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HKR Epoxides

Aldrich ChemFiles 2005, 5.4, 17.

Aldrich ChemFiles 2005, 5.4, 17.

One of the most effective and recent methods for obtaining several classes of chiral building blocks is Jacobsen’s hydrolytic kinetic resolution technique (HKR). The method provides general access to many chiral epoxides and 1,2-diols that are otherwise difficult to obtain, in high conversions and enantiopurities, from inexpensive racemic starting materials. Sigma-Aldrich is the exclusive distributor of chiral compounds manufactured by Rhodia Pharma Solutions, under license, using Jacobsen HKR technology.

Styrene oxide

Starting from (R)-(+)-styrene oxide, Bassingdale and co-workers were able to synthesize a family of chiral ligands which were subsequently employed in a Mg-mediated enantioselective deprotonation process showing high general selectivity (Scheme 32).1


Scheme 32

Kang and Chang used (R)-styrene oxide as a starting material, while also employing HKR techniques to produce a homologated epoxide as part of their synthetic approach to (+)-allosedamine (Scheme 33).2


Scheme 33

Epichlorohydrin

(S)-Epichlorohydrin was recently employed by Moriarty and co-workers as a building block for the synthesis of a key intermediate in the synthesis of stable PGI2 analogue UT-15, an effective candidate for the treatment of pulmonary hypertension (Scheme 34).3


Scheme 34

The (R)-enantiomer was used by Munkata and co-workers to make a few key (E)-iodoalkene intermediates used in the total syntheses of Macquarimicins (Scheme 35), which have demonstrated cytotoxicity against the P388 leukemia cell line and anti-inflammatory activity.4


Scheme 35

Burova and McDonald have also recently used (R)-epichlorohydrin to synthesize the C10–C16 module in their total synthesis of the macrolide RK-397 (Scheme 36).5


Scheme 36

Glycidyl tosylate

Both glycidyl tosylate isomers were used in the first enantioselective syntheses of (R)- and (S)-4-acetyl-3-(hydroxymethyl)-3,4-dihydro-2H-pyrido[3,2-b]oxazines (Scheme 37).6


Scheme 37

Ghosh and Liu employed (2S)-glycidyl tosylate in the synthesis of a vinyl ether fragment in their enantioselective total synthesis of (+)-amphidinolide T1 (Scheme 38).7


Scheme 38

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Materials

     

References

  1. Bassingdale, M. J. et al. Tetrahedron Lett. 2004, 45, 4175.
  2. Kang, B.; Chang, S. Tetrahedron 2004, 60, 7353.
  3. Moriarty, R. M. et al. J. Org. Chem. 2004, 69, 1890.
  4. (a) Munakata, R. et al., J. Am. Chem. Soc. 2004, 126, 11254; (b) Munakata, R. et al. J. Am. Chem. Soc. 2003, 125, 14722.
  5. Burova, S. A.; McDonald, F. E. J. Am. Chem. Soc. 2004, 126, 2495.
  6. Henry, N. et al. Tetrahedron Lett. 2004, 45, 1465.
  7. Ghosh, A. K.; Liu, C. J. Am. Chem. Soc. 2003, 125, 2374.

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