Green Chemistry for Catalytic Carbonyl Propargylation

该项目的重点是开发金属催化剂，以促进醇和pi-不饱和化合物的直接无副产物C-C偶联反应。在拟议的资助期内，这一新的反应性模式将被应用于烯炔介导的羰基化合物的醇氧化水平的丙烷化反应。这些转化的一个特点是能够通过利用醇和共轭烯炔作为氧化还原对直接从醇的氧化态实现羰基加成。在这里，醇脱氢驱动还原生成的烯基金属物种和醛亲电剂，它们结合在一起提供高-丙炔醇。与传统的羰基丙烯酰化反应方法不同，传统的方法需要羰基亲电试剂与预金属化的亲核试剂(如有机锡或有机镁试剂)相结合，而C-C偶联过程使用pi-不饱和化合物作为预金属亲核试剂的替代物，从而避免产生化学计量的金属废物。此外，通过醇的直接C-C偶联，人们避开了预生成醛亲电试剂所需的离散氧化还原操作。通过这一奖项，化学合成计划正在支持德克萨斯大学奥斯汀分校化学和生物化学系的迈克尔·J·克里什教授的研究。Krische教授是绿色化学和催化中心的负责人，他致力于开发催化C-C键形成过程，使可持续、无副产品的化学产品能够从丰富的可再生资源中生产出来。该方法的成功发展将对任何需要合成有机分子的活动领域产生影响，例如制药、化工、农业以及生物和化学研究活动。此外，该项目将为学生提供极好的培训，从本科前到博士后，包括那些在科学界历来代表性不足的学生。

This project focuses on the development of metal-catalysts that promote direct byproduct-free C-C coupling of alcohols and pi-unsaturated compounds. In the proposed funding period, this novel pattern of reactivity will be applied to enyne-mediated propargylation of carbonyl compounds from the alcohol oxidation level. A feature of these transformations is the ability to achieve carbonyl addition directly from the alcohol oxidation state by exploiting alcohols and conjugated enynes as redox-pairs. Here, alcohol dehydrogenation drives reductive generation of allenylmetal species and aldehyde electrophiles, which combine to furnish homo-propargyl alcohols. Unlike classical approaches to carbonyl propargylation, which require carbonyl electrophiles in combination with pre-metallated nucleophiles (e.g. organo-tin or organo-magnesium reagents), the C-C coupling processes employ pi-unsaturated compounds as surrogates to pre-metallated nucleophiles, thus avoiding generation of stoichiometric metallic waste. Further, through the direct C-C coupling of alcohols, one circumvents discrete redox manipulations otherwise required for pre-generation of aldehyde electrophiles. With this award, the Chemical Synthesis Program is supporting the research of Professor Michael J. Krische of the Department of Chemistry and Biochemistry at the University of Texas at Austin. Professor Krische, who leads the Center for Green Chemistry and Catalysis, is engaged in the development of catalytic C-C bond forming processes that enable sustainable, byproduct-free manufacture of chemical products from abundant, renewable resources. Successful development of the methodology will have an impact on any area of activity in which the synthesis of organic molecules is needed, such as the pharmaceutical, chemical, agricultural industry, and the biological and chemical research activities. In addition, this project will provide excellent training of students, from pre-undergraduate to post-doctoral, including those from groups historically underrepresented in the sciences.