C O M M U N I C A T I O N S
Table 2. Decarboxylative Aldol Reactions of â-Keto Esters
Catalyzed by Pd(0)- and YbCl3-DIOP Complexesa
In summary, we have developed a mild and selective heterobi-
metallic-catalyzed decarboxylative aldol reaction. The reaction is
promoted by Pd(0)- and Yb(III)-DIOP complexes and involves
the in situ formation of a ketone enolate from allyl â-keto esters
followed by addition of the enolate to aldehydes. The reaction is a
new example of heterobimetallic catalysis17 in which the optimized
reaction conditions require the addition of both metals. Future
investigations will focus on expansion of the reaction scope to
include other electrophiles.
Acknowledgment. This research was supported by Boston
University, Amgen, and an NSF CAREER Grant (CHE-0349206).
We gratefully acknowledge Profs. Mark Grinstaff and John A.
Porco, Jr. (BU) for helpful comments in the preparation of this
manuscript.
Supporting Information Available: Experimental procedures and
characterization of all new compounds (PDF). This material is available
References
(1) For reviews, see: (a) Heathcock, C. H. In Asymmetric Synthesis; Morrison,
J. D., Ed.; Academic Press: New York, 1984; Vol. 3, part B, p 111. (b)
Kim, B. M.; Williams, S. F.; Masamune, S. In ComprehensiVe Organic
Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon Press: Oxford, 1991;
Vol. 2, p 239. (c) Mukaiyama, T. Org. React. 1982, 28, 203. (d) Evans,
D. A.; Nelson, J. V.; Taber, T. Top. Stereochem. 1982, 13, 1.
(2) (a) Trost, B. M.; Ito, H.; Silcoff, E. R. J. Am. Chem. Soc. 2001, 123,
3367. (b) Trost, B. M.; Silcoff, E. R.; Ito, H. Org. Lett. 2001, 3, 2497. (c)
Trost, B. M.; Ito, H. J. Am. Chem. Soc. 2000, 122, 12003. (d) Yoshikawa,
N.; Yamada, Y. M. A.; Das, J.; Sasai, H.; Shibasaki, M. J. Am. Chem.
Soc. 1999, 121, 4168. (e) Yamada, Y. M. A.; Yoshikawa, N.; Sasai, H.;
Shibasaki, M. Angew. Chem., Int. Ed. Engl. 1997, 36, 1871.
(3) (a) Taylor, S. J.; Morken, J. P. J. Am. Chem. Soc. 1999, 121, 12202. (b)
Taylor, S. J.; Duffey, M. O.; Morken, J. P. J. Am. Chem. Soc. 2000, 122,
4528. (c) Zhao, C.-X.; Duffey, M. O.; Taylor, S. J.; Morken, J. P. Org.
Lett. 2001, 3, 1829.
(4) Lalic, G.; Aloise, A. D.; Shair, M. D. J. Am. Chem. Soc. 2003, 125, 2852.
(5) (a) Tang, Z.; Jiang, F.; Yu, L.-T.; Cui, X.; Gong, L.-Z.; Mi, A.-Q.; Jiang,
Y.-Z.; Wu, Y.-D. J. Am. Chem. Soc. 2003, 125, 5262. (b) Northrup, A.
B.; MacMillian, D. W. C. J. Am. Chem. Soc. 2002, 124, 6798. (c) List,
B.; Lerner, R. A.; Barbas, C. F., III. J. Am. Chem. Soc. 2000, 122, 2395.
(d) Notz, W.; List, B. J. Am. Chem. Soc. 2000, 122, 7386. (e) Hajos, Z.
G.; Parrish, D. R. J. Org. Chem. 1974, 39, 1615.
a Reactions were carried out using 2.5 mmol allyl â-keto ester, 1 mmol
aldehyde, 2.5 mol % Pd2dba3, 5 mol % YbCl3, and 10 mol % DIOP in
CH2Cl2 (0.5 M) at room temperature for 24 h under Ar, followed by flash
chromatography on silica gel. b Isolated yield. c 2.5 mol % Pd2dba3, 10 mol
% YbCl3, and 15 mol % DIOP were used in the reaction. d 5 mol % Pd2dba3,
10 mol % YbCl3, and 20 mol % DIOP were used in the reaction. e The
ratio was determined by 1H NMR of the crude reaction mixture. f The ratio
was determined by isolation of each diastereomer.
(6) (a) Nokami, J.; Mandai, T.; Watanabe, H.; Ohyama, H.; Tsuji, J. J. Am.
Chem. Soc. 1989, 111, 4126. (b) Nokami, J.; Konishi, H.; Matsura, H.
Chem. Lett. 1991, 2023.
(7) (a) Culkin, D. A.; Hartwig, J. F. J. Am. Chem. Soc. 2001, 123, 5816. (b)
Albeniz, A. C.; Catalina, N. M.; Espinet, P.; Redon, R. Organometallics
1999, 18, 5571. (c) Collum, D. B.; Wanat, R. A. Organometallics 1986,
5, 120.
Scheme 1. Proposed Catalytic Cycle for the Heterobimetallic
Decarboxylative Aldol Condensation
(8) (a) Fujii, A.; Hagiwara, E.; Sodeoka, M. J. Am. Chem. Soc. 1999, 121,
5450. (b) Pagenkopf, B. L.; Kru¨ger, J.; Stojanovic, A.; Carreira, E. M.
Angew. Chem., Int. Ed. 1998, 37, 3124.
(9) For Zn0-promoted aldol reactions of 2,2,2-trichloroethyl-â-keto esters,
see: Muraiyama, T.; Sato, T.; Suzuki, S.; Inoue, T.; Nakamura, H.
Tetrahedron Lett. 1976, 17, 95.
(10) (a) Shimizu, I.; Yamada, T.; Tsuji, J. Tetrahedron Lett. 1980, 21, 3199.
(b) Tsuda, T.; Chujo, Y.; Nishi, S.; Tawara, K.; Saegusa, T. J. Am. Chem.
Soc. 1980, 102, 6381. (c) Carroll, M. F. J. Chem. Soc. 1940, 1226.
(11) Masuyama, Y.; Sakai, T.; Kato, T.; Kurusu, Y. Bull. Chem. Soc. Jpn.
1994, 67, 2265.
(12) When (R,R)-DIOP was used in the reaction, the product 5a was obtained
in racemic form.
(13) For Yb-phosphine complexes, see: (a) Karsch, H. H.; Ferazin, G.;
Steiglemann, O.; Kooijman, H.; Hiller, W. Angew. Chem., Int. Ed. Engl.
1993, 32, 1739. (b) Tilley, T. D.; Anderson, R. A.; Zalkin, A. Inorg. Chem.
1983, 22, 856.
(14) Allyl-â-keto esters successfully utilized in the reaction include allyl 3-oxo-
3-phenylpropanoate and allyl-3-oxopentanoate; see Supporting Information
for experimental details.
exchange reaction then results in the formation of the aldol product
and 9, which undergoes an alkylation reaction with the Pd(II) allyl
species to regenerate a Pd(0) species and yield the R-allyl-â-keto
ester 10. The reaction requires >2 equiv of allyl â-keto ester to be
present for this purpose, and a stoichiometric amount of 10 is
produced. Conducting the reaction with an equivalent amount of
methyl acetoacetate and allyl-â-keto ester 6 was also successful.
Mechanistic investigations of the role of each metal in the reaction
are ongoing.
(15) Sakai, R.; Stroh, J. G.; Sullins, D. W.; Rinehart, K. L. J. Am. Chem. Soc.
1995, 117, 3734.
(16) For Yb(OTf)3-mediated cross aldol reactions see: Fukuzawa, S.; Tsuchim-
oto, T.; Kanai, T. Bull. Chem. Soc. Jpn. 1994, 67, 2227.
(17) (a) Hamashima, Y.; Sawada, D.; Kanai, M.; Shibasaki, M. J. Am. Chem.
Soc. 1999, 121, 2641. (b) Funabashi, K.; Ratni, H.; Kanai, M.; Shibasaki,
M. J. Am. Chem. Soc. 2001, 123, 10784. (c) Kamijo, S.; Yamamoto, Y.
Angew. Chem., Int. Ed. 2002, 41, 3230.
JA045981K
9
J. AM. CHEM. SOC. VOL. 126, NO. 37, 2004 11441