Trapping of a phosphazide intermediate in the Staudinger reaction of tertiary phosphines with azides and its application to the synthesis of analogs of the marine alkaloid midpacamide

A new method based on the reaction of an E-phosphazide, an intermediate in the Staudinger reaction between triphenylphosphine with an azide, with heterocumulenes allows the one-pot, two-component synthesis of a number of analogs of the pyrrole–imidazole marine alkaloid midpacamide. The procedure, which involves sequential treatment of the appropriate α-azido ester with triphenylphosphine and isothiocyanate leads to the thiohydantoin product after aqueous workup. The cyclization conditions can also be adapted to the synthesis of hydantoins by using isocyanates.