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Synlett 2010(6): 924-930  
DOI: 10.1055/s-0029-1219563
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A New Facile Approach to Isoindole and Pyrrole Derivatives

Nasima Yasmin, Jayanta K. Ray*
a Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, India
e-Mail: jkray@chem.iitkgp.ernet.in;
Further Information

Publication History

Received 13 November 2009
Publication Date:
02 March 2010 (online)

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Abstract

A highly efficient protocol for the synthesis of N-substituted di-/tetrahydroisoindole derivatives and N-substituted pyrroles fused with seven-membered rings has been developed by reaction of amines with 3-(2-formyl-cycloalkenyl) α,β-unsaturated esters or nitriles, which, in turn, were prepared from β-bromovinyl aldehydes by a Pd(0)-catalyzed Heck reaction. Bisisoindoles were also achieved by this room-temperature procedure.

Key words

nitrogen heterocycles - isoindoles - pyrroles - synthetic method - amines

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General Procedure for the Heck Reaction in Water (Procedure A)
β-Bromovinyl aldehyde (1 mmol), Na2CO3 (4 mmol), Bu4NBr (1 mmol), PdCl2 (10 mol%), and H2O (5 mL) were placed in a two-neck round-bottom flask. Methyl acrylate (4 mmol) was added, the mixture stirred for 2 h, diluted with aq NH4Cl solution and extracted with Et2O (3 × 25 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and then concentrated. The product was purified by column chromatography using EtOAc-PE as eluent.

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General Procedure for the Heck Reaction in Acetonitrile (Procedure B) β-Bromovinyl aldehyde (1 mmol), Ph3P (0.25 mmol), Et3N (1.5 mmol), and dry MeCN (5 mL) were placed in a two-neck round-bottom flask fitted with a condenser. The solvent was degassed with N2 and then Pd(OAc)2 (10 mol%) and acrylonitrile (4 mmol) were added. The mixture was heated at 80 ˚C for 1 h, cooled; solvent was evaporated, diluted with H2O and extracted with Et2O (3 × 25 mL). The organic layers were combined, washed with brine, dried over Na2SO4, and then concentrated. The product was purified by column chromatography using EtOAc-PE as eluent.

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General Procedure for the Preparation of Pyrroles
To a solution of 3-(2-formyl cycloalkenyl)acrylic ester (0.5 mmol) or 3-(2-formyl cycloalkenyl)acrylonitrile (0.5 mmol) in CH2Cl2 (3 mL), amine (0.5 mmol) was added and stirred at r.t. for 5-30 min. The solvent was evaporated, and then the product was purified by column chromatography using EtOAc-PE as eluent.