METALATED NITRILES: UNMASKING FUNDAMENTAL REACTIVITY

金属化腈：揭示基本反应性

• 批准号: 1639875
• 负责人: Fraser Fleming
• 金额: $ 7.35万
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-01-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1639875&HistoricalAwards=false
• 关键词: METALATED; NITRILES; UNMASKING; FUNDAMENTAL; REACTIVITY

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.

在这个由化学系化学合成项目资助的项目中，Fraser F.迪克讷大学化学系的弗莱明将探索金属化腈的全新反应。初步结果表明，烷基化烯烃，芳烃，并创建中型碳环的几个新的反应模式的可行性。将开展研究，将这些尝试扩展和发展为强大的合成方法。锌化和镁化腈的不对称烷基化将通过筛选和机械探针的组合来进行，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。该研究可能会导致立体选择性组装受阻季中心的新方法。医学和材料等不同领域都依赖于这种强大的化学。基于腈的芳基化反应特别适合于合成几种含腈的药物和药物先导物，因为该方法使用廉价，丰富的铜催化剂，而不是钯催化剂，目前需要相同的transformation.Three更广泛的影响将达到通过这项研究：机构发展，腈化学的海拔，和学生培训。作为一个教师学者机构，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，学生的研究将在一定程度上由博士后助理指导，并从PI到博士后助理进行相互指导。