Dr. Wolfe

    

Good morning class! Today I'm going to show you exactly how to do a citation for SSG. Here is a picture showing you the jist of it.

  1. Carrër, A.; Florent, J.-C.; Auvrouin, E.; Rousselle, P.; Bertounesque, E. J. Org. Chem. 2011, 76, 2502-2520.

  2. Bradshaw, R. W.; Gibson, M. S.;

  3. Ing, H. R.; Manske, R. H. F. J. Chem. Soc. 1926, 129, 2348–2351.

  4. Yamatsugu, K.; Kamijo, S.; Suto, Y.; Kanai, M.; & Shibasaki, M. Tetrahedron Lett. 2007, 48, 1403-1406.

    Acyl azide formation is formed through substitution of the two leaving chlorines(1-2). This is done by two molecules of TMSN3 and using the base DMAP. Acyl azide formation occurs by the TMSN3 substituting with the chlorine. DMAP was used as a catalyst to provide diacyl azide which then undergoes the key curtius rearrangement(3-4). This step provides a conceptually different third generation short synthesis of Tamiflu. It also allows for rapid (12 step) access to the core structure of Tamiflu. This mechanism of formation allowed for a quicker and more efficient synthesis of Tamiflu. The success of the curtius rearrangement was due to intramolecular trapping of the intermediate isocyanate by the alpha-allyl alcohol (3-4) followed by intermolecular addition of t-BuOH to the other isocyanate(5-6). This isocyanate trap (3-4) was so fast that neither di-tert-butylcarbamate derived from double addition of t-BuOH nor the intramolecular addition of tert-butyl-carbamate to the other isocyanate was detected.

     

     

    

   

Jeremy Tervo:

I found four articles citing your fourth citation! Did I cite them correctly?

  1. He, X.; Cao, C.; Liang, J.; Li, X.; Zhang, T.; Meng, F. Synlett. 2017, 28, 386-390.
    1. Acyl Azides are converted into Isocyanates in this application of the Curtius Rearrangement. The isocyanates react to form amine derivatives that are analogous to those used in the Synthesis of Lysergic Acid.
  2. Chen, S.; Chang, C.; Fang, J. Tetrahedron Lett. 2016, 57, 4293-4296.
    1. This article cites the use of the Diels-Alder chemistry using 1-trimethylsilyoxy-1,3-butadiene to get to the core ring structure of Tamiflu.
  3. Matveenko, M; Willis, A. C.; Banwell, M. G. Tetrahedron Lett.  2008, 49, 7018-7020.
    1. This article cites the use of the Diels-Alder reaction to create the cyclohexane core of the target.
  4. Morita, M.; Sone, T.; Yamatsugu, K.; Sohtome, Y.; Matsunaga, S.; Kanai, M.; Watanabe, Y.; Shibasaki, M. Tetrahedron Lett. 2008, 18, 600-602.
    1. This citation refers to the use of the Curtius rearrangement to create a racemic carbamate.