Fig. 1: Rationale for the efficient construction of HUMs.
From: Near quantitative synthesis of urea macrocycles enabled by bulky N-substituent
a Trans conformation preference of typical unhindered amide. b Trans conformation preference of typical unhindered N, N′-di-substituted urea. c Cis conformation preference of amide with bulky N-substituent. d Proposed cis conformation of ureas with bulky N-substituents. e Schematic illustration of the hindered urea bond (HUB). The bulky substituent broke the bond co-planarity, rendering HUB dynamic. f Schematic illustration for ‘bulky urea-turn’ and hindered urea chains. g Schematic illustration for the cis-urea facilitated macrocyclization. If the bulky group induced ‘cis-urea preference’ holds true, the hindered urea chain will bend and can easily undergo macrocyclization with several bond rotations.
