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5-Ethyl-2-methylpyridine borane (PEMB): A New Reagent for Reductive Aminations

By: Troy Ryba, Chemfiles Volume 10 Article 4

Figure 1: Structure of the new reductive amination reagent,PEMB (725080).

The reaction of a primary amine with an aldehyde or ketone in the presence of an appropriate hydride source provides quick access to an array of secondary amines. Critical to the success of this transformation is the nature of the reducing agent. Highly reactive hydrides will be intolerant not only with the weak Brönsted acid catalysts commonly employed but also with water generated upon iminium ion formation.

Scheme 1: Representative transformation conditions for reduction amination with PEMB.

5-Ethyl-2-methylpyridine (PEMB) exhibits enhanced shelf stability relative to other amine-boranes for reductive aminations (Scheme 1). Studies have shown solvolysis is slow (less than 7% daily) in water/THF or methanol solutions.

Reductive aminations with PEMB can be run in methanol. However, solvent can be eliminated completely and the reactions can be run neat, often with better yield than when run in solution (Scheme 2). Unlike some other hydride reducing agents, two of the three borane hydrides are utilized and usually an excess of reagent is not required. 

Scheme 2: Selected reductive amination examples run in methanol and neat.

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Materials

     

References

  1. Burkhardt, E. R.; Coleridge, B. M. Tetrahedron Lett. 2008, 49, 5152–5155.

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