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Patrick J. Walsh教授正在研究一种新的催化原理，该原理基于使用含硫和含硒化合物，这些化合物在反应循环中可逆地改变其氧化状态，从而从廉价和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本身通常是有用的，有时显示出生物活性，它们也可以作为其他更复杂分子的基础。因此，这项研究将促进包括精细化学品在内的对社会重要材料的制造。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催化剂和感兴趣的过程的发展。资助项目的更广泛影响延伸到进行研究的研究生的教育和培训，以及沃尔什教授和他的同事在高中和其他场所从事外展活动所产生的社会效益。值得注意的是，该奖项将使沃尔什教授能够继续与墨西哥科学家一起参与国际推广计划，以促进跨境合作并广泛促进科学和技术教育。这项资助的研究利用了+2和+4氧化态的硫基有机催化剂的可逆氧化还原化学，以实现新的反应流形，可能为合成有机化学中的当代问题提供解决方案。将追求两个目标，一个集中于合成叠氮嘧啶，另一个集中于合成环丙烷，在每种情况下，一旦建立了反应化学的基本前提，将探索对映选择性变体。目的1是在亚胺和苯基氯化物之间建立一个碱介导的亚磺酸阴离子催化的叠氮化反应，该反应通过原位生成亚砜（s原子上亚磺酸阴离子的烷基化）进行，然后是一个类似darzens的过程，再生亚磺酸催化剂。该方法对反式叠氮嘧啶的生成具有很高的非对映选择性，并将研究其在反式-2,3-二芳基、2-芳基-3-烷基甚至2,3-二烷基叠氮嘧啶合成中的潜在应用。在目标2中，相关的亚磺酸盐/硒酸盐阴离子催化原理将应用于苯乙烯衍生物的环丙烷化。值得注意的是，正在探索的方法可以实现原子转移化学，而无需使用传统上用于此目的的危险“类烯”试剂（例如叠氮化物和重氮烷烃），也无需求助于昂贵和稀缺的过渡金属催化剂。在整个过程中，将探讨所开发方法的范围和局限性，并进行广泛的参数筛选和机制调查。除了上述的社会效益外，Walsh研究小组在追求上述努力的过程中所取得的基本进展预计将刺激迄今为止很少研究的氧化态交替有机催化领域的进一步研究，并承诺在这里感兴趣的过程之外提供机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值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 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.