Curtius rearrangement

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The Curtius rearrangement (or Curtius reaction or Curtius degradation), as first defined by Theodor Curtius, is a chemical reaction that involves the rearrangement of an acyl azide to an isocyanate.[1][2] Several reviews have been published.[3][4]

The isocyanate can be trapped by a variety of nucleophiles. Often water is added to hydrolyze the isocyanate to an amine.[5] When done in the presence of tert-butanol, the reaction generates Boc-protected amines, useful intermediates in organic synthesis.[6][7]

Carboxylic acids 1 can be easily converted to acyl azides 3 using diphenylphosphoryl azide 2.[8][9][10][11]

Likewise, when the Curtius reaction is performed in the presence of benzyl alcohol, Cbz-protected amines are formed.[12]

Reaction mechanism

The first step of the Curtius rearrangement is the loss of nitrogen gas forming an acyl nitrene (2). Once formed, acyl nitrenes very quickly rearrange by migration of R-group forming the desired isocyanate (3).

Scope

In one variation called the Darapasky Degradation (A. Darapsky, 1936) a Curtius rearrangement takes place as one of the steps from an α-cyanoester to an amino acid [13].

References

  1. ^ Curtius, T. Ber. 1890, 23, 3023.
  2. ^ Curtius, T. J. Prakt. Chem. 1894, 50, 275.
  3. ^ Smith, P. A. S. Org. React. 1946, 3, 337-449. (Review)
  4. ^ Scriven, E. F.; Turnbull, K.; Chem. Rev. 1988, 88, 297-368. (Review)
  5. ^ Kaiser, C.; Weinstock, J. Organic Syntheses, Coll. Vol. 6, p.910 (1988); Vol. 51, p.48 (1971). (Article)
  6. ^ Ende, D. J. a.; DeVries, K. M.; Clifford, P. J.; Brenek, S. J. Org. Proc. Res. Dev. 1998, 2, 382-392.
  7. ^ Lebel, H.; Leogane, O.; Org. Lett. 2005, 7(19), 4107-4110. (doi:10.1021/ol051428b)
  8. ^ Shioiri, T.; Yamada, S. Organic Syntheses, Coll. Vol. 7, p.206 (1990); Vol. 62, p.187 (1984). (Article)
  9. ^ Shioiri, T.; Ninomiya, K.; Yamada, S. J. Am. Chem. Soc. 1972, 94, 6203-6205. (doi:10.1021/ja00772a052)
  10. ^ Ninomiya, K.; Shioiri, T.; Yamada, S. Tetrahedron 1974, 30, 2151-2157.
  11. ^ Wolff, O.; Waldvogel, S. R. Synthesis 2004, 1303-1305.
  12. ^ Jessup, P. J.; Petty, C. B.; Roos, J.; Overman, L. E. Organic Syntheses, Coll. Vol. 6, p.95 (1988); Vol. 59, p.1 (1979). (Article)
  13. ^ http://www.chempensoftware.com/reactions/RXN051.htm

See also

de:Curtius-Reaktion nl:Curtius-omlegging


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