Direct synthesis of macrodiolides via hafnium(IV) catalysis

Efficient direct synthesis of macrodiolides via catalysis using Hf(OTf)4 is possible in high yields, forming water as the sole by-product. The first protocol for the direct synthesis of macrodiolides from equimolar mixtures of diols and dicarboxylic acids was developed (58-96%). In addition, modification of the reaction concentration allows for the synthesis of head-to-tail macrodiolides from the corresponding seco acids. The catalytic preparation of the macrodiolides using a commercially available catalyst without the need for slow addition or azeotropic condition provides an operationally simple alternative to protocols which employ toxic tin catalysts or stoichiometric activation strategies.