METALATED NITRILES: UNMASKING FUNDAMENTAL REACTIVITY

在这个由化学系化学合成项目资助的项目中，杜肯大学化学系的 Fraser F. Fleming 教授将探索金属化腈的全新反应。初步结果证明了几种新的反应模式对于烷基化烯烃、芳烃和产生中等大小的碳环的可行性。将进行研究以扩展和开发这些稳健的合成方法。锌化和镁化腈的不对称烷基化将通过筛选和机械探针的结合进行，以解决该领域最困难的挑战之一：手性金属化腈的立体选择性烷基化。这项研究可能会带来立体选择性组装受阻四元中心的新方法。医学和材料等多种领域都依赖于这种强大的化学反应。基于腈的芳基化特别适合合成多种含腈药物和先导药物，因为该方法使用廉价、丰富的铜催化剂，而不是目前相同转化所需的钯催化剂。这项研究将产生三个更广泛的影响：机构发展、腈化学的提升和学生培训。作为一所教师学者机构，在追求卓越研究的同时，非常重视本科生和研究生的指导。在这种情况下，学生的研究将部分由博士后助理指导，PI 与博士后助理相互指导。

In this project funded by the Chemical Synthesis Program of the Chemistry Division, Professor Fraser F. Fleming of the Department of Chemistry at Duquesne University will explore fundamentally new reactions of metalated nitriles. Preliminary results demonstrate the viability of several new reactivity patterns for alkylating alkenes, aromatics, and creating medium-sized carbocycles. Studies to expand and develop these forays into robust synthetic methods will be undertaken. Asymmetric alkylations of zincated and magnesiated nitriles will be performed through a combination of screening and mechanistic probes to address one of the most difficult challenges in the field: stereoselective alkylation of a chiral, metalated nitrile.The research is likely to lead to new methods for stereoselectively assembling hindered, quaternary centers. Fields as diverse as medicine and materials rely on exactly this type of robust chemistry. The nitrile-based arylation is particularly well suited to the synthesis of several nitrile-containing pharmaceuticals and drug leads because the method uses an inexpensive, abundant copper catalyst rather than palladium catalysts that are currently required for the same transformation.Three broader impacts will be reached through this research: institutional development, elevation of nitrile chemistry, and student training. As a teacher-scholar institution a strong emphasis is placed on undergraduate and graduate mentoring while pursuing research excellence. In this context, the student research will, in part, be guided by a post-doctoral associate with reciprocal mentoring from the PI to the post-doctoral associate.