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Please login or sign up for a free trial to access the full content. Intermolecular [2+2+2] Cyclization of Diynes and Nitriles: Synthesis of Pyridines

DOI: 10.1055/sos-SD-001-00322

Malacria, M.; Aubert, C.; Renaud, J.-L.Science of Synthesis, (20011448.

Several groups independently discovered that cobalt complexes could cocyclize alkynes with nitriles to furnish pyridines 21 (Scheme 11). Wakatsuki and Yamazaki first reported a stoichiometric[‌44‌] and then a catalytic synthesis of pyridines using cobaltacyclopentadienes to promote the reactions.[‌45‌] These reactions took place under relatively mild conditions, even at room temperature. Further developments by Bönnemann established the scope and limitations of the totally intermolecular cycloaddition process.[‌5‌] Later, a more comprehensive and authoritative study of this reaction with full details of the correlations between catalyst and structure/reactivity was published.[‌46‌,‌47‌] It was demonstrated that there were practical improvements in convenience and overall yield through the use of more labile [CoCpL2] sources, while chemoselectivity was maximized by maintaining an excess of nitrile and adding the alkyne in portions. In this way, excellent yields of 2-alkyl- and 2-arylpyridines are synthesized from acetylenes and nitriles, using either cycloocta-1,5-diene(η5-cyclopentadienyl)cobalt(I) (2) as catalyst or cobaltocene[‌48‌] or other more exotic sources of cobalt(I). Yields of pyridines 90% were obtained using this methodology; the reaction required only 23hours at 120130°C and exhibited catalytic turnover numbers of several hundred. Pyridine itself is also accessible from acetylene and hydrogen cyanide.[‌49‌] Applications of this methodology in the synthesis of pyridines containing chiral substituents at C2 have been developed as well.[‌50‌,‌51‌]

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