G. Zou, J. R. Falck / Tetrahedron Letters 42 (2001) 5817–5819
5819
played sluggish reactivity with (dppf)PdCl2 as catalyst
even at elevated temperatures and prolonged reaction
times, but could be successfully coupled using
(dba)3Pd2/tBu3P/KF in THF, e.g. 21 to 22 (entry
11).2a,7a The conversion of terminal olefin 23 and ace-
tonide 25 to 24 (entry 12) and 27 (entry 13), respec-
tively, demonstrated that a variety of functional groups
are well tolerated in the lithium borate moiety. Finally,
it is important to note that for the demanding cases of
methyl and trimethylsilylmethyl cross-couplings, 28 to
29 (entry 14) and 30 to 31 (entry 15), no transfer of the
sec-butyl radical was observed.
7. (a) Wright, S. W.; Hageman, D. L.; McClure, L. D. J.
Org. Chem. 1994, 59, 6095–6097; (b) Mu, Y.; Gibbs, R.
A. Tetrahedron Lett. 1995, 36, 5669–5672; (c) Zhou, X.;
Tse, M. K.; Wan, T. S. M.; Chan, K. S. J. Org. Chem.
1996, 61, 3590–3593.
8. Sato, M.; Miyaura, N.; Suzuki, A. Chem. Lett. 1989,
1405–1408.
9. Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.;
Satoh, M.; Suzuki, A. J. Am. Chem. Soc. 1989, 111,
314–321.
10. Soderquist, J. A.; Santiago, B. Tetrahedron Lett. 1990,
31, 5541–5542.
11. Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393–396.
12. For the application of hypervalent tin reagents to cross-
couplings, see: Martinez, A. G.; Barcina, J. O.; del
Rosario Colorado Heras, M.; de Fresno Cerezo, A.
Organometallics 2001, 20, 1020–1023.
In summary, we describe a practical two-step, one-pot
strategy for the Suzuki–Miyaura cross-coupling of
unactivated primary alkyl groups from n-alkyl-
boronates under mild conditions.
13. For the cross-coupling of lithium alkenylborates medi-
ated by nickel catalysis, see: Usmani, S. B.; Takahisa, E.;
Koyayashi, Y. Tetrahedron Lett. 1998, 39, 601–604.
14. Pelter, A.; Singaram, B.; Williams, L.; Wilson, J. W.
Tetrahedron Lett. 1983, 24, 623–626.
General procedure: Commercial sec-BuLi (0.1 mmol,
1.3 M in cyclohexane) was added dropwise to a −78°C
solution of boronate ester (0.11 mmol) in THF (6 mL).
The mixture was gradually warmed to ambient over 1.5
h, then cannulated into a stirring suspension of Pd
catalyst (0.05 equiv.) and NaOAc (3–5 equiv.) in THF
(5 mL) under argon followed after a few minutes by the
electrophile (0.1 mmol). The resulting brown solution
was heated at 70–80°C for 8–12 h, cooled to room
temperature, and quenched with 30% H2O2/10% aq.
NaOH. The reaction mixture was extracted thrice with
Et2O and the combined ethereal extracts were concen-
trated in vacuo. Purification of the residue via SiO2
chromatography provided the adducts in the indicated
yields.
15. Ishiyama, T.; Itoh, Y.; Kitano, T.; Miyaura, N. Tetra-
hedron Lett. 1997, 38, 3447–3450.
16. No significant differences in reactivities of the esters were
observed, so we favored the less expensive pinacol for
large scale experiments.
17. Pd(PPh3)4 and (PPh3)2PdCl2, for example, were inferior.
18. ten Brink, G.-J.; Arends, I. W. C. E.; Sheldon, R. A.
Science 2000, 287, 1636–1639.
19. Spectral data for 3: 1H NMR (400 MHz, CDCl3) l
7.64–7.69 (m, 4H), 7.34–7.44 (m, 6H), 5.29–5.40 (m, 2H),
3.66 (t, J=6.4 Hz, 2H), 1.99–2.08 (m, 4H), 1.54–1.63 (m,
2H), 1.40–1.48 (m, 2H), 1.27–1.36 (m, 4H), 1.05 (s, 9H),
0.89 (t, J=7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) l
135.8, 134.4, 130.8, 129.9, 129.7, 127.8, 64.1, 32.4, 32.2,
27.2, 27.1, 26.2, 22.6, 19.4, 14.2. Adduct 5: 1H NMR (400
MHz, CDCl3) l 7.64–7.70 (m, 4H), 7.33–7.45 (m, 6H),
5.34–5.40 (m, 2H), 3.65 (t, J=6.4 Hz, 2H), 1.92–2.01 (m,
4H), 1.50–1.62 (m, 2H), 1.37–1.46 (m, 2H), 1.24–1.36 (m,
4H), 1.04 (s, 9H), 0.88 (t, J=7.2 Hz, 3H); 13C NMR (75
MHz, CDCl3) l 135.8, 134.4, 130.8, 130.3, 129.7, 127.8,
64.1, 32.5, 32.3, 32.0, 27.1, 26.0, 22.4, 19.4, 14.2. Adduct
27: 1H NMR (400 MHz, CDCl3) l 5.32–5.36 (m, 1H),
4.02–4.14 (m, 2H), 3.51 (t, J=7.2 Hz, 1H), 2.26–2.33 (m,
2H), 2.22 (apparent t, 2H), 2.10 (apparent t, 2H), 1.81–
1.89 (m, 2H), 1.43–1.69 (complex m, 4H), 1.42 (s, 3H),
1.36 (s, 3H); 13C NMR (75 MHz, CDCl3) l 144.5, 123.9,
108.8, 76.3, 69.7, 35.2, 33.6, 32.6, 31.3, 27.2, 26.0, 24.1,
23.6. Adduct 29: 1H NMR (400 MHz, CDCl3) l 7.65–
7.70 (m, 4H), 7.34–7.44 (m, 6H), 5.32–5.48 (m, 2H), 3.66
(t, J=6.4 Hz, 2H), 2.02 (apparent q, J=7.2 Hz, 2H),
1.55–1.64 (m, 5H), 1.40–1.48 (m, 2H), 1.05 (s, 9H); 13C
NMR (100 MHz, CDCl3) l 135.8, 134.4, 130.8, 129.7,
127.8, 124.1, 64.0, 32.4, 27.1, 26.8, 26.0, 19.5, 13.0.
Acknowledgements
Supported financially by the USPHS NIH (GM31278,
DK38226), the Robert A. Welch Foundation, and an
unrestricted grant from Taisho Pharmaceutical.
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1
Adduct 31: H NMR (400 MHz, CDCl3) l 7.65–7.70 (m,
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