Synthesis 2016; 48(09): 1301-1317
DOI: 10.1055/s-0035-1561384
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© Georg Thieme Verlag Stuttgart · New York

A General and Direct Reductive Amination of Aldehydes and Ketones with Electron-Deficient Anilines

Jakob Pletz
Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Email: breinbauer@tugraz.at
,
Bernhard Berg
Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Email: breinbauer@tugraz.at
,
Rolf Breinbauer*
Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, 8010 Graz, Austria   Email: breinbauer@tugraz.at
› Author Affiliations
Further Information

Publication History

Received: 01 December 2015

Accepted after revision: 20 January 2016

Publication Date:
01 March 2016 (online)


In memoriam Philipp Köck

Abstract

In our ongoing efforts in preparing tool compounds for investigating and controlling the biosynthesis of phenazines, we recognized the limitations of existing protocols for C–N bond formation of electron-deficient anilines when using reductive amination. After extensive optimization, we have established three robust and scalable protocols for the reductive amination of ketones with electron-deficient anilines, by using either BH3·THF/AcOH/CH2Cl2 (method A), with reaction times of several hours, or the more powerful combinations BH3·THF/TMSCl/DMF (method B) and NaBH4/TMSCl/DMF (method C), which give full conversions for most substrates within 10 to 25 minutes. The scope and limitations of these reactions have been defined for 12 anilines and 14 ketones.

Supporting Information

 
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