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(2-Trimethylsilyl)-ethanesulfonyl Reagents

Aldrich ChemFiles 2007, 7.3, 5.

Aldrich ChemFiles 2007, 7.3, 5.

In 1986, Weinreb first reported the (2-trimethylsilyl)ethanesulfonyl (SES) group (Figure 1) as an alternative to a tosyl sulfonamide for mild sulfonyl protection of amines.1 The SES-protected amines are stable compounds that can be readily cleaved by fluoride sources to regenerate the parent free amine and other volatile products, whereas the tosyl sulfonamide often proves difficult to deprotect.2

Figure 1


SES-Cl can be used to protect amino acids, and can be carried through syntheses as easily as Boc-, Fmoc-, or Z-protected amino acids. Boger and co-workers have recently employed SES-Cl to protect the amino side chain on d- or l-ornithine prior to protection of the carboxylic acid function (Scheme 1). Boger used these protected ornithines in their syntheses of Ramoplanin analogues3 and the cyclic peptide of Chlorofusin.4

Scheme 1


Ohno and Tanaka also used the SES protecting group in the palladium(0)-catalyzed synthesis of 1,4-oxazepines. The facile deprotection of the SES group compared to the tosyl group allowed for the creation of the heterocycle product bearing a free amino group (Scheme 2).5

Scheme 2


In certain reactions, 2-(trimethylsilyl)ethanesulfonamide (SES-NH2), can be used to directly introduce a protected nitrogen-functionality into a substrate. One example is in the work of Bolm and Mancheño, who reported the use of SES-NH2 in the iron-catalyzed imination of sulfoxides to yield sulfoximines (Scheme 3).6

Scheme 3


Lamaty and co-workers have employed SES-NH2 in an aza- Baylis–Hillman reaction to prepare a series of SES-protected baminoesters. These b-aminoesters were then further elaborated to provide a series of 2,3-disubstituted pyrroles through a ringclosing metathesis protocol (Scheme 4).7

Scheme 4


SES-NH2 has also be used in the selective synthesis of various triazamacrocycles.8,9The macrocycles are constructed using a modular approach, which allows the researcher considerable control in the carbon bridge architecture of the macrocycle (Scheme 5).

Scheme 5


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References

  1. Weinreb, S. M.; Ralbovsky, J. L. “b-Trimethylsilylethanesulfonyl Chloride,” in Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.; Wiley: Chichester, U.K., 1995, Vol. 7, p. 5255–5256.
  2. Ribière, P. et al. Chem. Rev. 2006, 106, 2249.
  3. (a) Rew, Y. et al. J. Am. Chem. Soc. 2004, 126, 1041. (b) Jiang, W. et al. J. Am. Chem. Soc. 2003, 125, 1877. (c) Jiang, W. et al. J. Am. Chem. Soc. 2002, 124, 5288.
  4. Desai, P. et al. Org. Lett. 2003, 5, 5047.
  5. Ohno, H. et al. J. Am. Chem. Soc. 2004, 126, 8744.
  6. Mancheño, O. G.; Bolm, C. Org. Lett. 2006, 8, 2349.
  7. Declerck, V. et al. J. Org. Chem. 2004, 69, 8372.
  8. Masllorens, J. et al. Tetrahedron 2005, 61, 10105.
  9. Parker, L. L. et al. Tetrahedron 2003, 59, 10165.

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