Trifluoromethylated Thiopyranoid Glycals: Synthesis and Ferrier (I) Type Reactions

The synthesis of a single diastereomer of 3‐acetoxy‐2‐(trifluoromethyl)‐4‐hydroxy‐3,4‐dihydro‐2H‐thiopyran from the mixture of diastereomeric cycloadducts of p‐tolyl trifluorodithioacetate and 1‐acetoxybutadiene is described. Its acetylation and nucleophilic chlorination provides glycosylating agents with different leaving groups have been prepared. Their reactions with various O‐, S‐, N‐ and C‐nucleophiles have been studied. Depending on the conditions of the experiments, the reactions proceed as Ferrier (I) reactions affording 3‐acetoxy‐2‐(trifluoromethyl)‐6‐substituted‐3,6‐dihydro‐2H‐thiopyrans or as formal direct replacement of the leaving group in the position 4 giving 3‐acetoxy‐2‐(trifluoromethyl)‐4‐substituted‐3,4‐dihydro‐2H‐thiopyrans. The stereochemistry of the resulting products and all their precursors is discussed. Trifluoromethyl containing thioglycal analogs were synthesized and studied as glycosylating agents in Ferrier rearrangement. The first examples of Ferrier rearrangement in fluorine containing thiopyran series were described. Influence of substrate nature on stereochemical outcome of reactions thiopyranoid glycals with different nucleophiles was discussed.