Enhancing the nucleophilicity of benzylic boronates enables the divergent formation of C−C and C−X bonds

13 April 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Tetracoordinated boron species generated from the complexation of organoboron compounds with bases are highly important intermediates in molecular fragments coupling. The type of base significantly impacts both the reaction activity and mechanism of organoboron compounds. Herein, our structural and mechanistic insights show that the full heterolytic cleavage of the C−B bond in benzylic boronates, leading to the formation of benzyl potassium species, can be achieved by increasing the amount of alkoxides. This, in turn, significantly enhances the nucleophilicity of both secondary and tertiary benzylic boronates. This mechanistic insight has proven valuable in the divergent construction of C(sp3)−C(sp3 or sp2) and other C−X bonds (X = Si, Ge, Sn, S, Se), as demonstrated through the integration of base-catalyzed silylboration/diborylation reactions. Through machine-learning-assisted screening of approximately 104 substrate combinations, we have expanded the scope of electrophiles for this transformation to include challenging aromatic heterocycles. Moreover, the synthetic potential of this protocol was demonstrated through the construction of drug-relevant molecules that contain 1,1-diaryl pharmacophores.


C−B activation
difunctionalization of alkenes
free carbanion
DFT calculations

Supplementary materials

Supplementary Information
The data supporting the findings of this study, including material and methods, optimization details, synthetic procedures, mechanistic studies, DFT calculations, machine learning, and NMR spectra, are available in Supplementary Information.


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