Regiocontrolled Asymmetric alpha-Alkylation of Ketones via Activated Hydrazones

通过活化腙对酮进行区域控制的不对称 α-烷基化

• 批准号: 1305821
• 负责人: Don Coltart
• 金额: $ 10.49万
• 依托单位: University of Houston
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-10-01 至 2014-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1305821&HistoricalAwards=false
• 关键词: Regiocontrolled; Asymmetric; alpha; Alkylation; Ketones

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.

杜克大学化学系的Don M. Coltart教授将在化学合成项目资助下，探索区域控制的酮类不对称烷基化的新方法。计划研究的中心假设是，活化的腙（在远端氮上至少有一个吸电子基团的腙）和肟将为酮的不对称α -烷基化的各种新方法提供基础。从这项工作中，从根本上说，利用现有技术无法产生的新的区域化学替代模式将以不对称的方式获得。此外，它将有可能进行非对称的α -烷基化，从而能够结合使用烯醇酸基方法无法引入的功能。这项工作可能导致酮的不对称烷基化的简便方法。简单有效地制备α -烷基化酮的单一对映体形式的能力将极大地有助于我们合成光学纯净的天然产物、药物和相关化合物的能力，从而在重要方面影响科学和社会。此外，该项目将为本科生和研究生提供优秀的培训，包括那些来自历史上在科学领域代表性不足的群体的学生。