Application Of Palladium-Catalyzed Aryl C-H Alkylation In Total Synthesis Of (-)-Berkelic Acid

An unprecedented palladium(II)-catalyzed ortho-alkylation of N-methoxybenzamide with epoxides has been applied to the total synthesis of the isochroman natural product (-)-berkelic acid. Combining this strategy with a well documented spiroacetalization cascade reaction, (-)-berkelic acid is obtained in 13.9% overall yield with the longest linear sequence of 11 steps. The results of preliminary biological studies on the synthesized natural product and its analogues are also reported.