Two main investigations based on the Pauson-Khand reaction were performed. / The use of bidentate ligands in the directed Pauson-Khand reaction was investigated. Substrates with a three-carbon linkage between the two heteroatoms gave better results than substrates containing two-carbon tethers. Higher yields and better regioselectivities were observed with thioamines and bisthioethers compared to diamines. Overall, only a few bidentate substrates showed marked improvements over previous results obtained with analogous monodentate compounds. Rationalizations based on the possible modes of cycloaddition operative for the various substrates studied are presented. / Investigations were performed on two main approaches towards the total synthesis of Asteriscanolide, both of which employ the Pauson-Khand reaction at a crucial juncture. Studies towards the preparation of the bridged bicyclic intermediate needed for the key cycloaddition reaction in the first strategy were not encouraging. Intermolecular Pauson-Khand reactions of alkynoate complexes were studied towards developing a useful methodology for use within the second synthetic scheme. The amine oxide-promoted reaction between propene and (ethyl 5- (t-butyldimethylsilyl) oxy)-2-pentynoate)dicobalthexacarbonyl gave the desired cyclopentenones in $>$30:1 ratio and 90% yield. Succeeding steps were performed in excellent yield. Attempts to reduce the double bond in a number of intermediates are described. / Source: Dissertation Abstracts International, Volume: 55-04, Section: B, page: 1438. / Major Professor: Marie E. Krafft. / Thesis (Ph.D.)--The Florida State University, 1994.

The use of a total synthesis of taxol for producing a supply of taxol, while not a viable option at the present, may someday aid in the development of second generation taxoid drugs that are more potent and have less side-effects. This dissertation will describe synthetic studies undertaken by this researcher towards the total synthesis of taxol. The research described in Part I and Part II will cover photochemical studies designed to address the problem of synthesis of the D-ring oxetanol of taxol. The Norrish II photocyclization of a C-ring $\alpha$-methoxy ketone to produce an oxetanol will be discussed in Part I, and a Paterno-Buchi photocyclization of an aldehyde and an enol acetate will be discussed in Part II. In Part III, a methodology for the oxidation of C-9 and C-10 of taxol using a protocol based on the benzeneseleninic anhydride oxidation of an enolate via a 2,3 sigmatropic rearrangement is described. / Source: Dissertation Abstracts International, Volume: 55-09, Section: B, page: 3892. / Major Professor: Robert A. Holton. / Thesis (Ph.D.)--The Florida State University, 1994.

Part one describes a study undertaken to extend the synthetic application of the Michael reaction. This involved developing methodology that enabled construction of vicinal quaternary centers via the Michael reaction. In addition, factors influencing diastereoselectivity in additions of enolates to $\alpha$-(phenylthio)butenolide were examined. / A palladium-mediated approach to the alkaloid gelsemine is described in part two. New Lewis acid mediated carbonylation chemistry had to be developed for this project. This chemistry was applied to several representative examples to demonstrate its generality. / Part three relates the details of part of a total synthesis of taxusin, a simple taxane diterpene. The remainder of part three is devoted to a description of ongoing efforts towards the total synthesis of taxol, a potent antitumor agent and the most complex member of this class of compounds. / Source: Dissertation Abstracts International, Volume: 53-11, Section: B, page: 5729. / Major Professor: Robert Holton. / Thesis (Ph.D.)--The Florida State University, 1989.

Reaction of bis(triphenylphosphine)chlorocobaltaindane-1,3-dione with 1 equivalent of AgBF(,4) followed by treatment with various ligands resulted in the formation of cationic phthaloylcobalt complexes. Reaction of these cationic complexes with alkynes produced naphthoquinones. Comparison of the structure and reactivity of various cationic cobalt complexes led to several important conclusions regarding the mechanistic nature of the quinone forming reaction. These conclusions were used as a guide in the design of a neutral phthaloylcobalt complex featuring a diequatorially coordinated dimethylglyoxime ligand which was found to give high yields of substituted 1,4-naphthoquinones on treatment with functionalized alkynes. Addition of 1 equivalent of CoCl(,2)(.)6H(,2)O was found to significantly increase the reaction rate of the neutral cobalt complexes. / The information obtained from reaction studies of the phthaloyl-cobalt complexes was applied to several maleoylcobalt complexes in order to develop an organotransitionmetal approach to benzoquinone synthesis. In order to generalize such a synthetic route, a general synthesis of substituted cyclobutenediones adaptable to the synthesis of multigram quantities of dione was developed. This synthesis was based on a cyclo-addition reaction of dichloroketene with vinyl sulfides. The resulting cycloadducts underwent an unusual elimination-readdition sequence resulting in the formation of 4-thiophenyl-2-chlorocyclobut-2-ene-1-ones which on oxidation with MCPBA underwent a {2,3}sigmatrophic shift to afford substituted cyclobutenediones. Several of these diones were converted to maleoyl dimethylglyoxime complexes which gave good yields of substituted benzoquinones on treatment with alkynes. / Source: Dissertation Abstracts International, Volume: 45-01, Section: B, page: 0185. / Thesis (Ph.D.)--The Florida State University, 1984.

Investigations of the triplet states of 1-phenyl-2-(2-naphtyl) ethylene (2-NPE), under steady-state conditions in the presence of competing energy-transfer and spin-exchange quenchers have allowed obtention of effective triplet lifetimes, and decay parameters. Direct transient observations, done in collaboration with H. Gorner, have confirmed the steady-state results, as well as defined triplet state parameters for two distinct 2-NPE species. Investigations of both types on conformationally restricted analogs, representative of conformers formed by 1-(alpha) rotation of the 2-naphthyl moiety, have confirmed the identification of the two 2-NPE species as conformational isomers. / Studies in the excited singlet manifold have focused on separation and independent treatment of the properties of the multiple emissive 2-NPE species. Observations of fluorescence spectra under conditions of variable excitation wavelength, temperature, viscosity, and added singlet state quenchers were performed and quantitated in terms of component contributions by application of Principal Component Analysis (PCOMP); which determines the number of significant contributing species, their intrinsic spectra, and their relative amounts without any prior knowledge of component properties. Again, similar studies performed on the conformationally defined analogs, have indicated their similarity to the 2-NPE species observed and indicate their formation via the proposed ground state conformational equilibrium. Aside from confirming the previously proposed ground state conformational control of excited state behavior, the detailed analysis strongly suggests the dynamic involvement of allowed and forbidden pairs of states within each excited conformer. / In addition, photochemical investigations of all substrates in both the singlet and triplet manifold have provided evidence for direct cis-trans isomerization via the excited singlet, as well as exhibiting behavior in many respects similar the the symmetrical homolog, stilbene. In all cases, correlation of 2-NPE comformer behavior to that of the analogs has been successful, and suggests a direct effect of single-bond rotation in determining excited state properties. Analysis of this effect in terms of excited transitions and energetics is proposed to account for the observations. / Source: Dissertation Abstracts International, Volume: 45-04, Section: B, page: 1194. / Thesis (Ph.D.)--The Florida State University, 1984.

The interactions of singlet oxygen with 1-vinylcycloalkenes after P(OEt)(,3) reduction led to 1,2-dioxins 1 via 1,4-cycloaddition, secondary diene alcohols 3 by the "ene" reaction pathway and trans- and cis-1,2-dioxin alcohols 4 and 5 by further 1,4-cycloaddition of ('1)O(,2) to 3. Small amounts of competitive "ene" reaction product, the tertiary diene alcohols 2, were obtained only in the case of medium size rings (n = 9, 10 and 12). The stereochemistry of the various products was elucidated by NMR spectrometry. The product ratios showed that five and seven membered ring semicyclic dienes undergo predominantly the "ene" reaction. As ring size increases, 1,4-cycloaddition competes closely with the "ene" process, the crossover point being at ring size ten. The six membered ring semicyclic diene was an exception, 1,4-cycloaddition for this compound surpassing the "ene" reaction. The above results held also when 1-isopropenylcycloalkenes were used as substrates. Possible explanations in terms of the conformations of the alicyclic rings are presented. The predominant formation of secondary diene alcohols (Markovnikov directive effect) in the "ene" reaction process excluded the participation of a concerted ene mechanism involved in the semicyclic 1,3-diene systems. / The 1,2-dioxins and 1,2-dioxin alcohols (except those derived from five membered semicyclic dienes) were converted to furans on treatment with FeSO(,4) and successful syntheses of (R)-menthofuran, (R)-evodone and ((+OR-)) chromolaenin were accomplished. Thus, the ('1)O(,2)-FeSO(,4) sequence for the transformation of semicyclic 1,3-dienes into cyclic furanoterpenoids may indeed have biogenetic significance. / Source: Dissertation Abstracts International, Volume: 45-04, Section: B, page: 1196. / Thesis (Ph.D.)--The Florida State University, 1984.

The mechanism of the photochemical formation of tricyclo{6.4.0.0('2,7)}7,8-cis-dodec-1-ene (CB), 1'-methoxybicyclohex-1-ene (1,2 ET), and a new product, 2'-methoxybicyclohex-1-ene (1,4ET), from the sensitized irradiation of 1,1-bicyclohexenyl (BCH) in methanol has been investigated using steady state kinetic techniques. The effects of added acid, sensitizer energy, methanol concentration, BCH concentration, and temperature on the product quantum yields were evaluated. The solvent deuterium isotope effect on the product quantum yields was measured. Correlation of the steady state results with transient absorption flash spectroscopic measurements performed in collaboration with R. Bonneau (University of Bordeux, France) has provided proof that the intermediate responsible for all of the observed photochemistry is a strained ground state twisted transoid isomer of BCH, c,t-BCH, formed from the BCH triplet state. Reaction of c,t-BCH with methanol gives the methyl ethers, 1,2 ET and 1,4 ET. Cyclobutene (CB) formation occurs by a conrotatory electrocyclization of c,t-BCH. / The mechanism of photoproduct formation from the direct irradiation of BCH has also been investigated. The observed photoproducts are CB, 1,2 ET, 1,4 ET and 1,3'-bicyclohexenyl (UD). Steady state photochemical measurements of product quantum yields provide evidence that methanol addition to c,t-BCH formed from a BCH excited singlet state accounts for all of the observed ether formation. A reaction pathway to CB independent of c,t-BCH accounts for 36% of the observed CB formation. The formation of UD is consistent with its production from a BCH excited singlet state. The effects of changing the excitation wavelength on the CB/UD product ratio is discussed on the basis of ground state s-cis - s-trans conformational control of the photochemistry. / Source: Dissertation Abstracts International, Volume: 45-06, Section: B, page: 1780. / Thesis (Ph.D.)--The Florida State University, 1984.

Part one describes a systematic study of the diastereoselectivity of the kinetic Michael addition of ester, ketone and amide enolates to $\alpha$-(sulfinyl)butenolides. Numerous examples of high facial selectivity of $\alpha$-(t-butylsulfinyl)butenolide towards enolates have been discovered, and the factors that influence this selectivity were examined. The structure of the major adduct of the Michael addition of the lithium enolate of methyl acetate to $\alpha$-(t-butylsulfinyl)butenolide was solved by single crystal X-ray crystallography. The results indicate that the facial selectivity of $\alpha$-(sulfinyl)butenolides is determined by the orientation and the size of the sulfinyl group. The sulfur-oxygen bond of the sulfinyl group is antiperiplanar to the carbonyl group of the butenolide in the transition state. / Part two describes an efficient partial synthesis of the antitumor drug taxol. The synthetic equivalent of the taxol side chain precursor, optically pure (+)-3(R)-hydroxy-4(S)-phenyl-2-azetidinone, was obtained via either chemical resolution of racemic $\beta$-lactam or by an efficient asymmetric synthesis from the readily available and recyclable chiral auxiliary 4(R)-phenyloxazolidone. The first example of formation and reaction of a lithium enolate in dichloromethane solvent was discovered. The identity and stability of lithium hexamethyldisilazide in dichloromethane, as well as the reactivity of n-butyllithium in dichloromethane, were examined. N-Benzoyl-$\beta$-lactams were found to undergo DMAP-catalyzed rearrangement to oxazinone. In the presence of DMAP, N-benzoyl-3(R)-(1-ethoxyethoxy)-4(S)-phenyl-2-azetidinone and the corresponding oxazinone reacted with 7-TES-baccatin III to give, after deprotection, a high yield of taxol. / Source: Dissertation Abstracts International, Volume: 54-12, Section: B, page: 6209. / Major Professor: Robert A. Holton. / Thesis (Ph.D.)--The Florida State University, 1991.

The Kamlet-Taft solvatoohromic comparison method has been used to characterize the dipolarity/polarizability ((pi)*) and hydrogen-bond accepting basicity ((beta)) of supercritical carbon dioxide at various densities. The fluid medium is shown to be less polar (and/or polarizable) than cyclohexane by the (pi)* parameter. As the density of the medium is decreased the (pi)* parameter decreases on a smooth curve toward the gas phase value of (pi)*. Variation between the gas phase value of (pi)* and the value of (pi)* in supercritical carbon dioxide at different densities is quantitatively accounted for by a function of the refractive index which has been shown to be directly proportional to the dispersion force contribution to the free energy of interaction in solution. / The solvatochromism of the internal charge transfer absorption band of 4-diethylamino-4'-nitroazobenzene, DENAB, correlates linearly with the (pi)* parameter in conventional solvents and in supercritical carbon dioxide at various densities. The free energy of activation, (DELTA)G('(tau)), for the thermal cis to trans relaxation of DENAB correlates roughly with (pi)* in conventional solvents, however, this same correlation fails to continue in supercritical carbon dioxide. A correlation between (DELTA)G('(tau)) and (pi)* is found in supercritical carbon dioxide and two conventional non-polar solvents. This correlation has a much smaller slope than the rough correlation found in conventional polar aprotic solvents, and is of opposite sign. The change in behavior of (DELTA)G('(tau)) as a function of (pi)* is interpreted as indication a change of mechanism on going from polar to non-polar solvents. / The decomposition of phenylazotriphenylmethane (PAT) has been studied in supercritical carbon dioxide. PAT gives a poor material balance upon decomposition even though the solvent does not appear to be reacting with the radical species formed during the decomposition. The observed rate of decomposition is intermediate to that in cyclohexane and the proposed "zero" viscosity rate. / The decompositions of two secondary diacyl peroxides have been studied in supercritical carbon dioxide, cyclobutanecarboxoyl- m-chlorobenzoyl peroxide and isobutyryl peroxide. Experiments with ('13)C labels in the acyl moiety of the peroxides show that an exchange of 13CO2 groups with carbon dioxide solvent molecules occurs during carboxy-inversion. (Abstract shortened with permission of author.) / Source: Dissertation Abstracts International, Volume: 48-02, Section: B, page: 0446. / Thesis (Ph.D.)--The Florida State University, 1986.

This work focuses on the development of new synthetic methods for the preparation of various N-heterocycles. While I have encountered many road blocks throughout my PhD, it has taught me how to solve a wide variety of challenges through perseverance, critical thinking and collaboration. I have successfully developed multiple projects stemming from my independent ideas for new chemical transformations. The projects range from cyclizations of o-alkenylisocyanides using a variety of radical precursors to C(sp3)-H amination (with and without transition metals) reactions. The discovery of selective addition of radicals to isonitriles could be harnessed to initiate a radical cascade that was designed to overcome the stereoelectronic restrictions on homoallylic ring expansion in alkyne reactions by using alkenes as synthetic equivalents of alkynes. This allowed us to establish a new route for N-heteroaromatics by coupling a homoallylic ring expansion with a stereoelectronically assisted C-C bond scission to yield the formal “6-endo” products. Additionally we have developed multiple protocols for C(sp3)-H aminations. Firstly, a transition metal mediated approach using FeCl3/DDQ for an intramolecular C(sp3)-H oxidative amination. In this reaction, an aniline group can activate the molecule for single-electron-transfer while also acting as an internal nucleophile to trap reactive intermediates. Following a consecutive electron transfer oxidation process, we can couple free amines with -CH2- groups to afford aromatic N-heterocycles using inexpensive reagents. Expansion of the intramolecular oxidative C(sp3)-H amination to unprotected anilines and amides and C(sp3)-H bonds to occur under mild conditions using t-BuOK, DMF and O2. This protocol relies on a synergy between base, radical and oxidizing species to promote a coordinated sequence of deprotonation followed by H-atom transfer and oxidation that constructs a new C-N bond. We were able to apply this chemistry to the preparation of a wide variety of N-heterocycles, ranging from small molecules to extended aromatics without the need for transition metals or strong oxidants. / A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy. / Spring Semester 2018. / April 13, 2018. / Development, Methodology, N-heterocycles, Organic, Reaction / Includes bibliographical references. / Igor V. Alabugin, Professor Directing Dissertation; Michael Blaber, University Representative; Kenneth Hanson, Committee Member; Justin Kennemur, Committee Member.