CAREER: Synthesis and Applications of Multipurpose Halomucononitrile Linchpin Reagents

在化学系化学合成计划的支持下，北卡罗来纳大学教堂山分校的西德尼·威尔克森-希尔正在研究一类迄今鲜有研究的卤代聚氰酸酯分子的合成和反应活性。这些多功能材料是高活性中间体的良好替代品，将探索的独特转化预计将导致化学制造的改进，并在从药物发现到材料科学等不同领域产生积极影响。该资助项目的广泛影响将扩大到为社会带来的好处，因为国际和平协会和威尔克森-希尔研究小组的其他成员开展了广泛的教育和外联活动，涉及北卡罗来纳大学教堂山分校与全国黑人化学家和化学工程师专业促进会(NOBCChE)和科学与工程界少数群体和妇女联盟(AMWISE)等组织之间的伙伴关系。这些努力的很大一部分集中在增加属于STEM(科学、技术、工程和数学)领域传统上代表性较低的基团的个人对科学事业的参与。卤代聚丙烯腈[双-3，3‘-(2-卤代丙烯腈)]是含有1，4-二氰基丁二烯基序的有价值的关键试剂，该基序允许通过各种可控的多步骤反应序列顺序形成C-C和C-N键。将在三个目标的背景下探索卤代丁腈的合成用途及其形成的新路线：(1)由伯胺与卤代丁腈加成生成的吡二亚胺合成具有药用价值的7-烷基氮杂环醚，(2)将卤代丁腈用作双乙烯酮的合成等价物，通过双([4+2]，[3+2]或[2+2])环加成，然后将α-卤腈转化为酮，以及(3)通过氧化开环过程从卤代苯胺生成卤代尿腈。最后一个目标是为一种新的芳烃解构策略铺平道路，使苯衍生物能够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好处外，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丁腈化学用于不同的应用，如赖氨酸结合策略、DNA编码的文库合成和聚合物科学。最后指出，该奖项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中追求未来的职业生涯。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.