Studies towards tandem 'one-way' Bergman radical cyclizations of aromatic enediynes and synthesis of anti-1,3-diols by the cationic coupling of nucleophiles with 4-acetoxy-1,3-dioxanes

A new methodology for the synthesis of aromatic enediynes by the Hagihara coupling of terminal alkynes with aromatic 1,2-ditriflates was developed. The addition of halide salts was observed to greatly accelerate the coupling reaction. Tandem radical reactions of aromatic enediynes appear to proceed through a 5-exo cyclization pathway.; The synthesis of anti-1,3-diols by the cationic coupling of nucleophiles with 4-acetoxy-1,3-dioxanes was studied. A number of nucleophiles were examined, including heteroatomic nucleophiles such as PhSH, enol silanes, vinyl organometallics, alkynyl diethylalanes and tributylstannanes, and dialkylzincs.; Alkynyl diethylalanes that were substituted with silyl or sp{dollar}sp2{dollar}-centered groups coupled readily to give anti-1,3-dioxanes in 290:1 diastereoselectivity. Alkyl substituted alkynyll tributylstannanes were found to couple, as well. The anti-1,3-dioxanes produced proved to be excellent precursors for the corresponding E- and Z-allylic anti-1,3-diols upon acidic removal of the acetal protecting group and selective reduction to the desired olefin geometry. The usefulness of this methodology was demonstrated in the total synthesis of ({dollar}-{dollar})-E-1-chlorotridec-1-ene-6,8-diol.; A wide variety of dialkylzincs were found to couple with 4-acetoxy-1,3-dioxanes to give the corresponding anti-1,3-dioxanes in 290:1 diastereoselectivity. An interesting exception to this diastereoselectivity was found in the coupling of ether containing dialkylzincs with the O atom {dollar}gamma{dollar} to the C-Zn bond. The anti-1,3-dioxanes formed in this reaction were found to be readily deprotected to give the corresponding anti-1,3-diols. An intramolecular transketalization deprotection strategy was determined to be feasible.