Synthesis of Chiral Benzimidazolylidenes from 1,10-Phenathrolines and 1,10-Phenathroline-2,9-dione /

A^-heterocyclic carbenes (NHCs) have become the focus of much interest as ancillary ligands for transition metal catalysts in recent years. Their structural variability and strong cy-donation properties have led to the preparation of demonstrably useful organometallic catalysts. Among the three general structural types of NHCs (imidazolylidenes, imidazolinylidenes, and benzimidazolylidenes), benzimidazolylidenes are the least investigated because of the limitation of current synthetic approaches. The preparation of chiral analogues is even more challenging. Previously, our group has demonstrated an alternative approach to synthesizing benzimidazolylidenes with a tetracyclic framework in three steps from 1,10-phenanthroline. This thesis is focused on approaches to chiral benzimidazolylidenes derived from substituted 1,10-phenanthrolines. A key step in the preparation of these ligands involves a reduction of the pyridyl rings in 1,10-phenanthrolines. Chirality can be introduced to phenanthrolines before, during, or after the reduction as illustrated by three approaches: 1) de novo construction of the phenanthroline from chiral ketones with endo and exo faces to provide a degree of diastereoselectivity during subsequent reduction; 2) introduction of substituents into the 2- and 2,9- position of phenanthroline by nucleophilic aromatic substitution, followed by a reduction-resolution sequence; and 3) use of the protected octahydrophenanthroline as a substrate for chiral induction a to nitrogen.

Iridium(I) complexes of phenanthroline-derived benzimidazolylidenes : synthetic, structural and catalytic studies

N-heterocyclic carbenes (NHCs) have undergone rapid development in recent years. Due to their strong a-electron donation and structural variability properties, NHCs are becoming a major class of ligands in organometallic chemistry. Compared with the other two types of NHCs (imidazolylidenes and imidazolinylidenes), benzimidazolylidenes have not been well represented. Limited synthetic approaches may impede the development ofbenzimidazolylidenes. This thesis is focused on the synthesis of phenanthroline-derived benzimidazolylidene ligands and their metal complexes. A series of benzimidazolylidene-iridium complexes were synthesized and characterized spectroscopically and crystallographic ally. All of the new complexes showed varying degrees of catalytic activity and enantioselectivity toward transfer hydrogenation and asymmetric hydrogenation. The best results were achieved in hydrogenation of methyl-2-acetamidoacrylate, which afforded (-)-(R)-methyl-2-acetamidopropanoate in 97% yield and 81 % ee.

1,1-enediamines and β-substituted enamines in heterocyclic synthesis

The work in this thesis mainly deals with l,l-enediamines and ~ -substituted enamines (push-pull olefines) and their reactions, leading to the formation of a number of heterocycles. Various ~-substituted enamines were prepared by a 'one pot synthesis' in which a l,l-enediamine presumably acts as an intermediate. These enamines, various substituted crotonamides and propenamides, were made by using two different orthoesters, various secondary and primary amines and cyanoacetamide. Their structures, mechanism of formation and geometry are discussed. A synthetic route to various unsymmetrically substituted pyridines was examined. Two substituted pyridinones were obtained by using two different ~-substituted enamines and cyanoacetamide. In one case a dihydropyridine was isolated. This dihydropyridine, on heating in acidic conditions, gave a pyridinone, which confirmed this dihydropyridine as an intermediate in this pyridine synthesis. A new synthetic method was used to make highly substituted pyridinones, which involved the reaction of l,l-enediamines with the ~-substituted enamines. A one pot synthesis and an interrupted one pot synthesis were used to make these pyridinones. Two different orthoesters and three different secondary amines were used. Serendipitous formation of a pyrimidinone was observed when pyrrolidine was used as the secondary amine and triethyl orthopropionate was used as the orthoester. In all cases cyanoacetamide was used as the carbon acid. This pyridine synthesis was designed with aI, l-enediamine as the Michael donor and the ~ -substituted enamines as Michael acceptors. Substituted ureas were obtained in two cases, which was a surprise. Some pyrimidines were made by reacting two substituted enamines with two different amidines. When benzamidine was used, the expected pyrimidines were obtained. But, when 2-benzyl-2-thiopseudourea (which is also an amidine) was used, of the two expected pyrimidines, only one was obtained. In the other case, an additional substitution reaction took place in which the S-benzyl group was lost. An approach to quinazolone and benzothiadiazine synthesis is discussed. Two compounds were made from 1, I-dimorpholinoethene

The chemistry of heterocyclic methine bases and of their acyl and thioacyl derivatives

The work described in this thesis has been dtvided into six sections . The first section involves the reaction of 3,5-diphenyl-2-methyl-l,3,4-oxadiazolium perchlorate with acetic and benzoic anhydrides. The second section deals with the preparation and reactions of 1,3,4-thia diazolium salts. Some monomeric 1,3,4-thiadiazoline methine bases have also been prepared by reacting 1,3,4-thia d iaz ol ium s al t s with concen trated ammonium hydroxide solution. Variable temperature p.m.r. of 2-(3-acetylacetonylidene)-3,5-diphenyl-A4 -1,3,4-thiadiazoline has also been described. The third section deals with prepar a tion and reactions of some compounds in benzoxazole series. The fourth section deals with the prep a ration and reactions of N-alkyl-2-methylbenzothi azolium salts with base , a nd with some a cetylating and thioacetylating agents. Treatment of 2,3-dimethylbenzothiazolium iodide and of 3-ethyl-2-methylbenzothia zolium iodide with base wa s found to give the corresponding dimeric methine b a ses and evidence supporting their structure is also given. Thiol acetic acid was found to exchange 0 for S in its reactions with 2-acetonylidene-3-methylbenzothiazoline and 2-acetophenonylidene-3-methylbenzothi a zoline. (ii) In th e fifth section, the r eactions of 2,3-dimethylbenzselenazolium iodide with a variety of ac e tylating and thioacetylating agents has been described. The treatment of 2,3-dimethylbenzselenazolium iodide with base was found to give rise to a dimeric methine base and evidence supporting its structure is also given. The reactions of this dimeric methine b a se with benzoic anhydride and phenylisothiocyanate have also been described. The sixth section deals with the preparation and reactions of l-alkyl-2-methylquinolinium salts. Treatment of 1,2-dimethylquinolinium iodide and l-ethyl-2-methylquinolinium iodide was found to give the corresponding monomeric methine bases and evidence supporting their structure is also given. The E-type geometry of the olefinic bond in 2-acetonylidene-l-methylquinoline has been established on the basis of an N.O.E. experiment.

Intramolecular carbenoid insertions : the reactions of [alpha]-diazoketones derived from furanyl, thienyl, benzofuranyl and benzothienyl acetic acids with rhodium (II) acetate /

A number of synthetically useful ring systems can be prepared via the intramolecular insertion of a metal-stabilized carbenoid into a heteroaromatic systems. The chemical outcome of these reactions are dependent not only on the nature of the heteroatom but also on the length of the aliphatic tether linking the carbenoid moiety with the aromatic fragment. Our work with furanyl and thienyl systems containing a single methylene tether have allowed for some rather atypical chemistry. For example, treatment of l-diazo-3-(2-thienyl)-2-propanone (6) with catalytic rhodium (II) acetate yields 5,6- dihydro-4^-cyclopenta[Z>]thiophen-5-one (3) while, the isomeric l-diazo-3-(3-thienyl)-2- propanone(15) gives a spiro-disulphide (20). Novel chemistry was also exhibited in the analogous furanyl systems. While treatment of l-diazo-3-(3-furanyl)-2-propanone (52) with Rh2(OAc)4 resulted in the expected 2-(4-Oxo-2-cyclopentenyliden)acetaldehyde (54), isomeric l-diazo-3-(2- furanyl)-2-propanone (8) undergoes vinylogous Wolff rearrangement to give a mixture of 6a-methyl-2,3,3a,6a-tetrahydrofuro[2,i-^>]furan-2-one (44) and 2-(2-methyl-3-furyl)acetic acid (43). Rhodium acetate catalyzed decomposition of l-diazo-3-(3-benzofuranyl)-2- propanone (84) and l-diazo-3-(2-benzofuranyl)-2-propanone (69)also allows for vinylogous Wolff rearrangement, a chemistry unseen in benzofuranyl systems with longer tethers. A number of interesting products were isolated from the trapping of intermediate ketenes. Decomposition of l-diazo-3-(3-benzothienyl)-2-propanone (100) resulted in the formation of 2,3-dihydro-l//-benzo[^]cyclopenta[^thiophen-2-one (102). However, in addition to (102), a dimer was also generated from the decomposition of l-diazo-3-(2- benzothienyl)-2-propanone (109). The insight into the mechanistic underpinnings of the above reactions are provided by molecular modeling at a PM3 level.

Intramolecular carbenoid insertion : reactions of [alpha] -diazoketones derived from benzothienyl, pyrolyl and indolyl alkanoic acids with rhodium (II) acetate

Recent studies have shown that the rhodium (II) acetate decomposition chemistry observed for a-diazoketones tethered to thienyl, furanyl, and benzofuranyl moieties is dependent not only on the nature of the heteroatom but also on the length of the aliphatic tether linking the diazoketone moiety with the aromatic fragment. The present thesis expands on these results and focuses on a-diazoketones tethered to benzothiophenes, pyrroles and indoles by a methylene linker. In the case of benzothiophenes, it was shown that the rhodium catalyst decomposition of I-diazo-4-(3-benzothienyl)-2-butanone (146) and 1-diazo-4-(3benzothienyl)- 2-butanone (152) allow for the isolation of 1,2,3a,3b-tetrahydro-3Hbenzo[ b]cyclopenta[1,3]cyclopropa- [1 ,2-d]thiophen-3-one (147) and 1,2,3a,3btetrahydro- 3H-benzo[b]cyclopenta[1,3]cyclopropa[1,2-d]thiophen-3-one (153). However treatment of 1-diazo-3-(3-Benzothienyl)-2-Propanone (165) with Rh(II) acetate results in the formation of 2,3-Dihydro-1H-benzo[b]cyclopenta[d]thiophen-2-one (159), while 1diazo- 3-(2-Benzothienyl)-2-Propanone with the same condition gives 5,5-bis( 1benzothiophen- 2-ylmethyl)-2(5H)-furanone (166) along with the tricycle 159. The chemistry of the pyrrolyl and the indolyl moieties linked to terminal adiazoketone systems was also investigated. The decomposition of I-diazo-(2-pyrrolyl)-2propanone (173) results in the formation of two products; the N-H insertion product IHpyrrolizin- 2(3H)-one (176) and the alkylation product 4,6-dihydrocyclopenta[b]pyrrol5( 1 H)-one (180). When 1-Diazo-3-(3-indoly)-3-propanone (194) is treated with catalytic amount of Rh (II) 3,4-dihydrocyclopenta[b]indol-2(1H)-one (193) is isolated quantitatively. The later reaction when monitored using IH NMR the intermediate 200 can be seen whose structure was confirmed by the comparison to series of model compounds. The mechanisms underlying these reactions as well as their synthetic utility is discussed.

Synthesis and spectral studies of methyl heterocylic systems

2-Carboxy-2?-methyldiphenyl sulfide was prepared by the Ullmann reaction and cyclodehydrated by sulfuric acid to afford 4-methylthioxanthone. 1-Methylthioxanthone was separated from the reaction mixture obtained upon cyclodehydration of 2-carboxy-3f-methyldiphenyl sulfide. In addition, 1-, 2-, 3- and 4-methylthioxanthone 10,10-dioxides were synthesized by oxidation of the corresponding thioxanthones. o-, m- and p-N-Tolylanthranilic acids were prepared by the Ullmann reaction and used as precursors for the preparation of 1-, 2- and 4- methyl-9-chloroacridine and finally 1-, 2-, 3- and 4-methylacridone. High resolution, 60 MHz PMR spectra were obtained on the four monomethyl isomers of xanthone, thioxanthone, thioxanthone 10,10-dioxide and acridone, and on 1-, 2- and 4-methyl-9-chloroacridine. For some compounds, coupling of all three different aromatic protons to the methyl was observed, two of the couplings typically being smaller than the third. With the large (ortho) coupling being on the order of 0.5 to 1.0 Hz, it was necessary to decouple the aromatic part of the spectrum. The magnitude of the ortho benzylic constant may be related to an incomplete Tr-bond delocalization in the molecules.

The preparation and reactions of some 1, 2-dipolar species /|nI. D. Brindle. -- 260 St. Catharines, Ont. : [s. n.],

This research was directed mainly towards the investigation of the reactions of allylic amineimides. The work can be divided into two main sections. Section 1 of the thesis deals mainly with thermolysis studies of amineimides. Sections 1a and 1b represent a comprehensive survey of amineimide literature up to 1971. N-A1ly1-N,N-dirnethylarnine-benzirnide was prepared and rearranged at 1400 to l-allyl-1-benzoyl-2,2-dimethylhydrazine. A tentative mechanism involving an initial migration to the carbonyl oxygen was disproved by incorporating the amineimide system into a five-membered ring. N,N~Dimethyl-N-propargylamine-benzimidedid not rearrange on heating; but the hydrobromide, on heating, disproportionated to give 1-benzoyl~2,2,2-trimethylhydraziniumbromide and I-benzoyl-2,2~ dimethylhydrazine. l-Ally'l--l, I-dimethyl-2-benzoy-lhydrazinium bromide and 1~benzoy-1-2,2, 2-trimethy-lhydrazinium iodide both disproportionated to give l~benzoyl-2,2-dimethylhydrazine. Section 1 concludes with a discussion of the mechanisms of ally'lic migrations in amineimides proposed by J. E. Baldwin. Section 2 deals with the formation of five-membered heterocyclic compounds from amineimides by bromination. 1,1-Dimethyl-2benzoyl- 4-bromopyrazolidinium bromide was formed from N-allyl-N,Ndime thy-lamtne-benzimide , 1,1-dimethyl-2-benzoyl-4-bromopyrazol-3enium bromide from N,N~dimethyl-N-propargylamine~benzimidevia the unusual acetylenic "bromonium" ion. Hydrogenolysis of both heterocyclic compounds gave the same product. The preparation was extended by forming 2,2-dimethyl-4-bromoisoxazolinium bromide from N-allylN, N-dimethylamine-N-oxide. Sections 3 and 4 cover a number of unsuccessful attempts to synthesise other amineimides and l,2-dipolar species.

The Smiles rearrangement in hydrazidic systems and related syntheses /|nG. A. Pawelchak. -- 260 St. Catharines, Ont. : [s. n.],

This research was directed towards the investigation of the Smiles rearrangement in hydrazidic systems and the synthesis of related heterocyclic compounds. The work can be conveniently divided into two main sections. Section 1 of the thesis relates to the synthesis and examination of the O+N migration of phenoxy- derivatives of hydrazidic halides. In general, hydrazidic halides were found to react with 2-nitrophenol and 4-nitrophenol to give corresponding a-nitrophenoxy- compounds. These a-nitrophenoxy- compounds were found to rearrange in warm base to give the corresponding N-benzoyl compounds via a proposed five-membered transition state. Experiments conducted in styrene revealed no radical contribution to the rearrangement. Cross-over product analysis indicated the rearrangement as intramolecular and consistent with the Smiles rearrangement. The preparation of N-a-chlorobenzylidene-N'-2-nitrophenyl- -N'-(2,4-dibromophenyl)hydrazine from N-benzoyl-N'-2-nitrophenyl- N'-(2,4-dibromophenyl)hydrazine was accomplished using phosphorus oxychloride. Examination of this hydrazidic chloride indicated a marked decrease .in reactivity as compared to the N-a-chlorobenzylidene-N'-phenylhydrazine case. Section 2 concerns itself with the preparation of heterocyclic compounds using an analogy of the five-membered transition state present in the Smiles rearrangement of a substituted benzylidene derivatives A new preparation of 2,4-phenyl1,3,4- oxadiazol-S-one using N-benzoyl-N'-phenylhydrazine and ethyl thiochloroformate is reported. Two new preparations of N-a-thiobenzoyl-N'-(2,4-dibromophenylhydrazine are reported using sodium hydrosulfide in conjunction with N-a-bromobenzylidene-N'-(2,4-dibromophenyl)hydrazine in the first, and phosphorus pentasulfide with N-benzoylN'-( 2,4-dibromophenyl)hydrazine in the second. The latter is preferred due to the formation of a sulfide co-product in the former. Two preparations of 2-phenyl-4-(2,4-dibromophenyl)-1,3,4- thiadiazol-S-one are reported using N-thiobenzoyl-N'-(2,4-dibromophenyl) hydrazine and ethyl chloroformate and ethyl thiochloroformate Two rapid and easy preparations of 2-phenyl-4-(2,4-dibromophenyl)- 1,3,4-triazol-S-one are reported using ethyl chloroformate and ethyl thiochloroformate. Sodium cyanate in conjunction with a-aminobenzylidene-N'-(2,4-dibromophenyl)hydrazine also provided 2-phenyl-4-(2,4-dibromophenyl)-1,3,4-triazol-S-one Section 2 concludes with an examination of two possible mechanistic routes to the prepared heterocycles.

Stereoselective synthesis of 5-substituted pyrrolo[1,2-c]imidazol-3-ones. Access to aldosterone synthase inhibitors and chiral precatalysts

Compounds containing the pyrrolidine moiety are key substructures of compounds with biological activity and organocatalysts. In particular, annulated chiral pyrrolidines with alpha stereogenic centers have aldostereone synthase inhibition activity. In addition, 5-substituted pyrroloimidazol(in)ium salts precursors to N-heterocyclic carbene (NHC) precatalysts are rare due to a lack of convenient synthetic routes to access them. In this thesis is described a rapid synthesis of NHC precursors and a possible route to 5-substituted pyrroloimidazole biologically active compounds. The method involves the preparation of chiral saturated and achiral unsaturated pyrrolo[I,2- c]imidazol-3-ones from N-Cbz-protected t-Butyl proline carboxamide. The resulting starting materials may be used to prepare the target chiral annulated imidazol(in)ium products by a two-step sequence involving first stereoselective lithiation-substitution, followed by POCh induced salt formation.

The Synthesis and Coordination Chemistry of Two Families of Polydentate Ligands - Exploring Their Potential for the Preparation of Molecule-Based Magnets

The synthesis and studies of two classes of poly dentate ligands are presented as two projects. In project 1, four new carboxamide ligands have been synthesised via the condensation of 2,2',6,6'-tetrachloroformyl-4,4'-bipyridine or 2,6-dichloroformyl pyridine together with heterocyclic amines containing pyridine or pyrazole substituents. The coordination chemistry of these ligands has been investigated and studies have shown that with a Cu(II) salt, two carboxamide ligands LJ and L2 afford large clusters with stoichiometries [Cu8(L1)4Cl16].CHCl3.5H2O.7CH3OH (I) and [Cu9(L2)6Cl6].CH3OH.5H2O.(C2H5)3N (II) respectively. [molecular diagram availabel in pdf]. X-ray diffraction studies of cluster (I) reveal that it has approximate S4 symmetry and is comprised of four ligands and eight copper (II) centers. Here, coordination takes place via amide 0 atoms, and pyrazole nitrogens. This complex is the first reported example of an octanuclear copper cluster with a saddle-shaped structure. The second cluster comprises nine copper ions that are arranged in a cyclic array. Each ligand coordinates three copper centers and each copper ion shares two ligands to connect six ligands with nine copper ions. The amide nitrogens are completely deprotonated and both amide Nand 0 atoms coordinate the metal centres. The cluster has three-fold symmetry. There are six chloride ions, three of which are bridging two neighbouring Cu(II) centres. Magnetic studies of (I) and (II) reveal that both clusters display weak antiferromagnetic interactions between neighbouring Cu(II) centers at low temperature. In the second project, three complexes with stoichiometries [Fe[N302](SCN)2]2 (III), R,R-[Fe[N3O2](SCN)2 (IV) and R,R-]Fe[N3O2](CN)2] (V) were prepared and characterized, where [N302] is a pentadentate macrocycle. Complex (III) was prepared via the metal templated Schiff-base condensation of 2,2',6,6'-tetraacetyl-4,4'-bipyridine together with 3,6-dioxaoctane-I,8-diamine and comprises of a dimeric macro cycle where the two Fe(II) centres are in a pentagonal-bipyramidal environment with the [N302] ligands occupying the equatorial plane and two axial NCS ligands. Complexes (IV) and (V) were prepared via the condensation of 2,6-diacetylpyridine together with a chiral diamine in the presence of FeCh. The synthetic strategy for the preparation of the chiral diamine (4R,5R)-4,5-diphenyl-3,6-dioxa-I,8-octane-diamine was elucidated. The chirality of both macrocycles (IV) and (V) was probed by circular dichroism spectroscopy. The crystal structure of (IV) at 200 K contains two independent molecules in the unit cell, both of which contain a hepta-coordinated Fe(II) and axial NCS ligands. Variable temperature magnetic susceptibility and structural studies are consistent with a high spin Fe(II) complex and show no evidence of any spin crossover behaviour. In contrast, the bis cyanide derivative (V) crystallizes with two independent molecules in the unit cell, both of which have different coordination geometries consistent with different spin states for the two Fe(II) centres. At 250 K, the molecular structure of (V) shows the presence of both 7- and a 6-coordinate Fe(II) complexes in the crystal lattice. As the temperature is lowered, the molecules undergo a structural change and at 100 K the structural data is consistent with a 6- and 5-coordinate Fe(II) complex in the unit cell. Magnetic studies confirm that this complex undergoes a gradual, thermal, spin crossover transition in the solid state. Photomagnetic measurements indicate this is the first chiral Fe (II) sea complex to exhibit a LIESST.

Ligand design for molecule-based magnetic and/or conducting materials

Work in the area of molecule-based magnetic and/or conducting materials is presented in two projects. The first project describes the use of 4,4’-bipyridine as a scaffold for the preparation of a new family of tetracarboxamide ligands. Four new ligands I-III have been prepared and characterized and the coordination chemistry of these ligands is presented. This project was then extended to exploit 4,4’-bipyridine as a covalent linker between two N3O2 macrocyles. In this respect, three dimeric macrocycles have been prepared IV-VI. Substitution of the labile axial ligands of the Co(II) complex IV by [Fe(CN)6]4- afforded the self-assembly of the 1-D polymeric chain {[Co(N3O2)H2O]2Fe(CN)6}n•3H2O that has been structurally and magnetically characterized. Magnetic studies on the Fe(II) complexes V and VI indicate that they undergo incomplete spin crossover transitions in the solid state. Strategies for the preparation of chiral spin crossover N3O2 macrocycles are discussed and the synthesis of the novel chiral Fe(II) macrocyclic complex VII is reported. Magnetic susceptibility and Mössbauer studies reveal that this complex undergoes a gradual spin crossover in the solid state with no thermal hysteresis. Variable temperature X-ray diffraction studies on single crystals of VII reveal interesting structural changes in the coordination geometry of the macrocycle accompanying its SCO transition. The second project reports the synthesis and characterization of a new family of tetrathiafulvalene derivatives VIII – XII, where a heterocyclic chelating ligand is appended to a TTF donor via an imine linker. The coordination chemistries of these ligands with M(hfac)2.H2O (M( = Co, Ni, Mn, Cu) have been explored and the structural and magnetic properties of these complexes are described.

Triarylamminium radical-cation complexes: design and magnetic properties and Base-catalyzed hydrosilylation: mechanism and substrate scope

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.

Synthesis of unnatural analogues of pancratistatin and narciclasine

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

Diastereoselective Lithiation-Substitution of N-Silyl-Protected-(S)-Tetrahydro-1H-pyrrolo[1,2-c]imidazole-3(2H)-ones and Applications of Their Derivatives

This thesis describes a method involving the preparation of an L-proline-derived imidazolone protected with an N-triethylsilyl group that undergoes diastereoselective lithiation followed by electrophile quench to give C5-substituted products with syn stereochemistry. The N-silylated derivatives may be more easily N-deprotected as compared to previous N-t-Bu analogues to give secondary ureas. These may serve as precursors to N-phenyl chiral bicyclic guanidines or as NHC precursors for synthesis of corresponding complexes.