基于[2，2]對環芳烷骨架手性配體的設計、合成及其在不對稱反應中的應用研究進展報告

姜標++邢萍

摘 要：該報告圍繞[2，2]對環芳烷類骨架的手性化合物，設計并合成了一些具有應用潛力的環芳烷骨架手性配體并對其參與的不對稱反應進行了研究。（1）手性含硫配體的設計合成及應用研究設計并合成了含有手性亞砜官能團的4，12-二取代手性膦-亞砜類配體。通過亞砜官能團的還原，還可以得到相應的膦-硫醚配體。膦-亞砜類配體在不對稱烯丙基化反應中取得了48%ee，膦-硫醚類配體在不對稱氫化中可取得85%ee。（2）柔性骨架氮膦配體的設計合成及應用研究在環芳烷的剛性骨架結構中引入柔性因素，設計了一類氮膦配體，以吡啶或喹啉為含氮配位官能團。這類配體在鈀催化的烯丙基烷基化反應、銅催化的格氏試劑對共軛烯酮的不對稱加成反應、鈀催化的吲哚不對稱傅克烷基化反應、鈀催化的吲哚-2-甲酸酯不對稱氮烷基化反應中均表現出優秀的活性和選擇性。對反應結果的分析充分證明了芐位取代基所起的關鍵作用，它的引入使得配體結構的剛性因素增加，控制了中間體的構象。（3）雙羥基[2，2]對環芳烷化合物及其衍生的單膦配體的合成及應用從延伸碳鏈的角度出發，合成到一種雙酚羥基化合物，可以順利得到氨基亞磷酸酯配體。這類配體在銅催化的非環狀α-β不飽和酮的共軛加成反應中得到應用，取得了很好的結果（99% ee，95% ee），底物適用性也非常廣泛。

關鍵詞：不對稱催化 [2.2]對環芳烷 膦-硫配體 氮膦配體 單膦配體

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