Applications of Chalcogen-based Oxidation State Alternating Organocatalysts

硫族氧化态交替有机催化剂的应用

• 批准号: 2154593
• 负责人: Patrick Walsh
• 金额: $ 55.5万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-08-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2154593&HistoricalAwards=false
• 关键词: Applications; Chalcogen; based; Oxidation; State

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.

在化学催化计划中，宾夕法尼亚大学的帕特里克·J·沃尔什（Patrick J.值得注意的是，所研究过程的产物通常会自身有用，有时会显示生物学活动，并且还可以作为可以从中可以从中准备好其他更精致的分子的基础。因此，这项研究将有助于制造对社会重要性的材料，包括精美的化学物质。广泛的机械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开发。该资金项目的更广泛影响扩展到了进行研究和社会福利的研究生的教育和培训，因为沃尔什教授及其同事在高中和其他场所进行外展活动。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加一项国际宣传计划，该计划促进了跨境的合作，并广泛促进科学和技术教育。这项资助的研究利用了基于Chalcogen的有机促进的可逆氧化还原化学基于Chalcogen的氧化还原化学，基于+2和+4的氧化氧化状态，以便将新的反作用造型提供了综合的综合构造。将追求两个目标，一个目标是侧重于Aziridines的合成，另一个目标是一个目标，而在每种情况下，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是开发碱性硫酸阴离子阴离子催化的亚胺和苯基氯化物之间的叠氮化反应，该反应通过原位硫氧化物形成（S-Atom上的硫酸盐阴离子的烷基化）进行，然后是darzens样过程，可再生硫酸盐催化剂。该方法为反式氮杂胺的形成具有很高的非对映选择性，并将检查IT的潜在应用，用于合成Trans-2,3-二芳基，2-ARYL-3-烷基甚至2,3-二烷基偶氮胺。在目标2中，相关的硫酸盐/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，所探索的方法实现了原子转移化学，而无需使用传统上用于此目的的危险的“ Enoid”试剂（例如叠氮化物和重氮烷烷），而无需求助于昂贵且稀缺的过渡金属催化剂。在整个过程中，将探索开发方法的范围和局限性，并进行了广泛的参数筛选和机械研究。除了上述社会利益外，预计沃尔什研究小组在追求上述努力期间的基本进步将刺激对迄今为止对迄今氧化状态交替研究领域进行进一步研究的进一步研究，从而交流了有机分析的领域优点和更广泛的影响审查标准。

项目成果

Catalytic Chemo‐ and Regioselective Radical Carbocyanation of 2‐Azadienes for the Synthesis of α‐Amino Nitriles

2-氮杂二烯的催化化学和区域选择性自由基碳氰化用于合成α-氨基腈

• DOI: 10.1002/anie.202300605
• 发表时间: 2023
• 期刊: Angewandte Chemie International Edition
• 作者: Duan, Shengzu;Du, Ya;Wang, Lingling;Tian, Xun;Zi, Yujin;Zhang, Hongbin;Walsh, Patrick J.;Yang, Xiaodong
• 通讯作者: Yang, Xiaodong

Recent trends and developments in the asymmetric synthesis of profens

• DOI: 10.1016/j.gresc.2023.02.002
• 发表时间: 2023-05-01
• 期刊: GREEN SYNTHESIS AND CATALYSIS
• 作者: Wang，Qiuyue;Qi，Yuchen;Walsh，Patrick J.
• 通讯作者: Walsh，Patrick J.

Cation-controlled chemoselective synthesis of N -aroylureas and imides via amidation of N -Boc arylamides

通过 N-Boc 芳酰胺的酰胺化，阳离子控制化学选择性合成 N-芳酰脲和酰亚胺

• DOI: 10.1039/d3qo00352c
• 发表时间: 2023
• 期刊: Organic Chemistry Frontiers
• 影响因子: 5.4
• 作者: Wang, Jiamin;Shuai, Sujuan;Gan, Lishe;Luo, Yongxin;Jin, Huimin;Chen, Lingfeng;Zou, Dong;Liang, Guang;Walsh, Patrick J.;Li, Jie
• 通讯作者: Li, Jie

Sulfenate Anion Catalyzed Diastereoselective Synthesis of Aziridines

硫酸根阴离子催化非对映选择性合成氮丙啶

• DOI: 10.1002/anie.202303069
• 发表时间: 2023
• 期刊: Angewandte Chemie International Edition
• 作者: Zheng, Zhipeng;Pu, Youge;Adrio, Javier;Walsh, Patrick J.
• 通讯作者: Walsh, Patrick J.

Palladium‐Catalyzed Benzylic C(sp 3 )−H Carbonylative Arylation with Aryl Bromides

钯催化的苯甲基 C(sp 3 )·H 与芳基溴的羰基化芳基化反应

• DOI: 10.1002/anie.202300073
• 发表时间: 2023
• 期刊: Angewandte Chemie International Edition
• 作者: Hu, Bowen;Zhao, Haoqiang;Wu, Yu;Walsh, Patrick J.
• 通讯作者: Walsh, Patrick J.