Asymmetric Friedel-Crafts alkylation of 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 2 a-l and methyl (E)-2-oxo-4-aryl-3-butenoates 3 a-c has been efficiently catalyzed by the scandium(III) triflate complex of (4'S,5'S)-2,6-bis[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 4 a-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 4 m indicated the 4R absolute configuration, thus confirming the proposal of Jørgensen for 4 i. 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.
Desimoni
Giovanni
G
Dipartimento di Chimica Organica dell'Università di Pavia, Viale Taramelli 10, 27100 Pavia, Italy. desim oni@unipv.it
Faita
Giuseppe
G
Toscanini
Marco
M
Boiocchi
Massimo
M
D000478:Alkylation; D002087:Butyrates / Q000737:chemistry*; D002384:Catalysis; D018360:Crystallography, X-Ray; D004952:Esters / Q000138:chemical synthesis / Q000737:chemistry; D007211:Indoles / Q000737:chemistry*; D008698:Mesylates / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D010080:Oxazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012538:Scandium / Q000737:chemistry*; D013237:Stereoisomerism
C530038:(4'S,5'S)-2,6-bis(4'-(triisopropylsilyl)oxymethyl-5'-phenyl-1',3'-oxazolin-2'-yl)pyridine; D002087:Butyrates; D004952:Esters; D007211:Indoles; D008698:Mesylates; D009942:Organometallic Compounds; D010080:Oxazoles; D011725:Pyridines; C436603:scandium triflate; D012538:Scandium