Mechanochemical Copper-Catalyzed Asymmetric Michael-Type Friedel-Crafts Alkylation of Indoles with Arylidene Malonates.

A mechanochemical version of the asymmetric Michael-type Friedel-Crafts alkylation of indoles with arylidene malonates was developed. The reaction proceeds under ambient atmosphere using a chiral bis(oxazoline)copper catalyst in a mixer mill. Under these reaction conditions nineteen 3-substituted indole derivatives were synthesized in good to excellent yields (up to 98 %), and with good enantioselectivities (up to 91:9 e.r.) after short milling times.