Base-mediated C-B bond activation of benzylic boronate for the rapid construction of β-silyl/boryl functionalized 1,1-diarylalkanes from aromatic alkenes

The effect of tBuOK on the existing state of benzylic boronates in the solution phase has been investigated in detail by NMR analysis and DFT calculations. It was determined that simply using an excess of tBuOK (2.0 equivalents) can result in the full deborylation of benzylic boronates to afford free benzyl potassium species. These mechanistic insights were leveraged for the facile construction of beta-silyl/boryl functionalized 1,1-diarylalkanes from aromatic alkenes via the combination of base-mediated silylboration or diborylation of aromatic alkenes and nucleophilic-type reactions with various electrophiles. Based on further machine-learning-assisted screening, the scope of electrophiles for this transformation can be generalized to the challenging aromatic heterocycles. Late-stage functionalization performed on several drug-relevant molecules generates the highly valuable 1,1-diaryl framework. By shifting the chemical equilibrium of the benzylic boronate-base complex to the free carbanion state, we developed a general, practical, and simple method for the construction of beta-silyl/boryl functionalized 1,1-diarylalkanes.

Automated summary

The effect of tBuOK on benzylic boronates in solution phase was investigated using NMR analysis and DFT calculations. It was found that using excess tBuOK leads to the complete deborylation of benzylic boronates, resulting in the formation of free benzyl potassium species. These insights were utilized for the synthesis of beta-silyl/boryl functionalized 1,1-diarylalkanes from aromatic alkenes through a combination of base-mediated silylboration or diborylation reactions and nucleophilic reactions with various electrophiles. Machine-learning-assisted screening expanded the scope of electrophiles to challenging aromatic heterocycles. Late-stage functionalization of drug-relevant molecules yielded valuable 1,1-diaryl frameworks.