A New Twist on the Fischer Indole Synthesis

In the traditional Fischer Indole Synthesis an aromatic hydrazine is reacted with a ketone and then cyclized to produce the indole.  This new twist from Paul Knochel’s group is to react organozinc reagents with aromatic diazonium salts at -60ºC in THF.  After warming to room temp, half the solvent is removed and TMSCl is added.  The mixture is then subjected to microwave heating at 125°C for 30 minutes.  After cooling and aqueous work up the indole is isolated in 65-90% yield.  20 examples.

B.A. Haag, Z.-G. Zhang, and P. Knochel, Angew. Chem. Internat. Ed., 2010, 49, 9513-9516.

Another version of the Fischer indole synthesis has also just been published.  In this paper a tosylhydrazone is reacted with a benzyne (generated in situ under mild conditions at room temperature) to give initially the standard hydrazine intermediate which is cyclized by addition of an acid or a Lewis acid (typically boron trifluoride etherate).

12 examples, yields 51-80% (mainly 60-70%).
D. McAusland, S. Seo, D.G. Pintori, J. Finlayson, and M.F. Greaney, Org. Lett., 2011, 13, 3667-3669.