基于[2，2]对环芳烷骨架手性配体的设计、合成及其在不对称反应中的应用研究进展报告

姜标++邢萍

摘 要：该报告围绕[2，2]对环芳烷类骨架的手性化合物，设计并合成了一些具有应用潜力的环芳烷骨架手性配体并对其参与的不对称反应进行了研究。（1）手性含硫配体的设计合成及应用研究设计并合成了含有手性亚砜官能团的4，12-二取代手性膦-亚砜类配体。通过亚砜官能团的还原，还可以得到相应的膦-硫醚配体。膦-亚砜类配体在不对称烯丙基化反应中取得了48%ee，膦-硫醚类配体在不对称氢化中可取得85%ee。（2）柔性骨架氮膦配体的设计合成及应用研究在环芳烷的刚性骨架结构中引入柔性因素，设计了一类氮膦配体，以吡啶或喹啉为含氮配位官能团。这类配体在钯催化的烯丙基烷基化反应、铜催化的格氏试剂对共轭烯酮的不对称加成反应、钯催化的吲哚不对称傅克烷基化反应、钯催化的吲哚-2-甲酸酯不对称氮烷基化反应中均表现出优秀的活性和选择性。对反应结果的分析充分证明了苄位取代基所起的关键作用，它的引入使得配体结构的刚性因素增加，控制了中间体的构象。（3）双羟基[2，2]对环芳烷化合物及其衍生的单膦配体的合成及应用从延伸碳链的角度出发，合成到一种双酚羟基化合物，可以顺利得到氨基亚磷酸酯配体。这类配体在铜催化的非环状α-β不饱和酮的共轭加成反应中得到应用，取得了很好的結果（99% ee，95% ee），底物适用性也非常广泛。

关键词：不对称催化 [2.2]对环芳烷 膦-硫配体 氮膦配体 单膦配体

Design， Synthesis and Application in the Asymmetric Reaction of Chiral Ligands Based on the [2， 2]-Paracyclophane Backbone

Jiang Biao Xing Ping

（Shanghai Institute of Organic Chemistry， Chinese Academy of Sciences）

Abstract： This report was mainly focused on the use of chiral [2.2]paracyclophane derived compounds in asymmetric syntheses. Several potentially useful chiral ligands especially structurally flexible chiral ligands based on the skeleton were designed and synthesized. （1）Phosphino-sulfoxide a ligands were designed and synthesized， reduction of the sulfoxide could provide corresponding sulfur ether compounds. By using chiral palladacycle optical pure 4-bromo-12-diphenylphosphino[2.2]paracyclophane was obtained which was derived to afford several different sulfur substituted chiral P，S-ligands. These ligands were employed in the asymmetric allylic alkylation and asymmetric hydrogenations， up to 48% ee and 85% ee were obtained.（2）With the idea of tuning structural flexibility and rigidity， several [2.2]paracyclophane-derived P，N-ligands were designed and synthesized. A full investigation of the relationship between the ligands structures and their abilities to induce asymmetry in palladium-catalyzed asymmetric allylic alkylations， copper-catalyzed Michael reaction， palladium-catalyzed Friedel-Craft reaction and etc. were carried out， and high yields and enantioselectivities were observed while using ligands bearing matched planar and central chirality.（3）After attempts at synthesizing phosphoramidite ligands from some di-hydroxyl [2.2]-paracyclophane structures， a flexible di-hydroxyl [2.2]-paracyclophane backbone has proven to be a good candidate for forming chiral phosphoramidite ligands. One of the ligands was found to be highly efficient in the copper-catalyzed asymmetric conjugate addition of diethylzinc to substituted chalcones. The results obtained （up to 95% ee） were among the best of this field. The ligands were also tested in some other asymmetric catalytic reactions， 72% ee was observed in the asymmetric hydrogenation of dehydro amino acid ester.

Key Words： Asymmetric catalysis； [2.2]paracyclophane； P-S Ligand； P-N Ligands