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Synthesis 2002(3): 0331-0338
DOI: 10.1055/s-2002-20025
PAPER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2,5-Disubstituted Pyrroles and Pyrrolidines by Intramolecular Cyclization of 6-Amino-3-keto Sulfones

Simonetta Benettia, Carmela De Risib, Paolo Marchettib, Gian P. Pollini*b, Vinicio Zaniratoc
a Dipartimento di Chimica, Via L. Borsari 46, 44100 Ferrara, Italy
b Dipartimento di Scienze Farmaceutiche, Via Fossato di Mortara 19, 44100 Ferrara, Italy
Fax: +39(532)291296; e-Mail: pol@unife.it;
c Dipartimento Farmaco-Chimico-Tecnologico, Via A. Moro, 53100 Siena, Italy
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Publication History

Received 2 October 2001
Publication Date:
28 July 2004 (online)

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Abstract

Wittig reaction of 4-[(4-methylphenyl)sulfonyl]-1-(triphenylphosphoranylidene)butan-2-one (1) with N-protected α-amino aldehydes furnished N-protected γ-amino-α,β-unsaturated keto sulfones which have been conveniently utilized as precursors of both aromatic and non-aromatic 2,5-disubstituted five-membered heterocyclic compounds. While 2,5-disubstituted pyrroles are efficiently formed by cyclodehydration of the starting materials, 2,5-disubstituted pyrrolidines and pyrrolenines could be obtained by prior reduction of the conjugated double bond followed by acid- or base-mediated cyclization. The ready availability of the materials required for the whole sequence makes this methodology a convenient way to generate both aromatic and saturated 2,5-disubstituted five-membered heterocyclic compounds.

Key words

pyrroles - pyrrolidines - amino aldehydes - cyclodehydration - sulfones

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6

The configurational stability of 11c was tested by chiral HPLC (see Experimental Section).