Transition Metal-Catalyzed Chemistry in Water at Room Temperature

室温水中过渡金属催化的化学反应

• 批准号: 8186402
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 32.13万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA BARBARA
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-08-15 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8186402
• 关键词: Area; Benign; Boronic Acids; Bromides; Catalysis; Characteristics; Chemicals; Chemistry; Coupled; Coupling; DNA Sequence Rearrangement; Development; Drug Industry; Engineering; Environment; Felis catus; Generations; Heating; In Situ; Investments; Iodides; Ligands; Literature; Metals; Micelles; Names; Nanotechnology; Nickel; Organic solvent product; Outcome; Particle Size; Pharmacologic Substance; Preparation; Process; Reaction; Reagent; Relative (related person); Solvents; Technology; Temperature; Transition Elements; Water; alpha-tocopheryl polyethylene glycol succinate; aqueous; aryl halide; base; catalyst; design; nanoparticle; new technology; novel; stereochemistry; success; surfactant; vitamin E succinate; wasting

DESCRIPTION (provided by applicant): A new paradigm for Pd-catalyzed cross-couplings between alkyl and aryl halides in water at room temperature will be further developed. Reactive, highly water-sensitive sp3-based organozinc reagents can be generated in situ and used as coupling partners, protected from their aqueous surroundings by a micellar environment. A study on the use of alkyl bromides as a less costly alternative to iodides will be undertaken. This new micellar nanotechnology will be applied to related cross-couplings of stereo-defined alkenyl halides. Such couplings would be an especially attractive alternative to Suzuki-Miyaura couplings that normally require prior formation of boronic acids or the equivalent. The stereochemistry of the products resulting from these couplings in water relative to that seen in organic solvents will also be compared. Related couplings applied to heteroaromatic halides will be studied, given the importance of heterocycles to the pharmaceutical industry. Novel transition metal-catalyzed tandem processes will be developed, both reactions of in this sequence to be conducted in water at room temperature. Stille couplings involving organostannane intermediates will also be investigated as coupling partners in micellar media. The first cases of couplings using nickel catalysis will also be further investigated in reactions of alkenyl halides with in situ-generated organozinc halides. A newly designed, inexpensive yet "healthy" surfactant has been identified and will be developed that enables room temperature couplings for several name reactions to be done in water. Higher levels of conversion relative to those seen in previous studies can be achieved, and hence, better yields of cross-coupling products are to be expected. The secret to this success is based on proper engineering of particle size, which better accommodates the intended chemistry. PUBLIC HEALTH RELEVANCE: New technologies are to be developed that "get organic solvents out of organic reactions"; that replace traditional processes that use strictly organic media with a "green" alternative: water. These studies are driven by the potential for decreasing the amount of solvent waste, to be carried out by investigating several reactions in water that are important to the pharmaceutical and fine chemicals areas. All are to be done at room temperature, and thus, without any investment of energy for either heating or cooling purposes.

描述（由申请人提供）：将进一步开发室温下pd催化烷基和芳基卤化物在水中交叉偶联的新范式。反应性强、水敏感性高的sp3基有机锌试剂可以在原位生成，并作为偶联伙伴使用，通过胶束环境保护其不受水环境的影响。将进行一项关于使用烷基溴作为较便宜的碘化物替代品的研究。这种新的胶束纳米技术将应用于相关的立体定义烯酰卤化物的交叉偶联。这种耦合将是一个特别有吸引力的替代铃木-宫浦耦合，通常需要事先形成硼酸或等同物。由这些偶联在水中产生的产物的立体化学相对于在有机溶剂中看到的也将进行比较。考虑到杂环化合物对制药工业的重要性，将研究应用于杂芳烃卤化物的相关偶联。新的过渡金属催化串联工艺将被开发，这两个顺序的反应将在室温下在水中进行。涉及有机硅烷中间体的静态偶联也将作为胶束介质中的偶联伙伴进行研究。在烯基卤化物与原位生成的有机卤化锌反应中，还将进一步研究使用镍催化的第一例偶联。一种新设计的、价格低廉但“健康”的表面活性剂已经被确定，并将被开发出来，使几种命名反应能够在室温下在水中进行耦合。与以前的研究相比，可以实现更高的转化水平，因此可以预期交叉偶联产品的产量会更高。这种成功的秘诀是基于适当的颗粒尺寸工程，它更好地适应预期的化学。