Escalante Carlos H, Martínez-Mora Eder I, Espinoza-Hicks Carlos, Camacho-Dávila Alejandro A, Ramos-Morales Fernando R, Delgado Francisco, Tamariz Joaquín
Departamento de Química Orgánica, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, Prolongación de Carpio y Plan de Ayala S/N, 11340 Mexico City, Mexico.
Departamento de Química Orgánica, Facultad de Ciencias Químicas, Universidad Autónoma de Coahuila, Blvd. Venustiano Carranza e Ing. J. Cárdenas S/N, 25280 Saltillo, Coah., Mexico.
Beilstein J Org Chem. 2020 Jun 17;16:1320-1334. doi: 10.3762/bjoc.16.113. eCollection 2020.
A highly regio-, chemo- and stereoselective divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles is herein described, starting from 2-formylpyrrole and employing Diels-Alder and Heck arylation reactions. 3-(Benzyl-2-pyrrolyl)acrylates and 4-(pyrrol-2-yl)butenones underwent a highly Diels-Alder cycloaddition with maleimides to furnish octahydropyrrolo[3,4-]indoles, which served as precursors in the regioselective synthesis of aza-polycyclic skeletons via an intramolecular Heck arylation reaction. Through the latter reaction, the 3-(benzyl-2-pyrrolyl)acrylates give rise to 3-(pyrrolo[2,1-]isoindol-3-yl)acrylates. A further oxidative aromatization of the polycyclic intermediates provides the corresponding polycyclic pyrrolo-isoindoles and isoindolo-pyrrolo-indoles. A theoretical study on the stereoselective Diels-Alder reactions, carried out by calculating the transition states, revealed the assistance of non-covalent interactions in governing the stereocontrol.
本文描述了一种从2-甲酰基吡咯出发，利用狄尔斯-阿尔德反应和赫克芳基化反应，高度区域选择性、化学选择性和立体选择性地合成异吲哚并和吡咯并稠合多环吲哚的方法。3-(苄基-2-吡咯基)丙烯酸酯和4-(吡咯-2-基)丁烯酮与马来酰亚胺发生高度区域选择性的狄尔斯-阿尔德环加成反应，生成八氢吡咯并[3,4-]吲哚，这些八氢吡咯并[3,4-]吲哚作为前体，通过分子内赫克芳基化反应用于区域选择性合成氮杂多环骨架。通过后一反应，3-(苄基-2-吡咯基)丙烯酸酯生成3-(吡咯并[2,1-]异吲哚-3-基)丙烯酸酯。多环中间体的进一步氧化芳构化反应生成相应的多环吡咯并异吲哚和异吲哚并吡咯并吲哚。通过计算过渡态对立体选择性狄尔斯-阿尔德反应进行的理论研究表明，非共价相互作用有助于控制立体化学。
