Macrocycles Derived from Cinchona Alkaloids:  A Thermodynamic vs Kinetic Study

Abstract

Cyclization of the quinine-derived monomer ( 2a ): HO-Cq-OMe, under thermodynamic control, gives mainly cyclic trimer Cq 3 (7a), whereas kinetic cyclization of the similar monomer HO-Cq-OH (8) gives a mixture of cyclic products. This difference in product distribution is attributed to predisposition of the monomer unit, which means the building block adopts a more stable conformation in cyclic trimer than it can in cyclic tetramer. The reversibility of the thermodynamic reaction was demonstrated using electrospray mass spectrometry to monitor the catalyzed mixing of the two cyclic trimers Cq 3 (7a) and Cc 3 (7b), which results in the statistically expected 1:3:3:1 ratio of all possible cyclic trimers Cc 3:Cc 2 Cq:CcCq 2:Cq 3 .