Synthesis of indoles: Efficient functionalisation of the 7-position

被引:24
作者
Charrier, Nicolas [1 ]
Demont, Emmanuel [1 ]
Dunsdon, Rachel [1 ]
Maile, Graham [1 ]
Naylor, Alan [1 ]
O'Brien, Alistair [1 ]
Redshaw, Sally [1 ]
Theobald, Pam [1 ]
Vesey, David [1 ]
Walter, Daryl [1 ]
机构
[1] GlaxoSmithKline Inc, Neurol & Gastrointestinal Ctr Excellence Drug Dis, Harlow CM19 5AW, Essex, England
来源
SYNTHESIS-STUTTGART | 2006年 / 20期
关键词
indoles; Heck reaction; palladium; 2-vinylanilines; Larock's cyclisation;
D O I
10.1055/s-2006-950223
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Traditional strategies in indole chemistry do not allow high-yielding access to some substitution patterns such as 3,5,7-trisubstituted indoles. We report in this article the efficient synthesis of this type of indole. The Heck cyclisation strategy we used allows the synthesis of 7-iodo-, 7-alkoxy-, 7-amino-, and 7-nitroindoles bearing other functionalities at the 3- and 5-positions. We believe that the mild conditions used should allow the preparation of indoles with a wide range of substituents in these two positions as shown by the synthesis of a 5-bromo-7-iodoindole. However, this strategy has some limitations in the case of very electron-deficient indoles such as a 7-nitroindole where the aromatisation of the 7-nitrodihydroindole intermediate is not complete. In this case, Larock's indole synthesis from disubstituted acetylenes proved to be more appropriate.
引用
收藏
页码:3467 / 3477
页数:11
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