Diastereoselective formation of tetrahydrofurans via Pd-catalyzed asymmetric allylic alkylation: synthesis of the C13-C29 subunit of amphidinolide N.

An efficient synthesis of the C13-C29 fragment of amphidinolide N is described. The synthesis relies on a new strategy involving Pd-catalyzed asymmetric allylic alkylation to generate diastereoselectively the cis- or trans-THF unit simply by varying the enantiomer of the ligand. The C19 hydroxyl-bearing stereocenter was introduced using a chelation-controlled allylation which led exclusively to a single diastereoisomer.