New Technologies in Organic Synthesis in Water

水中有机合成新技术

• 批准号: 1856406
• 负责人: Bruce Lipshutz
• 金额: $ 50.2万
• 依托单位: University of California-Santa Barbara
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1856406&HistoricalAwards=false
• 关键词: New; Technologies; Organic; Synthesis; Water

The Chemical Synthesis Program of the Chemistry Division supports the research of Professor Bruce Lipshutz at the University of California at Santa Barbara. This project aims to develop more environmentally-friendly methods of making organic chemicals, specifically by switching from petroleum-based (organic) solvents to water as the medium to conduct the chemical reaction. Organic solvents are often flammable and toxic, representing a major waste stream as they may be separated from both the starting and ending products of a chemical reaction. The increased use of water as a solvent has considerable potential impact for reducing the use of organic solvents. In an example research theme, micelles (similar to soap bubbles) are used as a way to avoid the use of organic solvents in bringing compounds in close contact so that they react. In addition to the scientific research which may benefit the advanced manufacturing of many commodity chemicals such as fertilizers and pharmaceuticals, the team provides training on the principles of sustainability to high school students and teachers. These students and teachers spend their summer gaining hands-on experience in the implementation of environmentally-friendly reaction chemistries. Research being conducted under this NSF award focuses on development of new technologies in organometallic chemistry, conducted under Green Chemistry conditions. Envirionmentally-friendly reactions will be accomplished by developing palladacycle backbones that include the new ligand HandaPhos, which enables the Suzuki-Miyaura (SM) couplings at the 300 parts per million (ppm) level of catalyst loading. A new ligand recently disclosed, EvanPhos, offers new opportunities for SM couplings. Other projects of value include the development of new nickel nanoparticles that dehalogenate dihalocyclopropanes in water under very mild conditions as well as a new reductive amination protocol done in water at room temperature. Also included in this research is the discovery of a new palladium catalyst that converts Buchwald-Hartwig aminations into an environmentally friendly processes and, for the first time, allows for this chemistry to be done at the ppm level of catalyst loading. New directions also presented include using conformational control within crowded nanomicelles, rather than temperature, to maximize enantiomeric excesses in asymmetric catalysis, and the further advancement of continuous flowtechniques using micellar catalysis as the reaction medium.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.

化学系的化学合成项目支持圣巴巴拉的加州大学的布鲁斯·利普舒茨教授的研究。该项目旨在开发更环保的有机化学品制造方法，特别是通过从石油基（有机）溶剂转换为水作为介质进行化学反应。有机溶剂通常易燃且有毒，是主要的废物流，因为它们可以从化学反应的起始产物和最终产物中分离出来。 增加使用水作为溶剂对减少有机溶剂的使用具有相当大的潜在影响。 在一个示例研究主题中，胶束（类似于肥皂泡）被用作避免使用有机溶剂的一种方法，使化合物紧密接触，使它们发生反应。 除了可能有利于化肥和药品等许多商品化学品的先进制造的科学研究外，该团队还为高中学生和教师提供可持续发展原则的培训。 这些学生和教师花了他们的夏天获得实践经验，在实施环保的反应化学。根据NSF的这一奖项进行的研究重点是在绿色化学条件下进行的有机金属化学新技术的开发。环境友好的反应将通过开发包括新配体HandaPhos的palladacetylene主链来实现，该配体使Suzuki-Miyaura（SM）偶联能够在300 ppm的催化剂负载水平下进行。最近公开的一种新的配体EvanPhos为SM偶联提供了新的机会。其他有价值的项目包括开发新的镍纳米颗粒，在非常温和的条件下在水中脱卤二卤代环丙烷，以及在室温下在水中进行的新的还原胺化方案。 这项研究还发现了一种新的钯催化剂，可以将Buchwald-Hartwig胺化转化为环境友好的过程，并且首次允许在催化剂负载的ppm水平下进行这种化学反应。新的方向还提出了包括使用拥挤的纳米胶束内的构象控制，而不是温度，以最大限度地提高对映体过量的不对称催化，并使用胶束催化作为反应medium.This奖项反映了NSF的法定使命的连续流动技术的进一步发展，并已被认为是值得通过使用该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。

项目成果

Continuous flow Suzuki–Miyaura couplings in water under micellar conditions in a CSTR cascade catalyzed by Fe/ppm Pd nanoparticles

• DOI: 10.1039/d0gc00378f
• 发表时间: 2020-06
• 期刊: Green Chemistry
• 影响因子: 9.8
• 作者: Alex B. Wood;K. Y. Nandiwale;Yiming Mo;Bo Jin;A. Pomberger;Victor Schultz;F. Gallou;K. Jensen;B. Lipshutz

An environmentally responsible 3-pot, 5-step synthesis of the antitumor agent sonidegib using ppm levels of Pd catalysis in water

• DOI: 10.1039/c9gc03495a
• 发表时间: 2019-11
• 期刊: Green Chemistry
• 影响因子: 9.8
• 作者: B. Takale;Ruchita R. Thakore;Fanxing Kong;B. Lipshutz

A Sustainable 1-Pot, 3-Step Synthesis of Boscalid Using Part per Million Level Pd Catalysis in Water

使用水中百万分之一级 Pd 催化可持续一锅三步合成啶酰菌胺

• DOI: 10.1021/acs.oprd.9b00455
• 发表时间: 2020
• 期刊: Organic Process Research & Development
• 影响因子: 3.4
• 作者: Takale, Balaram S.;Thakore, Ruchita R.;Mallarapu, Rushil;Gallou, Fabrice;Lipshutz, Bruce H.
• 通讯作者: Lipshutz, Bruce H.