Endo-oxacyclizations of polyepoxides: biomimetic synthesis of fused polycyclic ethers

Boron trifluoride-etherate promotes the endo-selective oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The mechanism of the oxacyclization reaction probably involves intramolecular nucleophilic addition of epoxide oxygen to open another epoxide that is activated as an electrophile by the Lewis acid. These oxacyclizations proceed stereospecifically with inversion of configuration upon opening of each epoxide to provide trans-fused polycyclic products. The oxacyclization cascade is terminated by a tethered nucleophile, which may be the carbonyl oxygen of a ketone, ester, or carbonate, or a trisubstituted alkene. The best oxacyclization yields are generally observed with tert-butyl carbonate as the terminating nucleophile, although in some cases the oxacyclization products include formation of tert-butyl ethers as a minor product. The oxacyclization transformations described herein may mimic ring-forming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products.     

Crystal Structure Models for the Aldaramide Units of Poly(pentaramides)

The X-ray crystal structures of seven structurally related diamides, N,N′-dihexyl- and N,N′-dimethylglutaramide, N,N′-dimethylxylaramide, N,N′-dimethyl-l-arabinaramide, N,N′-dimethylribaramide monohydrate, 2,3,4-tri-O-acetyl-N,N′-dimethylxylaramide, and 2,3,4-tri-O-acetyl-N,N′-dimethyl-l-arabinaramide, were determined. These diamides were chosen as solid-state conformational models for the diamido repeating units of the corresponding polyamides. Solid-state conformations of the two N,N-dialkyglutaramides, with no pendant groups, were compared to those of their stereochemically different trihydroxy derivatives N,N′-dimethylxylaramide, l-arabinaramide and ribaramide, and the two aforementioned tri-O-acetylpentaramides.     

A new strategy for the synthesis of taurine derivatives using the 'safety-catch' principle for the protection of sulfonic acids

The safety-catch principle has been applied for the development of a new method for protecting sulfonic acids. 2,2-Dimethylsuccinic acid was reduced to 2,2-dimethylbutane-1,4-diol, which was selectively silylated to give 4-(tert-butyldiphenylsilanyloxy)-2,2-dimethylbutan-1-ol. Reaction of the latter compound with 2-chloroethanesulfonyl chloride in the presence of triethylamine afforded 4-(tert-butyldiphenylsilyloxy)-2,2-dimethylbutyl ethenesulfonate directly. The ethenesulfonate underwent Michael-type addition with secondary amines to give protected derivatives of taurine (2-aminoethanesulfonic acid). Deprotection was achieved on treatment with tetrabutylammonium fluoride, whereby cleavage of the silicon-oxygen bond led to an intermediate alkoxide that immediately cyclised to 2,2-dimethyltetrahydrofuran with liberation of a sulfonate. Pure sulfonic acids were obtained from the crude product by ion exchange chromatography on a strongly basic resin, which was eluted with aqueous acetic acid. The method developed should be generally applicable to the protection of sulfonic acids and is amenable to a multiparallel format.     

Harnessing redox-active ligands for low-barrier radical addition at oxorhenium complexes

The addition of an [X](+) electrophile to the five-coordinate oxorhenium(V) anion [Re(V)(O)(ap(Ph))(2)](-) {[ap(Ph)](2-) = 2,4-di-tert-butyl-6-(phenylamido)phenolate} gives new products containing Re-X bonds. The Re-X bond-forming reaction is analogous to oxo transfer to [Re(V)(O)(ap(Ph))(2)](-) in that both are 2e(-) redox processes, but the electronic structures of the products are different. Whereas oxo addition to [Re(V)(O)(ap(Ph))(2)](-) yields a closed-shell [Re(VII)(O)(2)(ap(Ph))(2)](-) product of 2e(-) metal oxidation, [Cl](+) addition gives a diradical Re(VI)(O)(ap(Ph))(isq(Ph))Cl product ([isq(Ph)](?-) = 2,4-di-tert-butyl-6-(phenylimino)semiquinonate) with 1e(-) in a Re d orbital and 1e(-) on a redox-active ligand. The differences in electronic structure are ascribed to differences in the π basicity of [O](2-) and Cl(-) ligands. The observation of ligand radicals in Re(VI)(O)(ap(Ph))(isq(Ph))X provides experimental support for the capacity of redox-active ligands to deliver electrons in other bond-forming reactions at [Re(V)(O)(ap(Ph))(2)](-), including radical additions of O(2) or TEMPO(?) to make Re-O bonds. Attempts to prepare the electron-transfer series monomers between Re(VI)(O)(ap(Ph))(isq(Ph))X and [Re(V)(O)(ap(Ph))(2)](-) yielded a symmetric bis(μ-oxo)dirhenium complex. Formation of this dimer suggested that Re(VI)(O)(ap(Ph))(isq(Ph))Cl may be a source of an oxyl metal fragment. The ability of Re(VI)(O)(ap(Ph))(isq(Ph))Cl to undergo radical coupling at oxo was revealed in its reaction with Ph(3)C(?), which affords Ph(3)COH and deoxygenated metal products. This reactivity is surprising because Re(VI)(O)(ap(Ph))(isq(Ph))Cl is not a strong outer-sphere oxidant or oxo-transfer reagent. We postulate that the unique ability of Re(VI)(O)(ap(Ph))(isq(Ph))Cl to effect oxo transfer to Ph(3)C(?) arises from symmetry-allowed mixing of a populated Re≡O π bond with a ligand-centered [isq(Ph)](?-) ligand radical, which gives oxyl radical character to the oxo ligand. This allows the closed-shell oxo ligand to undergo a net 2e(-) oxo-transfer reaction to Ph(3)C(?) via kinetically facile redox-active ligand-mediated radical steps. Harnessing intraligand charge transfer for radical reactions at closed-shell oxo ligands is a new strategy to exploit redox-active ligands for small-molecule activation and functionalization. The implications for the design of new oxidants that utilize low-barrier radical steps for selective multielectron transformations are discussed.     

Synthesis and optical properties of diaza- and tetraazatetracenes

A series of functionalized diaza- and tetraazatetracenes was synthesized, either by condensation of an aromatic diamine with an ortho-quinone/diethyloxalate followed by chlorination with POCl(3) to give diazatetracenes or by palladium-catalyzed coupling of a phenylenediamine with various 2,3-dichloroquinoxalines to give tetraazatetracenes (after oxidation with MnO(2)). Representative examples included halogenated and nitrated derivatives. The optical properties of these azatetracenes were discussed with respect to their molecular structures and substitution patterns. The diazatetracenes and tetraazatetracenes formed two different groups that had significantly different electronic structures and properties. Furthermore, 1,2,3,4-tetrafluoro-6,11-bis((triisopropylsilyl)ethynyl)benzo[b]phenazine was synthesized, which is the first reported fluorinated diazatetracene. Single-crystal X-ray analysis of this compound is reported.     

A sonotrode for electroanalysis: the determination of copper in passivating media

A sonotrode consisting of a disc shaped glassy carbon electrode attached to a quartz rod and inserted into a drilled ultrasonic probe tip has been designed and used as a novel alternative to the traditional 'face on' cell arrangement where an ultrasonic micro-tip probe is placed opposite a glassy carbon working electrode. The 'single probe' arrangement is both convenient and optimised for electroanalysis. We first report how under ultrasonic agitation of the sonotrode the mass transport to the electrode surface is enhanced compared to that observed under silent conditions and also how the sonotrode cell geometry compares with the well-established 'face on' cell geometry for cobalt electrodeposition. Second, we will show that the new sonotrode can be used in the application for the determination of copper in a series of fouling media in which conventional silent electroanalysis fails. The passivation of the electrodes surface by surfactant species can be overcome by cavitationally induced streaming and/or erosion at the sonotrode surface with recoveries of 100% and 93.8% achieved at 42 W cm-2 for Triton X-100 and sodium dodecyl sulfate (SDS), respectively. Other data indicates that the sonotrode can be successfully employed for the detection of copper in beer (Marston's bitter), a system known to be complex and highly electrode fouling and difficult to analyse using standard, silent electroanalytical techniques.     

Molecular dynamics simulation of [Gd(egta)(H(2)O)](-) in aqueous solution: internal motions of the poly(amino carboxylate) and water ligands, and rotational correlation times

Molecular dynamics simulations of [Gd(egta)(H(2)O)](-) (egta(4-)=3,12-bis(carboxymethyl)-6,9-dioxa-3,12-diazatetradecanedioate(4-)) have been performed without any artificial constraint on the first coordination sphere, such as covalent bonds between the Gd(3+) and the coordination sites. Two new crystallographic structures were determined for this gadolinium chelate and used to start two molecular dynamics simulations. [Gd(egta)(H(2)O)](-) and [Gd(egta)](-) were both observed during the simulations, with a mean volume for the reaction of dissociation [Gd(egta)(H(2)O)](-)-->[Gd(egta)](-)+H(2)O of +7.2 cm(3)mol(-1), which corroborates the previously published experimental value of +10.5 cm(3)mol(-1). Changes in the conformation of the complex with the inversion of several dihedral angles are observed in the simulations independently from the water dissociation. Very fast changes of the third-order rotation axis direction of the Gd(3+) coordination polyhedron (of symmetry D(3h)) are observed during the simulations and are related to the mechanism of electronic relaxation of the complex. Different rotational correlation times (tau(R)) were calculated from the simulations on various observables of the complex. Protons of the inner sphere have different tau(R). The mean tau(R) of the two Gd-HW(HW=hydrogen of water molecule) vectors is 72% lower than tau(R) of the complex, and 75% lower than tau(R) of the vector Gd-OW (OW=oxygen of water molecule). This discrimination of the tumbling rates should be taken into account in future global (17)O NMR, EPR and NMRD (nuclear magnetic relaxation dispersion) data analysis.     

Tetrahydrofuran-mediated radical processes: stereoselective synthesis of d,l-hexestrol

The highly stereoselective synthesis of d,l-hexestrol (1), an inhibitor of microtubule assembly, is developed by using, as a key step, an intermolecular coupling of Co₂(CO)₆-complexed propargyl radicals. The latter are generated by novel complementary processes involving an interaction of tetrahydrofuran with Co₂(CO)₆-complexed propargyl alcohols and cations. An isomerically pure d,l-μ-η²-[3,4-di(4-methoxyphenyl)-1,5-hexadiyne]-bis-dicobalthexacarbonyl (d,l-6) is isolated in 69-91% yield with intermolecular coupling reactions exhibiting an excellent chemo- (0.5-7%) and d,l-diastereoselectivity (90-94%). The structure of d,l-6 is determined by X-ray diffraction. The subsequent steps include BBr₃-induced demethylation of 4-methoxyaryl groups, demetalation with cerium(IV) ammonium nitrate, and hydrogenation of acetylenic termini affording d,l-hexestrol (1).     

Semi-vacant Wells-Dawson anions. Synthesis of tri-tungsten-vacant derivatives and crystallographic studies of [alphabetabetaalpha-(Cu(II)OH2)2(Cu(II))2(AsW15(OH2)3(OH)O52)2]12-

The tri-tungsten-vacant polyoxometalate, [alpha-AsW15(OH)4O52]13-, derived from the semi-vacant Wells-Dawson complex [alpha-AsW18(OH)4O58]7-, reacts with the late-transition metal cations, Cu(II) or Zn(II), to form sandwich-type species; the X-ray crystal structure of [alphabetabetaalpha]-(Cu(II)OH2)2(Cu(II))2(AsW15(OH2)3(OH)O52)2]12-, prepared by the acidification of [alphabetabetaalpha]-(Cu(II)OH2)2(Cu(II))2(AsW15(OH)4O52)2]18-, reveals that the missing heteroatoms are distal to the central Cu4 unit and the vertices of the vacant tetrahedron are occupied by one OH- and three OH2 groups.