Green Chemistry for Catalytic Carbonyl Propargylation

该项目的重点是开发金属催化剂，促进醇和π-不饱和化合物的直接无副产物的C-C偶联。 在拟议的资助期内，这种新的反应模式将被应用于烯炔介导的炔丙基化羰基化合物从醇氧化水平。 这些转化的一个特征是能够通过利用醇和共轭烯炔作为氧化还原对直接从醇氧化态实现羰基加成。 在此，醇脱氢驱动丙二烯基金属物质和醛亲电体的还原生成，其联合收割机组合以提供高炔丙醇。 与需要羰基亲电试剂与预金属化亲核试剂（例如有机锡或有机镁试剂）组合的羰基炔丙基化的经典方法不同，C-C偶联方法采用π-不饱和化合物作为预金属化亲核试剂的替代物，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，避免了预先生成醛亲电试剂所需的离散氧化还原操作。有了这个奖项，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Michael J. Krische教授的研究。 Krische教授领导绿色化学和催化中心，致力于开发催化C-C键形成工艺，使丰富的可再生资源能够可持续地、无副产物地制造化学产品。 该方法的成功开发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，化学，农业以及生物和化学研究活动。 此外，该项目将为学生提供优秀的培训，从大学预科到博士后，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。

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.