Synthesis of the Marine Alkaloid Cylindricine C and Serendipitous Synthesis of Its 2,13-Di-epi Stereoisomer.

A new approach to the marine alkaloid cylindricine C afforded its previously unreported (±)-2,13-di-epi stereoisomer as the major product along with a minor amount of the racemic parent alkaloid. Key steps included a stereoselective dianion alkylation of a monoester of 1,2-cyclohexanedicarboxylic acid and an annulation based on the tandem conjugate addition of a primary amine to an acetylenic sulfone, followed by intramolecular acylation of the resulting sulfone-stabilized carbanion. The cis-azadecalin moiety thus formed, comprising the cyclohexane A-ring and enaminone B-ring of the products, was further elaborated by the selenenyl chloride-induced cyclofunctionalization of a pendant butenyl substituent with the enaminone moiety, followed by a seleno-Pummerer reaction. Desulfonylation and enaminone reduction afforded the final products. Molecular modeling and X-ray crystallography provided further insight into these processes.

Generation of Benzyne Species from Diphenylphosphoryl Derivatives: Simultaneous Exchange of Three Functional Groups.

Interaction of (2-diphenylphosphoryl-3-iodo-4-methoxy-phenyl) methanol with NaH in DMF at ambient temperature results in the generation of benzyne intermediates that can be trapped by furan or DMF. Trapping with DMF forms 3-(dimethylaminomethyl)-2-hydroxy-6-methoxybenzaldehyde demonstrating the simultaneous exchange of three functionalities in a single step. The presence of the alkoxy substituent adjacent to iodine is critical for high regioselectivity addition of DMF. The corresponding bromide or triflate can be used in place of the iodide with equal efficiency. This methodology was used to synthesize the reported structure of gigasol and leading to a structural reassignment of this biscoumarin natural product.

Anti-HIV activity of new pyrazolobenzothiazine 5,5-dioxide-based acetohydrazides.

A series of fifteen new 2-[3-(3-chlorophenyl)-5,5-dioxidobenzo[e]pyrazolo[4,3-c][1,2]thiazin-4(2H)-yl]-N'-arylmethyleneacetohydrazides (5a-o) were synthesized and screened for their anti-HIV-1 and cytotoxicity activity. Out of fifteen pyrazolobenzothiazine-based hydrazones, thirteen were found to be active inhibitors of HIV with EC50 values <20 µM. Moreover, the cytotoxicity results showed that most of the compounds were toxic to PBM, CEM and Vero cell lines. This information could be used for structural modifications to acquire good candidates of HIV drugs.

Ammonia Activation by a Nickel NCN-Pincer Complex featuring a Non-Innocent N-Heterocyclic Carbene: Ammine and Amido Complexes in Equilibrium.

A Ni(0)-NCN pincer complex featuring a six-membered N-heterocyclic carbene (NHC) central platform and amidine pendant arms was synthesized by deprotonation of its Ni(II) precursor. It retained chloride in the square-planar coordination sphere of nickel and was expected to be highly susceptible to oxidative addition reactions. The Ni(0) complex rapidly activated ammonia at room temperature, in a ligand-assisted process where the carbene carbon atom played the unprecedented role of proton acceptor. For the first time, the coordinated (ammine) and activated (amido) species were observed together in solution, in a solvent-dependent equilibrium. A structural analysis of the Ni complexes provided insight into the highly unusual, non-innocent behavior of the NHC ligand.

Reversible interconversion between a monomeric iridium hydroxo and a dinuclear iridium µ-oxo complex.

Treatment of the (PCsp(2)P)Ir(I)Cl complexes 2(R) (R = (i)Pr, (t)Bu) with cesium hydroxide in THF leads to the corresponding monomeric Ir(I) hydroxo complexes 5(R) in good to excellent yields of 70% (R = (i)Pr) and 92% (R = (t)Bu). The compounds are green in color and while they exhibit very similar (31)P NMR data to the chlorides 2, the (1)H NMR spectrum of each features a triplet ((3)JHP = 3.8 Hz) at 4.22 (R = (t)Bu) and 4.31 (R = (i)Pr) ppm that broadens in the presence of excess water and exchanges deuterium with D2O. Bands at 3642 and 3625 cm(-1) are observed in the IR spectrum for the νOH stretch. In the case of R = (i)Pr, a second product is observed in the crude reaction mixture and dominates when 5((i)Pr) is heated under vacuum and H2O is removed. This product is deep blue in color, and an X-ray crystal structure analysis reveals it to be the S4 symmetric dinuclear (PCsp(2)P)Ir-O-Ir(PCsp(2)P) complex 6((i)Pr), which features a µ-oxo ligand along an allene-like molecular core. Time-dependent DFT calculations with the M06 density functional show that a metal-to-ligand HOMO-LUMO excitation is mainly responsible for the blue color. Upon reaction of 6((i)Pr) with water, monomeric hydroxo complex 5((i)Pr) is quantitatively regenerated. Further, reaction of 6((i)Pr) with an excess of phenol smoothly yields the previously prepared (PCsp(2)P)IrOPh complex 3((i)Pr). Kinetic studies of the reaction indicated that it is first order in both [6((i)Pr)] and [HOPh] and exhibits a kH/kD of 1.9 when DOPh is employed. Eyring analysis is consistent with the bimolecular nature of the reaction, with ΔH(‡) = 13.1(5) kcal mol(-1) and ΔS(‡) = -13(2) cal K(-1). Finally, kobs is observed to increase when electron-withdrawing groups are incorporated in the para position of the phenol substrate and decrease when electron-donating groups are employed. These observations suggest that the rate-limiting step in this reaction is protonation of the µ-oxo ligand by the phenol substrate. This reaction serves as a model system for the reversible condensation of metal hydroxo ligands to form metal oxo moieties.

Selective hydrosilation of CO2 to a bis(silylacetal) using an anilido bipyridyl-ligated organoscandium catalyst.

A rigid anilido bipyridyl ligand has been designed for use in an organoscandium-based carbon dioxide hydrosilation catalyst. Ligand attachment by alkane elimination results in metalation of an aryl C-H bond in a 3,5-di-tert-butylphenyl group installed on the pyridyl unit, thus rendering the ligand tetradentate. Insertion of CO2 into the newly formed Sc-C bond leads to a κ(1) carboxylate which, when treated with the borane B(C6F5)3, becomes hemilabile. In addition to activating the catalyst, the k(1) carboxylate effectively sequesters free B(C6F5)3 and the ensemble is able to effectively hydrosilate CO2, in the presence of excess Et3SiH, almost exclusively to R3SiOCH2OSiR3. A maximum turnover number of about 3400 (conversion of silane) is observed. Mechanistic experiments suggest that the sequestration of free B(C6F5)3 by the hemilabile carboxylate contributes to the selectivity observed and prevents over reduction to methane.

Activation of water, ammonia, and other small molecules by PC(carbene)P nickel pincer complexes.

Nickel complexes of a PC(carbene)P pincer ligand framework are described. Dehydrobromination of the precursor (PC(sp)(3)P)NiBr in the presence of a donor (PPh3 or NC(t)Bu) leads to the title complexes, which feature a rare nickel-carbene linkage as the pincer ligand anchor point. This strongly donating, nucleophilic carbene center engages in a variety of E-H bond activations (E = H, C, N, O), some of which are reversible. This represents a new mode of bond activation by ligand cooperativity in nickel pincer complexes.

Synthesis, characterization, and electrochemical studies of PPh(3-n)(dipp)(n) (dipp = 2,6-diisopropylphenyl): steric and electronic effects on the chemical and electrochemical oxidation of a homologous series of triarylphosphines and the reactivities of the corresponding phosphoniumyl radical cations.

Activation barriers to the electrochemical oxidation for the series PPh3-n(dipp)n (dipp = 2,6-diisopropylphenyl) in CH2Cl2/Bu4NPF6 were measured using large amplitude FT ac voltammetry. Increasing substitution across this series, which offers the widest range of steric requirements across any analogous series of triarylphosphines reported to date, increases the energetic barrier to electron transfer; values of 18, 24, and 25 kJ mol(-1) were found for compounds with n = 1, 2, and 3, respectively. These values are significantly greater than those calculated for outer sphere activation barriers, with deviations between observed and calculated values increasing with the number of dipp ligands. This suggests that the steric congestion afforded by these bulky substituents imposes significant reorganizational energy on the electron transfer processes. This is the first investigation of the effect of sterics on the kinetics of heterogeneous electron transfer across a structurally homologous series. Increased alkyl substitution across the series also increases the chemical reversibility of the oxidations and decreases the oxidation peak potentials. As the compounds for which n = 1 and 2 are novel, the synthetic strategies employed in their preparation are described, along with their full spectroscopic, physical, and crystallographic characterization. Optimal synthesis when n = 1 is via a Grignard reagent, whereas when n = 2 an aryl copper reagent must be employed, as use of a Grignard results in reductive coupling. Chemical oxidation studies were performed to augment the electrochemical work; the O, S, and Se oxidation products for the parent triarylphosphines for which n = 1 and 2 were isolated and characterized.

Silver(I) complex formation with cysteine, penicillamine, and glutathione.

The complex formation between silver(I) and cysteine (H2Cys), penicillamine (H2Pen), and glutathione (H3Glu) in alkaline aqueous solution was examined using extended X-ray absorption fine structure (EXAFS) and (109)Ag NMR spectroscopic techniques. The complexes formed in 0.1 mol dm(-3) Ag(I) solutions with cysteine and penicillamine were investigated for ligand/Ag(I) (L/Ag) mole ratios increasing from 2.0 to 10.0. For the series of cysteine solutions (pH 10-11) a mean Ag-S bond distance of 2.45 ± 0.02 Å consistently emerged, while for penicillamine (pH 9) the average Ag-S bond distance gradually increased from 2.40 to 2.44 ± 0.02 Å. EXAFS and (109)Ag NMR spectra of a concentrated Ag(I)-cysteine solution (C(Ag(I)) = 0.8 mol dm(-3), L/Ag = 2.2) showed a mean Ag-S bond distance of 2.47 ± 0.02 Å and δ((109)Ag) 1103 ppm, consistent with prevailing, partially oligomeric AgS3 coordinated species, while for penicillamine (C(Ag(I)) = 0.5 mol dm(-3), L/Ag = 2.0) the mean Ag-S bond distance of 2.40 ± 0.02 Å and δ((109)Ag) 922 ppm indicate that mononuclear AgS2 coordinated complexes dominate. For Ag(I)-glutathione solutions (C(Ag(I)) = 0.01 mol dm(-3), pH ∼11), mononuclear AgS2 coordinated species with a mean Ag-S bond distance of 2.36 ± 0.02 Å dominate for L/Ag mole ratios from 2.0 to 10.0. The crystal structure of the silver(I)-cysteine compound (NH4)Ag2(HCys)(Cys)·H2O (1) precipitating at pH ∼10 was solved and showed a layer structure with both AgS3 and AgS3N coordination to the cysteinate ligands. A redetermination of the crystal structure of Ag(HPen)·H2O (2) confirmed the proposed digonal AgS2 coordination environment to bridging thiolate sulfur atoms in polymeric intertwining chains forming a double helix. A survey of Ag-S bond distances for crystalline Ag(I) complexes with S-donor ligands in different AgS2, AgS2(O/N), and AgS3 coordination environments was used, together with a survey of (109)Ag NMR chemical shifts, to assist assignments of the Ag(I) coordination in solution.

1,4,6,9-Tetra-tert-butyl-2,7-dioxa-tricyclo-[6.3.0.0(3,6)]deca-3,8-diene.

The title compound, C(24)H(40)O(2), lies on an inversion center with a half-mol-ecule in the asymmetric unit. The central dioxane ring adopts a chair conformation. The four-membered ring is slightly puckered with a butterfly angle of 13.50 (14)°.

BN-Dibenzo[a,o]picenes: analogues of an unknown polycyclic aromatic hydrocarbon.

Reflecting on synthetic pinnacles: Whereas the parent hydrocarbon is not readily accessible, several examples of BN substituted-dibenzo[a,o]picenes can be prepared in two steps from known starting materials. These non-linear heptacene analogues are water-stable materials. Their preparation utilizes a potentially general method for preparing extended BN analogues of difficult-to-synthesize polycyclic aromatic hydrocarbon frameworks.

Carbon monoxide activation via O-bound CO using decamethylscandocinium-hydridoborate ion pairs.

Ion pairs [Cp*(2)Sc](+)[HB(p-C(6)F(4)R)(3)](-) (R = F, 1-F; R = H, 1-H) were prepared and shown to be unreactive toward D(2) and α-olefins, leading to the conclusion that no back-transfer of hydride from boron to scandium occurs. Nevertheless, reaction with CO is observed to yield two products, both ion pairs of the [Cp*(2)Sc](+) cation with formylborate (2-R) and borataepoxide (3-R) counteranions. DFT calculations show that these products arise from the carbonyl adduct of the [Cp*(2)Sc](+) in which the CO is bonded to scandium through the oxygen atom, not the carbon atom. The formylborate 2-R is formed in a two-step process initiated by an abstraction of the hydride by the carbon end of an O-bound CO, which forms an η(2)-formyl intermediate that adds, in a second step, the borane at the carbon. The borataepoxide 3-R is suggested to result from an isomerization of 2-R. This unprecedented reaction represents a new way to activate CO via a reaction channel emanating from the ephemeral isocarbonyl isomer of the CO adduct.

A photo Lewis acid generator (PhLAG): controlled photorelease of B(C6F5)3.

A molecule that releases the strong organometallic Lewis acid B(C(6)F(5))(3) upon irradiation with 254 nm light has been developed. This photo Lewis acid generator (PhLAG) now enables the photocontrolled initiation of several reactions catalyzed by this important Lewis acid. Herein is described the synthesis of the triphenylsulfonium salt of a carbamato borate based on a carbazole function, its establishment as a PhLAG, and the application of the photorelease of B(C(6)F(5))(3) to the fabrication of thin films of a polysiloxane material.

Unexpected anomeric selectivity of a 1-C-arylglycal donor in Kdo glycoside synthesis.

A novel class of 1-C-arylglycals was developed and subjected to N-iodosuccinimide-mediated glycosylations with alcohols. Unexpectedly, all reactions provided 2-iodo-ß-D-ketopyranosides in high yields and excellent stereoselectivity. After removal of the 2-iodide by radical conditions, the aryl group was smoothly oxidized to provide the corresponding ß-Kdo glycosides. A mechanism for the stereoselective formation of ß-D-ketopyranosides was proposed, which was supported by evidence from X-ray crystallography.

Cyclic seleninate esters as catalysts for the oxidation of sulfides to sulfoxides, epoxidation of alkenes, and conversion of enamines to α-hydroxyketones.

Cyclic seleninate esters serve as catalysts for the rapid oxidation of sulfides to sulfoxides, alkenes to epoxides, and enamines to α-hydroxyketones. Optimal conditions were found that minimize the overoxidation of the product sulfoxides to sulfones and the hydrolysis of epoxides to diols. In some examples such as styrene derivatives, oxidative cleavage was observed instead of epoxidation. The enamine oxidations proceed via the initial formation of dimeric 2,5-diamino-1,4-dioxane species, which were hydrolyzed in situ to the final products. The structure of one such dimer was confirmed by X-ray crystallography.

Monomeric platinum(II) hydroxides supported by sterically dominant α-diimine ligands.

The use of two new highly sterically bulky α-diimine ligands for the stabilization of neutral, monomeric platinum(II) hydroxo complexes is described. Halide abstraction from LPtCl(2) complexes of these ligands in the presence of water, followed by deprotonation of the cationic aquo complex, leads to LPt(OH)Cl and LPt(OH)(2). The latter can be reprotonated with HNTf(2) to yield a highly fluxional hydroxoaquoplatinum(II) cation.

Tetra-aqua-bis-(thio-urea-κS)cadmium(II) triaqua-tris(thio-urea-κS)cadmium(II) disulfate.

The title compound, [Cd(CH(4)N(2)S)(2)(H(2)O)(4)][Cd(CH(4)N(2)S)(3)(H(2)O)(3)](SO(4))(2), contains two mol-ecules of each of the Cd complexes and four sulfate ions in the asymmetric unit: all the Cd atoms exhibit distorted octa-hedral geometries. The Cd-S and Cd-O bond lengths around the Cd atoms in the bis-(thio-urea) cations are in the ranges 2.580 (4)-2.599 (4) and 2.323 (8)-2.421 (9) Å, respectively, and the S atoms are in a cis orientation. In the tris-(thio-urea) cations, the corresponding bond lengths around the Cd atoms are slightly longer and are in the ranges 2.559 (4)-2.706 (3) and 2.303 (7)-2.480 (10) Å, respectively, and the S atoms are in a fac disposition. The crystal structure features numerous N-H⋯O, N-H⋯N, O-H⋯O and O-H⋯N hydrogen bonds. Two O atoms of a sulfate anion were found to be disordered over two orientations in a 0.620 (9):0.380 (9) ratio. The crystal studied was a racemic twin with BASF = 0.17 (5).

Dichlorido(5,10,15,20-tetra-phenyl-porphyrinato-κ(4)N)anti-mony(V) hemi{di-µ-chlorido-bis-[trichloridoanti-monate(III)]} dichloro-methane monosolvate.

The asymmetric unit of the title complex, [Sb(C(44)H(28)N(4))Cl(2)][Sb(2)Cl(8)](0.5)·CH(2)Cl(2), is composed of a Sb(V) complex cation wherein the Sb atom is hexa-coordinated by four N atoms of the pyrrole rings of the tetra-phenyl-porphyrinate (TPP) ligands and two chloride ions, a half di-µ-chlorido-bis-[trichloridoanti-monate(III)] counter-anion and a dichloro-methane solvent mol-ecule. In the cation, the average Sb-N distance is 2.066 (2) Å, while the Sb-Cl distances are 2.3410 (11) and 2.3639 (12) Å. The central unit of the cation, SbN(4)C(20), is far from being planar, with deviations of atoms from the least-squares plane ranging from -0.110 (4) to 0.124 (4) Å. The Sb-Cl distances in the anion, which is located about an inversion center, lie in the wide range 2.3715 (13)-2.7489 (13) Å, the longest distances being between the Sb and bridging Cl atoms. The crystal structure is stabilized by inter-molecular C-H⋯Cl inter-actions involving the cations, the anions and the solvent mol-ecules. The solvent mol-ecule is disordered over two orientations in a 0.901 (13):0.099 (13) ratio.

Redetermination of (d-penicillaminato)lead(II).

In the title coordination polymer, [Pb(C(5)H(9)NO(2)S)](n) {systematic name: catena-poly[(µ-2-amino-3-methyl-3-sulfido-butano-ato)lead(II)]}, the d-penicillaminate ligand coordin-ates to the metal ion in an N,S,O-tridentate mode. The S atom acts as a bridge to two neighbouring Pb(II) ions, thereby forming a double thiol-ate chain. Moreover, the coordinating carboxyl-ate O atom forms bridges to the Pb(II) ions in the adjacent chain. The overall coordination sphere of the Pb(II) ion can be described as a highly distorted penta-gonal bipyramid with a void in the equatorial plane between the long Pb-S bonds probably occupied by the stereochemically active inert electron pair. The amino H atoms form N-H⋯S and N-H⋯O hydrogen bonds, resulting in a cluster of four complex units, giving rise to an R(4) (4)(16) ring lying in the ab plane. The crystal structure of the title compound has been reported previously [Freeman et al. (1974 ▶). Chem. Soc. Chem. Commun. pp. 366-367] but the atomic coordinates have not been deposited in the Cambridge Structural Database (refcode DPENPB). Additional details of the hydrogen bonding are presented here.

3,5-Dibromo-2,2,6,6,7,7-hexa-methyl-octane-4-one.

In the title mol-ecule, C14H26Br2O, the central carbonyl group (C3O) is essentially planar (r.m.s. deviation = 0.0021 Å). The Br atoms lie on the same side of the mol-ecule and are approximately syn, with a Br-C⋯C-Br torsion angle of -43.52 (13)°. The crystal structure is devoid of any specific inter-molecular inter-actions.