Using Fluorophobicity in Pd-catalyzed C-O Couplings

描述（由申请人提供）： 该提议的目标是通过疏氟加速来扩展钯催化的C-O键形成交叉偶联反应的效用。先进的芳基和二芳基醚的一般和温和的形成新的协议，其中固有的疏氟性的芳基，烯基和烷基单元被利用，以加快产品的形成，通过疏氟包装在还原消除的过渡态。由于芳基醚在生物活性分子中的普遍存在，开发一种通用的催化方法来产生这种结构基序是一个重要的挑战。二芳基，芳基烯丙基，和芳基烷基醚的形成是解决。在芳基-烯丙基醚形成的情况下，有人提出，克莱森重排，这也是加速在氟溶剂中，将迅速遵循还原消除。任何预先安装到烯丙醇单元中的手性将被转移到克莱森重排的产物中，导致手性季中心的潜在形成。因此，一个简单和廉价的进入复杂的手性积木在药物合成中的潜在用途也是先进的。

DESCRIPTION (provided by applicant): The goal of this proposal is the expansion of the utility of palladium-catalyzed C-O bond-forming cross-coupling reactions through fluorophobic acceleration. Novel protocols for the general and mild formation of aryl and diaryl ethers are advanced in which the intrinsic fluorophobicity of aryl, alkenyl, and alkyl units is exploited to expedite product formation through fluorophobic packing in the transition state of reductive elimination. On account of the ubiquity of aryl ethers in biologically-active molecules, it is an important challenge to develop a general catalytic method to produce this structural motif. The formation of diaryl, aryl-allyl, and aryl-alkyl ethers is addressed. In the case of aryl-allyl ether formation, it is proposed that a Claisen rearrangement, which is also accelerated in fluorous solvents, will quickly follow reductive elimination. Any chirality that is pre-installed into the allylic alcohol unit will be transferred into the product of the Claisen rearrangement, leading to the potential formation of a chiral quaternary center. Thus, a simple and cheap entry into complicated chiral building blocks for potential use in pharmaceutical synthesis is also advanced.