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Leighton’s Chiral Allylation Reagents

By: Daniel Weibel, Chemfiles Volume 10 Article 3

Daniel Weibel, Ph.D. European Market Segment Manager, Chemistry

Daniel Weibel, Ph.D. European Market 
Segment Manager, Chemistry 

daniel.weibel@sial.com

The asymmetric allylation of carbonyl compounds remains one of the most important and fundamental addition reactions for the synthesis of optically active chiral building blocks homoallylic alcohols.

In 2002, Leighton and co-workers developed strained silacycle compounds as versatile reagents for the practical enantioselective allylation of aldehydes.1

A newly developed chiral auxiliary based on the cyclohexane-1,2- diamine scaffold successfully allylated a broad range of aldehydes highly enantioselectively (Scheme 1).2


Scheme 1. Leighton’s silacycle reagent for the enantioselective allylation of aldehydes

Scheme 1. Leighton’s silacycle reagent for the enantioselective allylation of aldehydes (704725)

The development of practical enantioselective syntheses of chiral amines is of great importance to synthetic organic and medicinal chemists. In 2003, Leighton and co-workers successfully used a pseudoephedrine-derived, five-membered-ring strained silacycle reagent for the enantioselective allylation of acylhydrazones (Scheme 2).3


Scheme 2. Practical, enantioselective allylation of acylhydrazones using strained silacycles

Scheme 2. Practical, enantioselective allylation of acylhydrazones using strained silacycles (706671)

The reaction scope of these silacycles was extended to a practical method for the enantioselective synthesis of tertiary carbinamines based on the addition of this chiral allylsilane reagent to a structurally diverse array of ketone-derived benzoylhydrazones (Scheme 3).4 While many methods for the synthesis of quaternary α-amino acids have been published, far fewer reports have dealt with the synthesis of tertiary carbinamines.


Scheme 3. Practical synthesis of tertiary carbinamines by enantioselective allylation of ketone-derived benzoylhydrazones

Scheme 3. Practical synthesis of tertiary carbinamines by enantioselective allylation of ketone-derived benzoylhydrazones (706671)

The free amines are easily accessed in good yields by subjecting the different hydrazones to reduction with SmI2 (409340).

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Materials

     

References

  1. Leighton, J. L. Aldrichimica Acta 2010, 43, 3.
  2. Kinnaird, J. W. A.; Ng, P. Y.; Kubota, K.; Wang, X.; Leighton, J. L. J. Am. Chem. Soc. 2002, 124, 7920.
  3. Kubota, K.; Leighton, J. L. Angew. Chem., Int. Ed. 2003, 42, 946.
  4. Berger, R.; Rabbat, P. M. A.; Leighton, J. L. J. Am. Chem. Soc. 2003, 125, 9596.
  5. Berger, R.; Duff, K.; Leighton, J. L., J. Am. Chem. Soc. 2004, 126, 5686.

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