Fürstner indole synthesis

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The Fürstner indole synthesis is a name reaction in organic chemistry . It was first described in 1991 by the chemist Alois Fürstner (born July 23, 1962 ), who received his doctorate in Austria, as a reductive cyclization of oxoesters and oxoamides. The Fürstner indole synthesis thereby provides a further development of the McMurry reaction is, in which a coupling is carried out by aldehydes or ketones with addition of a Titanreagenzes.

Overview reaction

The reaction is exemplified at this point using N - ( o -acetylphenyl) acetamide. Alternatively, the terminal methyl groups on the carbonyl groups can be replaced by organic radicals. The compound is converted to 2,3-dimethylindole with the addition of titanium on graphite (as a reagent):

Overview reaction of the Fürstner indole synthesis


The reagent is produced in situ via the reaction of titanium (III) chloride and potassium graphite (as a strong reducing agent ) with the formation of potassium chloride:

Formation of the catalyst in the Fürstner indole synthesis


The reaction can be carried out, for example, in solvents such as THF , DMF or ethyl acetate . The literature also talks about adapting the reaction through the use of zinc dust, titanium chloride in a catalytic amount and chlorosilanes. This enables the titanium chloride to be recovered.

Reaction mechanism

The titanium-graphite reagent first attaches itself to the carbonyl group of the N - ( o -acetylphenyl) acetamide ( 1 ). In a further step, the ring is closed by attack of the amide group on one of the titanium atoms. Finally, the indole ( 2 ) is formed with elimination of titanium oxide and the graphite residue, provided that the work is carried out without the addition of zinc dust and chlorosilanes.

Reaction mechanism of the Fürstner indole synthesis


See also

Atomic economy

Apart from the reaction variant with chlorosilanes, there are residues of graphite and metal waste in the form of titanium oxide, which means that atomic efficiency is not very good . Even the catalytically effective variation of the reaction requires the addition of chlorosilanes, which are obtained as by-products in the course of the reaction (with elimination of chlorine and absorption of oxygen).

Individual evidence

  1. ↑ a b c d e f g h i Daniel Zerong Wang: Comprehensive Organic Name Reactions and Reagents . tape 1 . John Wiley & Sons, Inc., John Wiley & Sons, Inc., Hoboken, New Jersey 2009, ISBN 978-0-471-70450-8 , pp. 1170-1175 , doi : 10.1002 / 9780470638859.conrr197 .
  2. ↑ a b c d e f g Alois Fürstner, Achim Hupperts: Carbonyl Coupling Reactions Catalytic in Titanium and the Use of Commercial Titanium Powder for Organic Synthesis. In: Journal of the American Chemical Society. Volume 117, No. 16, 1995, pp. 4468-4475, DOI: 10.1021 / ja00121a004 .
  3. ^ Author profile: Alois Fürstner. In: Angewandte Chemie International Edition. Volume 50, No. 13, 2011, pp. 2880–2882, DOI: 10.1002 / anie.201007191 .
  4. ↑ a b Alois Fürstner, Denis N. Jumbam, Hans Weidmann: Titanium-induced syntheses of furans and indoles. In: Tetrahedron Letters. Volume 32, No. 46, 1991, pp. 6695-6696, DOI: 10.1016 / S0040-4039 (00) 93577-9 .