Modular Synthesis of Indoles from Imines and o-Dihaloarenes or o-Chlorosulfonates by a Pd-Catalyzed Cascade Process
Modular Synthesis of Indoles from Imines and o-Dihaloarenes or o-Chlorosulfonates by a Pd-Catalyzed Cascade Process
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DOI：
10.1021/ja808652a
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发表时间：
2009-03-25
影响因子：
15
通讯作者：
Valdes, Carlos
中科院分区：
文献类型：
--
作者：
Barluenga, Jose;Jimenez-Aquino, Agustin;Valdes, Carlos
本文详细研究了钯催化下由1，2-二卤代芳烃、邻卤代苯磺酸盐和亚胺合成吲哚的新方法。级联反应包括亚胺α-芳基化，随后是由相同Pd催化剂促进的分子内C-N键形成反应。反应。与1，2-二溴苯的反应显示出宽的范围，并且允许在吲哚的五元环的不同位置引入芳基、烷基和乙烯基取代基。利用I、Br和Cl在氧化加成反应中的不同反应活性，采用具有两种不同卤素的邻二卤代苯衍生物，可以进行六元环取代吲哚的区域选择性合成。本文还介绍了一种有效的N-叔丁基裂解的方法，从而允许通过相同的方法制备N-H吲哚。最后，研究了它与邻卤代磺酸盐的反应。最好的底物是邻氯萘磺酸酯，其导致吲哚的产率非常高。该反应特别适用于合成具有挑战性的6-取代吲哚。鉴于邻氯苯酚是氯萘磺酸酯的直接前体，因此该反应有效地进入六元环取代的吲哚。该概念通过从天然存在的茴香脑制备4，6-二取代吲哚来说明。
A detailed study of the scope of a new Pd-catalyzed synthesis of indoles from 1,2-dihaloarenes and o-halobenzene sulfonates and imines is described. The cascade reaction comprises an imine alpha-arylation followed by an intramolecular C-N bond-forming reaction promoted by the same Pd catalyst. The reaction. with 1,2-dibromobenzene shows wide scope and allows the introduction of aryl, alkyl, and vinyl substituents at different positions of the five-membered ring of the indole. The regioselective synthesis of indoles substituted in the six-membered ring can be carried out by employing o-dihalobenzene derivatives with two different halogens, taking advantage of the different reactivities of I, Br, and Cl in oxidative addition reactions. This paper also introduces a method for the efficient cleavage of the N-t-butyl group, thus allowing for the preparation of N-H indoles through the same methodology. Finally, the reaction with o-halosulfonates has been studied. The best substrates are o-chlorononaflates, which lead to indoles in very high yield. The reaction is particularly appropriate for the synthesis of the challenging 6-substituted indoles. In view of the availability of o-chlorophenols, which are direct precursors of the chlorononaflates, this reaction represents an efficient entry into indoles substituted in the six-membered ring. The concept is illustrated by the preparation of a 4,6-disubstituted indole from naturally occurring anethole.