Synthesis 2016; 48(17): 2873-2880
DOI: 10.1055/s-0035-1562458
paper
© Georg Thieme Verlag Stuttgart · New York

One-Pot Cascade Synthesis of Fused Nitrogen-Containing Heterocycles in Aqueous Media – Utility of N-Protective Groups in Intramolecular Diels–Alder Reaction of Furan

Aydin Demircan*
a   Department of Chemistry, Nigde University, Kampus, 51240, Nigde, Turkey   Email: ademircan@nigde.edu.tr
,
Muhammet K. Kandemir
a   Department of Chemistry, Nigde University, Kampus, 51240, Nigde, Turkey   Email: ademircan@nigde.edu.tr
,
Medine Colak
a   Department of Chemistry, Nigde University, Kampus, 51240, Nigde, Turkey   Email: ademircan@nigde.edu.tr
,
Muhsin Karaarslan
b   Department of Chemistry, Aksaray University, Kampus, 68000, Aksaray, Turkey
› Author Affiliations
Further Information

Publication History

Received: 18 March 2016

Accepted after revision: 01 June 2016

Publication Date:
22 July 2016 (online)


Abstract

A metal-free, thermal, intramolecular Diels–Alder (IMDA) reaction of furan in aqueous media without the use of microwave irradiation was investigated. Protection of the amine functionality and the cycloaddition reaction were performed as a one-pot, two-component process. Various nitrogen-protecting groups and their electronic and steric effects on the cycloaddition reaction were studied. The protection–intramolecular Diels–Alder reaction sequence proceeds under environmentally benign aqueous conditions, which are tolerated by substrates with a broad range of nitrogen-protecting groups such as benzyloxycarbonyl (Cbz), trityl, tert-butoxycarbonyl (Boc), trifluoroacetyl, tosyl, mesyl, and p-nosyl [(4-nitrophenyl)sulfonyl]. This study allowed the development of a stereoselective, tandem allylamine isomerization–Diels–Alder cycloaddition sequence leading to the rapid assembly of complex nitrogen-containing heterocycles in a simple one-pot process.

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