Development of perfluoroarene-arene interactions for macrocyclic en-yne metathesis and the total synthesis of macrocyclic natural products.

The Journal of organic chemistry

PubMedID: 17636956

Collins SK, El-Azizi Y, Schmitzer AR. Development of perfluoroarene-arene interactions for macrocyclic en-yne metathesis and the total synthesis of macrocyclic natural products. J Org Chem. 2007;72(17):6397-408.
Efficient direct en-yne metathesis of strained macrocyclic systems is possible using highly active Grubbs-Hoveyda second-generation catalyst and when exploiting fluoroarene-arene gearing interactions. These interactions are effective even under high reaction temperatures and in the presence of a competitive pi-rich solvent such as toluene. These results suggest that efficient pi-pi stacking or pi-lp interactions between auxiliaries containing pentafluorophenyl and 3,5-bis(trifluoromethyl)phenyl groups are responsible for the good yields of macrocyclization products. The 3,5-bis(trifluoromethyl)benzyl gearing elements provide higher yields and greater E-selectivity in the macrocyclic en-yne metathesis to form model paracyclophanes that could be applied toward the preparation of members of the longithorone family of natural products.