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hydration of TMB is a facile process.11 MBA esters MeB(OR)2 were inferior to TMB.
x
Treatment of the dichloride with Me3Al10 (1.1 equiv. DMF, 10 mol% Pd(PPh3)4, 70 C internal, overnight) leads to
monomethylation ortho to the nitro function (84% yield).
{ 1
Complete consumption of 5-bromo-m-xylene was achieved under conditions C (24 h) as evidenced by H NMR and
TLC analysis of the crude product; however, the puri®ed yield of mesitylene was low, possibly due to volatility.
**
The cheaper and more robust Pd(OAc)2/4PPh3 combination has proved comparable to Pd(PPh3)4 for certain sub-
strates.
6239
Table 1
Methylation of aryl halides with trimethylboroxine (TMB)
In conclusion, trimethylboroxine (TMB) is a practical methylating agent for a variety of aryl halides
under palladium catalysis.
Typical experimental procedure (entry 7)
1,5-Dichloro-2-nitro-4-(tri¯uoromethyl)benzene (1.02 g, 3.92 mmol), potassium carbonate
(1.63 g, 11.76 mmol), Pd(PPh3)4 (0.45 g, 0.39 mmol), 10% aq. 1,4-dioxane (10 mL) and TMB
6240
(0.55 mL, 3.92 mmol) were charged to a ¯ask and the contents heated to 105±115 C (oil bath
temperature) under nitrogen for 6 h and then stirred overnight at ambient temperature. The
reaction mixture was ®ltered through a pad of Celite1, washed with THF and concentrated in
vacuo. Flash column chromatography (SiO2, 10:1 hexane:Et2O) a€orded 1,5-dimethyl-2-nitro-4-
1
(tri¯uoromethyl)benzene as a low melting solid, 0.72 g (84%): Rf 0.45 (5:1 hexane:Et2O); H
5
NMR (400 MHz, CDCl3) 8.27 (s, 1H), 7.30 (s, 1H), 2.65 (s, 3H), 2.54 (q, J(H,F)=1.5 Hz, 3H);
13 3 5
C NMR (100 MHz, CDCl3) 146.5 (bs), 142.3 (q, J(C,F)=1.5 Hz), 137.5 (q, J(C,F)=1.0 Hz),
2 1 3
136.5 (bs), 127.8 (q, J(C,F)=31.7 Hz), 123.3 (q, J(C,F)=273.6 Hz), 122.7 (q, J(C,F)=5.4 Hz),
4
20.3 (s), 19.0 (q, J(C,F)=2.4 Hz); LRMS (EI+) m/z (relative intensity) 219 (M+, 22), 202 (100),
189 (5); HRMS (EI+) m/z calcd for C9H8NO2F3 219.0507, found 219.0496.
Acknowledgements
The invaluable support of Mrs G. Smith and Mr A. Bateman with the SK-233TM workstation
and on-line HPLC analysis is gratefully acknowledged.
References
1. Suzuki, A. J. Organomet. Chem. 1999, 576, 147±168 and cited references.
2. Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh, M.; Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314±321.
3. Furstner, A.; Seidel, G. Tetrahedron 1995, 51, 11165±11176 and cited references.
È
4. Mu, Y.-Q.; Gibbs, R. A. Tetrahedron Lett. 1995, 36, 5669±5672.
5. Zhou, X.; Tse, M. K.; Wan, T. S. M.; Chan, K. S. J. Org. Chem. 1996, 61, 3590±3593.
6. Niu, C.; Li, J.; Doyle, T. W.; Chen, S.-H. Tetrahedron 1998, 54, 6311±6318.
7. For a recent application of a methyl oxa-borane see: Braun, M. P.; Dean, D. C.; Melillo, D. G. J. Label. Comps.
Radiopharm. 1999, 42, 469±476.
8. Trost, B. M.; Spagnol, M. D. J. Chem. Soc., Perkin Trans. 1 1995, 2083±2096.
9. For an example of the use of triphenylboroxine in Suzuki±Miyaura coupling see: Goodson, F. E.; Wallow, T. I.;
Novak, B. M. J. Am. Chem. Soc. 1997, 119, 12441±12453.
10. Blum, J.; Gelman, D.; Baidossi, W.; Shakh, E.; Rosenfeld, A.; Aizenshtat, Z.; Wassermann, B. C.; Frick, M.;
Heymer, B.; Schutte, S.; Wernik, S.; Schumann, H. J. Org. Chem. 1997, 62, 8681±8686 and cited references.
11. Brown, H. C.; Cole, T. E. Organometallics 1985, 4, 816±821.
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