Division of Applied Chemistry, Graduate School of Engineering, Hokkaido University, Sapporo, Hokkaido 060-8628, Japan.
Organic R&D Department, Nippon Chemical Industrial Co., Ltd., Kameido, Koto-Ku, Tokyo 136-8515, Japan.
J Am Chem Soc. 2021 May 5;143(17):6413-6422. doi: 10.1021/jacs.0c08899. Epub 2021 Apr 23.
A new -symmetrical -chirogenic bisphosphine ligand with silyl substituents on the ligand backbone, (,)-5,8-TMS-QuinoxP*, has been developed. This ligand showed higher reactivity and enantioselectivity for the direct enantioconvergent borylation of cyclic allyl electrophiles than its parent ligand, (,)-QuinoxP* (e.g., for a piperidine-type substrate: 95% ee vs 76% ee). The borylative kinetic resolution of linear allyl electrophiles was also achieved using (,)-5,8-TMS-QuinoxP* (up to 90% ee, = 46.4). An investigation into the role of the silyl groups on the ligand backbone using X-ray crystallography and computational studies displayed interlocking structures between the phosphine and silyl moieties of (,)-5,8-TMS-QuinoxP*. The results of DFT calculations revealed that the entropy effect thermodynamically destabilizes the dormant dimer species in the catalytic cycle to improve the reactivity. Furthermore, in the direct enantioconvergent case, detailed calculations indicated a pronounced enantioselective recognition of carbon-carbon double bonds, which is virtually unaffected by the chirality at the allylic position, as a key for the borylation from both enantiomers of racemic allyl electrophiles.
一种具有硅取代基的新型手性双膦配体（,）-5,8-TMS-QuinoxP*，已经被开发出来。与母体配体（,）-QuinoxP相比，该配体在手性直接对映选择性硼化环状烯丙基亲电试剂方面具有更高的反应性和对映选择性（例如，对于哌啶型底物：95%ee 对 76%ee）。使用（,）-5,8-TMS-QuinoxP还可以实现线性烯丙基亲电试剂的硼化动力学拆分（高达 90%ee， = 46.4）。使用 X 射线晶体学和计算研究对手柄骨架上硅取代基的作用进行了研究，结果显示（,）-5,8-TMS-QuinoxP*的膦和硅部分之间存在互锁结构。DFT 计算的结果表明，熵效应在热力学上使休眠二聚体物种不稳定，从而提高了反应性。此外，在手性直接对映选择性的情况下，详细的计算表明，对碳-碳双键的显著对映选择性识别是关键，这几乎不受烯丙基位置的手性影响，这是来自外消旋烯丙基亲电试剂的两种对映体硼化的关键。
