Regioselective Alkyne Hydration Mediated by Gold(I) For the Synthesis of Polycarbonylated Compounds

The outstanding ability of gold to activate triple C≡C bonds toward nucleophilic attack1 allowed gold-catalyzed hydration of terminal alkynes to become an efficient method for the synthesis of aldehydes.2 However, the use of internal alkynes commonly leads to the formation of regioisomeric mixtures of ketones.3 Although the regioselectivity in these reactions can be improved using a neighboring nucleophile as a directing group, it remains an unsolved problem.4
In this work, we hypothesized that an electron-withdrawing fragment in the triple bond would differentiate the two Csp atoms favoring the water attack at C3 instead of C2. We then synthetized enynes from Morita-Baylis-Hillman (MBH) adducts in two steps and, in fact, they provided polycarbonylated products as single regioisomers. Selected highly functionalized ketones were further converted into -lactones by reduction.
In short, we have achieved compounds with great increase in structural complexity, from MBH-adducts, in excellent yields and total regioselectivity using gold catalysis.