Chiral Amines

Aldrich ChemFiles 2005, 5.4, 13.

Chiral amines have found widespread application in asymmetric synthesis serving, for instance, as chiral bases in enantioselective deprotonation reactions1 or being valuable substances for resolving racemic mixtures of acids. Additionally, chiral amines are prevalent, essential parts of many drugs and drug candidates.

α-Ethylbenzylamine

Alexakis has recently reported on a practical solvent-free reductive amination reaction. In a one-pot synthesis, C2-symmetrical secondary amines could be obtained in high diastereoselectivities starting from (R)-α-ethylbenzylamine or (S)-α-ethylbenzylamine, respectively (Scheme 27).


Scheme 27

These secondary amines also serve as valuable chiral building blocks for the synthesis of atropisomeric phosphoramidites used in highly enantioselective copper-catalyzed conjugate additions2 or in iridium-catalyzed allylic substitutions.3

2-Amino-3-methylbutane

Diazoxide BPDZ-44 was found to be a tissue selective ATP-sensitive potassium channel opener, resulting in inhibition of important physiological processes such as insulin release or muscle tone and contractility. The straightforward synthesis of BPDZ-44 used (S)-2-amino-3-methylbutane as a chiral building block in a key step (Scheme 28).4


Scheme 28

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Materials

     

References

  1. (a) Cox, P. J.; Simpkins, N. S. Tetrahedron: Asymmetry 1991, 1, 1; (b) O’Brien, P. Tetrahedron 2002, 58, Symposium-in-print, Recent Developments in Chiral Lithium Amide Base Chemistry, 4567
  2. (a) Alexakis, A. et al. J. Org. Chem. 2004 69, 5660; (b) Alexakis, A.; Benhaim, C. Eur. J. Org. Chem. 2002, 3221.
  3. Alexakis, A.; Polet, D. Org. Lett. 2004, 6, 3529.
  4. Khelili, S. et al. Bioorg. Med. Chem. 1999, 7, 1513.

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