Lavernhe, RemiWang, QianZhu, Jieping2023-05-082023-05-082023-05-082023-04-2110.1002/anie.202303537https://infoscience.epfl.ch/handle/20.500.14299/197346WOS:000973171200001Transition-metal-catalyzed [4+2] heteroannulation of alpha,beta-unsaturated oximes and their derivatives with alkynes has been developed into a powerful strategy for the synthesis of pyridines. It nevertheless lacks regioselectivity when unsymmetrically substituted alkynes are used. We report herein the unprecedented synthesis of polysubstituted pyridines by a formal [5+1] heteroannulation of two readily accessible building blocks. A copper-catalyzed aza-Sonogashira cross-coupling between beta,gamma-unsaturated oxime esters and terminal alkynes affords ynimines, which, without isolation, undergo an acid-catalyzed domino reaction involving ketenimine formation, 6 pi-electrocyclization and aromatization to afford pyridines. Terminal alkynes served as a one-carbon donor to the pyridine core in this transformation. Di- through pentasubstituted pyridines are accessible with complete regioselectivity and excellent functional-group compatibility. The first total synthesis of anibamine B, an indolizinium alkaloid with potent antiplasmodial activity, was accomplished featuring this reaction as a key step.Chemistry, MultidisciplinaryChemistrydomino reactionsheterocyclesindolizinium alkaloidspyridinesyniminesfree 2+2+2 cycloadditioninverse electron-demandhetero-diels-alderalpha,beta-unsaturated ketoximesregioselective synthesisoxidative alkynylationsubstituted pyridinesc,n-dialkynyl iminesnatural-productynamidestext::journal::journal article::research article