Li Yin, Chen Zhi-Hao, Lin Shuang, Liu Yuan, Qian Jiasheng, Li Qingjiang, Huang Zhi-Shu, Wang Honggen
Guangdong Key Laboratory of Chiral Molecule and Drug Discovery, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
Adv Sci (Weinh). 2023 Oct;10(30):e2304282. doi: 10.1002/advs.202304282. Epub 2023 Aug 26.
Electrophilic addition reaction to alkynes is of fundamental importance in organic chemistry, yet the regiocontrol when reacting with unsymmetrical 1,2-dialkyl substituted alkynes is often problematic. Herein, it is demonstrated that the rarely recognized β-boron effect can confer a high level of site-selectivity in several alkyne electrophilic addition reactions. A broad range of highly functionalized and complex organoborons are thus formed under simple reaction conditions starting from propargylic MIDA (N-methyliminodiacetic acid) boronates. These products are demonstrated to be valuable building blocks in organic synthesis. In addition to the regiocontrol, this study also observes a drastic rate enhancement upon B(MIDA) substitution. Theoretical calculation reveals that the highest occupied molecular obital (HOMO) energy level of propargylic B(MIDA) is significantly raised by 0.3 eV, and the preferential electrophilic addition to the γ position is due to its higher HOMO orbital coefficient and more negative natural bond orbital (NBO) charge compared to the β position. This study demonstrates the potential of utilizing the β-boron effect in stereoelectronic control of chemical transformations, which can inspire further research in this area.
炔烃的亲电加成反应在有机化学中具有至关重要的地位，然而，当与不对称的1,2 - 二烷基取代炔烃反应时，区域选择性控制常常存在问题。在此，研究表明，鲜为人知的β - 硼效应能在几种炔烃亲电加成反应中赋予高水平的位点选择性。因此，在简单的反应条件下，从炔丙基MIDA（N - 甲基亚氨基二乙酸）硼酸酯出发，可形成多种高度官能化且复杂的有机硼化合物。这些产物被证明是有机合成中有价值的构建单元。除了区域选择性控制，本研究还观察到B(MIDA)取代后反应速率大幅提高。理论计算表明，炔丙基B(MIDA)的最高占据分子轨道（HOMO）能级显著提高了0.3 eV，与β位相比，亲电加成优先发生在γ位是由于其具有更高的HOMO轨道系数和更负 的自然键轨道（NBO）电荷。本研究展示了利用β - 硼效应进行化学转化立体电子控制的潜力，这能够激发该领域的进一步研究。
