CAREER: Synthesis and Applications of Multipurpose Halomucononitrile Linchpin Reagents

在化学系化学合成计划的支持下，查佩尔山的北卡罗来纳州大学的西德尼·威尔克森-希尔正在研究一类迄今为止研究得很少的称为卤代糖腈的分子的合成和反应性。这些多功能材料是高活性中间体的良好替代品，预计将探索的独特转化将导致化学制造的改进，并对从药物发现到材料科学的不同领域产生积极影响。资助项目的更广泛的影响将扩展到社会的利益，因为PI和Wilkerson-Hill研究小组的其他成员参与了广泛的教育和推广活动，涉及查佩尔山和组织之间的伙伴关系，如全国黑人化学家和化学工程师专业促进协会（NOBCChE）少数民族和妇女在科学和工程同盟（AMWISE）。这些努力的很大一部分集中在增加属于传统上在STEM中代表性不足的群体的个人对科学事业的参与（科学、技术、工程和数学）领域。卤代粘腈[bis-3，3 ′-（2-卤代丙烯腈）]是有价值的关键试剂，4-二氰基丁二烯基序，其允许通过各种可控的多步反应序列连续形成C-C和C-N键。将在三个目标的背景下探索卤代粘菌腈的合成效用及其形成的新途径：（1）由通过将伯胺加成到卤代粘腈上产生的吡啶亚胺合成医学相关的7-烷基氮杂吲哚，（[4+2]、[3+2]或[2+2]）环加成，然后α-卤代腈转化为酮，和（3）通过氧化开环过程由卤代苯胺生成卤代粘菌腈。最后一个目标为一种新的芳烃解构策略铺平了道路，使苯衍生物净转化为吡啶和其他重要的氮杂环。除了对合成有机化学的直接益处之外，从这些研究中获得的新知识可能使来自不同领域的研究人员能够将卤代粘菌腈关键化学用于多种应用，如赖氨酸缀合策略，DNA编码的文库合成和聚合物科学。最后，值得注意的是，该奖项所支持的研究将为研究生提供宝贵的培训机会，使他们能够在化学科学和相关学科的未来职业生涯的追求。该奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。

With the support of the Chemical Synthesis Program in the Division of Chemistry, Sidney Wilkerson-Hill of the University of North Carolina at Chapel Hill is studying the synthesis and reactivity of a class of hitherto little studied molecules called halomucononitriles. These versatile materials are well-behaved surrogates for highly reactive intermediates and the unique transformations to be explored are anticipated to lead to improvements in chemical manufacturing with positive impacts in disparate areas ranging from drug discovery to materials science. The broader impacts of the funded project will extend to the benefits accrued to society as the PI and other members of the Wilkerson-Hill research group engage in a wide range of educational and outreach activities involving partnerships between UNC Chapel Hill and organizations such as the National Association for the Professional Advancement of Black Chemists and Chemical Engineers (NOBCChE) and the Allies for Minorities and Women in Science and Engineering (AMWISE). A significant portion of these efforts focus on increasing participation in the scientific enterprise by individuals belonging to groups traditionally underrepresented in STEM (Science, Technology, Engineering and Mathematics) fields.Halomucononitriles [bis-3,3´-(2-haloacrylonitriles)] are valuable linchpin reagents containing a 1,4-dicyanobutadiene motif that permits the sequential formation of C-C and C-N bonds through a variety of controllable multistep reaction sequences. The synthetic utility of halomucononitriles and new routes for their formation will be explored in the context of three aims: (1) synthesis of medicinally-relevant 7-alkylazaindoles from pyridinimines generated by addition of primary amines to halomucononitriles, (2) use of halomuconitriles as a synthetic equivalent of bisketene to access 1,4-diketones via double ([4+2], [3+2], or [2+2]) cycloadditions followed by alpha-halonitrile to ketone conversion, and (3) generation of halomucononitriles from haloanilines by oxidative ring-opening processes. The last aim paves the way for a new arene deconstruction strategy enabling the net transmutation of benzene derivatives into pyridines and other important azacycles. Beyond its immediate benefits to synthetic organic chemistry, the new knowledge gained from these studies may enable researchers from different fields to use halomucononitrile linchpin chemistry for diverse applications such as lysine conjugation strategies, DNA-encoded library synthesis, and polymer science. Finally, it is noted that the research supported by the award will provide valuable training opportunities for graduate students to enable their pursuit of future careers in the chemical sciences and allied disciplines.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.