Regiochemistry in Cobalt-Mediated Intermolecular Pauson-Khand Reactions of Unsymmetrical Internal Heteroaromatic Alkynes with Norbornene

The intermolecular Pauson-Khand (PK) reactions of sterically comparable (2-phenylethynyl)heteroaromatic compounds with norbornene, mediated by Co-2(CO)(8) to give cyclopentenone products, were examined in this study. A synthetic protocol utilizing focused-microwave dielectric heating proved indispensable in the efficient synthesis of the PK cyclopentenone products. pi-Deficient heteroaromatic substrates, e.g., 2-pyrones, and some pi-excessive heteroaromatics such as 2- and 3-thiophene and 2-furan favor the beta-position in the newly formed cyclopentenone ring. Other pi-excessive heteroaromatics such as 2-pyrrole or 2-indole favor the alpha-position. A pi-excessive 3-indole derivative gave a nearly equal mixture of regioisomers. The position of the nitrogen in pyridyl-containing alkyne substrates also affects the regiochemical outcome of the PK reaction. A 2-pyridyl alkyne, possessing a proximal nitrogen, influences the regioselectivity relative to a 4-pyridyl variant quite dramatically, favoring the beta-position in the newly formed cyclopentenone ring. A 2-pyrimidylalkyne exhibits similar behavior to the 2-pyridylalkyne. Compounds that do not participate in PK reactions with norbornene include (2-phenylethynyl)imidazoles and the related benzimidazoles, which promote rapid decomposition of the in situ generated (mu(2)-alkyne)Co-2(CO)(6) complexes. This stands in contrast with other nitrogen-containing heteroaromatics, e.g., pyrrole-, indole-, and pyrimidine-derived compounds which effectively undergo PK reactions. Overall, the type of heteroaromatic group dramatically influences PK regioselectivity, which can in part be explained by rationalization of the current reaction mechanism, but not fully.