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New Approaches for Stereoselective Formation of Quaternary Carbon Stereocenters and Fragment Coupling

立体选择性形成季碳立构中心和片段偶联的新方法

基本信息

批准号：
1661612
负责人：
Larry Overman
金额：
$ 54万
依托单位：
University of California-Irvine
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1661612&HistoricalAwards=false
关键词：
New Approaches Stereoselective Formation Quaternary

项目摘要

The Chemical Synthesis Program of the Chemistry Division supports the project by Professor Overman. Professor Overman is a faculty member in the Department of Chemistry at the University of California, Irvine. He proposes to develop new ways to join complex molecular fragments to prepare high-value organic molecules. By building complex pieces of a molecule independently and then coupling them together at the end of a synthesis, inefficient linear sequences that build the entire structure one step at a time can be avoided. The method under development is particularly impressive in that it combines the complex fragments in a one to one ratio. Thus, it avoids the more common need to waste valuable material by using one of the complex fragments in excess. In these studies, Professor Overman and his coworkers employ photoredox catalysis for the coupling reactions. Such transformation are attractive because they use visible light as the energy source for making new bonds. This use of sustainable energy for the reactions help to minimize their environmental impact. The broad scope of the research involving photocatalysis, mechanistic and target-directed synthesis objectives is well suited for the education of scientists at all levels. Professor Overman's group has a long established record of providing the highest level of education and training for coworkers including those underrepresented in science. Many of these students now hold leading positions in both academics and the pharmaceutical industry. Bimolecular chemical reactions that combine complex fragments in good yield, and, where important, with high stereocontrol, are fundamental for implementing convergent synthetic strategies. When the atoms joined in a fragment-coupling step are chiral, this union is particularly challenging. Recent discoveries from Professor Overman's laboratories show that bimolecular reactions of structurally elaborate tertiary carbon radicals and electron-deficient alkenes can join complex fragments by forming new bonds in high yields and high stereocontrol using equimolar (or nearly equimolar) amounts of the two coupling partners. Such chemical transformations are not currently a common part of the repertoire of organic synthesis, yet hold exciting potential to solve formidable challenges in constructing complex organic molecules. The proposed studies define the mechanism and optimize the generation and coupling of tertiary radicals formed from tertiary alcohol hemioxalate precursors, explore 1,6-additions of carbon radicals to electrophilic dienes and develop multicomponent radical-anionic crossover reactions, and define the utility of tertiary-radical fragment coupling strategies in the enantioselective total synthesis of structurally elaborate diterpenoids harboring dioxobicyclo[3.3.0]octanone fragments and ent-kaurene diterpenoids. These organic reactions have important technical broader impacts on the pharmaceutical industry.

化学系的化学合成计划支持奥弗曼教授的项目。奥弗曼教授是加州大学欧文分校化学系的教员。他建议开发连接复杂分子片段的新方法，以制备高价值的有机分子。通过独立构建分子的复杂片段，然后在合成结束时将它们偶联在一起，可以避免一次一步构建整个结构的低效线性序列。正在开发的方法特别令人印象深刻，因为它以一比一的比例组合复杂的片段。因此，它避免了更常见的需要浪费有价值的材料，通过使用过量的复杂片段之一。在这些研究中，奥弗曼教授和他的同事采用光氧化还原催化的偶联反应。这种转变很有吸引力，因为它们使用可见光作为形成新键的能量来源。这种使用可持续能源的反应有助于最大限度地减少其对环境的影响。研究的范围广泛，涉及机械，机械和有针对性的合成目标，非常适合各级科学家的教育。奥弗曼教授的团队长期以来一直为同事提供最高水平的教育和培训，包括那些在科学领域代表性不足的同事。这些学生中的许多人现在在学术界和制药行业都担任领导职务。以良好产率结合联合收割机复杂片段的双分子化学反应，重要的是，具有高度立体控制，是实施收敛合成策略的基础。当在片段偶联步骤中连接的原子是手性的时，这种结合特别具有挑战性。Overman教授实验室的最新发现表明，结构复杂的叔碳自由基和缺电子烯烃的双分子反应可以通过使用等摩尔（或接近等摩尔）量的两种偶联伙伴以高产率和高立体控制形成新键来连接复杂的片段。这种化学转化目前还不是有机合成的一个常见部分，但在解决构建复杂有机分子的艰巨挑战方面具有令人兴奋的潜力。所提出的研究定义了机制并优化了由叔醇半草酸盐前体形成的叔自由基的产生和偶联，探索了碳自由基对亲电二烯的1，6-加成，并开发了多组分自由基-阴离子交叉反应，并定义了叔自由基片段偶联策略在对映选择性全合成含有二氧双环[3.3.0]的结构复杂的二萜类化合物中的效用辛酮片段和对映贝壳杉烯二萜类。这些有机反应对制药工业具有重要的技术影响。

项目成果

期刊论文数量（12）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

General Access to Concave-Substituted cis -Dioxabicyclo[3.3.0]octanones: Enantioselective Total Syntheses of Macfarlandin C and Dendrillolide A

凹取代顺式二氧杂双环[3.3.0]辛酮的通用方法：Macfarlandin C 和 Dendrillolide A 的对映选择性全合成

DOI：
10.1021/acs.joc.0c02273
发表时间：
2020
期刊：
The Journal of Organic Chemistry
影响因子：
0
作者：
Allred, Tyler K.;Dieskau, André P.;Zhao, Peng;Lackner, Gregory L.;Overman, Larry E.
通讯作者：
Overman, Larry E.

Tertiary Alcohols as Radical Precursors for the Introduction of Tertiary Substituents into Heteroarenes