New Catalytic Methods for Conjugate Additions with ⍺-Boryl Nucleophiles

In this work, we investigate a new metal-free catalytic method for 1,4-addition of boryl nucleophiles. 1,4-addition reactions, or conjugate additions, are versatile reactions for insertion of nucleophiles at the beta position to a carbonyl, enabling site-selective functionalizations, but often requiring harsh conditions. As such, phase-transfer catalysts were utilized to facilitate mild and selective activation of the silicon-substituted alpha-diboryl nucleophile, which could then add to a dimethyl benzylidene malonate Michael acceptor. In utilizing cesium fluoride as a fluoride activator, a THF and DMF solvent mixture, and cinchonidine and pyrazolium phase transfer catalysts, the reaction was able to reach excellent yields with minimal byproducts. This work has far-reaching implications for the site-selective installation of boronic ester functional handles under mild conditions, which can give way to further functionalization and molecular expansion via a diverse array of boron reactions like oxidations, cross-couplings, and aminations. Future studies will examine tuning phase-transfer catalysts in order to impart enantioselectivity in the reaction, which will further enhance this method's utility in medicinal chemistry and drug molecule expansion.