Shi Epoxidation Diketal Catalyst

Aldrich ChemFiles 2006, 6.10, 11.

Aldrich ChemFiles 2006, 6.10, 11.

Catalytic asymmetric epoxidation of alkenes has been the focus of many research efforts over the past two decades, the best known methods probably being those developed by Sharpless1 and Jacobsen-Katsuki.2 Shi has also developed a very efficient method for asymmetric epoxidation, using ketone-derived organocatalyst 2 based on d-fructose (Figure 7).3 This organocatalyst is able to epoxidize trans alkenes and certain cis alkenes with good to excellent yields and selectivities. More recently, Shi has achieved excellent results using hydrogen peroxide as an oxidant instead of Oxone, which allows a significant reduction in the amount of additional salts introduced and solvent used in the reaction (Scheme 19).4

Figure 7

Scheme 19

Other groups have found use of Shi’s methodology in pursuit of various unique moieties. For example, McDonald and coworkers recently reported a robust and selective synthesis of 2-amino-3,5-diols that employs the Shi epoxidation in a key step (Scheme 20).5 These 2-amino-3,5-diols are 1-deoxy- 5-hydroxysphingosine analogues, which show promise as anticancer agents.

Scheme 20

The Shi epoxidation has also appeared in various total syntheses. In one example, Morimoto and coworkers have used Shi’s methodology to achieve the cis conformation of the D ring in the total synthesis of (+)-aurilol (Scheme 21).6 (+)-Aurilol has been shown to exhibit significant cytotoxicity against HeLa S3 cells.7

Scheme 21

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  1. Johnson, R. A.; Sharpless, K. B. In Catalytic Asymmetric Synthesis, 2nd Ed. Ojima, I., Ed.; Wiley-VCH: New York, 2000; Chapter 6A.
  2. Jacobsen, E. N. In Catalytic Asymmetric Synthesis, 1st Ed. Ojima, I., Ed.; VCH: New York, 1993; Chapter 4.2.
  3. (a) Shi, Y. Acc. Chem. Res. 2004, 37, 488.
    (b) Frohn, M.; Shi, Y. Synthesis 2000, 1979.
    (c) Wang, Z.-X. et al. J. Am. Chem. Soc. 1997, 119, 11224.
    (d) Tu, Y. et al. J. Am. Chem. Soc. 1996, 118, 9806.
  4. Shu, L.; Shi, Y. Tetrahedron 2001, 57, 5213.
  5. Wiseman, J. M. et al. Org. Lett. 2005, 7, 3155.
  6. Morimoto, Y. et al. J. Am. Chem. Soc. 2005, 127, 5806.
  7. Suenaga, K. et al. J. Nat. Prod. 1998, 61, 515.

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