C O M M U N I C A T I O N S
Table 1. Cyclization of 2-Alkenyl Indoles Catalyzed by PtCl2 (2
mol %) in Dioxane That Contained a Trace (5 mol %) of HCl at 60
°C for 18-24 h (E ) CO2Me)
Scheme 3
In summary, we have developed a mild and effective platinum-
catalyzed procedure for the intramolecular alkylation of indoles with
unactivated olefins. We have established a mechanism for indole
alkylation involving nucleophilic attack on a platinum-complexed
olefin, and we have demonstrated the feasibility of asymmetric
carbocyclization employing this protocol.
Acknowledgment. We acknowledge the NSF (CHE-03-04994)
for support of this research. R.W. thanks the Camille and Henry
Dreyfus Foundation and GlaxoSmithKline for financial assistance.
We thank Dr. Rudolf Schmid (Hoffmann-LaRoche) for a generous
gift of BIPHEP ligands, Dr. Peter S. White for determining the
structure of 5, and Dr. Anthony Ribero for NMR spectral analysis
of 5-d2.
Supporting Information Available: Experimental procedures and
spectroscopic data for new compounds and products (PDF). This
References
(1) Bergman, J.; Pelcman, B. Pure Appl. Chem. 1990, 62, 1967.
(2) Cox, E. D.; Cook, J. M. Chem. ReV. 1995, 95, 1797.
(3) Saxton, J. E. Nat. Prod. Rep. 1997, 559.
(4) Sundberg, R. J. Indoles; Academic Press: San Diego, 1996.
(5) Olah, G. A.; Krishnamurti, R.; Prakash, G. K. S. Friedel-Crafts
Alkylations. In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, 1991; Vol. 3, pp 293-339.
(6) Morrison, G. C.; Waite, R. O.; Serafin, F.; Shavel, J. J. Org. Chem. 1967,
32, 2551.
(7) (a) Pei, T.; Widenhoefer, R. A. J. Am. Chem. Soc. 2001, 123, 11290. (b)
Pei, T.; Wang, X.; Widenhoefer, R. A. J. Am. Chem. Soc. 2003, 125,
648. (c) Qian, H.; Widenhoefer, R. A. J. Am. Chem. Soc. 2003, 125, 2056.
(d) Pei, T.; Widenhoefer, R. A. Chem. Commun. 2002, 650. (e) Wang,
X.; Pei, T.; Han, X.; Widenhoefer, R. A. Org. Lett. 2003, 5, 2699.
(8) (a) Franze´n, J.; Ba¨ckvall, J.-E. J. Am. Chem. Soc. 2003, 125, 6056. (b)
Dorange, I.; Lo¨fstedt, J.; Na¨rhi, K.; Franze´n, J. Ba¨ckvall, J.-E. Chem.-
Eur. J. 2003, 9, 3445.
(9) For recent reports of the palladium-catalyzed intramolecular oxidative
alkylation of indoles with unactivated olefins, see: (a) Ferreira, E. M.;
Stoltz, B. M. J. Am. Chem. Soc. 2003, 125, 9578. (b) Abbiati, G.; Beccalli,
E. M.; Broggini, G.; Zoni, C. J. Org. Chem. 2003, 68, 7625.
(10) Fanizzi, F. P.; Intini, F. P.; Maresca, L.; Natile, G. J. Chem. Soc., Dalton
Trans. 1992, 309.
(11) See Supporting Information for details concerning optimization.
(12) Treatment of 1-methyl-2-(4-methyl-4-pentenyl)indole (Table 1, entry 6)
with HCl (30 mol %) in dioxane at 60 °C in the absence of platinum
formed no detectable amounts of 4,4,9-trimethyl-2,3,4,9-tetrahydro-1H-
carbazole after 24 h.
(13) (a) Tan, K. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2002,
124, 3202. (b) Kakiuchi, F.; Murai, S. Acc. Chem. Res. 2002, 35, 826.
(14) (a) Merrifield, J. H.; Ferna´ndez, J. M.; Buhro, W. E.; Gladysz, J. A. Inorg.
Chem. 1984, 23, 4022. (b) De Luca, N.; Wojcicki, A. J. Organomet. Chem.
1980, 193, 359.
a Contained a small amount (∼3%) of a second isomer. b Reaction run
at 90 °C for 47 h.
bis(phosphine) complexes catalyzed the cyclization of alkenyl
indoles. In a preliminary screen of enantiomerically pure platinum
bis(phosphine) catalysts,11 the hindered platinum BIPHEP complex
(R)-6 proved effective for the asymmetric alkylation of alkenyl
indoles (Scheme 3). For example, reaction of 7 with a catalytic
1:1 mixture of (R)-6 and AgOTf at 60 °C for 24 h led to the isolation
of 8 in 84% yield with 69% ee (Scheme 3).
(15) The anti relationship between the indole carbon atom and the secondary
proton â- to the indole of anti-5-d2 was unambiguously determined by
1H NMR spectroscopy (see Supporting Information).
JA031814T
9
J. AM. CHEM. SOC. VOL. 126, NO. 12, 2004 3701