Regioselective reactions of 3,4-pyridynes enabled by the aryne distortion model.

ABSTRACT: The pyridine heterocycle continues to play a vital role in the development of human medicines. More than 100 currently marketed drugs contain this privileged unit, which remains highly sought after synthetically. We report an efficient means to access di- and trisubstituted pyridines in an efficient and highly controlled manner using transient 3,4-pyridyne intermediates. Previous efforts to employ 3,4-pyridynes for the construction of substituted pyridines were hampered by a lack of regiocontrol or the inability to later manipulate an adjacent directing group. The strategy relies on the use of proximal halide or sulfamate substituents to perturb pyridyne distortion, which in turn governs regioselectivities in nucleophilic addition and cycloaddition reactions. After trapping of the pyridyne

SUBMITTER: Goetz AE 

PROVIDER: S-EPMC3531798 | biostudies-literature | 2013 Jan

REPOSITORIES: biostudies-literature