Highly Enantioselective Allylic C–H Alkylation of Terminal Olefins with Pyrazol-5-ones Enabled by Cooperative Catalysis of Palladium Complex and Brønsted Acid

A highly
enantioselective allylic C–H alkylation reaction
of allylarenes with pyrazol-5-ones has been established by the cooperative
catalysis of a chiral palladium complex and chiral Brønsted acid
to afford a wide spectrum of functionalized chiral N-heterocycles
with an all-carbon quaternary stereogenic center in high yields and
with high levels of enantioselectivity (up to 96% ee), wherein the
chiral ligand and phosphoric acid showed synergistic effect on the
control of stereoselectivity. In addition, a palladium-catalyzed asymmetric
allylic C–H alkylation of 1,4-pentadienes with pyrazol-5-ones
has been realized to furnish highly functionalized pyrazol-5-ones
in high enantioselectivities. In this case, the chiral ligand controls
the stereoselectivity while the achiral Bronsted acid, 2-fluorobenzoic
acid, turns out to be a better cocatalyst than the chiral phosphoric
acid. The installation of electron-deficient substituents at 3,3′-positions
of binaphthyl backbone of chiral phosphoramidites is actually beneficial
to the allylic C–H oxidation due to their survival in the presence
of quinone derivative oxidants. These allylic C–H alkylation
reactions undergo smoothly under mild conditions and tolerate a wide
range of substrates. The resultant highly functionalized chiral pyrazol-5-ones
have been applied to the preparation of more structurally diverse
heterocycles by classical transformations.

本研究通过手性钯配合物（chiral palladium complex）与手性布朗斯特酸（chiral Brønsted acid）的协同催化，成功构建了烯丙基芳烃（allylarenes）与吡唑-5-酮（pyrazol-5-ones）的高对映选择性烯丙基C-H烷基化反应（allylic C–H alkylation reaction），可得到一系列带有全碳季碳手性中心的官能团化手性氮杂环，反应收率优良且对映选择性极高（最高可达96% ee），其中手性配体与磷酸类催化剂在立体选择性调控方面展现出协同效应。此外，本研究还实现了1,4-戊二烯（1,4-pentadienes）与吡唑-5-酮的钯催化不对称烯丙基C-H烷基化反应，可高效制备高对映选择性的官能团化吡唑-5-酮。在此反应体系中，手性配体负责调控立体选择性，而非手性布朗斯特酸2-氟苯甲酸（2-fluorobenzoic acid）的助催化效果优于手性磷酸（chiral phosphoric acid）。研究发现，在手性亚磷酰胺配体（chiral phosphoramidites）的联萘骨架（binaphthyl backbone）的3,3'-位引入吸电子取代基，可显著提升烯丙基C-H氧化反应的兼容性，因其在醌类氧化剂（quinone derivative oxidants）存在下仍能保持稳定。上述烯丙基C-H烷基化反应均可在温和条件下顺利进行，且底物适用范围广泛。所得高官能团化手性吡唑-5-酮可通过经典转化反应进一步制备结构更为多样的杂环化合物。