Asymmetric Friedel–Crafts alkylationof indoles with methyl (E)-2-oxo-4-aryl-3-butenoates catalyzed by Sc(OTf)3/pybox

The asymmetric Friedel– Crafts reaction between a series of substituted indoles 2a–l and methyl (E)-2- oxo-4-aryl-3-butenoates 3a–c has been efficiently catalyzed by the scandium- ACHTUNGTRENUNG(III) triflate complex of (4’S,5’S)-2,6- bisACHTUNGTRENUNG[4’-(triisopropylsilyl)oxymethyl-5’- phenyl-1’,3’-oxazolin-2’-yl]pyridine (pybox; 1). Substituted 4-(indol-3-yl)-2- oxo-4-arylbutyric acid methyl esters 4a–n were usually formed in excellent yields and the enantioselectivity was up to 99% ee, irrespective of the electronic character of the substituent and its location on the indole ring, albeit with the exclusion of position 2. The adducts could be obtained as stable enol tautomers and the equilibrium with the keto structure is discussed. The X-ray crystal structure determination of 4m indicated the 4R absolute configuration, thus confirming the proposal of Jørgensen for 4i. The sense of the stereoinduction can be rationalized by the same octahedral complex 5 between 3, pybox 1, and scandium triflate already proposed for the Diels–Alder/hetero-Diels– Alder and the Mukaiyama–aldol reactions of pyruvates.