• Stereoselective synthesis of substituted hexahydro-3a,4a-diazacyclopentaphenanthren-4-ones and aminoferrocenes

      Zaifman, Joshua David; Department of Chemistry (Brock University, 2011-05-17)
      This thesis explored the development of several methodologies for the stereoselective construction of ligand frameworks and some of their applications. The first segment concerns the application of an enantioselective lithiation at an Sp3_ hybridized position adjacent to nitrogen by means of the widely used and typically highly effective enantioselective lithiation with ( -)-sparteine. This investigation was intended to develop a method to install chirality into a system that would be converted into a family of diaminoylidenes for use as phosphine mimics in transition metal catalysis or as nucleophilic reagents. Molecular modeling of the system revealed some key interactions between the substrate and (-)-sparteine that provided general insight into the diamine's mode of action and should lend some predictive value to its future applications. The second portion focuses on the development of methods to access 1,2- disubstituted aminoferrocenes, an underexplored class of metallocenes possessing planar chirality. Two routes were examined involving a diastereoselective and an enantioselective pathway, where the latter method made use of the first BF3-mediated lithiation-substitution to install planar chirality. Key derivatives such as 1,2- aminophosphines, made readily accessible by the new route, were evaluated as ligands for Pd(II), Pt(II) and Ir(I). These complexes show activity in a number of transformations with both achiral and prochiral substrates. Optimization experiments were conducted to prepare enantiomerically enriched 2-substituted-I-aminoferrocenes by direct asymmetric lithiation of BF3-coordinated tertiary aminoferrocenes. A predictive computational model describing the transition state of this reaction was developed in collaboration with Professor Travis Dudding's group (Department of Chemistry, Brock University). The predicted stereochemistry of the process was confirmed by single-crystal X-ray analysis of a 2-phosphino-l-dimethylaminoferrocene derivative. Enantiomerically pure samples of the aminophosphine ligands derived from this new process have given promising preliminary results in the enantioselective hydrogenation of prochiral alkenes and warrant further stUdy in metal-mediated catalysis.
    • Synthesis and Derivatization of Amaryllidaceae Constituents – Narciclasine and Pancratistatin

      Lapinskaite, Ringaile; Department of Chemistry
      This thesis describes the synthesis and derivatization of narciclasine and pancratistatin. A detailed description is given to the total formal synthesis of pancratistatin through a reductive transposition approach and the total and semi-syntheses of 2-epi-narciclasine and its discovery as a new natural product. The last part of this work focuses on the search for a divergent approach to access C-1 narciclasine and C-1-pancratistatin derivatives from natural narciclasine. Experimental and spectral data are provided for the new compounds.
    • Synthesis and Reactivity of Low Valent Main Group Element Complexes

      Chu, Terry; Department of Chemistry
      The β-diketiminate aluminum(I) complex NacNacAl (III-1) was shown to activate a range of substrates containing robust single and double bonds. Compound III-1 oxidatively adds a variety of H–X bonds (X = H, B, Al, C, Si, N, P, O) to give a series of four-coordinate aluminum hydride derivatives including the first example of an aluminum boryl hydride. In the case of Al–H addition, the reaction was shown to be in equilibrium and reversible. Furthermore, cleavage of aryl and alkyl C–F bonds, the latter a rare reaction with only a handful of examples in the literature, was observed with III-1. Robust C–O and C–S bonds were also activated by III-1 along with RS–SR and R2P–PR2 bonds. All novel aluminum complexes were characterized by spectroscopic methods and X-ray diffraction analysis for the majority of them. Activation of the C=S or P=S bonds in a thiourea or phosphine sulfide, respectively, was accomplished by III-1 to give the first examples of Lewis base-stabilized monomeric terminal aluminum sulfides. The nature of the Al=S bond was examined computationally as well as experimentally. Related reaction with a urea derivative gave an unexpected aluminum hydride while reaction of III-1 with phosphine oxides gave a putative aluminum oxide as a result of P=O bond cleavage. However, the aluminum oxo promptly deprotonates a neighbouring molecule to furnish an aluminum hydroxide as the isolated product. Reduction of the cationic germanium(II) complex IV-1 affords the formally zero valent germanium complex IV-4 stabilized by the bis(imino)pyridine platform. Compound IV-4 was fully characterized by spectroscopic methods and X-ray diffraction analysis. The molecule has a singlet ground state and DFT studies revealed partial delocalization of one of the germanium lone pairs into the ligand framework. Complex IV-4 was unreactive towards H–X bond activation, the lack of reactivity ascribed to the large singlet-triplet energy gap calculated. The same bis(imino)pyridine ligand was also used to prepare reduced zinc complexes. Monoreduction of the zinc dichloride precursor gave the formally Zn(I) compound IV-6. Further reduction of IV-6 in the presence of DMAP gave the formally zero valent zinc complex IV-9. Both compounds were fully characterized by spectroscopic methods, DFT calculations, and X-ray diffraction analysis which revealed that both zinc atoms are four-coordinate and adopt unusual square planar and see-saw geometry, respectively.
    • Synthesis and Reactivity of Main Group Complexes for Applications in Small Molecule Activation

      Nguyen, Minh Tho; Department of Chemistry
      The work described in this thesis is focused on the preparation of a series of novel main group complexes, featuring unusual structural and bonding situations, and the study of their reactivity toward small molecules. The new zinc complexes dimphZnBu (V-2) and dimphZnCl2Li(THF)3 (V-3), supported by a diiminophenyl (dimph) ligand were prepared. The reaction of complex V-3 with LiHBEt3 resulted in hydride transfer to the C=N imine group to give an unusual zinc dimer (V-7). The latter transformation occurs via formation of compound (ɳ1(C),ĸ1(N)- 2,6-(2,6-iPr2C6H3N=CH)2C6H3)2Zn (V-5) which can be also accessed by reduction of V-7 with KC8. Diiminophenyl (dimph) proved to be an excellent ligand platform to stabilise a low-valent phosphorus centre. The resultant compound dimphP (VI-2), which can be rationalised as an imino-stabilised phosphinidene or benzoazaphopshole, shows remarkable chemical stability toward water and oxygen. VI-2 reacts with excess strong acid HCl to generate the P(III) chloride (dimHph)PCl (VI-6). Surprisingly, substitution of the chloride under some nucleophilic (KOBut) and electrophilic conditions (Me3SiOTf) regenerates the parent compound VI-2 by proton removal from the weakly acidic CH2N position. A related species (dimH2ph)P (VI-10) is produced upon thermal rearrangement of the hydride (dimHph)PH (VI-9). The molecular structure and reactivity of compounds VI-2 and other related compounds are also discussed. The reduction of the O,C,O-chelated phosphorus (III) chloride (VI-16) ( O,C,O = 2,6-bis[(2,6-diisopropyl)phenoxyl]phenyl) with KC8 or PMe3 resulted in the formation of a cyclic three-membered phosphorus compound (VI-18). The intermediacy of phosphinidene VI-17 was confirmed by trapping experiments and a VT 31P{1H} NMR study. The reaction of in-situ generated phosphinidene with either PhSiH3 or HBpin resulted in the formation of an unprecedented phosphine (VI-23). The treatment of VI-16 with two equivalents of DippNHC carbene led to ArP(Cl)NHC product (VI-24). The germylone dimNHCGe (dimNHC = diimino N-Heterocyclic Carbene, VII-8) was successfully prepared by the reduction of germanium cation (VII-7) with KC8. The molecular structure of VII-8 was unambiguously established, using NMR spectroscopy and single-crystal X-ray diffraction analysis. The reactivity of VII-8 was investigated. VII-8 is inactive towards butadiene but undergoes an oxidative cyclization with tetrachloro-o-benzoquinone to give a tetragermanium derivative. VII-8 undergoes oxidation addition of CH3I and PhI, followed by an unusual migration of the Me and Ph groups from germanium to the carbene ligand. Related chemistry takes place upon protonation with dry HCl, which results in the migration of the hydride to the carbene ligand.
    • Synthesis of Cyclopropenium-Appended Organocatalysts and Applications

      Smajlagic, Ivor; Department of Chemistry
      Enclosed within this dissertation is the development and application of multiple cyclopropenium-containing compounds formally belonging to two closely-related classes of organocatalysts, namely thioureas and squaramides. The former catalyst, coined as a thiourea-cyclopropenium, is deployed in pyranylation reactions of alcohols and phenols, as well as Friedel–Crafts alkylation, while the latter—a squaramide-cyclopropenium catalyst—targets oxime ether bond formation. Accompanying these innovative synthetic methodologies are comprehensive experimental and computational mechanistic studies that work in synergy to delineate numerous key features, all of which provide valuable information with respect to understanding the multifaceted nature of catalysis. Experimental and spectral data are provided for all new compounds.
    • Synthesis of unnatural analogues of pancratistatin and narciclasine

      Vshyvenko, Sergey; Department of Chemistry (Brock University, 2014-05-07)
      Described herein is the chemoenzymatic synthesis of several different types of unnatural analogues of Amaryllidaceae constituents. Development and refinement of existing and design and execution of new approaches towards the synthesis of C-1 analogues of pancratistatin and A-ring heterocyclic analogues of narciclasine are discussed. Evaluation of the new analogues as cancer growth inhibitory agents is also described
    • Tetrathiafulvalene and 2,2'-Bipyridine: Bridging both Worlds in the Pursuit of Novel Molecular Materials

      Gumbau-Brisa, Roger; Department of Chemistry (Brock University, 2013-04-04)
      The preparation and characterization of two families of building blocks for molecule-based magnetic and conducting materials are described in three projects. In the first project the synthesis and characterization of three bis-imine ligands LI - L3 is reported. Coordination of LI to a series of metal salts afforded the five novel coordination complexes Sn(L4)C4 (I), [Mn(L4)(u-CI)(CI)(EtOH)h (II), [CU(L4)(u-sal) h(CI04)2 (sal = salicylaldehyde anion) (III), [Fe(Ls)2]CI (IV) and [Fe(LI)h(u-O) (V). All complexes have been structurally and magnetically characterized. X-ray diffraction studies revealed that, upon coordination to Lewis acidic metal salts, the imine bonds of LI are susceptible to nucleophilic attack. As a consequence, the coordination complexes (I) - (IV) contain either the cyclised ligand L4 or hydrolysed ligand Ls. In contrast, the dimeric Fe3+ complex (V) comprises two intact ligand LI molecules. In. this complex, the ligand chelates two Fe(III) centres in a bis-bidentate manner through the lone pairs of a phenoxy oxygen and an imine nitrogen atom. Magnetic studies of complexes (II-V) indicate that the dominant interactions between neighbouring metal centres in all of the complexes are antiferromagnetic. In the second project the synthesis and characterization two families of TTF donors, namely the cyano aryl compounds (VI) - (XI) and the his-aryl TTF derivatives (XII) - (XIV) are reported. The crystal structures of compounds (VI), (VII), (IX) and (XII) exhibit regular stacks comprising of neutral donors. The UV -Vis spectra of compounds (VI) - (XIV) present an leT band, indicative of the transfer of electron density from the TTF donors to the aryl acceptor molecules. Chemical oxidation of donors (VI), (VII), (IX) and (XII) with iodine afforded a series of CT salts that where possible have been characterized by single crystal X -ray diffraction. Structural studies showed that the radical cations in these salts are organized in stacks comprising of dimers of oxidized TTF donors. All four salts behave as semiconductors, displaying room temperature conductivities ranging from 1.852 x 10-7 to 9.620 X 10-3 Scm-I. A second series of CT salts were successfully prepared via the technique of electrocrystallization. Following this methodology, single crystals of two CT salts were obtained. The single crystal X-ray structures of both salts are isostructural, displaying stacks formed by trimers of oxidized donors. Variable temperature conductivity measurements carried out on this series of CT salts reveal they also are semiconductors with conductivities ranging from 2.94 x 10-7 to 1.960 X 10-3 S em-I at room temperature. In the third project the synthesis and characterization of a series of MII(hfac)2 coordination complexes of donor ligand (XII) where M2+ = Co2+, Cu2+, Ni2+ and Zn2+ are reported. These complexes crystallize in a head-to-tail arrangement of TTF donor and bipyridine moieties, placing the metal centres and hfac ligands are located outside the stacks. Magnetic studies of the complexes (XV) - (XVIII) indicate that the bulky hfac ligands prevent neighbouring metal centres from assembling in close proximity, and thus they are magnetically isolated.
    • Triarylamminium radical-cation complexes: design and magnetic properties and Base-catalyzed hydrosilylation: mechanism and substrate scope

      Revunova, Kseniya; Department of Chemistry (Brock University, 2014-02-20)
      1. Triarylamminium radical-cation complexes. The detailed study of manganese, copper and nickel metal-radical complexes with triarylamminium ligands was conducted. Stable, neutral and pseudo-octahedral coordination monometallic complexes with simple monodentate 2,2`-bipyridine ligand containing a redox-active N,N`-(4,4`-dimethoxydiphenyl-amino) substituent were synthesized and fully characterized. The one-electron oxidation process and formation of persistent radical-cation complexes was observed by cyclic voltammetry and spectroelectrochemical measurements. Evans method measurements were performed with radical-cation complexes generated by chemical one-electron oxidation with NOPF6 in acetonitrile. The experimental results indicate ferromagnetic coupling between metal and triarylamminium cation in manganese (II) complex and antiferromagnetic coupling in nickel (II) complex. This data is supported by DFT calculations which also lend weight to the  spin polarization mechanism as an operative model for magnetic exchange coupling. Neutral bimetallic complexes with a new ditopic ligand were synthesized and fully characterized, including magnetic and electrochemical studies. Chemical oxidation of these precursor complexes did not generate radical-cations, but dicationic complexes, which was confirmed by UV-vis and EPR-experiments, as well as varied temperature magnetic measurements. DFT calculations for radical-cation complexes are included. A synthetic pathway for polytopic ligand with multiple redox-active triarylamine sites was developed. The structure of the ligand is presumably suitable for -spin polarization exchange model and allows for production of polymetallic complexes having high spin ground states. 2. Base-catalyzed hydrosilylation. A simple reductive base-catalyzed hydrosilation of aldehydes and ketones was adapted to the use of the cheap, safe, and non-toxic polymethylhydrosiloxane (PMHS) instead of the common PhSiH3 and (EtO)3SiH, which present significant cost and safety concerns, respectively. The conversion of silane into pentacoordinate silicate species upon addition of a base was studied in details for the cases of phenyl silane and PMHS and is believed to be essential for the hydrosilylation process. We discovered that nucleophiles (a base or fluoride-anion) induced the rearrangement of PMHS and TMDS into light silanes: MeSiH3 and Me2SiH2, respectively. The reductive properties of PMHS under basic conditions can be attributed to the formation of methyl silane and its conversion into a silicate species. A procedure for the generation of methyl silane and its use in further efficient reductions of aldehydes and ketones has been developed. The protocol was extended to the selective reduction of esters and tertiary amides into alcohols and aldimines into amines with good isolated yields and reduction of heterocyclic compounds was attempted.
    • The Use of Ipso-dihydrodiols Enzymatically Derived from Benzoic Acid in Enantioselective Synthesis. Appoaches to Total Synthesis of Vinca Alkaloids

      Adams, David; Department of Chemistry (Brock University, 2014-07-18)
      The present studies describe our recent progress in target oriented synthesis of complex organic molecules from aromatic precursors. The latest synthetic approaches toward vinca alkaloids are described and include the construction of model substrates for the investigation into Diels-Alder, radical cascade, and tandem Michael addition reactions as possible routes to the family of alkaloids. Also described are the chemoenzymatic syntheses of the natural product (-)-idesolide and unnatural polyhydroxylated pyrrolidines generated from the biotransformation of benzoic acid with Ralstonia eutropha B9.