Macrocyclic olefin metathesis at high concentrations by using a phase-separation strategy.

Macrocyclic olefin metathesis has seen advances in the areas of stereochemistry, chemoselectivity, and catalyst stability, but strategies aimed at controlling dilution effects in macrocyclizations are rare. Herein, a protocol to promote macrocyclic olefin metathesis, one of the most common synthetic tools used to prepare macrocycles, at relatively high concentrations (up to 60 mM) is described by exploitation of a phase-separation strategy. A variety of macrocyclic skeletons could be prepared having either different alkyl, aryl, or amino acids spacers.