A Convenient 1,3-Dipolar Cycloaddition Approach to Pyridylpyrroles

Significance

Extending their previous work on nitrovinylindoles (J. M. Lopchuk, G. W. Gribble Heterocycles 2011, 82, 1617), the Gribble group reports the synthesis of 1,2,4,5-substituted pyrroles (4, 7 and 8) bearing pyridine functionality via a 1,3-dipolar cycloaddition approach. When nitrovinylpyridines 1, readily accessible via the Henry reaction of the corresponding aldehyde, were exposed to münchnones 2 and 5 in refluxing THF, the corresponding pyridylpyrroles (4, 7 and 8) were isolated in high yields. Particularly well suited to this approach are the symmetrical münchnones 2. Surprisingly, however, unsymmetrical münchnones 5a and 5b demonstrated impressive regioselectivity in the 1,3-cycloaddition process. The location of the pyridine nitrogen also proved important with the 2-substituted pyridines offering the highest levels of regioselectivity.