Gold-Catalyzed Cycloisomerization of 1,6-Cyclohexenylalkyne: An Efficient Entry to Bicyclo[3.2.1]oct-2-ene and Bicyclo[3.3.1]nonadiene.

An efficient and mild synthetic route for the preparation of functionalized bicyclo[3.2.1]oct-2-ene and bicyclo[3.3.1]nonadiene via gold-mediated cycloisomerization of 1,6-enynes has been developed. This atom-economical catalytic process was optimized and relied on the efficiency of IPrAuNTf allowing the formation of functionalized bicyclic adducts in 55-91% isolated yields (18 products). The reliable access to bicyclic derivatives was demonstrated on a 3 g scale with a low catalyst loading. The process occurred on a 5- versus 6- pathway depending on the substitution of the alkynyl moiety. Density functional theory (DFT) calculations were performed on the stability of intermediates, and this study corroborated the ratio and the mechanistic pathway with key intermediates. Reduction of the ester moiety and hydrogenation of the -methylene double bond of the bicyclo[3.2.1]oct-2-ene adduct illustrated the potential postfunctionalization of bicyclic derivatives.