) complex, copper(II), and barbital derivatives in water.

In our previous paper, we reported that a dimeric Zn(2+) complex with a 2,2'-bipyridyl linker (Zn2L(1)), cyanuric acid (CA), and a Cu(2+) ion automatically assemble in aqueous solution to form 4:4:4 complex 3, which selectively catalyzes the hydrolysis of mono(4-nitrophenyl)phosphate (MNP) at neutral pH. Herein, we report that the use of barbital (Bar) instead of CA for the self-assembly with Zn2L(1) and Cu(2+) induces 2:2:2 complexation of these components, and not the 4:4:4 complex, to form supramolecular complex 6 a, the structure and equilibrium characteristics of which were studied by analytical and physical measurements. The finding show that 6 a also accelerates the hydrolysis of MNP, similarly to 3.

Stabilization of β-peptide helices by direct attachment of trifluoromethyl groups to peptide backbones.

The 14-helix structure of oligo-β-peptides was significantly stabilized by direct attachment of CF3 groups to their backbones. Our studies indicate that this stabilization originates from the CF3-promoted increase in the intramolecular hydrogen-bonding ability of their backbone amides, leading to a novel strategy to stabilize peptide folding.

Synthesis and characterization of novel Wells-Dawson-type mono vanadium(V)-substituted tungsto-polyoxometalate isomers: 1- and 4-[S2VW17O62](5-).

Two vanadium(V)-substituted tungsto-polyoxometalate isomers, 1- and 4-[S2VW17O62](5-), were prepared as their tetra-alkyl ammonium salts from a W(VI)-H2SO4-V(V) reaction mixture in aqueous CH3CN solution. X-ray crystallographic structural analysis revealed that both isomers have a Wells-Dawson-type structure with a higher occupancy of vanadium at polar sites and belt sites for 1- and 4-[S2VW17O62](5-), respectively. The isomers were also characterized by elemental analysis, infrared, Raman, UV-vis, and (51)V NMR spectroscopies as well as voltammetry, and the data obtained were compared with that derived from [S2W18O62](4-).