C O M M U N I C A T I O N S
Table 2. Pd-Catalyzed Intramolecular Cross-Coupling Reactions
of 3a
exposure of the siloxanes under the optimal conditions established
above promoted the intramolecular cross-coupling effectively.
Again, both diastereomers, 11a and 11b, were obtained in good
yield with no difference in rate or efficiency.
In conclusion, we have demonstrated that Pd-catalyzed, silicon-
assisted intramolecular cross-coupling provides an effective and
potentially powerful method for construction of medium-sized rings
with an internal 1,3-cis-cis diene unit. Noteworthy features of this
process include: (1) a highly stereospecific intramolecular coupling
process, (2) flexible positioning of the hydroxy group, and (3)
potential extension to other medium-sized carbocycles and hetero-
cycles. Further application of this strategy for the syntheses of
natural products is currently in progress.
c
entry
3
APC, mol %
time, hb
product 5, yield/%
Acknowledgment. We are grateful to the National Science
Foundation (NSF CHE 9803124) and the National Institutes of
Health (GM 63167) for generous financial support.
1
2
3
4
5
6
3a
3b
3c
3d
3e
3f
7.5
7.5
7.5
10.0
10.0
10.0
60
45
45
75
75
60
5a+5a′ (60%, 1:1)d,e
5b (70%)
5c (63%)
5d (55%)
5e (72%)
Supporting Information Available: Full characterization of all
starting materials and products along with representative procedures
for the coupling reactions (PDF). This material is available free of
5f (71%)
a All reactions were performed on a 1.0 mmol scale (0.1 M in THF),
with TBAF (10.0 equiv), at room temperature. b Addition time. c Yield of
analytically pure materials. d Yield of chromatographically homogeneous
References
material. e The ratio was determined by H NMR analysis.
1
(1) For recent reviews, see: (a) Mitchell, T. N. In Metal-Catalyzed Cross-
Coupling Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH:
Weinheim, 1998; Chapter 4. (b) Farina, V.; Krishnamurthy, V.; Scott,
W. J. Org. React. 1997, 50, 1.
complex 7 produced only the 6- and 7-membered ring compounds
8a and 8b at room temperature. Furthermore, none of closure
products of 6c were observed under these conditions or in refluxing
CH2Cl2. Clearly, closure on the internal double bond of the diene
to afford smaller rings predominated.
(2) For recent reviews, see: (a) Suzuki, A. In Metal-Catalyzed Cross-Coupling
Reactions; Diederich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998;
Chapter 2. (b) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(3) Hiyama, T. In Metal-Catalyzed Cross-Coupling Reactions; Diederich, F.,
Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998; Chapter 10.
(4) Some recent examples of silicon-based cross-coupling, see: (a) Mowery,
M. E.; DeShong, P. J. J. Org. Chem. 1999, 64, 3266. (b) Hirabayashi, K.;
Kawashima, J.; Nishihara, Y.; Mori, A.; Hiyama, T. Org. Lett. 1999, 1,
299. (c) Hirabayashi, K.; Mori, A.; Kawashima, J.; Suguro, M.; Nishihara,
Y.; Hiyama, T. J. Org. Chem. 2000, 65, 5342. (d) Itami, K.; Nokami, T.;
Ishimura, Y.; Mitsudo, K.; Kamei, T.; Yoshida, J. J. Am. Chem. Soc. 2001,
123, 11577. (e) Mori, A.; Suguro, M. Synlett 2001, 845.
Scheme 1
(5) (a) Denmark, S. E.; Choi, J. Y. J. Am. Chem. Soc. 1999, 121, 5821. (b)
Denmark, S. E.; Wu, Z. Org. Lett. 1999, 1, 1495. (c) Denmark. S. E.;
Wehrli, D. Org. Lett. 2000, 2, 565. (d) Denmark, S. E., Sweis, R. F. J.
Am. Chem. Soc. 2001, 123, 6439. (e) Denmark, S. E.; Yang, S.-M. Org.
Lett. 2001, 3, 1749.
(6) (a) Yet, L. Chem. ReV. 2000, 100, 2963. (b) Rousseau, G. Tetrahedron
1995, 51, 2777. (c) Roxburgh, C. J. Tetrahedron 1993, 49, 10749. (d)
Petasis, N. A.; Patane, M. A. Tetrahedron 1992, 48, 5757. (e) Mehta, G.;
Singh, V. Chem. ReV. 1999, 99, 881. (f) Evans, P. A.; Holmes, A. B.
Tetrahedron 1991, 47, 9131.
(7) (a) Illuminati, G.; Mandolini, L. Acc. Chem. Res. 1981, 14, 95. (b)
Liebman, J. F.; Greenberg, A. Chem. ReV. 1976, 76, 311.
(8) The Stille coupling has been widely employed for construction of
macrocycles containing an internal diene unit. See: (a) Duncton, M. A.
J.; Pattenden, G. J. Chem. Soc., Perkin Trans. 1 1999, 1235.
To demonstrate the versatility and effectiveness of this process,
we next investigated extension to medium-sized heterocycles.
Medium ring ethers have attracted a great deal of attention as
synthesis targets in view of their occurrence in several classes of
marine natural product structures.13 The diastereomeric silyl ethers
9a and 9b, (prepared in seven steps from propargyl alcohol) were
selected to test this application by generation of the corresponding
9-membered oxacyclic dienes,14 11a and 11b (Scheme 2). Ring-
closing metatheses of both 9a and 9b proceed smoothly to afford
cyclic silyl ethers, 10a and 10b. Interestingly, the two diastereomers
reacted with equal facility and yield. More importantly, subsequent
(9) (a) Ma, S.; Negishi, E. J. Am. Chem. Soc. 1995, 117, 6345. (b) Nemoto,
H.; Yoshida, M.; Fukumoto, K. J. Org. Chem. 1997, 62, 6450. (c) Piers,
E.; Romero, M. A. J. Am. Chem. Soc. 1996, 118, 1215. (d) Huffman, M.
A.; Liebeskind, L. S. J. Am. Chem. Soc. 1993, 115, 4895.
(10) Grubbs alkylidene (PCy3)2Cl2RudCHPh (7) has been shown to react with
acetylenic halides through halide exchange. Vinyl halide containing dienes
failed to cyclize using either 7 or Mo-complex [(CF3)2MeCO]2Mo-
(dCHCMe2Ph)(dNC6H3-2,6-i-Pr2) (4), see: (a) Kim, S.-H.; Zuercher,
W. J.; Bowden, N. B.; Grubbs, R. H. J. Org. Chem. 1996, 61, 1073. (b)
Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310.
(11) (a) For a review on synthesis of medium-sized rings using RCM strategies,
see: Maier, M. E. Angew. Chem., Int. Ed. 2000, 39, 2073. (b) The first
10-membered carbocycle prepared by RCM has been reported, see: Neva-
lainen, M.; Koskinen, A. M. P. Angew. Chem., Int. Ed. 2001, 40, 4060.
(12) RCM of trienes have been reported for construction of macrocycles
containing a 1,3-diene system. (a) Wagner, J.; Martin Cabrejas, L. M.;
Grossmith, C. E.; Papageorgiou, C.; Senia, F.; Wagner, D.; France, J.;
Nolan, S. P. J. Org. Chem. 2000, 65, 9255. (b) Dvorak, C. A.; Schmitz,
W. D.; Poon, D. J.; Pryde, D. C.; Lawson, J. P.; Amos, R. A.; Meyers, A.
I. Angew. Chem., Int. Ed. 2000, 39, 1664. (c) Garbaccio, R. M.;
Danishefsky, S. J. Org. Lett. 2000, 2, 3127.
Scheme 2 a
(13) (a) Erickson, K. In Marine Natural Products; Scheuer, P., Ed.; Academic
Press: New York, 1983; Vol. 5; pp 131-257. (b) Faulkner, D. Nat. Prod.
Rep. 2001, 18, 1. (c) Elliott, M. Contemp. Org. Synth. 1994, 1, 457.
(14) Medium ring ethers with an internal 1,3-diene unit have been prepared
through cyclization of an acetylene cobalt complex. Yenjai, C.; Isobe,
M. Tetrahedron 1998, 54, 2509.
a Reagents and conditions: (a) 4 (10.0 mol %), benzene (0.1 M), rt, 36
h, 10a (81%); 10b (80%). (b) APC (7.5 mol %), TBAF (10.0 equiv), rt, 45
h, 11a (72%); 11b (77%).
JA0178158
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J. AM. CHEM. SOC. VOL. 124, NO. 10, 2002 2103