Sparteine-Free, Highly Stereoselective Construction of Complex Allylic Alcohols Using 1,2-Metallate Rearrangements

Stereotriads bearingallylic alcohols are privileged structuresin natural products, and new methods accessing these in a stereoselectivefashion are highly sought after. Toward this goal, we found that theuse of chiral polyketide fragments allows for performing the Hoppe-Matteson-Aggarwalrearrangement in the absence of sparteine with high yields and diastereoselectivities,rendering this protocol a highly valuable alternative to the Nozaki-Hiyama-Takai-Kishireaction. The switch of directing groups in most cases resulted inthe reversed stereochemical outcome, which could be explained by conformationalanalysis on density functional theory level and a Felkin-like model.

Automated summary

Stereotriads bearing allylic alcohols are important structures in natural products, and finding new stereoselective methods to access them is highly desired. We discovered that using chiral polyketide fragments allows for the efficient Hoppe-Matteson-Aggarwal rearrangement without the need for sparteine, resulting in high yields and diastereoselectivities. This protocol provides a valuable alternative to the Nozaki-Hiyama-Takai-Kishi reaction. The reversal of stereochemical outcome upon switching directing groups can be explained by conformational analysis and a Felkin-like model at the density functional theory level.