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: 8320894
• 负责人: BRUCE H. LIPSHUTZ
• 金额: $ 27.35万
• 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/8320894
• 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.

描述（由申请人提供）：将进一步开发出在室温下在水中烷基和芳基卤化物之间PD催化的跨偶联的新范式。可以原位生成反应性，高度水敏感的基于SP3的促进剂，并用作耦合伙伴，并通过胶束环境保护其水性环境。将进行有关将烷基溴化物用作碘化烷基溴化物的使用的研究。这种新的胶束纳米技术将应用于立体定义的烷基卤化物的相关跨耦合。这种耦合将是通常需要事先形成硼酸或同等形成的铃木 - 锯齿耦合的特别有吸引力的替代品。相对于有机溶剂中的这些耦合，这些耦合产生的产品的立体化学也将被比较。鉴于杂环对制药行业的重要性，将研究适用于异性卤化物的相关耦合。将开发新型的过渡金属催化的串联过程，这两种反应均在此序列中在室温下在水中进行。涉及Organostannane中间体的Stille耦合也将作为胶束媒体的耦合伙伴进行研究。使用镍催化的偶联病例也将进一步研究在烷烯基卤化物与原位生成的有类似卤化物的反应中。已经确定了一种新设计的，廉价但“健康”的表面活性剂，并将开发出可以在水中进行多种名称反应的室温耦合。相对于先前研究中的研究，可以实现较高的转化率，因此可以预期交叉偶联产品的更好产量。成功的秘诀是基于粒径的适当工程，可以更好地适应预期的化学。