Total Synthesis of Desoxoprosophylline: Application of a Lactam-Derived Enol Triflate to Natural Product Synthesis

The total synthesis of desoxoprosophylline 1 from a piperidinone-derived enol triflate 8 has been realized and is one of the first applications of such lactam-derived triflates to natural product synthesis. Palladium-catalyzed methoxycarbonylation of 8 followed by 1,2-reduction and protection introduces the required C2 hydroxymethyl group, affording 10 . The C3 hydroxy function is stereoselectively added by a novel N -tosylenamide hydroboration (de 88%), and the final C6 dodecyl chain is incorporated with complete stereocontrol, in a single step, via an N -tosyliminium ion−allylsilane coupling. Deprotection gives the natural product in an efficient 7.5% yield over nine steps.