Cu(II)-Catalyzed Enantioselective Friedel-Crafts/Michael Addition of Indoles

Significance

A Cu(II)-catalyzed enantioselective Michael addition of β-carbonyl alkylidenemalonates with an indole gave enantioenriched ­adducts in the presence of a catalytic amount of Cu(OTf)₂ and tert-butyl-bisoxazoline. Under the optimal conditions, a number of β-acyl-, ester-, and amide-bearing substrates as well as 1- or 5-substituted indoles were tolerated to give moderate to excellent enantiomeric excesses that could be further increased to >99% by recrystallization. When N-methylpyrrole was used instead of indole, the Friedel-Crafts reaction occurs on the 2-position of the pyrrole ring with much lower ee.