Building new discrete supramolecular assemblies through the interaction of iso-tellurazole N-oxides with Lewis acids and bases.

The supramolecular macrocycles spontaneously assembled by iso-tellurazole N-oxides are stable towards Lewis bases as strong as N-heterocyclic carbenes (NHC) but readily react with Lewis acids such as BR3 (R = Ph, F). The electron acceptor ability of the tellurium atom is greatly enhanced in the resulting O-bonded adducts, which consequently enables binding to a variety of Lewis bases that includes acetonitrile, 4-dimethylaminopyridine, 4,4'-bipyridine, triphenyl phosphine, a N-heterocyclic carbene and a second molecule of iso-tellurazole N-oxide.

Asymmetric Organocatalytic Stepwise [2+2] Entry to Tetra-Substituted Heterodimeric and Homochiral Cyclobutanes.

An asymmetric synthesis of tetra-substituted cyclobutanes involving an organocatalytic, stepwise [2+2]-cycloaddition is described. The secondary-amine-catalyzed method allows for the hetero-dimerization of two different cinnamic-acid-derived sub-units, opening a novel one-step assembly to densely functionalized, head-to-tail coupled dimeric cyclobutanes in high enantiomeric excess. A series of selective synthetic interconversions in these sensitive cycloadducts is also described.

Establishing the Coordination Chemistry of Antimony(V) Cations: Systematic Assessment of Ph4 Sb(OTf) and Ph3 Sb(OTf)2 as Lewis Acceptors.

The coordination chemistry of the stiboranes Ph4 Sb(OTf) (1 a, OTf = OSO2 CF3 ) and Ph3 Sb(OTf)2 (3) with Lewis bases has been investigated. The significant steric encumbrance of the Sb center in 1 a precludes interaction with most ligands, but the relatively low steric demands of 4-methylpyridine-N-oxide (OPyrMe) and OPMe3 enabled the characterization of [Ph4 Sb(OPyrMe)][OTf] (2 a) and [Ph4 Sb(OPMe3 )][OTf] (2 b), rare examples of structurally characterized complexes of stibonium acceptors. In contrast, 3 was found to engage a variety of Lewis bases, forming stable isolable complexes of the form [Ph3 Sb(donor)2 ][OTf]2 [donor=OPMe3 (6 a), OPCy3 (6 b, Cy=cyclohexyl), OPPh3 (6 c), OPyrMe (6 d)], [Ph3 Sb(dmap)2 (OTf)][OTf] (6 e, dmap=4-(dimethylamino)pyridine) and [Ph3 Sb(donor)(OTf)][OTf] [donor=1,10-phenanthroline (7 a) or 2,2'-bipy (7 b, bipy=bipyridine)]. These compounds exhibit significant structural diversity in the solid-state, and undergo ligand exchange reactions in line with their assignment as coordination complexes. Compound 3 did not form stable complexes with phosphine donors, with reactions instead leading to redox processes yielding SbPh3 and products of phosphine oxidation.

Synthesis of the cyanobacterial metabolite nostodione A, structural studies and potent antiparasitic activity against Toxoplasma gondii.

A total synthesis of the cyanobacterial natural product nostodione A is reported involving a convergent, diversity-oriented route, enabling the assembly of a mini-library of structural analogues. The first single crystal X-ray structural determination on a member of this series is reported along with SAR studies identifying potent inhibitors of invasion and replication of the parasitic protozoan Toxoplasma gondii.

Resolution of 2-chloromandelic acid with (R)-(+)-N-benzyl-1-phenylethylamine: chiral discrimination mechanism.

During the resolution of 2-chloromandelic acid with (R)-(+)-N-benzyl-1-phenylethylamine, the crystals of the less soluble salt were grown, and their structure were determined and presented. The chiral discrimination mechanism was investigated by examining the weak intermolecular interactions (such as hydrogen bond, CH/π, and van der Waals interactions) and molecular packing mode in crystal structure of the less soluble diastereomeric salt. A one-dimensional double-chain hydrogen-bonding network and a "lock-and-key" supramolecular packing mode are disclosed. The investigation demonstrates that hydrophobic layers with corrugated surfaces can fit into the grooves of one another to realize a compact packing, when the molecular structure of resolving agent is much larger than that of the racemate. This "lock-and-key" assembly is recognized to be another characteristic of molecular packing contributing to the chiral discrimination, in addition to the well-known sandwich-like packing by hydrophobic layers with planar boundary surfaces.

Uranium(iv) alkyl cations: synthesis, structures, comparison with thorium(iv) analogues, and the influence of arene-coordination on thermal stability and ethylene polymerization activity.

Reaction of [(XA2)U(CH2SiMe3)2] (1; XA2 = 4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene) with 1 equivalent of [Ph3C][B(C6F5)4] in arene solvents afforded the arene-coordinated uranium alkyl cations, [(XA2)U(CH2SiMe3)(η n -arene)][B(C6F5)4] {arene = benzene (2), toluene (3), bromobenzene (4) and fluorobenzene (5)}. Compounds 2, 3, and 5 were crystallographically characterized, and in all cases the arene is π-coordinated. Solution NMR studies of 2-5 suggest that the binding preferences of the [(XA2)U(CH2SiMe3)]+ cation follow the order: toluene ≈ benzene > bromobenzene > fluorobenzene. Compounds 2-4 generated in C6H5R (R = H, Me or Br, respectively) showed no polymerization activity under 1 atm of ethylene. By contrast, 5 and 5-Th (the thorium analogue of 5) in fluorobenzene at 20 and 70 °C achieved ethylene polymerization activities between 16 800 and 139 200 g mol-1 h-1 atm-1, highlighting the extent to which common arene solvents such as toluene can suppress ethylene polymerization activity in sterically open f-element complexes. However, activation of [(XA2)An(CH2SiMe3)2] {M = U (1) or Th (1-Th)} with [Ph3C][B(C6F5)4] in n-alkane solvents did not afford an active polymerization catalyst due to catalyst decomposition, illustrating the critical role of PhX (X = H, Me, Br or F) coordination for alkyl cation stabilization. Gas phase DFT calculations, including fragment interaction calculations with energy decomposition and ETS-NOCV analysis, were carried out on the cationic portion of 2'-Th, 2', 3' and 5' (analogues of 2-Th, 2, 3 and 5 with hydrogen atoms in place of ligand backbone methyl and tert-butyl groups), providing insight into the nature of actinide-arene bonding, which decreases in strength in the order 2'-Th > 2' ≈ 3' > 5'.

Diversity of metal-ligand interactions in halide (X = I, Br, Cl, F) and halide-free ambiphilic ligand rhodium complexes.

Reaction of the neutral ambiphilic ligand 2,7-di-tert-butyl-5-diphenylboryl-4-diphenylphosphino-9,9-dimethylthioxanthene (TXPB) with [{Rh(mu-Cl)(CO)(2)}(2)] yields [RhCl(CO)(TXPB)] (1) (Emslie et al. Organometallics 2006, 25, 5835). Complex 1 is square planar with the TXPB ligand bound to rhodium via the phosphine and thioether donors (these are features common to complexes 2-5, vide infra). Treatment of 1 with Me(3)SiBr and Me(3)SiI allowed for halide substitution to afford [RhBr(CO)(TXPB)] (2) and [RhI(CO)(TXPB)] (3), respectively. The halide co-ligands in complexes 1 and 2 form a strong bridging interaction between rhodium and the borane group in TXPB. The presence of stronger borane-halide coordination in 1 is clearly illustrated by an (11)B NMR chemical shift of 12 ppm versus 27 ppm in 2. In contrast, the iodide ligand in 3 forms only a weak bridging interaction to boron, leading to a B...I distance of 3.125(7) A, and an (11)B NMR chemical shift of 56 ppm (versus 69 ppm for free TXPB). A lower carbonyl stretching frequency in 3 (2002 cm(-1)) versus 1 or 2 (2008 and 2013 cm(-1), respectively) could be attributed to weakening of the Rh-X bond in 1 and 2 as a consequence of halide-borane coordination and/or a shorter Rh-S bond in complex 3. [Rh(CO)(TXPB-F)] (4) and the halide-free cation [Rh(CO)(TXPB)][PF(6)] (5) were accessed by reaction of 1 with [NMe(4)]F and Tl[PF(6)], respectively. Complex 4 is zwitterionic with fluoride bound to boron [(11)B NMR delta 4 ppm; B-F = 1.445(6) A; Rh...F = 3.261(3) A] and an eta(2)-interaction between the cationic rhodium center and the ipso- and ortho-carbon atoms of a B-phenyl ring in TXPB-F. By contrast, rhodium in 5 engages in an eta(2)-interaction with boron and the ipso-carbon of one B-phenyl ring; Rh-B and Rh-C(ipso) bond lengths in 5 are 2.557(3) and 2.362(2) A, respectively. The long Rh-B distance and an (11)B NMR chemical shift of 57 ppm are consistent with only a weak Rh-B interaction in 5, and a CO stretching frequency of 2028 cm(-1) (Nujol), versus 2004-2013 cm(-1) for complexes 1-4, is indicative of greatly reduced electron density in 5, relative to 1-4.

Persistent metal bis(hexafluoroacetylacetonato) complexes featuring a 2,2'-bipyridine substituted triarylamminium radical cation.

Herein, we describe the preparation of a 2,2'-bipyridine derivative containing a redox-active N,N'-(4,4'-dimethoxydiphenylamino) substituent (1), which readily coordinates M(hfac)(2) salts [M = Mn (2), Ni (3), Cu (4)] to generate stable, neutral, and pseudo-octahedral coordination complexes, which have been fully characterized. Cyclic voltammetry and spectroelectrochemical measurements on complexes 2-4 indicate stable one-electron oxidation processes, and the formation of persistent radical cation complexes. The neutral complexes (M = Mn or Ni) were subject to one-electron oxidation with NOPF(6) in acetonitrile, and magnetic moments of the resulting solutions were obtained using the Evans method at different temperatures. Our experimental results suggest that the first reported ferromagnetically coupled metal-triarylamminum radical cation complex is obtained when M = Mn(2+), and antiferromagnetic coupling results when M = Ni(2+). These results are supported by results from density functional theory calculations, which indicate that a π spin polarization mechanism for magnetic exchange coupling is operative in singly oxidized complexes, 2-4.

Preparation and magnetic properties of iron(3+) spin-crossover complexes bearing a thiophene substituent: toward multifunctional metallopolymers.

The synthesis of a new 3-ethynylthienyl-substituted QsalH ligand (QsalH is the short form for N-(8-quinolyl)salicylaldimine) (ThEQsalH 3), and the preparation, electronic, and magnetic properties of three homoleptic and cationic iron(3+) complexes containing this ligand with PF(6)(-) 4, SCN(-) 5, and ClO(4)(-) 6 counteranions are reported. In all three complexes a spin-crossover is observed in the solid state by variable temperature magnetic susceptibility measurements and Mossbauer spectroscopy, indicating that the synthetic modification of the QsalH ligand has not significantly altered the electronics at the metal center. This includes the observation of a very rare S = 5/2 to 3/2 spin-crossover in a non-porphyrin iron(3+) complex 5. The molecular structure and magnetic properties of an unusual iron(2+) complex 7 generated by reduction of complex 6 serendipitously during a recrystallization attempt in aerobic acetone solution is also reported. Complexes 4-6 feature iron(3+) reduction and oxidation of the thiophene ring at potentials of approximately -0.7 and +1.2 V (vs Fc), respectively.

Bimetallic iron(3+) spin-crossover complexes containing a 2,2'-bithienyl bridging bis-QsalH ligand.

We describe the synthesis of a new 3,3'-diethynyl-2,2'-bithienyl bridging bis-QsalH ligand (5), and the preparation of four bimetallic iron(3+) complexes containing 5 with Cl(-) (6), SCN(-) (7), PF(6)(-) (8), and ClO(4)(-) (9) counteranions. We show with variable temperature magnetic susceptibility, Mossbauer, and electron paramagnetic resonance (EPR) spectroscopy that each complex undergoes a spin-crossover in the solid state. In all four complexes, we observe very gradual and incomplete S = 5/2, 5/2 to S = 1/2, 1/2 spin-crossover processes, with three of the four complexes exhibiting nearly identical magnetic properties. We investigated the electronic properties of the complexes by cyclic and differential pulse voltammetry, and attempted electropolymerization reactions with acetonitrile solutions of the complexes, which were not successful. Each complex features a single iron(3+) reduction wave at approximately -0.7 V (versus ferrocene), and the oxidation of the 2,2'-bithienyl substituent occurs at +1.1 V. These materials represent a new structural paradigm for the study of rare bimetallic iron(3+) spin-crossover complexes.

(η-Cyclo-penta-dien-yl)(η-1,2-dipyrrolidin-1-ylbenzene)iron(II) hexa-fluoridophosphate.

Both complexed rings in the iron(II) complex cation of the title salt, [Fe(C(5)H(5))(C(14)H(20)N(2))]PF(6), are almost parallel [dihedral angle between planes = 5.34 (13)°]. Among the C atoms of the complexed arene ring, the quaternary C atoms are located at the longest, albeit unequal, distances from the Fe atom [2.252 (2) and 2.168 (2) Å].

1,1-Bis[4-(trifluoro-meth-yl)phen-yl]germetane.

The inter-nal C-Ge-C bond angle in the germacyclo-butane ring of the title compound, C(17)H(14)F(6)Ge or [Ge(C(3)H(6))(C(7)H(4)F(3))(2)], is 77.8 (3)°. The -CF(3) groups display rotational disorder [occupancies 0.604 (14):0.396 (14) and 0.410 (6):0.411 (6):0.179 (3)] and the germacyclo-butane ring also shows disorder [occupancies 0.604 (14):0.396 (14)].

The synthesis of densely functionalised α-acyloxy enaminals and enaminones via a novel homogeneous silver(i) catalysed rearrangement.

A synthesis of densely functionalised α-acyloxy enaminals and enaminones via a novel homogeneous silver(i) catalyzed rearrangement of 1-acyloxy-3-azido ketones is reported. This silver catalyzed reaction involves an internal redox process comprised of four net transformations: loss of nitrogen, reductive cleavage of the azide, 1,2-acyl migration and oxidation of the acyloxy position to an aldehyde (enaminal) or ketone (enaminone). These mild reaction conditions have been applied to acyclic, cyclic, and chiral substrates yielding the rearranged enaminals or enaminones in up to 91% yield, all of which prove to be stable, isolatable products.

Synthetic and structural investigations of bis(N-alkyl-benzoselenadiazolium) cations.

The synthesis, and spectroscopic and structural characterization of bridged dicationic derivatives of benzo-2,1,3-selenadiazoles are reported. The chloride salt of [H4C6NSeN-CH2-CH2-NSeNC6H4]2+ crystallizes forming a macrocyclic structure in which two cations are bridged by SeCl chalcogen bonds (ChBs), with a third chloride at the centre of the macrocycle. The structure of [1,2-(H4C6NSeN)2-C6H10]Cl2 consists of two selenadiazolium cations linked by a chiral cyclohexane and capped by SeCl ChBs. Tetrafluoroborate salts of a xylene bridge crystallize in two pseudopolymorphs in which the cations form SeF ChBs in an anti- or syn-conformation. The triflate salt of ethylene-bridged cations dimerizes through the formation of the [Se-N]2 supramolecular synthon with SeO ChBs capping the second selenium atom. In contrast, [H4C6NSeN-CH2-CH2-CH2-NSeNC6H4](CF3SO3)2 only forms SeO ChBs.

(η-Cyclo-penta-dien-yl)[η-diethyl eth-yl(phen-yl)malonate]iron(II) hexa-fluorido-phosphate.

At 223 (2) K, the complexed rings in the iron(II) complex cation of the title salt, [Fe(C(5)H(5))(C(15)H(20)O(4))]PF(6), are almost parallel [dihedral angle between planes = 4.10 (14)°]. Among the C atoms of the complexed arene ring, the quaternary C atom is located at the longest distance from the Fe atom. The F atoms of the PF(6) (-) anion were found to be equally disordered over two sites.

Thorium(iv) alkyl and allyl complexes of a rigid NON-donor pincer ligand with flanking 1-adamantyl substituents.

Palladium-catalyzed coupling of 1-adamantylamine (2 equiv.) with 4,5-dibromo-2,7-di-tert-butyl-9,9-dimethylxanthene afforded the proligand 4,5-bis(1-adamantylamino)-2,7-di-tert-butyl-9,9-dimethylxanthene, H2[XAd] (1), which upon deprotonation with excess KH or KCH2Ph in THF or dme generated [{K(THF)3}2(XAd)] (2a) and [K2(XAd)(dme)] (2b). Subsequent reaction of in situ generated 2a or 2b with [ThCl4(dme)2] yielded [(XAd)ThCl4K2]·x(dme) (3; x = 0.5-2), which reacted with 2 equiv. of LiCH2SiMe3 or K[allylTMS] to afford the bis(hydrocarbyl) complexes [(XAd)Th(CH2SiMe3)2(THF)] (4) and [(XAd)Th(η3-allylTMS)2] {5; allylTMS = 1-(SiMe3)C3H4}. Dialkyl complex 4 was stable at 80 °C for at least 2.5 hours, but decomposed over 4.5 hours at 110 °C. Diallyl complex 5 was stable for hours at 85 °C, and suffered less than 5% decomposition after 10 minutes at 155 °C. At room temperature, averaging of the syn and anti protons of the allyl CH2 groups of 5 occurred on the NMR timescale, as a consequence of rapid π-σ-π hapticity changes. Additionally, low temperature 1H and 13C NMR spectroscopy indicates that 5 exists as a rapidly exchanging mixture of two isomers with C1 and C2 symmetry. Compounds 2a, 4 and 5 were crystallographically characterized.

Epoxynemanione A, nemanifuranones A-F, and nemanilactones A-C, from Nemania serpens, an endophytic fungus isolated from Riesling grapevines.

Ten polyketide specialized metabolites, epoxynemanione A, nemanifuranones A-F, and nemanilactones A-C, were isolated from the culture filtrate of Nemania serpens (Pers.) Grey (1821), an endophytic fungus from a Riesling grapevine (Vitis vinifera) found in Canada's Niagara region. Additionally, four known metabolites 2-(hydroxymethyl)-3-methoxy-benzoic acid, phyllostine, 5-methylmellein and a nordammarane triterpenoid were isolated. A related known metabolite 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one has also been included for structural and biological comparison to the nemanifuranones. The latter was isolated from the culture filtrates of Mollisia nigrescens, an endophytic fungus from the leaves and stems of lowbush blueberry (Vaccinium angustifolium) found in the Acadian forest of Nova Scotia, Canada. Their structures were elucidated based on 1D and 2D NMR, HRESIMS measurements, X-ray crystallographic analysis of nemanifuranone A, the nordammarane triterpenoid and 2,3-dihydro-2-hydroxy-2,4-dimethyl-5-trans-propenylfuran-3-one compounds, and comparison of NOE and vicinal 1H-1H coupling constants to literature data for relative stereochemical assignments. Nemanifuranone A possesses a rare C2 hemiacetal and was active against both Gram-negative and Gram-positive bacteria.

Synthesis and structural characterisation of the aggregates of benzo-1,2-chalcogenazole 2-oxides.

Iodine oxidation of bis[2-(hydroxyiminomethyl)phenyl] dichalcogenides yields benzo-1,2-chalcogenazole 2-oxides. Annulated derivatives of iso-tellurazole N-oxides spontaneously aggregate into cyclic tetra- and hexamers through TeO chalcogen bonding; the structures of the co-crystals with benzene and CH2Cl2 illustrate the ability of these macrocycles to interact with small guest molecules. The selenium congener crystallizes forming a supramolecular polymer. VT NMR indicates that both compounds aggregate in solution but only at low temperature in the selenium case. The different abilities of these molecules to engage in supramolecular interactions are interpreted on the basis of their electronic properties evaluated with DFT-D3 calculations.

Synthetic, structural, and computational investigations of N-alkyl benzo-2,1,3-selenadiazolium iodides and their supramolecular aggregates.

Despite their versatility, the application of telluradiazoles as supramolecular building blocks is considerably constrained by their sensitivity to moisture. Albeit more robust, their selenium analogues form weaker supramolecular interactions. These, however, are enhanced when one nitrogen atom is bonded to an alkyl group. Here we investigate general methods for the synthesis of such derivatives. Methyl, iso-propyl and tert-butyl benzo-2,1,3-selenadiazolium cations were prepared by direct alkylation or cyclo-condensation of the alkyl-phenylenediamine with selenous acid. While the former reaction only proceeds with the primary and tertiary alkyl iodides, the latter is very efficient. Difficulties reported in earlier literature are attributable to the formation of adducts of benzoselenadiazole with its alkylated cations and side reactions initiated by aerobic oxidation of iodide. However, the cations themselves are resilient to oxidation and stable in acidic to neutral aqueous medium. X-ray crystallography was used in the identification and characterization of the following compounds: [C6H4N2(R)Se](+)X(-), (R = CH(CH3)2, C(CH3)3; X = I(-), I3(-)], [C6H4N2(CH3)Se](+)I(-), and [C6H4N2Se][C6H4N2(CH3)Se]2I2. Formation of SeN secondary bonding interactions (chalcogen bonds) was only observed in the last structure as anion binding to selenium is a strong competitor. The relative strengths of those forces and the structural preferences they enforce were assessed with DFT-D3 calculations supplemented by AIM analysis of the electron density.

iPSC Neuronal Assay Identifies Amaryllidaceae Pharmacophore with Multiple Effects against Herpesvirus Infections.

The Amaryllidaceae alkaloid trans-dihydrolycoricidine 7 and three analogues 8-10 were produced via asymmetric chemical synthesis. Alkaloid 7 proved superior to acyclovir, the current standard for herpes simplex virus, type 1 (HSV-1) infection. Compound 7 potently inhibited lytic HSV-1 infection, significantly reduced HSV-1 reactivation, and more potently inhibited varicella zoster virus (VZV) lytic infection. A configurationally defined (3R)-secondary alcohol at C3 proved crucial for efficacious inhibition of lytic HSV-1 infection.