Conformationally Fixed Chiral Bisphosphine Ligands by Steric Modulators on the Ligand Backbone: Selective Synthesis of Strained 1,2-Disubstituted Chiral cis-Cyclopropanes

A new series of C1-symmetric P-chirogenic bisphosphine ligands of the type (R)-5,8-Si-Quinox-tBu3 (Silyl = SiMe3, SiEt3, SiMe2Ph) have been developed. The bulky silyl modulators attached to the ligand backbone fix the phosphine substituents to form rigid chiral environments that can be used for substrate recognition. The ligand showed high performances for a copper­(I)-catalyzed asymmetric borylative cyclopropanation of bulky silyl-substituted allylic electrophiles to afford higher disfavored 1,2-cis-silyl-boryl-cyclopropanes than the other possible isomers, trans-cyclopropane and allylboronate (up to 97% yield; 98% ee; cis/trans = >99:1; cyclopropane/allylboronate = >99:1). Detailed computational studies suggested that the highly rigid phosphine conformation, which is virtually undisturbed by the steric interactions with the bulky silyl-substituted allyl electrophiles, is key to the high stereo- and product-selectivities. Furthermore, the detailed computational analysis provided insight into the mechanism of the stereoretention or -inversion of the chiral alkylcopper­(I) intermediate in the intramolecular cyclization.本研究开发了一系列新型C1对称P手性双膦配体，其结构通式为(R)-5,8-Si-Quinox-tBu3（硅基取代基分别为SiMe3、SiEt3、SiMe2Ph）。连接于配体骨架的大位阻硅基调控基团可固定膦取代基，形成刚性手性环境，可用于底物识别。该配体在铜(I)催化的大位阻硅基取代烯丙基亲电试剂的不对称硼基化环丙烷化反应中表现出优异性能：相较于其他可能的异构体（反式环丙烷与烯丙基硼酸酯），可高效生成即便通常为劣势异构体的1,2-顺式-硅基-硼基-环丙烷产物，最高产率可达97%，对映体过量值为98% ee，顺反比大于99:1，环丙烷与烯丙基硼酸酯的比例大于99:1。详细的计算研究表明，几乎不受大位阻硅基取代烯丙基亲电试剂空间位阻干扰的高度刚性膦配体构象，是实现高立体选择性与产物选择性的关键所在。此外，详细的计算分析还为分子内环化过程中手性烷基铜(I)中间体的立体保留或立体反转机理提供了深入见解。