Department of Chemistry, Faculty of Science , Ochanomizu University , 2-1-1 Otsuka , Bunkyo-ku, Tokyo 112-8610 , Japan.
Center for Analytical Instrumentation , Chiba University , Yayoi-cho , Chiba-shi, Chiba 263-8522 , Japan.
J Org Chem. 2018 Apr 20;83(8):4606-4617. doi: 10.1021/acs.joc.8b00349. Epub 2018 Apr 11.
N-Alkylbenzanilides generally exist in cis conformation both in the crystalline state and in various solvents, and this cis conformational preference can be utilized to construct dynamic helical oligoamides. Here, we synthesized the pyrrole-containing amides 2-5 and their oligomers 6-8 and examined their conformations in the crystalline state and in solution. All the N-methylated amides showed cis conformational preference in solution, but the ratio of the cis isomer was decreased when the amide bond was attached at the 4-position of the pyrrole ring, probably because the destabilization of the trans conformer due to electronic repulsion between the pyrrole π electrons and the amide carbonyl lone-pair electrons is reduced due to the small torsion angle between the 5-membered N-pyrrole and the amide bond. In the crystalline state, N-methylated amides showed cis structure, except for compound 5, and cis conformational preference was observed for the pyrrole amides. The CD spectra of oligoamides 15-18 bearing chiral N-substituents were consistent with the presence of dynamic and well-defined chiral foldamers, which were structurally distinct from N-alkylated poly( p-benzamide)s 1.
N-烷基苯甲酰胺通常在晶态和各种溶剂中都以顺式构象存在，这种顺式构象的偏好可用于构建动态螺旋寡酰胺。在这里，我们合成了含吡咯的酰胺 2-5 及其低聚物 6-8，并在晶体状态和溶液中研究了它们的构象。所有 N-甲基化酰胺在溶液中均表现出顺式构象偏好，但当酰胺键连接在吡咯环的 4-位时，顺式异构体的比例降低，这可能是由于吡咯π电子和酰胺羰基孤对电子之间的电子排斥导致反式构象的不稳定降低由于 5 元 N-吡咯和酰胺键之间的小扭转角。在晶体状态下，除了化合物 5 之外，N-甲基化酰胺均呈现顺式结构，并且吡咯酰胺也表现出顺式构象偏好。具有手性 N-取代基的寡聚物 15-18 的 CD 谱与动态且明确的手性折叠体的存在一致，这些折叠体在结构上与 N-烷基化聚（对苯二甲酰胺）1 不同。
