A. P. Lightfoot et al. / Tetrahedron Letters 44 (2003) 7645–7648
7647
The data in Table 1 also suggest that boronate 6 is an
improvement over pinacol ester 1, although the reac-
Stewart, S. K.; Whiting, A. Tetrahedron Lett. 1995, 36,
3929–3932.
3. (a) H e´ naff, N.; Whiting, A. Org. Lett. 1999, 1, 1137–1139;
(b) H e´ naff, N.; Whiting, A. Tetrahedron 2000, 56, 5193–
5204.
2
tion conditions previously employed are slightly differ-
ent to the ones shown above. Most striking are entries
9
and 10 (Table 1), involving the coupling of 2-bro-
mothiophene and 3-bromofuran, respectively. Previ-
ously, it had been found that 2-iodothiophene afforded
the Heck product in 46% yield (92:8 Heck/Suzuki) only
if silver(I) acetate was added and 3-bromofuran failed
to react at all. Using ester 6, both 2-bromothiophene
and 3-bromofuran are selectively converted to the cor-
responding Heck products. However, coupling with
pyridine halides is still not possible (entries 11 and 12,
Table 1), although there is evidence of slow reaction;
only styrene is produced due a low level of aryl-
4. (a) Nakagawa, M.; Furihata, K.; Hayakawa, Y.; Seto, H.
Tetrahedron Lett. 1991, 32, 659–662; (b) Hasegawa, T.;
Kamiya, T.; Henmi, T.; Iwasaki, H.; Yamatodani, S. J.
Antibiot. 1975, 28, 167–175; (c) Nakagawa, M.; Toda, Y.;
Furihata, K.; Hayakawa, Y.; Seto, H. J. Antibiot. 1992,
45, 1133–1138.
5. Boronate 6 was prepared via a modification of the proce-
dure described by Hoffmann, R. W.; Landmann, B.;
Chem. Ber. 1986, 119, 2013–2024, substituting rac-2-
methyl-2,4-pentanediol for n-octanol.
6. (a) Cizmeciyan, D.; Sonnichsen, L. B.; Garcia-Garibay, M.
A. J. Am. Chem. Soc. 1997, 119, 184–188; (b) Kaupp, G.;
Haak, M.; Toda, F. J. Phys. Org. Chem. 1995, 8, 545–551.
7. (a) Fitton, P.; Rick, E. A. J. Organomet. Chem. 1971, 28,
287–291; (b) Heck, R. F.; Nolley, J. P., Jr. J. Org. Chem.
1972, 37, 2320–2322. For general reviews of Heck chem-
istry and recent mechanistic discussions, see: (b) Belet-
skaya, I. P.; Cheprakov, A. V. Chem. Rev. 2000, 100,
3009–3066; (c) Crisp, G. T. Chem. Soc. Rev. 1998, 27,
427–436.
2b,9
exchange with the phosphine ligand.
In order to obtain a direct comparison between the
esters 1 and 6, a competition experiment was run using
iodobenzene, as outlined in Eq. (5). After complete
consumption of the iodobenzene, styrylboronates 12
1
and 10a were formed in a 54:46 ratio by H NMR of
the crude product, which clearly shows that ester 6 is
similar in reactivity, behaving as though it is slightly
more hindered that the corresponding pinacol ester.
This result probably explains why generally ester 6 is a
more selective reagent in these Heck reactions and may
well also explain its greater stability upon storage.
8. All new compounds had satisfactory analytical and spectro-
scopic properties. Selected data: 10a) l (300 MHz) 1.22 (3H,
H
s, CH ), 1.27 (6H, s, 2×CH ), 1.38–1.44 (1H, m, CH), 1.68–
3
3
(5)
Further applications of ester 6 for the synthesis of
polyene systems will be reported in due course.
1.70 (1H, m, CH), 4.10–4.17 (1H, m, CH), 6.09 (1H, d, J
18.1 Hz, CHB), 7.11–7.18 (4H, m, ArH), 7.22 (1H, dd, J
6.9, 1.2 Hz, ArH), 7.57 (1H, d, J 18.1 Hz, CH); 10b) lH
(
400 MHz) 1.20 (3H, s, CH ), 1.24 (6H, s, 2×CH ), 1.39–
3
3
Acknowledgements
1.47 (1H, m, CH), 1.63–1.67 (1H, m, CH), 4.14–4.18 (1H,
m, CH), 2.24 (3H, s, CH ), 5.98 (1H, d, J 18.5 Hz, CHB),
3
7.19 (2H, d, J 8.1 Hz, ArH), 7.36 (1H, d, J 18.5 Hz, CH),
We are grateful to the EPSRC for a CASE studentships
7.39 (2H, d, J 8.1 Hz, ArH); 10c) lH (400 MHz) 1.21 (3H,
s, CH ), 1.23 (3H, s, CH ), 1.25 (3H, s, CH ), 1.41–1.46
(1H, m, CH), 1.68 (1H, dd, J 11.1, 2.6 Hz, CH), 3.68 (3H,
(
GR/99315155) to C.T. and for a DTA award to
3
3
3
S.J.R.T., and to Pfizer Global Research and Develop-
ment and GlaxoSmithKline Pharmaceuticals for addi-
tional funding.
s, OCH ), 4.18–4.22 (1H, m, CH), 5.87 (1H, d, J 18.2 Hz,
3
CHB), 6.98 (2H, dd, J 6.8, 2.1 Hz, ArH), 7.33 (1H, d, 18.2
Hz, CH), 7.46 (2H, dd, J 6.8, 2.1 Hz, ArH); 10d) lH (300
MHz) 1.22 (3H, s, CH ), 1.26 (3H, s, CH ), 1.32 (3H, s,
3
3
References
CH ), 1.37–1.43 (1H, m, CH), 1.59 (1H, dd, J 11.1, 3.0 Hz,
3
CH), 3.58 (2H, bs, NH ), 4.11–4.17 (1H, m, CH), 6.22
2
1
2
. Thirsk, C.; Whiting, A. J. Chem. Soc., Perkin Trans. 1
002, 8, 999–1023.
. (a) Hunt, A. R.; Stewart, S. K.; Whiting, A. Tetrahedron
Lett. 1993, 34, 3599–3602; (b) Stewart, S. K.; Whiting, A.
J. Organomet. Chem. 1994, 482, 293–300; (c) Stewart, S.
K.; Whiting, A. Tetrahedron Lett. 1995, 36, 3925–3928; (d)
(1H, d, J 18.2 Hz, CHB), 6.77 (1H, dd, J 7.9, 1.6 Hz,
ArH), 7.08 (dd, J 7.9, 1.6 Hz, ArH), 7.26 (1H, t, J 7.9 Hz,
ArH), 7.35 (1H, t, J 7.9 Hz, ArH), 7.47 (1H, d, J 18.2 Hz,
2
CH); 10e) lH (400 MHz) 1.23 (3H, s, CH ), 1.27 (3H, s,
3
CH ), 1.30 (3H, s, CH ), 1.40–1.46 (1H, m, CH), 1.60–1.64
3
3
(1H, m, CH), 4.08–4.13 (1H, m, CH), 6.21 (1H, d, J 18.3