Bi(III)-Initiated Chemistry: Mechanistic Investigations of Catalytic Activity

College Of William And Mary, Williamsburg VA

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Abstract

[unreadable] DESCRIPTION (provided by applicant): Bismuth compounds have recently blossomed as very useful reagents for organic synthesis and catalytic quantities initiate a wide-range of reactions. Some more recently developed Bi(III)-initiated methodologies have been used in the synthesis of antitumor and antifungal agents. Outside of these latest uses of bismuth catalysts, many of the previously documented reactions were simple carbonyl protection and deprotection protocols via intermediate oxocarbenium ions. The actual catalytically-active species in most of these reactions, however, is uncertain and currently under considerable debate. The growing use of bismuth(III) compounds is largely due to the facts that they are inexpensive, have very low toxicity (the LD50 for BiBr3 is comparable to that of NaCl), are relatively stable in the solid-state, and are fairly easy to handle under typical laboratory conditions (hygroscopic). In fact, bismuth compounds have been widely utilized in pharmaceutical preparations for over 400 years. Perhaps the most widely-known, medicinally important bismuth(III) compound is bismuth subsalicylate, the active ingredient in Pepto-Bismol (r). The specific aims of this project are to investigate the mechanisms of reaction non-toxic bismuth(III) compounds by studies in the following areas: (1) stoichiometric interactions between Bi(III) compounds and reactive organic substrates; reaction rates, yields, turnover numbers and molecularity of aldol and allylation reactions; (2) evaluation of the degree of crossover in Mukaiyama aldol reactions with ketene silyl acetals in efforts to document the true catalyst; and (3) the evaluation of Bi(III) in potentially diastereomeric reactions and direct comparisons to diastereoselectivities obtained using other Lewis and BrOnsted acids as initiators. The proposed studies will attempt to document the true source of the high catalytic activity in bismuth salts. These investigations are crucial to understanding this versatile metalloid and will provide the foundation for the development of new synthetic methodologies in potentially asymmetric syntheses. The organic synthesis of pharmaceuticals and materials often relies upon metals as catalysts for a number of key transformations. With increasing needs for medications and materials as Baby Boomers age, chemists are working toward finding more environmentally- friendly catalysts such as those based on non-toxic metals like bismuth. As Bi(III) compounds recently have enjoyed rapid growth in synthetic methodology, their role(s) as catalysts should be assessed to determine if they are, in fact, unique catalysts and if they are beneficial compared to other catalyst systems. We pose a number of mechanistic questions and propose experiments to answer those questions. [unreadable] [unreadable] [unreadable]