464
C. M. Crawforth et al. / Tetrahedron Letters 45 (2004) 461–465
Table 2. Competition reactions between 2 and 28 for cross-coupling
with Z-10
6. General procedure for Stille cross-coupling. The specified
precatalyst (5 mol %) was added to a solution of benzyl
bromide (0.25 mmol) and the stannane (0.3 mmol) in dry
degassed toluene (2.5 mL) and heated to 60 ꢁC in the dark,
under a N2 atmosphere, for the specified time. The reaction
was allowed to cool to ambient temperature, then saturated
aq KF (2.5 mL) was added and the mixture stirred
vigorously for 1 h. The mixture was filtered through Celite,
washed with saturated aq NaCl (2 · 2.5 mL) and dried
(MgSO4). Concentration in vacuo and subsequent purifi-
cation by column chromatography using ethyl acetate/
petroleum ether 40–60 ꢁC mixtures (1:20 to 1:9, v/v
afforded the desired product as colourless oils. The
employment of a DBU/I2/Et2O workup (see: Curran, D.
P.; Chang, C.-T. J. Org. Chem. 1989, 54, 3140), to remove
the organotin side products results in rapid regio- and
stereo-isomerisation in the vast majority of examples. This
should be avoided for these types of products.
Catalyst (5 mol%)
CO2Et
Toluene
Br
60 o
C
Br
+
CO2Et
Bu3Sn
Z-10
2
28
Z-29
+
CO2Et
Z-30
Entry Precatalyst
Yield (%)
Z-29
Z-30 (E-30)
1
2
3
Pd(NCOC2H4CO)(PPh3)2Br 1 86
––
36
Pd(Bn)(PPh3)2Br 31
Pd(PPh3)2Br2 32
16
––
7. All new compounds have been fully characterised (IR, 1H,
13C NMR, LRMS/HRMS and/or elemental analysis).
8. This has been previously noted, see: Pilcher, A. S.;
DeShong, P. J. Org. Chem. 1996, 61, 6901.
21 (15)
9. Generally, the cross-coupling of geranyl substrates occurs
preferentially at the a-position using standard palla-
dium(0) catalysts, see: Malkov, A. V.; Baxendale, I. R.;
Cat. 1
ꢀ
ꢁ
Mansfield, D. J.; Kocovsky, P. J. Chem. Soc., Perkin
Trans. 1 2001, 1234, and references cited therein.
10. Fairlamb, I. J. S.; Pike, A. C.; Ribrioux, S. P. C. P.
Tetrahedron Lett. 2002, 43, 5327, and references cited
therein.
Toluene
°
60
C
Br
Br
+
Br
Br
+
Bu3Sn
84%
7%
33
8
34
35
11. Fairlamb, I. J. S.; Lu, F.-J. Unpublished results.
12. Lee, J.-H.; Kim, W.-S.; Lee, Y. L.; Cho, C.-G. Tetrahe-
dron Lett. 2002, 43, 5779.
13. We did not observe cross-coupling onto the 5-position of
the 2-pyrone ring.
0%
36
14. There are a large number of reports on the Stille cross-
coupling of benzyl bromides, whereas uses of benzylic
chlorides are very limited, see Ref. 2.
Scheme 2. Csp3 cross-coupling versus Csp2 cross-coupling.
15. For references related to AsPh3, see: Kamlage, S.; Sefkow,
M.; Peter, M. G. J. Org. Chem. 1999, 64, 2938; (b)
Anderson, J. C.; Roberts, C. A. Tetrahedron Lett. 1998,
39, 159; (c) Crisp, G. T.; Glink, P. T. Tetrahedron 1994, 50,
Acknowledgements
ꢂ
3213; (d) Miniere, S.; Cintrat, J.-C. J. Org. Chem. 2001,
We thank the EPSRC for a Ph.D. studentship for
C.M.C. (GR/N06977). I.J.S.F. acknowledges the Uni-
versity of York for financial support.
66, 7385; (e) with added CuCl, Timbart, L.; Cintrat, J.-C.
Chem. Eur. J. 2002, 8, 1637. For references related to P(2-
furyl)2, see: (a) Farina, V.; Baker, S. R.; Benigni, D. A.;
Hauck, S. I.; Sapino, C., Jr. J. Org. Chem. 1990, 55, 5833;
(b) Palmisano, G.; Santagostino, M. Synlett 1993, 771; (c)
Bailey, T. R. Synthesis 1991, 242; (d) Nagano, N.; Itahana,
H.; Hisamichi, H.; Sakamoto, K.; Hara, R. Tetrahedron
Lett. 1994, 35, 4577; (e) Andersen, N. G.; Keay, B. A.
Chem. Rev. 2001, 101, 997.
References and Notes
1. (a) Kosugi, M.; Shimizu, Y.; Migita, T. Chem. Lett. 1977,
1423; (b) Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1978,
100, 3636; (c) Stille, J. K. Angew. Chem., Int. Ed. 1986, 25,
508.
16. Sustmann, R.; Lau, J.; Zipp, M. Tetrahedron Lett. 1986,
27, 5207.
17. Milstein, D.; Stille, J. K. J. Am. Chem. Soc. 1979, 101,
4992.
18. van Asselt, R.; Elsevier, C. J. Organometallics 1992, 11,
1999, a number of other examples are also reported only in
HMPA, see Ref. 2.
19. Murakami, M.; Amii, H.; Takizawa, N.; Ito, Y. Organo-
metallics 1993, 12, 4223.
20. Godschalx, J.; Stille, J. K. Tetrahedron Lett. 1980, 21,
2599.
21. Mitchell, T. N.; Wickenkamp, R.; Amamria, A.; Dicke,
R.; Schneider, U. J. Org. Chem. 1987, 52, 4868.
22. Halide effects are known to play important roles in
palladium-catalysed cross-coupling reactions. For more
detailed information see the following comprehensive
reviews: (a) Fagnou, K.; Lautens, M. Angew. Chem., Int.
2. For a complete review of the Stille reaction, see: Farina,
V.; Krishnamurthy, V.; Scott, W. J. Org. React. 1997,
50, 1.
3. For use of the Stille coupling in our research, see: (a)
Macdonald, G.; Alcaraz, L.; Wei, X.; Taylor, R. J. K.
Tetrahedron 1998, 54, 9823; (b) Alcaraz, L.; Macdonald,
G.; Ragot, J.; Lewis, N. J.; Taylor, R. J. K. Tetrahedron
1999, 55, 3707; (c) Marrison, L. R.; Dickinson, J. M.;
Ahmed, R.; Fairlamb, I. J. S. Tetrahedron Lett. 2002, 43,
8853; (d) Marrison, L. R.; Dickinson, J. M.; Fairlamb, I.
J. S. Bioorg. Med. Chem. Lett. 2002, 12, 3509.
4. Littke, A. F.; Fu, G. Angew. Chem., Int. Ed. 2002, 41,
4176, and references cited therein.
5. Crawforth, C. M.; Burling, S.; Fairlamb, I. J. S.; Taylor,
R. J. K.; Whitwood, A. C. Chem. Commun. 2003, 2194.