New Methods for the Synthesis of Hindered Quaternary Carbons

在这个由化学系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，包括全碳季和三级中心。一般的反应是通过环加成和重排反应的级联进行的。该反应在机理上是新颖的，因此建议使用化学计量方法进一步阐明该机制并使其不对称。虽然存在一些用于合成季碳的方法，但它们的范围有限，并且这种新方法允许制备现有方法不可用的结构基序。整个转化相当于两个烯醇化物的氧化交叉偶联，从而制备1，4-二羰基化合物。目前还没有直接以立体选择性方式实现这种转化的方法，该方法具有这种受阻碳，并且这项工作的主要目的是提供用于制备这类分子的新的和更有效的方法。这将导致合成该结构基序的步骤计数的显著减少，并且更高的效率意味着更少的浪费和更少的副产物。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剂和新材料的合成。此外，该项目还将为本科生和研究生提供出色的培训，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，将这些方法纳入本科有机化学实验室将被认为是因为这种反应是容易的和cycloadditions和sigmatropic重排是不常见的本科生。

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.