Damas Liliana, Carrilho Rui M B, Nunes Sandra C C, Pais Alberto A C C, Kollár László, Pineiro Marta, Pereira Mariette M
Coimbra Chemistry Centre, Departamento de Química, Universidade de Coimbra, Rua Larga, 3004-535 Coimbra, Portugal.
Department of Inorganic Chemistry, University of Pécs and Szentágothai Research Centre, PO Box 266, 7624 Pécs, Hungary.
R Soc Open Sci. 2018 Sep 12;5(9):181140. doi: 10.1098/rsos.181140. eCollection 2018 Sep.
An unprecedented palladium-catalysed sequential aminocarbonylation/cyclization synthetic strategy, using carbon monoxide and structurally different aliphatic diamines as -nucleophiles, gives access, in one pot, to a new family of indole-based -heterocyclic derivatives (hydropyrazinones, benzodiazepinones and hydroquinoxalines). Optimization of the reaction conditions towards double carbonylation ( = 30 bar, = 80°C, iodoindole/diamine ratio = 1 : 1.5, toluene as solvent) allowed the target cyclic products, which are formed via intramolecular cyclization of the ketocarboxamide intermediates, to be obtained through a nucleophilic addition/elimination reaction with the pendant terminal amine groups. The structure of the diamine nucleophile was revealed to affect the reaction's selectivity, with the best yields for the cyclic products being obtained in the presence of (1,)-(+)-cyclohexane-1,2-diamine () as the nucleophile, using either 5- or 7-iodoindole as the substrate. The reaction's selectivity was rationalized based on electronic structure calculations, which explain the effect of the diamine structure on the predominant formation of the cyclic products.
一种前所未有的钯催化顺序氨基羰基化/环化合成策略，使用一氧化碳和结构不同的脂肪族二胺作为亲核试剂，可在一锅反应中得到一个新的基于吲哚的杂环衍生物家族（氢吡嗪酮、苯并二氮杂䓬酮和氢喹喔啉）。针对双羰基化反应条件进行优化（(p = 30) bar，(T = 80^{\circ}C)，碘代吲哚/二胺比例 = (1 : 1.5)，以甲苯为溶剂），使得通过酮羧酰胺中间体的分子内环化形成的目标环状产物，能够通过与侧链末端胺基的亲核加成/消除反应得到。结果表明，二胺亲核试剂的结构会影响反应的选择性，以（(1,2)）-（+）-环己烷-1,2-二胺（(DACH)）作为亲核试剂，使用(5 -)碘代吲哚或(7 -)碘代吲哚作为底物时，环状产物的产率最高。基于电子结构计算对反应的选择性进行了合理化解释，该计算解释了二胺结构对环状产物主要形成的影响。
