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Stabilised 2,3‐Pyridyne Reactive Intermediates of Exceptional Dienophilicity
Author(s) -
Con Stephen J.,
Hegarty Anthony F.
Publication year - 2004
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400232
Subject(s) - chemistry , regioselectivity , substituent , medicinal chemistry , cycloaddition , alkoxy group , furan , reactive intermediate , lithium (medication) , chloride , organic chemistry , catalysis , medicine , alkyl , endocrinology
The enhanced dienophilicity of 4‐methoxy, 4‐aryloxy and 4‐thiophenoxy analogues 6−9 of 2,3‐pyridyne ( 2 ) relative to 2 itself is reported. The regioselective lithiation of 4‐alkoxy‐ ( 22 , 23 and 25 ) and 4‐thiophenoxy‐2‐chloropyridine ( 24 ) at low temperatures, followed by elimination of lithium chloride affords 4‐alkoxy‐ and 4‐thiophenoxypyridynes, which can be trapped in situ in a [4+2] cycloaddition reaction with furan to give endoxides 28−31 in moderate to good yields (25−58%). In contrast, precursors with a hydrogen ( 18 ) or methyl ( 12 ) substituent at C‐4 give no evidence for pyridyne formation under these conditions. Attempts to generate 6‐isopropoxy‐2,3‐pyridyne ( 10 ) from the low‐temperature lithiation of 2‐chloro‐6‐isopropoxypyridine were unsuccessful due to the instability of the 2‐chloro‐6‐isopropoxy‐5‐lithiopyridine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)