Nicholas Reactions with Carboxylic Acids for the Synthesis of Macrocyclic Diolides

We have developed a new strategy for the preparation of
diolides using a cascade of Nicholas reactions. The carboxylic
acid nucleophiles in these reactions are virtually unstudied
participants in transformations of this type. Using this
methodology, a 16-membered cobalt-complexed cyclic diyne
is available in 28% yield over eight steps (an average of 85%
per step). We can also easily access the uncomplexed diolide
in one additional step.