Construction of a Chiral Quaternary Carbon Center by Indium-Catalyzed Asymmetric α-Alkenylation of β-Ketoesters.

Construction of a nonracemic all-carbon quaternary stereocenter at the α-position of β-ketoesters was achieved by way of an indium(III)-catalyzed diastereoselective α-alkenylation reaction of chiral enamines with 1-alkynes. The enamine bearing a chiral auxiliary derived from l-isoleucine was added to the alkyne to give an α-alkenylated product in excellent yield and with a stereoselectivity better than 90% ee. One can ascribe the high selectivity to a chelate intermediate involving the auxiliary and the metal atom and the high yield to efficient interactions between the indium(III) atom and the alkyne. The selectivity increased as the reaction temperature was raised to 120 °C and decreased at higher temperatures.