Study of substrate dependence on the chemoselectivity of the gold-catalysed cycloisomerisation of aryl substituted 1,7-enynes

Abstract

The effects of starting material substitution patterns on reaction selectivity for the gold(I)-catalysed cycloisomerisations of aryl substituted 1,7-enynes were investigated. The results indicated the chemoselectivity of the reaction to be highly substrate and catalyst dependent. Either the piperidine or the tetrahydro-1H-azepine product was obtained in moderate to excellent yields depending on the steric and/or electronic nature of the substrate and the gold(I) catalyst. Overall, six-membered nitrogen ring formation was found to be favoured in reactions with 1,7-enyne derivatives containing a disubstituted alkene moiety or not bearing a sterically bulky substituent or a gold(I) catalyst with a pendant sterically unencumbered phosphine ligand. Formation of the seven-membered nitrogen heterocycle was observed in reactions where the substrate contained a tetrasubstituted alkene unit or a sterically demanding substituent.

Gold(I)-Catalyzed Activation of Alkynes for the Construction of Molecular Complexity

“…172 Related enynes bearing aryl substituents at the alkene give mixtures of products of single-cleavage along with seven-membered ring compounds by an endo -type single-cleavage rearrangement. 186 …”

“…Gold­(I) complexes are in general the best catalysts for the cycloisomerization of these substrates, leading to 1,3-dienes 179 through a single-cleavage process (Scheme ) . Related enynes bearing aryl substituents at the alkene give mixtures of products of single-cleavage along with seven-membered ring compounds by an endo -type single-cleavage rearrangement …”

“…172 Related enynes bearing aryl substituents at the alkene give mixtures of products of single-cleavage along with seven-membered ring compounds by an endo-type single-cleavage rearrangement. 186 Gold(I) complexes also catalyze Conia-ene reactions, which can be considered as cyclizations of 1,6-enynes via the corresponding enol tautomers (Scheme 55). 187 Thus, cyclopentane derivatives 180 were obtained in excellent yields and good diastereoselectivities.…”

Recent Advances in the Cascade Cyclization Reactions of 1,7‐Enynes

“…[51] This gold-catalyzed reaction, which possessed excellent functional group tolerance, provided atom-economical and In the same year, the Chan group developed a goldcatalyzed cycloisomerisation of aryl substituted 1,7enynes, thereby delivering a sequence of piperidine or tetrahydro-1H-azepine products in moderate-to-good yields (Scheme 36). [52] It turned out that the chemoselectivity of the reaction was dependent on the substrates and catalysts. This protocol, which exhibited excellent functional group tolerance, achieved a concise approach to a class of the six-and sevenmembered nitrogen heterocycles using space-compact gold(I) complex as the catalyst.…”

Gold-Catalyzed Synthesis of Small Rings

“…Gold-catalyzed cycloisomerizations of 1,7- and higher enynes very rarely lead to cyclopropane-containing products, because the initially formed cyclopropyl gold carbene rearranges. Treatment of 1,7-enynes with Au­(I) catalysts can afford linear or cyclic 1,3-dienes, , 1,4-dienes, or hydroacenes, depending on enyne tether and substitution at the termini. Kumar and Waldmann observed the formation of cyclopropyl-fused compounds 207 in very low yields during the 8- endo -dig cyclization of 1,7-enynes 205 (Scheme ).…”