Paul J. Gates

Catalytic Dehydrocoupling/Dehydrogenation of N-Methylamine-Borane and Ammonia-Borane: Synthesis and Characterization of High Molecular Weight Polyaminoboranes

The catalytic dehydrocoupling/dehydrogenation of N-methylamine-borane, MeNH(2)·BH(3) (7), to yield the soluble, high molecular weight poly(N-methylaminoborane) (8a), [MeNH-BH(2)](n) (M(W) > 20 000), has been achieved at 20 °C using Brookharts Ir(III) pincer complex IrH(2)POCOP (5) (POCOP = [μ(3)-1,3-(OPtBu(2))(2)C(6)H(3)]) as a catalyst. The analogous reaction with ammonia-borane, NH(3)·BH(3) (4), gave an insoluble product, [NH(2)-BH(2)](n) (8d), but copolymerization with MeNH(2)·BH(3) gave soluble random copolymers, [MeNH-BH(2)](n)-r-[NH(2)-BH(2)](m) (8b and 8c). The structures of polyaminoborane 8a and copolymers 8b and 8c were further analyzed by ultrahigh resolution electrospray mass spectrometry (ESI-MS), and 8a, together with insoluble homopolymer 8d, was also characterized by (11)B and (1)H solid-state NMR, IR, and wide-angle X-ray scattering (WAXS). The data indicate that 8a-8c are essentially linear, high molecular weight materials and that the insoluble polyaminoborane 8d possesses a similar structure but is of lower molecular weight (ca. 20 repeat units), presumably due to premature precipitation during its formation. The yield and molecular weight of polymer 8a was found to be relatively robust toward the influence of different temperatures, solvents, and adduct concentrations, while higher catalyst loadings led to higher molecular weight materials. It was therefore unexpected that the polymerization of 7 using 5 was found to be a chain-growth rather than a step-growth process, where high molecular weights were already attained at about 40% conversion of 7. The results obtained are consistent with a two stage polymerization mechanism where, first, the Ir catalyst 5 dehydrogenates 7 to afford the monomer MeNH═BH(2) and, second, the same catalyst effects the subsequent polymerization of this species. A wide range of other catalysts based on Ru, Rh, and Pd were also found to be effective for the transformation of 7 to polyaminoborane 8a. For example, polyaminoborane 8a was even isolated from the initial stage of the dehydrocoupling/dehydrogenation of 7 with [Rh(μ-Cl)(1,5-cod)](2) (2) as the catalyst at 20 °C, a reaction reported to give the N,N,N-trimethyl borazine, [MeN-BH](3), under different conditions (dimethoxyethane, 45 °C). The ability to use a variety of catalysts to prepare polyaminoboranes suggests that the synthetic strategy should be applicable to a broad range of amine-borane precursors and is a promising development for this new class of inorganic polymers.

Ru-Catalysed C-H Arylation of Indoles and Pyrroles with Boronic Acids : Scope and Mechanistic Studies

The Ru-catalysed C2–H arylation of indoles and pyrroles by using boronic acids under oxidative conditions is reported. This reaction can be applied to tryptophan derivatives and tolerates a wide range of functional groups on both coupling partners, including bromides and iodides, which can be further derivatised selectively. New indole-based ruthenacyclic complexes are described and investigated as possible intermediates in the reaction. Mechanistic studies suggest the on-cycle intermediates do not possess a para-cymene ligand and that the on-cycle metalation occurs through an electrophilic attack by the Ru centre.

Electrospray Ionisation Fourier-transform Ion Cyclotron Resonance Mass Spectrometry of Dynamic Combinatorial Libraries

The use of electrospray ionisation Fourier-transform ion cyclotron resonance tandem mass spectrometry (ESI-FTICR-MS/MS) for the analysis of dynamic combinatorial libraries (DCLs) of pseudo-peptide macrocyclic hydrazone oligomers is presented. The design of library building blocks results in mixtures of compounds with greater diversity than libraries generated by conventional combinatorial chemistry and so presents increased demands for analysis. The extended capabilities of the FTICR technique, specifically selective ion trapping, sensitivity, high resolution and mass accuracy over a broad mass range, are compatible with these increased demands and, most importantly, without the need for chromatography. Preliminary studies on the sequencing of cyclic oligomers and confirmation of the presence of sequence isomers are presented. These studies highlight the potential of FTICR-MS as a superior technique for the analysis of combinatorially generated compounds.

A simple modification of a silicic acid lipid fractionation protocol to eliminate free fatty acids from glycolipid and phospholipid fractions

When fractionating natural and standard lipid mixtures according to the most widely used method for the analysis of soil and other environmental materials, free fatty acids (FFAs) were not recovered quantitatively in the fraction expected to contain all simple lipids. Rather than being eluted from activated silicic acid adsorption chromatographic columns with chloroform, FFAs in standard lipid mixtures appeared only in the two subsequent fractions eluted with acetone and methanol, respectively. Substantial quantities of FFAs from cow dung lipid samples were eluted using chloroform as expected but appreciable amounts also eluted in the acetone (glycolipid) fraction. The fatty acid distribution of the methanol (phospholipid) fraction from dung displayed slightly more FFA compositional character than when FFAs were excluded but this influence was not significant (p=0.08). A simple modification to the silicic acid column technique ensures that FFAs are reproducibly eluted in the chloroform/acetic acid (100:1 v/v; simple lipid) fraction. The modification had no deleterious effect upon the elution characteristics of any phospholipid from a variety of headgroup classes tested. The carry-over of FFAs into glycolipid fractions was confirmed by nanospray ionisation mass spectrometry of the intact polar lipid fractions. As far as could be inferred from the distinctive molecular weight distributions of the glycolipid and phospholipid fractions, none of the complex lipids in dung eluted in both fractions.

Chemoselective Cross-Coupling Reactions with Differentiation between Two Nucleophilic Sites on a Single Aromatic Substrate

A new thiophene building block, containing both a stannyl group and a boronic ester, was prepared. From this starting material, a general, nucleophile-selective one-pot reaction was developed, exploiting the different reactivities of the Stille and Suzuki-Miyaura cross-coupling reactions. A series of aromatic electrophiles were used to demonstrate the high functional group tolerance.

Highly tin-selective stille coupling: synthesis of a polymer containing a stannole in the main chain.

The incorporation of heavier Group 14 element heteroles into semiconducting polymers leads to unusual optoelectronic properties. However, polymers containing stannoles have not been accessible to date. We report a synthetic route to a well-defined, stannole-containing polymer, the first example of this class of π-conjugated polymers. This route was made possible by developing difunctionalized stannole monomers and highly tin-selective Stille coupling reactions that leave the tin in the stannole untouched. Compared to poly(3-n-hexylthiophene), the resulting polymer displays a remarkable bathochromic shift in its absorption.

Boryl (Hetero)aryne Precursors as Versatile Arylation Reagents: Synthesis through C-H Activation and Orthogonal Reactivity.

(Pinacolato)boryl ortho-silyl(hetero)aryl triflates are presented as a new class of building blocks for arylation. They demonstrate unique versatility by delivering boronate or (hetero)aryne reactivity chemoselectively in a broad range of transformations. This approach enables the unprecedented postfunctionalization of fluoride-activated (hetero)aryne precursors, for example, as substrates in transition-metal catalysis, and offers valuable new possibilities for aryl boronate postfunctionalization without the use of specialized protecting groups.

Dual Selectivity: Electrophile and Nucleophile Selective Cross-Coupling Reactions on a Single Aromatic Substrate

The development of a high yielding, both nucleophile and electrophile selective cross-coupling reaction with aromatic rings is presented. The reaction is general with respect to functional groups. Furthermore, the products still contain a boronic ester and a bromide. These two functional groups allow them to be easy-to-prepare, highly complex starting materials for further reactions, avoiding protecting group transformations.

Electrospray MS-based characterization of β-carbolines - mutagenic constituents of thermally processed meat.

The beta-carbolines 1-methyl-9H-pyrido [3,4-b]indole and 9H-pyrido[3,4b]indole have been implicated as having causative roles in a number of human diseases, such as Parkinsons disease and cancer. As they can be formed during the heating of protein-rich food, a number of analytical methodologies have been proposed for their detection and quantification in foodstuff. For this purpose, LC-MS and LC-MS/MS have emerged as the most specific analytical methods, and the quantification is based on the occurrence of unusual ions, such as [M+H-(H(*))]+ and [M+H-2H]+. In this study, we have investigated the formation of these ions by accurate-mass electrospray MS/MS and demonstrated that these ions are formed from gas-phase ion-molecule reactions between water vapor present in the collision cell and the protonated molecule of 1-methyl-9H-pyrido [3,4-b]indole and 9H-pyrido[3,4b]indole. Although this reaction has been previously described for heterocyclic amine ions, it has been overlooked in the most of recent LC-MS and LC-MS/MS studies, and no complete data of the fragmentation are reported. Our results demonstrate that additional attention should be given with respect to eliminating water vapor residues in the mass spectrometer when analysis of beta-carbolines is performed, as this residue may affect the reliability in the results of quantification.

Characterisation of flavonoid aglycones by negative ion chip-based nanospray tandem mass spectrometry.

Flavonoids are one of the most important classes of natural products having a wide variety of biological activities. There is wide interest in a range of medical and dietary applications, and having a rapid, reliable method for structural elucidation is essential. In this study a range of flavonoid standards are investigated by chip-based negative ion nanospray mass spectrometry. It was found that the different classes of flavonoid studied have a combination of distinct neutral losses from the precursor ion [M-H]− along with characteristic low-mass ions. By looking only for this distinct pattern of product ions, it is possible to determine the class of flavonoid directly. This methodology is tested here by the analysis of a green tea extract, where the expected flavonoids were readily identified, along with quercetin, which is shown to be present at only about 2% of the most intense ion in the spectrum.