在三氟乙酸中，酰氧基硼氢化物促进缺电子苯胺与醛的简便还原胺化反应：应用于二氮杂吲哚啉的放大合成。

Facile reductive amination of aldehydes with electron-deficient anilines by acyloxyborohydrides in TFA: application to a diazaindoline scale-up.

作者信息

Boros Eric E, Thompson James B, Katamreddy Subba R, Carpenter Andrew J

机构信息

GlaxoSmithKline Research & Development, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA.

出版信息

J Org Chem. 2009 May 1;74(9):3587-90. doi: 10.1021/jo900157z.

DOI:10.1021/jo900157z

PMID:19351107

Abstract

A scale-up of diazaindoline 1 was achieved in four stages and 32% overall yield. The key step involved rapid reductive amination of aldehyde 8 with aniline 5 by sodium triacetoxyborohydride (STAB-H) and TFA followed by ring closure of intermediate amine 9 to compound 1 in the same pot. These reaction conditions were also applied to facile reductive aminations with anilines known to have little reactivity under STAB-H/AcOH conditions. Spectral data supported the tris(trifluoroacetoxy)borohydride anion (16) as the active reducing agent.

摘要

通过四个步骤实现了二氮杂吲哚1的放大合成，总产率为32%。关键步骤包括用三乙酰氧基硼氢化钠（STAB-H）和三氟乙酸使醛8与苯胺5快速进行还原胺化反应，随后在同一反应釜中将中间体胺9闭环生成化合物1。这些反应条件也适用于与在STAB-H/乙酸条件下反应活性较低的苯胺进行的简便还原胺化反应。光谱数据支持三（三氟乙酰氧基）硼氢阴离子（16）作为活性还原剂。