Transition Metal-Catalyzed Chemistry in Water at Room Temperature

描述（由申请人提供）：将进一步开发室温下在水中烷基和芳基卤化物之间Pd催化的交叉偶联的新范例。反应性的，高度水敏感的sp3-基有机锌试剂可以在原位生成，并用作偶联伙伴，保护其从水环境中的胶束环境。将开展一项关于使用烷基溴作为碘替代品的成本较低的研究。这种新的胶束纳米技术将被应用于立体定向的烯基卤化物的相关交叉偶联。这种偶联将是通常需要预先形成硼酸或等同物的Suzuki-Miyaura偶联的特别有吸引力的替代方案。还将比较这些偶联产物在水中的立体化学与在有机溶剂中的立体化学。考虑到杂环化合物对制药工业的重要性，将研究应用于杂芳族卤化物的相关偶联。新型过渡金属催化的串联过程将被开发出来，这两个反应的顺序是在室温下在水中进行。涉及有机锡烷中间体的施蒂勒耦合也将作为胶束介质中的耦合伙伴进行研究。使用镍催化的偶联的第一个案例也将在烯基卤化物与原位生成的有机锌卤化物的反应中进一步研究。一种新设计的，廉价的，但“健康”的表面活性剂已经确定，并将开发，使室温耦合的几个名称的反应在水中进行。可以实现相对于先前研究中所见的更高水平的转化，因此，预期交叉偶联产物的产率更高。这种成功的秘诀是基于适当的粒度工程，这更好地适应了预期的化学反应。 公共卫生相关性：将开发新技术，“从有机反应中去除有机溶剂”;用“绿色”替代品：水取代严格使用有机介质的传统工艺。这些研究是由减少溶剂废物量的潜力驱动的，通过研究对制药和精细化学品领域很重要的水中几种反应来进行。所有这些都是在室温下进行的，因此，没有任何用于加热或冷却目的的能量投资。

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.