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.

化学部的化学合成计划支持Overman教授。 Overman教授是加州大学尔湾分校化学系的教职员工。他建议开发新的方法来加入复杂的分子碎片以制备高价值有机分子。通过独立地构建分子的复杂部分，然后在合成的末尾将它们耦合在一起，可以避免一次构建整个结构一步的线性序列。正在开发的方法特别令人印象深刻，因为它将复杂片段结合在一起。因此，它避免了通过使用过度的一个复杂片段之一浪费有价值材料的更普遍的需求。在这些研究中，Overman教授和他的同事采用Photoredox催化作用进行耦合反应。这种转换很有吸引力，因为它们使用可见光作为建立新键的能源。可持续能源对反应的使用有助于最大程度地减少其环境影响。涉及光催化，机理和目标综合目标的研究范围非常适合各个级别的科学家的教育。 Overman教授的小组长期以来一直在为同事提供最高水平的教育和培训记录，包括科学领域的人数不足。这些学生中的许多人现在在学者和制药行业中担任领先地位。将复杂片段以良好的产率结合在一起，并且在重要的情况下，具有高立体控制的双分子化学反应是实施收敛合成策略的基础。当原子以碎片耦合步骤加入时，这种结合特别具有挑战性。 Overman教授实验室的最新发现表明，结构上精细的第三级碳自由基和电子缺陷烷烃的双分子反应可以通过高产的高产量和高立体控制的新键使用等效（或几乎等于等分极）的两个耦合群落来加入复杂的碎片。这种化学转化目前并不是有机合成曲目的常见部分，而是在构建复杂的有机分子方面具有令人兴奋的潜力。拟议的研究定义了由高等教育半氧化物前体形成的三级自由基的机制，并优化了碳自由基对亲电的二烯的1,6-碳的产生和偶联具有二Xobicyclo [3.3.0] Octanone片段和Ent-kaurene二萜类化合物的结构上精心构造的二萜的对映选择性总合成中的根部碎片耦合策略。这些有机反应对制药行业具有重要的技术广泛影响。

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