Mechanistic Study of Indolizine Heterocycle Formation by Ruthenium(II)-Assisted Three-Component Cross-Coupling/Cyclization

In the presence of the acid HBF4, 3-alkenyl-2-phosphonium indolizines 3a–c can be produced respectively by adding PhCCCOCH3 (2a), CH3OCOCCCOOCH3 (2b), and CH3CH2CCCOCH3 (2c) to a mixture of ruthenium complex RuCl2(PPh3)3 and the propargyl alcohol (2-Py)­CH­(OH)­CCH (1). We carefully investigated the mechanism of this reaction by means of structurally characterizing two key intermediates, ruthenium vinyl (4) and ruthenium carbene (5), and by deuterium-labeling experiments. A plausible mechanism is proposed, which involves addition of a proton to an alkyne carbon and the insertion of an alkyne into the Cα bond of an alkenylcarbene group, followed by an α-H elimination and reductive elimination.