Generation of Benzyne Species from Diphenylphosphoryl Derivatives: Simultaneous Exchange of Three Functional Groups

Interaction of (2-diphenylphosphoryl-3-iodo-4-methoxy-phenyl) methanol with NaH in DMF at ambient temperature results in the generation of benzyne intermediates that can be trapped by furan or DMF. Trapping with DMF forms 3-(dimethylaminomethyl)-2-hydroxy-6-methoxybenzaldehyde demonstrating the simultaneous exchange of three functionalities in a single step. The presence of the alkoxy substituent adjacent to iodine is critical for high regioselectivity addition of DMF. The corresponding bromide or triflate can be used in place of the iodide with equal efficiency. This methodology was used to synthesize the reported structure of gigasol and leading to a structural reassignment of this biscoumarin natural product.