Organic synthesis allows access complex materials in the context of fine chemicals, pharmaceuticals, and natural products, but many contemporary methods are wasteful – the focus is on the target rather than the process. Stoichiometric reagents, protecting groups, and multi-step processes are often involved to synthesize moieties such as chiral lactones and lactams, which are prevalent in biologically-relevant molecules like antibiotics (for example, the macrolides, typified by erythromycin) and cyclic peptides (such as cyclosporin and gramicidin). We have developed a rhodium-catalyzed lactonization of prochiral keto-aldehydes to access chiral lactones in a mild and atom-economical fashion, and a synthesis of cyclic peptides from achiral dehydropeptides using asymmetric rhodium-catalyzed hydrogenation to set the chirality in the peptide. In this fashion, we avoid using expensive and wasteful activating agents, protecting groups, and a host of other drawbacks endemic in lactonizations and peptide synthesis. This dissertation details: 1) the development of asymmetric rhodium-catalyzed hydroacylation, elucidation of the mechanism of this transformation through experimental and theoretical analyses, and the synthesis of chiral benzoxazecinones using this method, and 2) the synthesis of prochiral linear dehydropeptides, efficient cyclization of these molecules, and asymmetric reduction of multiple enamides in a highly enantio- and diastereoselective manner to access cyclic peptides.

A range of air- and moisture-stable phosphonium salts was prepared. Compounds were isolated in high yield and fully characterized. The properties of these compounds and the nature of their formation were explored. The phosphonium salts react with base to give phosphino-aldehydes which are important building blocks in the synthesis of PNNP ligands. The condensation reaction between phosphino-aldehydes and a diamine usually employed for the preparation of PNNP ligands was not applicable to the phosphino-aldehydes derived from these phosphonium salts as a result of the high reactivity of the nucleophilic phosphorus causing uncontrollable side-reaction. In order to resolve this problem, a template reaction with iron(II) Lewis acid was used to suppress the reactivity of the phosphorus via coordination. The reaction was successful and gave rise to bis-tridentate complexes with PNN ligands ([Fe(Ph2PCH2CH=N---NH2)2][BPh4]2, where N---NH2 depends on diamine used) as the kinetic product and to desired tetradentate complexes with PNNP ligands (trans-[Fe(Ph2PCH2CH=N---N=CHCH2PPh2)(CH3CN)2][BPh4]2, where N---N depends on diamine used) as a thermodynamic product of the reaction. The reaction appeared to be very general; complexes iii with various diamines incorporated in the ligand backbone were prepared in high yield and fully characterized. Mono-carbonylation reaction of the complexes containing tetradentate PNNP ligands resulted in the formation of the precatalysts with a general formula (trans-[Fe(Ph2PCH2CH=N---N=CHCH2PPh2)(CO)(Br)][BPh4]. These precatalysts give active (TOF up to 28000 h-1) and enantioselective (up to 95 % ee) catalytic systems for the ATH of ketones when activated with base in a solution of 2-propanol as the reducing agent. On the basis of a kinetic study and other evidence, we propose a mechanism of activation and operation of the catalytic system involving the precatalyst trans-[Fe(CO)(Br)(Ph2CH2CH=N-((S,S)-C(Ph)H-C(Ph)H)-N=CHCH2PPh2)][BPh4] and acetophenone as a model substrate. We determined that the activation of the precatalyst to the active species involves the stereoselective reduction of one imine group of the ligand, since when the active species are quenched with acid, the complex trans-[Fe(CO)(Cl)(Ph2CH2CH-(H)N-((S,S)-C(Ph)H-C(Ph)H)-N=CHCH2PPh2)][BPh4] containing amine and imine functionalities in the backbone is produced.

Organic synthesis allows access complex materials in the context of fine chemicals, pharmaceuticals, and natural products, but many contemporary methods are wasteful – the focus is on the target rather than the process. Stoichiometric reagents, protecting groups, and multi-step processes are often involved to synthesize moieties such as chiral lactones and lactams, which are prevalent in biologically-relevant molecules like antibiotics (for example, the macrolides, typified by erythromycin) and cyclic peptides (such as cyclosporin and gramicidin). We have developed a rhodium-catalyzed lactonization of prochiral keto-aldehydes to access chiral lactones in a mild and atom-economical fashion, and a synthesis of cyclic peptides from achiral dehydropeptides using asymmetric rhodium-catalyzed hydrogenation to set the chirality in the peptide. In this fashion, we avoid using expensive and wasteful activating agents, protecting groups, and a host of other drawbacks endemic in lactonizations and peptide synthesis. This dissertation details: 1) the development of asymmetric rhodium-catalyzed hydroacylation, elucidation of the mechanism of this transformation through experimental and theoretical analyses, and the synthesis of chiral benzoxazecinones using this method, and 2) the synthesis of prochiral linear dehydropeptides, efficient cyclization of these molecules, and asymmetric reduction of multiple enamides in a highly enantio- and diastereoselective manner to access cyclic peptides.

<p>Over the recent past, organometallic chemistry has grown and the impact of catalytic applications in various chemical technologies has rapidly evolved from the realm of academic laboratories into full-scale industrial processes. Pyrrole-imine ligands were prepared by condensation of pyrrole-2-carboxylaldehyde with propyl amine, 2,6-diisopropylanaline, poly(propylene) imine dendrimer and 3-aminopropyl-triethoxysilane to give the desired ligands in good yields. These ligands were charaterized via combination of techniques to establish the molecular structure. Microanalysis was performed to confirm the purity of the product.</p>

Thesis (DSc(DoctorateofScience))--University of South Australia, 2003.

This thesis describes the preparation and characterization of a variety of methyl-, trimethylsilyl-, and diphenylphosphino-substituted indenes. The indenes were then used in the preparation of bis(indenyl)iron(II) complexes. The bis(indenyl)iron(II) complexes were characterized by ¹H, ¹³C, and ³¹P-NMR, UV/visible spectroscopy, cyclic voltammetry, and mass spectrometry. The cyclic voltammetry shows an approximately linear relationship between the oxidation potential and the type of substituent and its ring position, but with increasing substitution leads to lower than expected oxidation potentials. The UV/visible spectra show two absorption bands in the visible region. The position of the bands are essentially unaffected by methyl-substitution, but the low energy band red-shifts with trimethylsilyl- and diphenylphosphino-substitution. Di(2-methylindenyl)iron(II), bis(4,7-dimethyl-indenyl)iron(II), bis(1,3-bis(trimethylsilyl)indenyl)iron(II), rac-bis(1-diphenyl-phosphinoindenyl)iron(II), rac-bis(1-diphenylphosphino-3-methylindenyl)iron(II), and rac-bis(1-diphenylphosphino-2,3-dimethylindenyl)iron(II) were characterized by X-ray crystallography.The planar chiral ferrocenylphosphine bis(1-diphenylphosphinoindenyl)iron(II) is observed to undergo a facile ring-flipping isomerization from the meso isomer to the racemic isomer in THF at ambient temperature. The isomerization is slowed by the addition of the noncoordinating solvent chloroform, but is accelerated by the addition of LiCl. Rate and activation parameters for the isomerization have been determined to be: kobs = 1.6 x 10⁻⁵ s⁻¹ at 23 ℃, ΔH‡ = 58 ± 4 kJ mol⁻¹, ΔS‡ = −140 ± 15 J mol⁻¹ K⁻¹. Deuterium labeling of bis(1-diphenylphosphinoindenyl)iron(II) in the 3- and 3ʹ-position ruled out the isomerization proceeding by [1,5]-proton shifts or dissociative mechanisms. The proposed mechanism for the isomerization proceeds via coordination of two THF ligands with ring-slippage of one of the indenyl ligands until it is coordinated through the phosphine. Coordination of the indenyl ligand by the other face leads to the formation of the other isomer.The heterobimetallic complexes (bis(1-diphenylphosphinoindenyl)iron(II))-cis-dichloropalladium(II), (bis(1-diphenylphosphinoindenyl)iron(II))-cis-dichloro-platinum(II), and [(cyclooctadiene)(rac-bis(1-diphenylphosphinoindenyl)iron(II))-rhodium(I)] tetraphenylborate were prepared. Attempts to prepare dichloro(bis(1-diphenylphosphinoindenyl)iron(II))nickel(II) lead to the formation of trans-dichloro(bis(1-diphenylphosphinoindene))nickel(II). The complex (bis(1-diphenyl-phosphinoindenyl)iron(II))-cis-dichloropalladium(II) is able to catalyze the cross-coupling of bromobenzene with n-/sec-butylmagnesium chloride. However. the reaction is not selective with isomerization of the alkyl group and reduction of the halide occurring via a β-hydride elimination mechanism.

Thesis (Ph. D.)--Washington State University, May 2008. / Includes bibliographical references.

Thesis (Ph.D.)--University of Tulsa, 1994. / Includes bibliographical references (leaves 219-228).

Diss. (sammanfattning) Uppsala : Univ., 2001. / Härtill 4 uppsatser.

Thesis (Ph.D.)--University of Delaware, 2007. / Principal faculty advisor: Chin-Pao Huang, Dept. of Civil and Environmental Engineering. Includes bibliographical references.