Regiocontrolled Asymmetric alpha-Alkylation of Ketones via Activated Hydrazones

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In this project funded by the Chemical Synthesis program of the Chemistry Division, Professor Don M. Coltart of the Department of Chemistry at Duke University will explore the development of new methods for the regiocontrolled asymmetric alpha-alkylation of ketones. The central hypothesis of the planned research is that activated hydrazones - those having at least one electron withdrawing group on the distal nitrogen - and oximes will provide the basis for a variety of new approaches to the asymmetric alpha-alkylation of ketones. From this work, fundamentally new regiochemical substitution patterns that cannot be generated using existing technology will be accessible in an asymmetric manner. Moreover, it will be possible to conduct asymmetric alpha-alkylation in an umpolung sense, thus enabling the incorporation of functionality that cannot be introduced using enolate-based methods.This work could lead to facile methods for the asymmetric alpha-alkylation of ketones. The ability to easily and effectively prepare single enantiomer forms of alpha-alkylated ketones will contribute greatly to our ability to synthesize optically pure natural products, drugs and related compounds, thus impacting science and society in important ways. In addition, this project will provide excellent training of undergraduate and graduate students, including those from groups historically underrepresented in the sciences.