Thesis (Ph. D.)--University of Wisconsin--Madison, 1970. / Vita. Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

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Thesis (Ph. D.)--Ohio State University, 2005. / Title from first page of PDF file. Includes bibliographical references (p. 294-299).

Thesis advisor: X. Peter Zhang / Thesis advisor: James P. Morken / Chapter 1. Stereoselective Cyclopropanation of Alkenes with Alkynyl- and Vinyl-Substituted Diazo Compounds Alkynyl- and vinyl-substituted cyclopropanes are ubiquitous structural motifs in drug molecules and bioactive compounds. In addition, alkynyl- and vinyl-substituted cyclopropanes may serve as useful intermediates for stereoselective organic synthesis. Metal-catalyzed cyclopropanation of alkenes with alkynyl- and vinyl-substituted diazo compounds offers a potentially general approach for stereoselective construction of these valuable three-membered ring structures. This chapter summarizes the development of stereoselective olefin cyclopropanation with alkynyl- and vinyl-substituted diazo compounds. Chapter 2. Metalloradical Activation of In Situ-Generated α-Alkynyldiazomethanes for Asymmetric Radical Cyclopropanation of Alkenes We have developed a Co(II)-based metalloradical system that is highly effective for asymmetric radical cyclopropanation of alkenes with in situ-generated α-alkynyldiazomethanes. Through fine-tuning the cavity-like environments of D₂-symmetric chiral amidoporphyrins as the supporting ligand, the optimized Co(II)-based metalloradical system is broadly applicable to different alkynyldiazomethanes for asymmetric cyclopropanation of a broad range of alkenes, providing general access to valuable chiral alkynyl cyclopropanes in high yields with excellent diastereoselectivities and enantioselectivities. Chapter 3. Asymmetric Radical Process for Cyclopropanation of Alkenes with In Situ-Generated α-Vinyldiazomethanes We have demonstrated the feasibility of using vinyl aldehyde-derived sulfonylhydrazones as new metalloradicophiles for the generation of allylic radicals. Through fine-tuning the cavity-like environments of D₂-symmetric chiral amidoporphyrins as supporting ligands, the key α-Co(III)-allylic radical intermediates are exclusively engaged in the highly asymmetric cyclopropanation with wide-ranging alkenes in the optimized Co(II)-based metalloradical system, as shown broadly applicable to activate different α-vinyldiazomethanes. Chapter 4. Asymmetric Synthesis of Vinyl-Substituted Cyclopropanes by Radical C-H Alkylation from Alkynes and In Situ-Generated Alkyldiazomethanes via Co(II)-Based Metalloradical Catalysis We have successfully expanded the application of Co(II)-based MRC by applying in-situ generated alkyldiazomethanes as new radical precursors for stereoselective synthesis of vinyl-substituted cyclopropanes by radical cascade C-H alkylation of alkynes. Through fine-tuning of D₂-symmetric chiral amidoporphyrins as the supporting ligands, the Co(II)-catalyzed radical cascade process, which proceeds in a single operation under mild conditions, enables asymmetric construction of vinyl-substituted cyclopropanes in high yields with excellent diastereoselectivities and good enantioselectivities. / Thesis (PhD) — Boston College, 2022. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Chemistry.

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Since the discovery that diazomethane, CH2N2, can effect the cyclopropanation of alkenes under palladium catalysis in the 1960s, this reaction has been used to great effect in synthesis. However, the necessity of preparing and handling diazomethane, a toxic and explosive reagent, is unappealing. The substitution of diazomethane for a commercially-available and thermally-stable silylated congener, namely trimethylsilyldiazomethane (TMSDAM), has been investigated. Under optimised conditions, designed to promote protodesilylation, use of this reagent affords the same products as would be obtained with the more hazardous diazomethane, with no trace of the corresponding silylated cyclopropanes. NMR spectroscopy has revealed that the protodesilylating agent employed in the reaction, tetrabutylammonium bifluoride (n-Bu4N+ HF2 -, TBABF), reacts cleanly with TMSDAM to generate diazomethane. Under catalytic conditions, the consumption of the desilylated diazo reagent by palladium is sufficiently rapid to prevent the accumulation of this hazardous reagent in solution. Spectroscopic titration studies also revealed a “hidden” mode of TBABF catalysis, whereby adventitious water drives the regeneration of the bifluoride salt. This observation was exploited by the development of an EtOH-driven reaction variant in which catalytic amounts (20 mol%) of TBABF could be employed. The ability to effect the in situ generation of diazomethane has allowed for mechanistic studies into the course of the cyclopropanation reaction to be undertaken. These reveal a partitioning in the consumption of nascent diazomethane between the desired cyclopropanation reaction and a side reaction. The product of the side reaction was identified as cyclopropane (C3H6), the product of formal methylene cyclotrimerisation, by employing EtOD in TBABF-catalysed deuterodesilylative cyclopropanation. The partitioning between the two pathways is dependent on the nature of the substrate, with efficient cyclopropanation dominating with electrondeficient alkenes. For an electronically-varied range of styrenes, the relative rate of productive diazomethane consumption correlates well with the energy of the frontier molecular orbitals (as determined by DFT calculations). These results are consistent with an initial, substrate-dependent partitioning of the palladium pre-catalyst between species able to effect alkene cyclopropanation, and those (likely higher-order) species which promote only the cyclotrimerisation of diazomethane.

&amp / #945 / ,&amp / #946 / -Unsaturated cyclic ketones were selectively oxidized on &amp / #945 / &#039 / - positions using Mn(OAc)3 and Pb(OAc)4, respectively. The resultant racemic &amp / #945 / &#039 / -acetoxylated substrates were resolved into corresponding enantiomerically enriched &amp / #945 / &#039 / -hydroxylated and &amp / #945 / &#039 / -acetoxylated compounds via PLE hydrolysis. &amp / #945 / &#039 / -Hydroxylated compounds are racemized quickly, so they were acetylated with acetyl chloride and pyridine in situ to give the corresponding &amp / #945 / &#039 / -acetoxylated compounds. Resultant &amp / #945 / &#039 / -acetoxy &amp / #945 / ,&amp / #946 / -unsaturated cyclic ketones reacted with excess amount of diazomethane under the catalsts of Pd(OAc)2 to give the resulting bicyclic diastereomeric products. At the end of the experiment, Enantiomeically enriched 2-oxobicyclo[3.1.0]hexan-3-yl acetate and 2-oxobicyclo[4.1.0]heptan-3-yl acetate were chemoenzymatically synthesized.

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The thesis describes the development of new and improved methods for analyzing degradation markers from organophosphorus Chemical Warfare Agents (CWAs). Paper I and II describes an innovative and significantly improved method for the enrichment, derivatization (trimethysilylation) and GC-MS analysis of a broad range of organophosphorus CWAs degradation markers, namely the alkylphosphonic acids and a zwitterionic compound. That was achieved using solid phase disc extraction in combination with solid phase derivatization. The new method overcomes most limitations observed with existing techniques: it offers almost 100 % recoveries, requires no elution or evaporation steps, facilitates miniaturization of the solid sorbent and reagent, is compatible with in-vial derivatization, and minimizes the chromatographic background due to the use of a highly selective anion exchange sorbent disc. Paper III describes the development of new fluorinated diazomethane derivatization reagents and their evaluation for rapid and high sensitivity screening and identification of nerve agent degradation markers. The reagents are water-tolerant to some extent, which simplifies the derivatization step. The best reagent identified was 3,5-bis(trifluoromethyl)benzyl diazomethane, which outperformed the other reagent isomers tested and also the established commercial alternative, pentafluorobenzylbromide, allowing for the rapid (5 min) and direct derivatization of a 25 μL aqueous sample in acetonitrile. The spectra of the formed derivatives (high-energy collision induced fragmentation MS/MS) were used to construct a database (Paper IV) that proved to be superior in terms of match factor and probability compared to EI data gathered for trimethylsilyl derivatives. The study also focused on efforts towards achieving detailed structure information on the alkyl chains of the compounds in question using diagnostic ion interpretation. The final paper (paper V) describes the first rapid direct derivatization method for analyzing nerve agent metabolites in urine at trace levels. The method is based on the derivative from the paper III and the unambiguous identification was proven using a combination of low resolution and high resolution negative ion chemical ionization selected ion monitoring techniques. Novel results presented in these papers include: the first in-situ derivatization of alkylphosphonic acids on an SPE disc; the first direct derivatization of nerve agent markers in water and biomedical samples; the first high sensitivity GC-MS screening for these markers; and the first highly reproducible high-energy isomer specific CID MS/MS library. Overall, the results presented in this thesis represent significant contributions to the analysis of nerve agent degradation products.

Thèse numérisée par la Division de la gestion de documents et des archives de l'Université de Montréal