Differentially Protected Glycols from α-Halo Boronic Esters and Lithiated Benzoates

In the presence of sparteine 2,4,6-triisopropylbenzoates were lithiated enantioselectively in order to generate chiral d1 reagents. Their reaction with alpha-halo boronic esters, resembling chiral a1 reagents, was explored. Enantiomerically enriched alpha-halo boronic esters are readily available by Matteson Homologation (MH). A model reaction with alpha-bromopentyl pinandiol boronate was optimized to an acceptable yield but proved to be quite sensitive. Generation of the d1 reagent from the corresponding stannane stabilized the protocol and delivered moderate yields for beta-unsubstituted alpha-halo boronic esters. Good to excellent yields were obtained for beta-substituted alpha-halo boronic esters, which can be generated by iterative MH, thus establishing this method as a useful terminus for an iterative Matteson sequence. The combination of spartein derived carbanions as chiral d1-reagents with Matteson-derived alpha-bromo boronic esters as chiral a1-reagents was explored. Good yields and d.r. values were obtained for alpha-bromo boronic esters with sufficient steric bulk in the beta-position, which opens up opportunities for downstream applications in syntheses based on iterative Matteson-Reactions.image

Automated summary

In the presence of sparteine, chiral d1 reagents were generated through enantioselective lithiation of 2,4,6-triisopropylbenzoates. These reagents were then reacted with alpha-halo boronic esters, similar to chiral a1 reagents. Enantiomerically enriched alpha-halo boronic esters can be easily obtained through Matteson Homologation. The protocol was stabilized by using the corresponding stannane to generate the d1 reagent, resulting in moderate yields for beta-unsubstituted alpha-halo boronic esters. Good to excellent yields were obtained for beta-substituted alpha-halo boronic esters, which can be generated through iterative Matteson Homologation.