Fig. 3: Validation of the t-Bu induced ‘cis-urea preference’.
From: Near quantitative synthesis of urea macrocycles enabled by bulky N-substituent
Partial NOESY spectrum of a HUM2 b MC1 and c MC1′. HUM2 and MC1 showed relatively restrained cis conformation while MC1′ had a relatively flexible conformation with free rotation. d Upper: structures of the model compounds used in the DFT calculations (MC2 and MC2′) and that used in the exchange kinetic studies (MC3). Lower: computed free energy differences between cis and trans conformations of MC2 and MC2′. e Exchange kinetics of HUM2 ([N2A2]1, red square) and its linear model compounds MC3 (blue dot) with 20 equivalents of butylisocyanate in CDCl3 at 55 °C. f Illustration showing the structures of the five different conformers of MC4, their respective degree of folding θ1, relative-free energies and chain-end distance d. Conformations were obtained after local energy minimization. DFT calculations shown here were based on the B3LYP/6-31G(d) levels of theory. Upper left inset: structure of the adduct MC4 and the corresponding calculated parameters. d: distance between the N of the free amine and C of the free isocyanate. θ1: angle between vectors v1 and v2; θ2: angle between vectors v3 and v4. Lower right inset: relationship between the free chain-end distance and the relative-free energy.
