Applications of Chalcogen-based Oxidation State Alternating Organocatalysts

在化学系化学催化项目的支持下，宾夕法尼亚大学的帕特里克·J·沃尔什教授正在研究一种新的催化原理，该原理基于使用含硫和硒的化合物，这些化合物在反应周期中可逆地改变其氧化态，从而从廉价且广泛可用的起始材料形成增值产品。值得注意的是，所研究的过程的产物通常本身是有用的，有时表现出生物活性，它们也可以作为构建模块，从中可以制备其他更精细的分子。因此，该研究将促进包括精细化学品在内的对社会具有重要意义的材料的制造。广泛的机理研究和现代高通量实验（HTE）方法的使用将有助于开发感兴趣的催化剂和工艺。资助项目的更广泛的影响延伸到研究生的教育和培训进行的研究和社会效益累积作为教授沃尔什和他的同事在高中和其他场所从事外展活动。值得注意的是，该奖项将使沃尔什教授能够继续参与与墨西哥科学家的国际外展计划，促进跨境合作，并广泛促进科学和技术教育。资助的研究利用硫属元素为基础的有机催化剂在+2和+4氧化态的可逆氧化还原化学，以实现新的反应歧管，这可能为合成有机化学中的当代问题提供解决方案。两个目标，一个集中在氮杂环丙烷和其他环丙烷的合成，将追求和在每种情况下，一旦反应化学的基本前提已经建立，将探讨对映选择性的变体。目的1是开发一种碱介导的亚磺酸根阴离子催化的亚胺和苄基氯之间的氮杂环丙烷化反应，该反应通过原位亚砜形成（在S原子上的亚磺酸根阴离子的烷基化），然后通过Darzens样过程再生亚磺酸根催化剂来进行。该方法对反式氮杂环丙烷的合成具有很高的非对映选择性，并可用于反式-2，3-二芳基、2-芳基-3-烷基甚至2，3-二烷基氮杂环丙烷的合成。在目标2中，将相关的次磺酸根/硒酸根阴离子催化原理应用于苯乙烯衍生物的环丙烷化。值得注意的是，正在探索的方法实现了原子转移化学，而不使用传统上用于此目的的危险的“类”试剂（例如，叠氮化物和重氮烷烃），并且不依赖于昂贵和稀缺的过渡金属催化剂。在整个过程中，开发的方法的范围和局限性将进行探索和广泛的参数筛选和机械调查。除了上述社会效益外，可以预见，沃尔什研究小组在进行上述工作的过程中所取得的重大进展，将促进人们对迄今为止很少研究的氧化态交替有机催化领域进行进一步的研究，并使人们有希望在本文所关注的过程之外获得更多的机会。该奖项反映了美国国家科学基金会的法定使命，并被认为值得通过评估予以支持使用基金会的知识价值和更广泛的影响审查标准。

With the support of the Chemical Catalysis Program in the Division of Chemistry, Professor Patrick J. Walsh of the University of Pennsylvania is studying a new principle for catalysis based on the use of sulfur- and selenium-containing compounds that change their oxidation state reversibly during a reaction cycle that results in the formation of value-added products from inexpensive and widely available starting materials. Significantly, the products of the processes under investigation are typically useful in their own right, sometime displaying biological activity, and they may also serve as building blocks from which other more elaborate molecules can be prepared. As such, the research will facilitate the manufacture of materials of importance to society including fine chemicals. Development of the catalysts and processes of interest will be aided by extensive mechanistic studies and the use of modern high throughput experimental (HTE) methods. The broader impacts of the funded project extend to the education and training of the graduate students conducting the research and societal benefits accrued as Professor Walsh and his coworkers engage in outreach activities at high schools and other venues. Of note, this award will enable Professor Walsh to continue to participate in an international outreach program with Mexican scientists that fosters cross-border collaborations and that promotes science and technical education broadly.The funded research leverages the reversible redox chemistry of chalcogen-based organocatalysts in the +2 and +4 oxidation states, to enable new reaction manifolds that may offer solutions to contemporary problems in synthetic organic chemistry. Two objectives, one focused on the synthesis of aziridines and the other on cyclopropanes, will be pursued and in each case, enantioselective variants will be explored once the basic premise of the reaction chemistry has been established. Objective 1 is to develop a base mediated sulfenate anion-catalyzed aziridination reaction between imines and benzylic chlorides that proceeds via in situ sulfoxide formation (alkylation of sulfenate anion on S-atom) followed by a Darzens-like process that regenerates the sulfenate catalyst. This method gives high diastereoselectivity for the formation of trans-aziridines and potential applications of it for the synthesis of trans-2,3-diaryl, 2-aryl-3-alkyl and even 2,3-dialkyl aziridines will be examined. In Objective 2, a related sulfenate/selenoate anion catalysis principle will be applied to the cyclopropanation of styrene derivatives. Significantly, the approaches being explored achieve atom transfer chemistry without the use of the hazardous 'enoid' reagents traditionally used for this purpose (e.g., azides and diazoalkanes) and without recourse to expensive and scarce transition metal catalysts. Throughout, the scope and limitations of the methods developed will be explored and extensive parameter screening and mechanistic investigations conducted. In addition to the aforementioned societal benefits, it is anticipated that the fundamental advances made by the Walsh research group during their pursuit of the above endeavors will stimulate further research into the hitherto little investigated area of oxidation state alternating organocatalysis and which promises opportunities beyond the processes of interest herein.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.