Access to valuable 1,4- and 1,5-diketones through gold(i) catalysis in water: application to chemoenzymatic cascades

Abstract

1,4- and 1,5-diketones are remarkable structures in different fields as they serve as precursors of many valuable derivatives such as heterocycles and they are also present in the skeleton of a wide variety of natural products and biologically active compounds. Herein, we propose a novel and general methodology that combines the use of both Weinreb and gold chemistries under mild conditions. Thus, starting from pent-4-ynoic or hex-5-ynoic acid, the corresponding Weinreb amides were efficiently obtained, and then after the reaction with a suitable Grignard reagent, a series of alk-4-yn-1-ones and alk-5-yn-1-ones were synthesized in high to excellent yields (74–94%). Later, these compounds were hydrated using the gold(I) catalyst JohnPhosAuCl and the additive NaBAr^F₄ at very low loadings in an aqueous medium and at mild temperature, affording the desired dicarbonylic derivatives at high extent (92–98%). This method was also applied to various aliphatic 1,ω-diynes, which were transformed into the corresponding diketones (88–93%). Due to the mildness of this reaction, it could be combined with different biocatalysts in a one-pot sequential or concurrent approach to access a valuable tetrahydropyridine (1 g scale, 94% isolated yield, >99% ee) or a relevant diol (200 mg scale, 88% isolated yield, >99% ee, >99% de).