New Methods for the Synthesis of Hindered Quaternary Carbons

在这个由化学部化学合成项目资助的项目中，科罗拉多大学化学和生物化学系的Tarek Sammakia教授将探索立体选择性形成受阻碳-碳键的方法，包括全碳的季中心和三级中心。一般的反应是由一连串的环加成和重排反应进行的。该反应在机理上是新颖的，因此建议进一步阐明机理并使用化学计量学方法使其不对称。虽然有一些方法可以合成季碳，但它们的范围有限，而这种新方法可以制备现有方法无法获得的结构基序。整个转化相当于两个烯醇酸酯的氧化交叉偶联，从而制备1,4-二羰基化合物。目前还没有一种方法可以直接以立体选择的方式完成这种转化，而这项工作的主要目的是为制备这类分子提供一种新的更有效的方法。这将导致合成该结构母题的步数显著减少，更高的效率意味着更少的浪费和更少的副产品。该方法的成功开发将对许多合成活动产生影响，包括具有该基序的药物制剂和新材料的合成。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。最后，考虑将这些方法纳入本科有机化学实验室，因为这种反应很容易，而且环加成和异位重排在本科生中并不常见。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Tarek Sammakia of the Department of Chemistry and Biochemistry at The University of Colorado will explore the development of methods for the stereoselective formation of hindered carbon-carbon bonds, including all-carbon quaternary and tertiary centers. The general reaction to be developed proceeds by a cascade of cycloaddition and rearrangement reactions. This reaction is mechanistically novel, and as such studies are proposed to further elucidate the mechanism and to render it asymmetric using stoichiometric methods. While some methods exist for the synthesis of quaternary carbons, they are limited in scope and this new method allows for the preparation of structural motifs that are not available by existing methods. The overall transformation is the equivalent of an oxidative cross-coupling of two enolates, thereby preparing 1,4-dicarbonyl compounds. There are currently no methods that directly accomplish this transformation in a stereoselective fashion bearing such hindered carbons and the major aim of this work is to provide a new and more efficient method for the preparation of this class of molecules. This will lead to a significant reduction in step-count for the synthesis of this structural motif, and the greater efficiency means less waste and fewer by-products. Successful development of this method will have an impact on many synthesis activities including the synthesis of pharmaceutical agents and new materials that bear this motif. In addition, this project will provide excellent training of undergraduate and graduate students, including those from groups historically underrepresented in the sciences. Finally, the incorporation of these methods into undergraduate organic chemistry laboratories will be considered as this reaction is facile and cycloadditions and sigmatropic rearrangements are not commonly encountered by undergraduates.