Tetraols as Templates for the Synthesis of Large endo‐Functionalized Macrocycles

Forty-six- and fifty-membered endo-functionalized macrocycles were obtained by template syntheses with new stiff tetracyclic tetraols 10 and 11. Reaction of dialkenylatedboronic acids 1 with template molecules 10 and 11 generated preorganized bisboronic esters 18 and 19, which were cyclized by ring-closing olefin metathesis. Resulting bimacrocycles 20 and 21 were obtained in ca. 60 % yield when alkenyl chains of sufficient lengths were used. The E/E, E/Z, and Z/Z mixtures were hydrogenated to give saturated bimacrocycles 24 and 25 in excellent yields. The removal of the tetraol templates was possible by hydrolysis in the presence of dimethyl sulfate, which was needed to trap the liberated template. Thus, bis-endo-boronic acids 27e and 27f were obtained. The relative stereochemistry of the diastereoisomeric templates and the bimacrocyclic nature of the cyclization products were proven by X-ray structure analyses (for 12 and 26d).