Asymmetric Synthesis of Chiral Spiroketal Bisphosphine Ligands and Their Application in Enantioselective Olefin Hydrogenation

A series of chiral spiroketal bisphosphine ligands containing 1,1′-spirobi­(3H,3′H)­isobenzofuran backbones was accessed through asymmetric synthesis and subsequently tested in enantioselective Rh-catalyzed hydrogenation of α-dehydroamino acid esters. The ligand providing the highest enantioselectivity (up to 99.5%) was obtained in seven steps in an overall 38% yield. The synthesis could be performed on a gram scale, and no kinetic resolution of enantiomers is required. Overall, the developed ligand provides an easily accessible alternative to SDP ligands as well as other chiral bisphosphine ligands.一系列带有1,1′-螺二(3H,3′H)异苯并呋喃骨架的手性螺环双膦配体（chiral spiroketal bisphosphine ligands）通过不对称合成制备得到，并随后应用于α-脱氢氨基酸酯的对映选择性铑（Rh）催化氢化反应中进行性能测试。其中对映选择性最高的配体（最高可达99.5%）经7步合成，总收率达38%。该合成路线可实现克级规模制备，且无需进行对映体的动力学拆分。综上，本研究开发的配体为SDP配体及其他手性双膦配体提供了一种易于获取的替代方案。