Macrocyclization Reactions at High Concentration (>=0.2M): The Role of Catalysis

Abstract

[EN] The synthesis ofmacrocycles is fundamental to obtainuseful quantitiesof this unique family of organic compounds. However, most currentsyntheses still require highly diluted conditions (generally <0.1M), which makes the synthesis extremely inefficient in the reactorvolume. Here we review, quantify, and analyze the few synthetic methodsfor macrocycles reported so far where the reaction solution is at & GE; 0.2 M concentration. Parametrization of the results withthe Emac (efficiency macrocyclization) index unveils that catalyticmethods are much more efficient than non-catalyzed methods. Beyondthis conclusion, the present study also shows clear evidence thathigh-concentration macrocyclization reactions are not only possiblebut necessary, and suggests the use of catalytic reactions, includingsolid catalysts and in-flow reactions, to develop macrocyclizationreactions under high concentration conditions.