Stereoselective Synthesis of Allylic Alcohols via Substrate Control on Asymmetric Lithiation

Allylic alcohols are a privileged motif in natural product synthesis and new methods that access them in a stereoselective fashion are highly sought after. Toward this goal, we found that chiral acetonide-protected polyketide fragments performing the Hoppe-Matteson-Aggarwal rearrangement in the absence of sparteine with high yields and diastereoselectivities rendering this protocol a highly valuable alternative to the Nozaki-Hiyama-Takai-Kishi reaction. Various stereodyads and -triads were investigated to determine their substrate induction. The mostly strong inherent stereoinduction was attributed to a combination of steric and electronic effects. Sparteine free Hoppe-Matteson-Aggarwal rearrangement was applied to various chiral acetonides. Utilizing different vinyl boronic esters a high level of substrate control was observed leading to excellent selectivities. These selectivities were attributed to stereoelectronic effects of the neighboring acetonide moiety. The obtained formal Felkin and anti-Felkin products feature up to four contiguous stereocenters representing structural motifs common in natural products.+image