Synthesis 2009(9): 1485-1493  
DOI: 10.1055/s-0028-1087991
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Base-Catalysed One-Pot Three-Component Coupling Reaction Leading to Nitrosubstituted Pyrroles

Ian R. Baxendale, Christopher D. Buckle, Steven V. Ley*, Lucia Tamborini
Innovative Technology Centre for Advanced Chemical Synthesis, Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, CB2 1EW, UK
Fax: +44(1223)336442; e-Mail: [email protected];
Further Information

Publication History

Received 22 December 2008
Publication Date:
06 March 2009 (online)

Abstract

Tosyl isocyanide and ethyl chloroformate react with nitrostyrenes to afford nitro-substituted pyrroles in good yield when a catch-and-release protocol was employed as a purification strategy.

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9

PS-BEMP refers to 2-tert-butylimino-2-diethylamino-1,3-dimethylperhydro-1,3,2-diazaphosphorine on polystyrene 2% DVB, loading 2.2 mmol/g. Commercially available from Aldrich Cat No. 20026-XXG where XX is the quantity in grams.

10

PS-TBD refers to 1,5,7-triazabicyclo[4.4.0]dec-5-ene-polystyrene cross-linked with 2% DVB, loading 1.33 mmol/g. Commercially available from Biotage Cat. No. 800422.

11

Available from Varian Inc. named as Bond Elut silica packed cartridges.

13

Experiments to try and exclude the possibility of excess ethyl chloroformate being responsible for the secondary products following addition to the nitrostyrene were conducted using sub-stoichiometric quantities to quench the original TosMIC anion. These reactions gave comparable crude mixtures accompanied by the components from the standard Barton-Zard condensation. The possibility that the TosMIC could still act as a leaving group and consequently as an ethyl formate transfer agent can still not be excluded.

14

The reaction between the lithio enolate 4 and ethyl acrylate gave only a mixture of products from which only 7% of a rearrangement product (ethyl 5-tosylpyrrole-1H-3-carboxylate) could be isolated. ¹H NMR and X-ray analysis was used to confirm the structure.