Stabilised 2,3‐Pyridyne Reactive Intermediates of Exceptional Dienophilicity

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)