Acid-catalysed cyclization of 1-aryl-2-thienylmethyl- and 1-aryl-2-furfuryl-aminoethanols via spiro intermediates

Abstract
1-(4-Chlorophenyl)-2-(5-chloro-2-thienylmethyl)methylaminoethanol (7) reacts in trifluoroacetic acid to give the spirothiolenone (10) and the two isomeric tetrahydrothieno[2,3-c]- and [3,2-c]-pyridines (8) and (9). Treatment of 1-aryl-2-furfurylaminoethanols (12a–d) with trifluoroacetic acid gives 7-aryl-4,5,6,7-tetrahydrofuro[3,2-c]pyridines (13a–d) as the major products. The corresponding reaction of 1-(3,4-dimethoxyphenyl)-2-furfuryl(methyl)aminoethanol (12e) yields the polycyclic spirodihydrof uran (23). For the formation of the tetrahydrofuro- and tetrahydrothieno-[3,2-c] pyridines a mechanistic pathway is discussed in which a spirocyclic intermediate is involved followed by a rearrangement reaction. The isolated spiro compounds support this mechanism.

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