Regioselective Electrophilic Addition to Propargylic B(MIDA)s Enabled by -Boron Effect

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 beta-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 gamma position is due to its higher HOMO orbital coefficient and more negative natural bond orbital (NBO) charge compared to the beta position. This study demonstrates the potential of utilizing the beta-boron effect in stereoelectronic control of chemical transformations, which can inspire further research in this area.