ORGANIC
LETTERS
2007
Vol. 9, No. 17
3393-3395
Iridium-Catalyzed Asymmetric Allylic
Substitution with Aryl Zinc Reagents
Alexandre Alexakis,* Samir El Hajjaji, Damien Polet, and Xavier Rathgeb
UniVersite´ de Gene`Ve, De´partement de chimie organique, 30 Quai Ernest Ansermet,
1211 Gene`Ve 4, Switzerland
Received June 12, 2007
ABSTRACT
Thanks to iridium catalysis, arylzinc reagents undergo regioselective allylic substitution with very high enantioselectivity, when associated
with phosphoramidite ligands.
The allylic substitution is a fundamental reaction in organic
chemistry.1 The reaction of carbon nucleophiles is usually
catalyzed by a transition metal, and chiral ligands around
this metal may allow the asymmetric version of this reaction.2
Copper is unique in this context, allowing nonstabilized
nucleophiles, such as alkyl groups, to be transferred.3 In
addition, the regiocontrol of the reaction, with unsymmetri-
cally substituted allylic substrates, is possible with this metal.4
We, and others, have developed efficient copper-catalyzed
procedures where a Grignard or a dialkylzinc reagent reacts,
enantioselectively, with an allylic substrate with high regio-
and stereocontrol (Scheme 1).5
nards or alkylzinc reagents, thanks to a chiral ligand to
copper. However, despite all efforts, the transfer of an aryl
group was not regioselective, resulting mainly in the achiral
R product.
Aryl metal reagents have scarcely been used with other
transition metals than copper.1 There are even fewer enan-
tioselective versions, most of them dealing with meso-type
π-allyl systems.6 For soft nucleophiles, most transition metals
show mainly R selectivity on the above type of allylic
(2) (a) Miyabe, H.; Takemoto, Y. Synlett 2005, 1641. (b) Trost, B. M.
J. Org. Chem. 2004, 69, 5813. (c) Trost, B. M.; Crawley, M. L. Chem.
ReV. 2003, 103, 2921.
(3) (a) Posner, G. H. Org. React. 1975, 22, 253. (b) Karlstro¨m, A. S. E.;
Ba¨ckvall, J. E. In Modern Organocopper Chemistry; Krause, N., Ed.; Wiley-
VCH: Weinheim, Germany, 2001; p 259.
(4) (a) Yamamoto, Y. Angew. Chem., Int. Ed. Engl. 1986, 25, 947. (b)
Karlstro¨m, A. S. E.; Ba¨ckvall, J. E. Chem. Eur. J. 2001, 7, 1981.
(5) For recent reviews in Cu-catalyzed asymmetric allylic substitution:
(a) Alexakis, A.; Malan, C.; Lea, L.; Tissot-Croset, K.; Polet, D.; Falciola,
C. Chimia 2006, 60, 124. (b) Yorimitsu, H.; Oshima, K. Angew. Chem.,
Int. Ed. 2005, 44, 4435. (c) Kar, A.; Argade, N. P. Synthesis 2005, 2995.
(6) (a) Cherest, M.; Felkin, H.; Umpleby, J. D. Chem. Commun. 1981,
681. (b) Hiyama, T.; Wakasa, N. Tetrahedron Lett. 1985, 26, 3259. (c)
Fiaud, J.-C.; Aribi-Zouioueche, L. J. Organomet. Chem. 1985, 295, 383.
(d) Consiglio, G.; Piccolo, O.; Roncetti, L.; Morandini, F. Tetrahedron 1986,
42, 2043. (e) Fotiadu, F.; Cros, P.; Faure, B.; Buono, G. Tetrahedron Lett.
1990, 31, 77. (f) Consiglio, G.; Indolese, A. Organometallics 1991, 10,
3425. (g) Nomura, N.; RajanBabu, T. V. Tetrahedron Lett. 1997, 38, 1713.
(h) Nagel, U.; Nedden, H. G. Inorg. Chim. Acta 1998, 269, 34. (i) Gomez-
Bengoa, E.; Heron, N. M. N. M.; Didiuk, M. T.; Luchaco, C. A.; Hoveyda,
A. H. J. Am. Chem. Soc. 1998, 120, 7649. (j) Chung, K.-G.; Miyake, Y.;
Uemura, S. J. Chem. Soc., Perkin Trans. I 2000, 2725. (k) Yasui, H.;
Mizutani, K.; Yoremitsu, H.; Oshima, K. Tetrahedron 2006, 62, 1410.
Scheme 1
The γ product could be obtained with >99:1 regioselec-
tivity and >98% enantioselectivity with many alkyl Grig-
(1) (a) Magid, R. M. Tetrahedron 1980, 36, 1901. (b) Trost, B. M.; van
Vranken, D. L. Chem. ReV. 1996, 96, 395. (c) Trost, B. M.; Lee, C. In
Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.; Wiley, New York,
2000; p 593. (d) Pfaltz, A.; Lautens, M. In ComprehensiVe Asymmetric
Catalysis I-III; Jacobsen, E. N., Pfaltz A., Yamamoto, H., Eds.; Springer:
Berlin, Germany, 1999; p 833.
10.1021/ol0713842 CCC: $37.00
© 2007 American Chemical Society
Published on Web 07/19/2007