Concave reagents, 51. Concave pyridines for bifunctional acid-base catalysis

摘要

Two bifunctional concave acid-base catalysts, 1 and 2, have been synthesized starting from 2,6-dibromopyridine (9) and 2,6-bis(omega-alkenyloxy)phenylboronic acids 8 and 10 which end up as bridgeheads in final bimacrocycles 1 and 2. One bridgehead contained an additional substituent in the 4-position. The respective protected 4-hydroxymethyl-substituted phenylboronic acids 8 were synthesized from 4-bromo-3,5-dihydroxybenzoic acid (3) in five steps. 4-Unsubstituted boronic acid 10 and 4-substituted boronic acid 8 were then attached to 9 by subsequent Suzuki couplings to give tetra-omega-alkenes 12. By ring-closing metathesis of 12, bimacrocyclic dienes 13 and 17 were formed. After deprotection of the 4-hydroxymethyl group of one bridgehead, a 3-hydroxybenzoate was coupled to 14 to give ester 15 which gave bifunctional acid-base catalyst 1 upon hydrolysis. Analogously, homologue 2 was synthesized, but before coupling the bi-macrocycle to the benzoate,. tetraene 14 was hydrogenated to 18. Acidic and basic centers in 1 (49% from 9) and 2 (19% from 9) are at least 5 angstrom apart. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007).