The only stoichiometric organometallic reaction required
in such a sequence would be for the synthesis of stannane 2
following our published procedure,11 a reaction we have
performed routinely on a 0.2 mol scale. We have described
Stille and Suzuki-Miyaura couplings of the corresponding
enol N,N-diethylcarbamate12 but were anxious, lest cleavage
of the MEM group should occur under Stille couplings. We
then prepared iodotriflates 3a-c (in 94%, 95%, and 93%
yield, respectively) following a standard procedure13 and
attempted the Stille couplings under modified Farina-
Liebeskind conditions (Scheme 2). We were able to use
was obtained for ortho-isomer 4a as a result of steric
hindrance caused by the TfO substituent.14 The presence of
Cu(I) salt was critical to minimize the coformation of enol
acetal 5, a significant byproduct when the cocatalyst was
omitted. Functionalized iodotriflate 3d also coupled ef-
ficiently. With diiodide 3f, we observed the formation of a
major coupling product 4f by 19F NMR, though the isolated
yield was low and a significant amount of 5 was formed
also. Coupling with bromobenzene failed, however, and we
recovered 5 and diene 6 only from the reaction.
Generally, slow oxidative addition of the halide to the
palladium catalyst leads to the formation of byproducts 5
and 6. However, attempted coupling with 2,5-dibromo-
pyridine (in which the heteroaryl C-Br bond is more labile)
did lead to some product formation (according to 19F NMR
spectra of crude reaction mixtures) though the reaction was
very slow (20% product after 18 h).
Scheme 2. Stille Couplings to Stannane 2
With 5-bromo-2-iodopyridine,15 we were able to isolate
4g in 30% yield. Except for 4h, all of the coupling products
were sufficiently stable to be characterized fully. Stille and
Suzuki-Miyaura couplings were then attempted for 4b and
4c to determine the stability of the enol acetal under the more
forcing conditions required for coupling with the less reactive
aryl triflates.
Suzuki-Miyaura couplings16 to 4c were successful, par-
ticularly under the conditions described by Oh-e and co-
workers,17 and a range of biarylethenes were isolated in
moderate to good yield (Scheme 3, Table 1).
Scheme 3. Suzuki Couplings to Triflates 4b and 4c
palladium(II) acetate directly in the reactions at a low loading
(2.5%), which reduced the cost and simplified the workup
relative to procedures that deploy Pd2dba3 complexes.
The meta- and para-congeners coupled efficiently (86%
for 4b and 96% for 4c), whereas as expected, a poor yield
a 5% PdCl2(PPh3)2, 4.0 eq. Et3N, 2.0 eq. 7, DMF, 90 °C. b 1%
Pd(OAc)2, 1.2% PCy3, 3.3 eq. KF, 2.0 eq. 7, THF, 65 °C. c 2.5%
Pd2dba3‚CHCl3, 20% PPh3, 1.5 eq. K3PO4, 2.0 eq. 7, 1.4-dioxane,
85 °C.
(7) Brigaud, T.; Doussot, P.; Portella, C. J. Chem. Soc., Chem. Commun.
1994, 2117.
(8) Fleming, I.; Roberts, R. S.; Smith, S. C. J. Chem. Soc., Perkin Trans.
1 1998, 1215.
(9) Jin, F. Q.; Xu, Y. Y.; Huang, W. Y. J. Chem. Soc., Perkin Trans. 1
1993, 795.
(10) Percy, J. M. Top. Curr. Chem. 1997, 193, 131.
(11) Patel, S. T.; Percy, J. M.; Wilkes, R. D. Tetrahedron 1995, 51, 9201.
(12) DeBoos, G. A.; Fullbrook, J. J.; Owton, W. M.; Percy, J. M.;
Thomas, A. C. Synlett 2000, 963.
The lower limit of boronic acid reactivity was reached at
the 3-nitrophenylboronic acid, which reacted very slowly
indeed with 4b and 4c; in fact, it was not possible to isolate
(13) Qing, F.-L.; Fan, J.; Sun, H.-B.; Yue, X.-J. J. Chem. Soc., Perkin
Trans. 1 1997, 3053.
(14) Kamikawa, T.; Hayashi, T. Synlett 1997, 163.
(15) Song, J. J.; Yee, N. K. J. Org. Chem. 2001, 66, 605.
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Org. Lett., Vol. 3, No. 18, 2001