Can simple enones be useful partners for the catalytic stereoselective alkylation of indoles?
A new catalytic system for the first example of enantioselective Friedel-Crafts-type (FC) addition of indoles to simple enones is described. The use of an equimolar amount of chiral [Al(salen)Cl] and 2,6-lutidine (10 mol %) was found to be effective in promoting the conjugate addition of indoles to (E)-arylcrotyl ketones, furnishing the corresponding beta-indolyl ketones in excellent yield and high enantioselectivity (ee up to 89%). The role of the base was investigated through spectroscopic as well as computational analyses, which suggested that in situ formation of a new chiral (base.[Al(salen)]) complex was operating under our reaction conditions. In particular, a stable cationic [Al(salen)] hexacoordinate trans complex with the additive base and the enone is suggested as being responsible for the stereocontrolled reaction. Finally, detailed monitoring of the reaction course was carried out showing that a conventional FC pathway induced by [Al(salen)Cl] acting as a Lewis acid is operating.
Bandini
Marco
M
Dipartimento di Chimica G. Ciamician, Via Selmi 2, 40126 Bologna, Italy. marco.bandini@unibo.it
Fagioli
Matteo
M
Garavelli
Marco
M
Melloni
Alfonso
A
Trigari
Valerio
V
Umani-Ronchi
Achille
A