The Development of Stereoselective Substrate and Reagent-Controlled Lithiation-Borylation Chemistry

Allylic alcohols are a privileged motif in polyketide-based natural product synthesis, and new methods that access them in a stereoselective fashion are highly sought after. Toward this goal, we found that the use of chiral polyketide fragments allows for performing the Hoppe-Matteson-Aggarwal rearrangement in the absence of sparteine with high yields and diastereoselectivities, rendering this protocol a highly valuable alternative to existing methods. Various stereodyads and -triads bearing different protecting and directing groups were investigated to determine their substrate induction. The mostly strong inherent induction was attributed to either steric or a combination of steric and electronic effects. The stereochemical outcome could be explained by (DFT-based) conformational analysis and a Felkin-like model, allowing guidance flowcharts to be created for the substrate- and reagent-controlled lithiation-borylation chemistry.