Brønsted acid-catalyzed allylboration: short and stereodivergent synthesis of all four eupomatilone diastereomers with crystallographic assignments

Abstract

This study describes a novel Brønsted acid-catalyzed allylboration method suitable for the most difficult, electronically deactivated allylboronate and aldehyde substrates. This method circumvents the use of metal ions, and rather employs a simple and cheap catalyst, triflic acid. Its usefulness as a complementary allylboration variant was demonstrated with a four-step, stereodivergent synthesis of all four diastereomers of eupomatilone-6 from a single allylboronate. A thorough proof of stereochemistry supported by as many as five X-ray crystallographic structures brings an end to the ambiguity of the original stereochemical assignments. Further to the TfOH-catalyzed allylboration, the synthetic route featured a number of remarkable observations: the surprising reactivity of 2-bromo-3,4,5-trimethoxybenzaldehyde, the subtle reagent control observed in the hydrogenation of an alpha-exo-methylene lactone intermediate, and the success of a difficult case of Suzuki biaryl coupling using Buchwald's conditions.