Synthesis of Mucononitriles by a pH-Dependent Periodate Oxidative Cleavage and Their Unconventional Cyclization to...

Arene "cracking" and subsequent cyclization steps are a unique approach to pyridine synthesis. Herein, we report a practical method for the synthesis of mucononitriles by oxidative cleavage of ortho-phenylenediamines and demonstrate that dilute basic conditions attenuate the undesired dimerization reactivity of ortho-quinonediimine intermediates. We show 35 examples of mucononitriles in moderate to high yield (27-90% isolated yields) and demonstrate that acidic (pH < 6) and concentrated conditions, like those previously reported in the literature, are unfavorable for mucononitrile formation and instead favor azobenzene, para-quinonediimine, and phenazine side products. Additionally, we discovered an unusual mechanism for the cyclization of these substrates to afford pyridines. When 2,5-disubstituted mucononitriles were reduced using stoichiometric B(C6F5)3 and (n-Hex)3SiH, 3,5-substituted pyridine products were obtained (17 examples). This observation is best rationalized mechanistically by a boron-mediated formal intramolecular [π4a + π2a] cycloaddition reaction to form an unexpected 6-cyano-2-azabicyclo[3.1.0]hexene intermediate and subsequent boron-facilitated fragmentation to form products.