Metalated Nitriles: Unmasking Fundamental Reactivity

金属化腈：揭示基本反应性

• 批准号: 1464494
• 负责人: Fraser Fleming
• 金额: $ 41.75万
• 依托单位: Drexel University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2019-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1464494&HistoricalAwards=false
• 关键词: Metalated; Nitriles; Unmasking; Fundamental; Reactivity

Non-technical AbstractIn this project, funded by the Chemical Synthesis Program of the Chemistry Division, the research team is exploring fundamentally new reactions of nitriles. The proposal has impact in several areas; the elevation of nitrile chemistry, student training and development, and improving the ability of students' writing. The research falls into three broad areas that will develop new reactions of nitriles for the synthesis of cyclic, carbon-based scaffolds of relevance for the synthesis of pharmaceuticals, agrochemicals, and new materials. The first third of the proposal focuses on an extremely rapid synthesis of bicyclic nitriles, the middle third develops counter-intuitive methods of creating new carbon-carbon bonds, and the last section of the proposal develops new routes to reactive nitrile intermediates to control the three dimensional shape of nitrile-substituted scaffolds. The project continues an excellent track record in training students and post-doctoral associates, particularly minorities and women, to provide a stream of bright, highly motivated students for careers in science. The approach features vigorous research training with synergistic mentoring of undergraduate and graduate students and an emphasis on career life balance through group educational events and annual professional development retreats. Improved writing skills are taught through a review writing strategy that transitions undergraduate and graduate students from novice learners to expert practitioners. The approach simultaneously addresses a general writing deficiency in many students while instilling tools to critically evaluate the primary literature. Publishing the strategy in the Journal of Chemical Education should allow others to replicate the strategy with other students.Technical AbstractThis project focuses on a blend of conceptually new bond constructions and new chemical entities, many of which challenge conventional processes. Preliminary results demonstrate the feasibility of preparing chiral decalones in a single synthetic operation, potentially replacing multi-step technology based on the Wieland-Miescher ketone. A highly unusual equilibration is under development which changes the stereochemistry of a quaternary bridgehead center; a process that challenges conventional notions. A counter-intuitive alkylation of metalated nitriles with unactivated alkenes is rapidly assembling tricyclic ketones. A complementary alkene addition uses S-ketenimines as particularly attractive nucleophiles to address two long-standing challenges: rapid access to stable ketenimine nucleophiles, and nitrile-based alkenylations. The last section of the proposal provides an orthogonal, innovative asymmetric alkylation with metalated nitriles. Collectively, the proposed research exploits the unique reactivity of nitriles consummate with the long-term objective of elevating metalated nitrile alkylations to a level of influence comparable to that of enolate alkylations.

非技术摘要在该项目中，由化学部化学合成项目资助，研究团队正在探索全新的腈反应。该提案在多个领域产生影响；腈化学的提升，学生的培养和发展，提高学生的写作能力。该研究分为三大领域，将开发新的腈反应，用于合成与药物、农用化学品和新材料合成相关的环状碳基支架。该提案的前三分之一重点关注双环腈的极快速合成，中间三分之一开发了创建新碳-碳键的反直觉方法，该提案的最后一部分开发了反应性腈中间体的新路线以控制这三种化学反应。腈取代支架的尺寸形状。该项目在培训学生和博士后助理（特别是少数族裔和女性）方面延续了良好的记录，为科学事业提供了一批聪明、积极主动的学生。该方法的特点是积极的研究培训，对本科生和研究生进行协同指导，并通过团体教育活动和年度专业发展务虚会强调职业生活的平衡。通过评论写作策略来提高写作技能，将本科生和研究生从新手转变为专家实践者。该方法同时解决了许多学生普遍存在的写作缺陷，同时灌输了批判性评估原始文献的工具。在《化学教育杂志》上发表该策略应该允许其他人与其他学生复制该策略。技术摘要该项目的重点是概念上新的键结构和新的化学实体的混合，其中许多挑战传统的过程。初步结果证明了在单次合成操作中制备手性十酮的可行性，有可能取代基于维兰德-米歇尔酮的多步技术。一种极不寻常的平衡正在开发中，它改变了四元桥头中心的立体化学；挑战传统观念的过程。金属化腈与未活化烯烃的反直觉烷基化正在快速组装三环酮。互补的烯烃加成使用 S-烯酮亚胺作为特别有吸引力的亲核试剂来解决两个长期存在的挑战：快速获得稳定的烯酮亚胺亲核试剂和基于腈的烯基化。该提案的最后一部分提供了一种与金属化腈的正交、创新的不对称烷基化反应。总的来说，拟议的研究利用了腈独特的反应性，最终实现了将金属化腈烷基化的影响力提高到与烯醇化物烷基化相当的水平的长期目标。