Unleashing Mesoionic Carbene-derived Super-reductants to Overcome the Limitations of NHC- Oxidative Organocatalysis Without a Co-Catalyst

释放介离子卡宾衍生的超级还原剂，克服无助催化剂的 NHC 氧化有机催化的局限性

• 批准号: 2153475
• 负责人: Guy Bertrand
• 金额: $ 52.5万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard 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=2153475&HistoricalAwards=false
• 关键词: Unleashing; Mesoionic; Carbene; derived; Super

With the support of the Chemical Catalysis (CAT) Program in the Division of Chemistry, Professor Guy Bertrand of the University of California, San Diego (UCSD) is studying new processes promoted by so-called "mesoionic carbenes." These chemical species are readily available organic compounds that have the potential to catalyze the same kinds of transformations currently conducted with expensive, toxic, and rare transition metal-based catalysts. Furthermore, the processes being explored have the capacity to convert simple compounds found in biomass to complex molecules of importance to science, engineering, and commerce. Accordingly, it is anticipated that the research being explored will facilitate the manufacture of value-added materials from simple feed stocks in a more sustainable and economical manner. The broader impacts of the funded project extend to the benefits accrued to the future STEM workforce from an international exchange program between UCSD and the French Centre National de la Recherche Scientifique (CNRS) that Professor Bertrand spearheads. The exchange of undergraduate and graduate students between UCSD and CNRS-associated universities enables these young scientists to develop an international perspective on both chemical production and the challenges facing the chemical industry as it transitions to deliver more environmentally responsible manufacturing methods.The aim of the funded research is to advance the field of catalysis on a fundamental level through the exploration of conceptually new and underdeveloped methods of substrate activation. There are few examples of NHC-catalyzed reactions via single electron transfer pathways involving Breslow intermediates (BIs), and the synthetic applications of such processes are limited by the moderate nucleophilicity and reduction potential of BIs derived from classical NHCs. In marked contrast, mesoionic carbenes, which were discovered in the Bertrand laboratory, are strongly nucleophilic and among the most potent organic reducing agents reported to date. The goal of the project is to exploit the unique attributes of mesoionic carbenes to expand NHC oxidative organocatalysis to less electrophilic substrates such as formaldehyde, and to less oxidizing agents such as aryl- and vinyl-halides. It is anticipated that the transformations of interest will be achieveable in both inter- and intramolecular modalities and that a wide range of useful products, including carbocycles and heterocycles, will be accessible.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.

在化学系化学催化 (CAT) 项目的支持下，加州大学圣地亚哥分校 (UCSD) 的 Guy Bertrand 教授正在研究由所谓的“介离子卡宾”推动的新过程。这些化学物质是容易获得的有机化合物，有可能催化目前使用昂贵、有毒和稀有的过渡金属催化剂进行的同类转化。此外，正在探索的过程能够将生物质中发现的简单化合物转化为对科学、工程和商业具有重要意义的复杂分子。因此，预计正在探索的研究将促进以更可持续和更经济的方式从简单原料制造增值材料。该资助项目的更广泛影响延伸到了由 Bertrand 教授牵头的 UCSD 与法国国家科学研究中心 (CNRS) 之间的国际交流计划，为未来的 STEM 劳动力带来的好处。加州大学圣地亚哥分校和法国国家科学研究中心附属大学之间的本科生和研究生交流使这些年轻科学家能够对化学生产以及化学工业在向提供更环保的制造方法转型过程中所面临的挑战形成国际视野。研究的目的是通过探索概念上新的和尚未开发的底物活化方法，从根本上推进催化领域的发展。通过涉及 Breslow 中间体 (BI) 的单电子转移途径进行 NHC 催化反应的例子很少，并且此类过程的合成应用受到经典 NHC 衍生的 BI 的中等亲核性和还原电位的限制。与此形成鲜明对比的是，伯特兰实验室发现的介离子卡宾具有强亲核性，是迄今为止报道的最有效的有机还原剂之一。该项目的目标是利用介离子卡宾的独特属性，将 NHC 氧化有机催化扩展到亲电子性较低的底物（例如甲醛）和氧化剂（例如芳基卤化物和乙烯基卤化物）。预计感兴趣的转化将在分子间和分子内模式中实现，并且将可以获得广泛的有用产品，包括碳环和杂环。该奖项反映了 NSF 的法定使命，并被认为值得通过以下方式获得支持：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。

项目成果

Mesoionic Carbene‐Catalyzed Formyl Alkylation of Aldehydes

介离子卡宾催化醛的甲酰烷基化

• DOI: 10.1002/anie.202303478
• 发表时间: 2023-05
• 期刊: Angewandte Chemie International Edition
• 作者: Liu, Chang;Zhang, Zengyu;Zhao, Liang‐Liang;Bertrand, Guy;Yan, Xiaoyu
• 通讯作者: Yan, Xiaoyu

The triplet state of deprotonated mesoionic carbene Breslow intermediates is thermally accessible: Distal difunctionalization of aldehydes

去质子化介离子卡宾 Breslow 中间体的三线态是热可接近的：醛的远端双官能化

• DOI: 10.1016/j.checat.2022.09.047
• 发表时间: 2022-10-01
• 期刊: Chem Catalysis
• 作者: Zengyu Zhang;Shiqing Huang;Chen;Liang L. Zhao;Wei Liu;M. Melaimi;G. Bertr;Xiaoyu Yan
• 通讯作者: Xiaoyu Yan

How To Enhance the Efficiency of Breslow Intermediates for SET Catalysis

如何提高 Breslow 中间体的 SET 催化效率

• DOI: 10.1021/acs.joc.2c02978
• 发表时间: 2023-02
• 期刊: The Journal of Organic Chemistry
• 作者: Mulks, Florian F.;Melaimi, Mohand;Yan, Xiaoyu;Baik, Mu;Bertrand, Guy
• 通讯作者: Bertrand, Guy