Using Fluorophobicity in Pd-catalyzed C-O Couplings

描述(由申请人提供)： 这项提议的目标是通过亲氟加速来扩大钯催化的形成C-O键的交叉偶联反应的用途。提出了用于芳基和二芳基醚的一般和温和形成的新方案，其中利用了芳基、烯基和烷基单元的固有憎氟性，以在还原消除的过渡态中通过憎氟填充来加速产物的形成。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制备这种结构基元是一个重要的挑战。讨论了二芳基、芳基烯丙基和芳基烷基醚的形成。对于芳基烯丙基醚的形成，有人认为在氟溶剂中也会加速Claisen重排，还原消除后会很快发生。任何预先安装在烯丙醇单元中的手性都将转移到Claisen重排的产物中，导致潜在的手性四元中心的形成。因此，还提出了一种简单且廉价的进入复杂的手性构建块的方法，以便在药物合成中潜在地使用。

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.