In addition to trans-12, alkenyl b-keto esters cis-12 and
14–16, which possessed either a cis or trans terminal olefinic
substituent, underwent palladium-catalyzed cyclization in the
presence of SiMe3Cl or SiMe3Cl/CuCl2 to form carbocycles 13
and 17–19, respectively, in ! 80% yield with excellent
regioselectivity (Table 1, entries 7–10). Alkenyl b-keto ester 20,
which possessed both an olefinic and allylic methyl substituent,
cyclized to form carbocycle 21 in 62% yield as a 5.8+1 mixture
of trans+cis diastereomers (Table 1, entry 11). Methyl 3-ox-
ooct-7-enoate (22), in which three methylene groups separate
the ketone and the olefin, underwent cyclization to form
carbocycle 18 in 72% isolated yield (Table 1, entry 12).
Preliminary experiments indicate that a range of carbon
pronucleophiles in addition to b-keto esters will undergo
palladium-catalyzed intramolecular addition to unactivated
olefins in the presence of SiMe3Cl. For example, treatment of
the simple ketone 1-phenylhex-5-en-2-one with 2 (10 mol%),
SiMe3Cl (2 equiv.), and CuCl2 (1 equiv.) in dioxane at 55 °C for
18 h formed 2-phenylcyclohexanone in 70% isolated yield as a
single regioisomer [eqn. (2)].
Table 1 Palladium-catalyzed cyclization of alkenyl b-keto esters
Con-
Yield
(%)b
Entry
Substrate
ditionsa Carbocycle
1
2
3
4
4 (R = Me)
A
A
A
A
5
9
10
11
91
6 (R = Et)
7 (R = Bn)
8 (R = i-Bu)
82 (45)
83 (32)
82
(2)
In summary, PdCl2(CH3CN)2 (2) catalyzed the cyclization of
alkenyl b-keto esters in the presence of SiMe3Cl to form
2-carboalkoxycyclohexanones in good yield with excellent
regioselectivity. These transformations presumably involve
intramolecular attack of an in situ-generated silyl enol ether on
a palladium-complexed olefin. Our current efforts are directed
toward the further utilization of SiMe3Cl in the palladium-
catalyzed addition of carbon pronucleophiles to unactivated
olefins.
5
6
trans-12
A
B
13
13
79
82
7
A
83
R. W. thanks DuPont for a Young Professor Award, the
Alfred P. Sloan Foundation for a Research Fellowship,
GlaxoSmithKline for a Chemistry Scholar Award, and the
Camille and Henry Dreyfus foundation for New Faculty and
Dreyfus Teacher-Scholar Awards.
cis-12
8
9
14 (R = Ph)
15 (R = Me)
A
B
17
18
93
87
Notes and references
‡ Heating a solution of 4 in the presence of excess SiMe3Cl and/or CuCl2 at
55 °C in the absence of 2 led to no detectable cyclization after 12 h. The
catalytic activity of 2 obtained from Aldrich was indistinguishable from 2
synthesized from PdCl2.
10
B
83
1 T. Pei and R. A. Widenhoefer, J. Am. Chem. Soc., 2001, 123, 11290.
2 B. B. Snider, Chem. Rev., 1996, 96, 339.
16
19
3 M. T. Reetz, I. Chatziiosifidis and K. Schwellnus, Angew. Chem., Int. Ed.
Engl., 1981, 20, 687.
4 T. Hosokawa, T. Shinohara, Y. Ooka and S.-I. Murahashi, Chem. Lett.,
1989, 2001.
11
12
B
B
62c
72
20
22
21
18
5 M. T. Rogers and J. L. Burdett, Can. J. Chem., 1965, 43, 1516.
6 (a) A. S. Kende, B. Roth, P. J. Sanfilippo and T. J. Blacklock, J. Am.
Chem. Soc., 1982, 104, 5808; (b) A. S. Kende, B. Roth and P. J.
Sanfilippo, J. Am. Chem. Soc., 1982, 104, 1784; (c) Y. Ito, H. Aoyama,
T. Hirao, A. Mochizuki and T. Saegusa, J. Am. Chem. Soc., 1979, 101,
494; (d) Y. Ito, H. Aoyama and T. Saegusa, J. Am. Chem. Soc., 1980, 102,
4519.
7 (a) K. Maeyama and N. Iwasawa, J. Am. Chem. Soc., 1998, 120, 1928; (b)
N. Iwasawa, K. Maeyama and H. Kusama, Org. Lett., 2001, 3, 3871.
8 L. S. Hegedus, Transition Metals in the Synthesis of Complex Organic
Molecules, University Science Books, Mill Valley, CA, 1999, ch. 7.2, pp.
188–204.
a A = substrate (33 mM), 2 (10 mol%), SiMe3Cl (2 equiv.), dioxane, 25 °C;
B = substrate (33 mM), 2 (10 mol%), SiMe3Cl (2 equiv.), CuCl2 (1 equiv.),
dioxane, 55 °C. b Value in parentheses refers to yield of carbocycle formed
in the absence of SiMe3Cl (ref. 1). c Isolated as a 5.8+1 mixture of trans+cis
diastereomers.
CHEM. COMMUN., 2002, 650–651
651