Tailor-Designed Phosphine Ligand for Palladium-Catalyzed Cross-Coupling Processes

A novel class of the indolylphosphine ligands was tailor-designed and prepared. The indolyl scaffold of such class of ligands could be easily synthesized and diversified from inexpensive oxindole and naphthalenol or arylhydrazines and substituted acetophenones via straightforward Fischer-Indolization. Various dihedral angles between indolyl-ring and aryl ring could be achieved by readily installing a varying number of carbons in tethered linkage. Possible resolution strategies of tethered indolylphosphine ligands in achieving an optically pure form were also demonstrated.The palladium complex employing tethered indolylphosphine ligands were found highly active towards Suzuki-Miyaura cross-coupling of unexplored potassium aryltrifluoroborates and aryl(heteroaryl) chlorides for tetra-ortho-substituted biaryl synthesis in good-to-excellent yields (up to 99%) with catalyst loading down to 0.1 mol%. A comprehensive DFT calculation showed that the mechanism includes three major steps, namely oxidative addition (OA), transmetalation and rate-determining reductive elimination (RE). The calculation results demonstrated that tethered indolylphosphine ligand stabilized the palladium complex and hence made the transmetalation step thermodynamically favorable. The novel "Pd-arene-walking" (Pd-ligand interaction) stabilized the transition state and thus minimized the activation energy of rate-determining step. The optically pure form of tethered indolylphosphine ligands showed enantioselectivity toward asymmetric catalysis processes.Modified Buchwald-type monophosphine ligands bearing −PPh2 moiety (instead of −PCy2 group) exhibited high efficiency for the first general examples of direct C−H arylation of electron-deficient polyfluoroarenes with challenging di-ortho-substituted aryl(heteroaryl) chlorides for tetra-ortho-substituted biaryl synthesis with catalyst loading down to 0.25 mol% notably.本文設計合成了一類新的吲哚基膦配體，並對Buchwald型單膦配體進行了改良。從容易獲得且便宜的原材料出發，通過簡單的費歇爾吲哚合成反應合成此類配體的吲哚基支架。並可以輕易通過安裝不同數目的碳在繫鏈上，微調吲哚環和芳基環的二面角。本文還順利把繫鏈吲哚基膦配體進行不對稱拆分，並將其用於不對稱交叉偶聯反應。本文把繫鏈吲哚基膦配體用於鈀催化的高位阻芳基氯及苯基三氟硼酸钾Suzuki-Miyaura交叉耦聯反應，有效地合成出高位阻聯芳。結果顯示只需要0.1摩爾%的催化劑就能有99%產量。全面的DFT計算顯示還原消除是速率控制步驟。繫鏈吲哚基膦配體能使中間體穩定以導致轉移金屬化在熱力學上變成有益，而且還能使過渡態穩定，從而降低速率控制步驟活化能。本文通過對Buchwald型單膦配體進行改良，把−PCy2基團改換成 −PPh2基團而成為更有效更便宜的膦配體。並將其用於鈀催化的高位阻芳基氯直接C−H鏈活化反應，合成出高位阻多氟聯芳。結果顯示只需要0.25摩爾%的催化劑就能有99%產量。LEUNG, Man Pan.Ph.D. Chinese University of Hong Kong 2021.Includes bibliographical references (leaves )Abstracts in English and Chinese.Title from PDF title page (viewed on ...