Leveraging Main-Group Redox Catalysis for Enantioselective Alkene Difunctionalization

在化学系化学催化项目的支持下，Scott E.伊利诺伊大学厄巴纳-香槟分校的丹麦将进行研究，开发烯烃选择性双官能化的新方法。烯烃和其他不饱和化合物的加成反应是有机化学中最古老和最可靠的转化反应之一。然而，控制反应选择性仍然是一个挑战。越来越多的复杂的天然产物，药物，和农业化学化合物含有邻位的氮和氧原子在立体中心强调了这一关键的缺陷，在合成方法。该建议通过基于机制的方法解决了设计对映体选择性双官能化过程中固有的挑战。计划的研究活动是理想的本科生，研究生和博士后同事的智力和实践培训。反应设计、开发和应用的相互作用代表了科学方法的本质。学生提出了假设的结果计划实验，他们必须学会收集和解释数据，以证实或消除假设。这项活动的统一主题是挑战当前思维的新化学反应的发明。在圣埃尔莫布雷迪夏季研究学者计划在UIUC的主持下的本科实习生将得到支持。该计划是一个为期10周的夏季研究经验，为代表性不足的少数民族学生（非洲裔美国人，西班牙裔，美洲原住民）从历史上的黑人学院在伊利诺伊大学化学系，以鼓励未来的博士课程招生。已经引入了无数的反应来实现双键的区域、非对映体和对映体选择性官能化，具有良好的通用性。然而，绝大多数现有方法采用过渡金属催化，例如二羟基化和氨羟基化（锇）以及二胺化（钯、铜）。尽管这些方法具有不可否认的实用性，但鉴于与金属污染相关的挑战，它们很少在工业上使用。该提案旨在提供一种植根于主族氧化还原催化的替代方法，其优点包括使用无害氧化剂来驱动催化循环的能力和Se（II）试剂对碳-碳双键的高亲和力。实现这一目标的可行路线图是为开发普遍适用和高度选择性的烯烃双官能化构建机械/物理有机基础。本项目的总体目标分为三个具体目标：（1）催化的、对映选择性的顺式-1，2-二胺化，（2）催化的、对映选择性的顺式-1，2-氧胺化和（3）催化的、对映选择性的顺式-1，2-碳胺化。对于每个具体目标，团队将：（1）细化机制（动力学，光谱学，晶体学，计算）研究催化反应，以了解实现高催化活性的规则（转换频率和转换数）（2）设计将赋予高立体选择性和高化学转化率以引入新的立构中心的手性催化剂，和（3）在代表广泛有用的结构基序的各种底物类别中表现出普遍性。该项目还支持在圣埃尔莫布雷迪夏季研究学者计划在UIUC主持下的本科生实习生。该奖项反映了NSF的法定使命，并已被认为是值得通过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的支持。

With the support of the Chemical Catalysis program in the Division of Chemistry, Professor Scott E. Denmark at the University of Illinois at Urbana-Champaign will conduct research to develop new methods for selective difunctionalizations of alkenes. Addition to alkenes and other unsaturated compounds is among the oldest and most reliable transformations in organic chemistry. However, controlling reaction selectivity remains a challenge. The growing number of complex natural products, pharmaceutical, and agrochemical compounds containing vicinal nitrogen and oxygen atoms at stereogenic centers underscores this critical deficiency in synthetic methodology. This proposal addresses the challenges inherent in the design of enantioselective difunctionalization processes through a mechanismbased approach. The research activities planned are ideal for the intellectual and practical training of undergraduates, graduate students, and postdoctoral coworkers. The interplay of reaction design, development and application represent the essence of the scientific method. Students are presented with hypotheses for the outcome of planned experiments and they must learn to collect and interpret data to substantiate or eliminate the hypothesis. The unifying theme of this activity is the invention of new chemical reactions that challenge current thinking. An undergraduate intern under the auspices of the St. Elmo Brady Summer Research Scholars Program at UIUC will be supported. This program is a 10-week summer research experience for underrepresented minority students (African American, Hispanic, Native Americans) from Historically Black Colleges at the University the Illinois Chemistry Department to encourage future enrollment in the PhD program. Countless reactions have been introduced to effect regio, diastereo and enantioselective functionalization of double bonds with good generality. However, the vast majority of the existing methods employ transition metal catalysis such as dihydroxylation and aminohydroxylation (osmium), and diamination (palladium, copper). Despite the undeniable utility of these methods, they are rarely employed industrially in view of the challenges associated with metal contamination. This proposal aims to provide an alternative approach that is rooted in Main Group redox catalysis the advantages of which include ability to use innocent oxidants to drive the catalytic cycle and the high affinity of Se(II) reagents for carbon-carbon double bonds. The actionable roadmap to achieve this goal is to construct the mechanistic/physical organic foundation for the development of generally applicable and highly selective alkene difunctionalization. The overall objective is divided into three Specific Aims of this project: (1) catalytic, enantioselective syn-1,2-diamination, (2) catalytic, enantioselective syn-1,2-oxyamination and (3) catalytic, enantioselective syn-1,2-carboamination. For each Specific Aim, the team will: (1) carry out detailed mechanistic (kinetic, spectroscopic, crystallographic, computational) investigations of the catalytic reactions to learn the rules for achieving high catalytic activity (turnover frequency and turnover number) for the target reactions (2) design chiral catalysts that will impart high stereoselectivity and high chemical conversion for the introduction of new stereocenters, and (3) demonstrate generality in a variety of substrate classes that represent broadly useful structural motifs. The project also supports an undergraduate intern under the auspices of the St. Elmo Brady Summer Research Scholars Program at UIUC.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.