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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.

化学部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一名教员。他建议开发新的方法，将复杂的分子片段连接起来，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连接在一起，可以避免一步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了复杂的片段。因此，它避免了更常见的浪费有价值的材料的需要，因为过度使用其中一个复杂的碎片。在这些研究中，Overman教授和他的同事使用光氧化还原催化来进行偶联反应。这种转变很有吸引力，因为它们使用可见光作为制造新键的能源。这种对反应可持续能源的使用有助于将其对环境的影响降至最低。涉及光催化、机械和定向合成目标的研究范围广泛，非常适合于各级科学家的教育。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，包括那些在科学界代表性不足的同事。这些学生中的许多人现在在学术界和制药业都拥有领先的职位。双分子化学反应以良好的产率结合复杂的片段，并且在重要的情况下，具有高立体控制性，是实施收敛合成策略的基础。当片段偶联步骤中加入的原子是手性的时，这种结合尤其具有挑战性。奥弗曼教授的实验室最近的发现表明，结构复杂的叔碳自由基和缺乏电子的烯烃的双分子反应可以通过使用两个偶联伙伴的等摩尔(或近等摩尔)量以高产率和高立体控制形成新的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常见部分，但在解决构建复杂有机分子方面的巨大挑战方面具有令人兴奋的潜力。这些研究确定了叔醇半草酸盐前驱体生成叔基的机理，优化了叔基的生成和偶联，探索了碳自由基与亲电双烯的1，6-加成反应，发展了多组分自由基-阴离子交叉反应，并确定了叔基片段偶联策略在含二氧双环[3.3.0]辛酮片段的结构精细的二萜类化合物和对位高岭烯类二萜类化合物的对映选择性全合成中的应用。这些有机反应对制药行业具有重要的技术和更广泛的影响。

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