5682
J. C. S. Woo et al. / Tetrahedron Letters 48 (2007) 5679–5682
Pd-catalyzed Suzuki–Miyaura couplings of aryl- and vinyl
PhB(OH)2
P2O5, +N(Bu)4Br-
toluene, 100oC
SPhos, Pd(OAc)2
tosylates: Huffman, M. A.; Yasuda, N. Synlett 1999, 471–
473; Lakshman, M. K.; Thompson, P. F.; Nuqui, M. A.;
Hilmer, J. H.; Sevova, N.; Boggess, B. Org. Lett. 2002, 4,
1479–1482; Nguyen, H. N.; Huang, X.; Buchwald, S. L. J.
Am. Chem. Soc. 2003, 125, 11818–11819; For Kumada
couplings: Limmert, M. E.; Roy, A. H.; Hartwig, J. F. J.
Org. Chem. 2005, 70, 9364–9370; For additional examples
of Suzuki, Sonogashira and Stille cross-coupling reactions:
Steinhuebel, D.; Baxter, J. M.; Palucki, M.; Davies, I. W.
J. Org. Chem. 2005, 70, 10124–10127.
O
O
K3PO4·H2O
HO
O
Br
O
THF, rt, 2h (90%)
1h (29%)
16
KOH
O
O
THF/MeOH (1.5:1)
80oC, 16h
(65%)
O
12
9
Scheme 6.
11. Guram, A. S.; King, A. O.; Allen, J. G.; Wang, X.;
Schenkel, L. B.; Chan, J.; Bunel, E. B.; Faul, M. M.;
Larsen, R. D.; Martinelli, M. J.; Reider, P. J. Org. Lett.
2006, 8, 1787–1789.
KOH, THF/MeOH
80oC, 16 h
(71%)
12. General procedure for tosylate cross-coupling: To a cold
(ꢁ45 °C) stirred mixture of propynylmagnesium bromide
in THF (3.4 mL, 0.50 M, 1.7 mmol) was added a solution
of ZnCl2 in THF (3.9 mL, 0.50 M, 1.95 mmol). The
reaction mixture was allowed to warm to rt and then
stirred for an additional 30 min. A mixture of tosylate
(1.14 mmol) and Pd catalyst [0.023 mmol Pd2(dba)3/
0.091 mmol RuPhos or 0.057 mmol (A-taPhos)2PdCl2] in
THF (2 mL) was added and the addition flask rinsed with
THF (1 mL). The resulting mixture was heated at 40 °C for
24 h, cooled, filtered and concentrated. The residue
obtained was purified by flash chromatography on silica
gel (ethyl acetate–hexanes) to afford the (Z)-enyne ester.
13. Enyne 8 was prepared in 70% yield via Negishi coupling
[Pd(PPh3)4, THF, rt, 16 h] of propynylzinc bromide with
iodide 4.
O
17
OEt
O
18
OH
Scheme 7.
In conclusion, we have developed a practical method to
assemble (Z)-enyne esters via Pd-catalyzed cross cou-
pling reactions of enol tosylates with alkynyl zinc re-
agents. We have demonstrated that rearrangement of
these enyne esters occurs through the action of base to
provide enones. Finally, we presented evidence that this
rearrangement occurs through a sequence of reactions
including (i) ester hydrolysis, (ii) 6-endo-dig cyclization,
(iii) pyranone hydrolysis, and (iv) decarboxylation
accompanied by alkene isomerization.
14. Additional base charges or extended heating times resulted
in competitive retro-aldol reaction of the enone products.
15. At higher temperatures (e.g., ethylene glycol, 200 °C)
acetophenone was obtained as the major product, pre-
sumably due to retro-aldol reaction of the initially formed
enone 3. Product 3 was not observed under neutral (LiCl,
DMSO) or acidic (TsOH, PhMe or HCl/H2O) conditions
were examined.
Acknowledgements
The authors would like to thank Dr. Anil Guram for
providing A-taPhos, Dr. Paul Schnier for HRMS analy-
ses and Dr. Johann Chan for helpful discussions.
16. General procedure for decarboxylative rearrangement: To a
stirred solution of (Z)-enyne ester (1.31 mmol) in THF
(1.5 mL) and MeOH (1 mL) was added aqueous KOH
(1.05 mL, 2.5 N, 2.62 mmol) and the resulting mixture was
heated at 80 °C for 16 h. The reaction mixture was cooled
to rt, diethyl ether (20 mL), aqueous HCl (5.0 mL, 1.0 N)
and water (10 mL) were added and the layers were
separated. The aqueous phase was extracted with ether
(20 mL) and the combined organic layers were concen-
trated. The residue obtained was purified by flash chro-
matography on silica gel (ethyl acetate–hexanes) to afford
the desired enone.
17. Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104,
2127–2198.
18. Harkat, H.; Weibel, J.-M.; Pale, P. Tetrahedron Lett. 2006,
6273–6276.
19. Uchiyama, M.; Ozawa, H.; Takuma, K.; Matsumoto, Y.;
Yonehara, M.; Hiroya, K.; Sakamoto, T. Org. Lett. 2006,
24, 5517–5520.
20. Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734–
736.
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