Synthesis of S,S,O-Orthoesters and 1,1-Difluoroalkyl Ethers via Reaction of Peroxides with Lithiated 1,3-Dithianes

Alkyl tetrahydropyranyl peroxides (ROOTI-113) transfer alkoxide -THP(OR) to lithiated 1,3-dithianes. The derived S,S,O-orthoesters undergo 9-0 fluorodesulfurization with HF/pyridine and N-brornosuccinamide (NBS) to A2 furnish difluoromethyl ethers. The overall protocol can be applied to synthesis of both terminal (ROCF2H) and internal (ROCF2R1 ethers. Application of the same set of reactions to a fithiated tris(alkylthio)alkane is shown to generate a trifluoromethyl ether.