S. E. Collibee, J. Yu / Tetrahedron Letters 46 (2005) 4453–4455
4455
13. General procedure for the synthesis of ortho-nitro-
phenylboronic acids: dry nitrogen-flushed 25 mL
ality (including many that are reactive toward Grignard
reagents) such as cyano, nitro, bromo, iodo, a-bromo-
methyl, methoxy, fluoro, and ester was tolerated, allow-
ing for further manipulation after cross-coupling
reactions. Interestingly, 2,4-dinitro and 2-nitro-4-iodo-
phenylboronic acids were prepared in 75% and 79%
yields, respectively, again demonstrating the aforemen-
tioned chelation effect (Table 2, entries 6 and 7).
A
round-bottomed flask equipped with a magnetic stirrer,
and a septum was charged with aryl iodide (4 mmol). Dry
THF (6 mL) was added, and the resulting solution was
cooled to À60 ꢁC using a dry ice/acetone bath, to which
was added PhMgCl (2 M in THF, 2.2 mL, 4.4 mmol,
Aldrich) dropwise. The I–Mg exchange was complete
within 5 min (monitored by TLC or HPLC of reaction
aliquots). Trimethyl borate (4.8 mmol, 536 lL) was added
dropwise into the reaction solution. The reaction mixture
was stirred for 30 min at À60 ꢁC and then quenched with
2 M aq HCl (4 mL) at À20 ꢁC. The reaction was extracted
with Et2O (3 · 20 mL), and the organic layers were
combined, dried over Na2SO4, filtered, and concentrated
in vacuo. The crude residue was recrystallized from
acetonitrile or ethyl acetate. Spectral data for new boronic
acids. Compound 2c: white solid, mp 158–160 ꢁC; 1H
NMR (300 MHz, CD3OD): d (ppm) 3.92 (s, 3H), 6.98 (d,
J = 2.6 Hz, 1H), 7.08 (dd, J = 2.6, 9.2 Hz, 1H), 8.21 (d,
J = 9.2 Hz, 1H); 13C NMR (75 MHz, CD3OD): d (ppm)
57.0, 116.1, 117.6, 127.0, 145.0, 166.7; HR-EIMS: m/z
calcd for C7H8BNO5, 197.0496. Found, 197.0492. Com-
pound 2d: off-white solid, mp 165–167 ꢁC; 1H NMR
(300 MHz, CD3OD): d (ppm) 7.58 (dd, J = 1.3, 7.3 Hz,
2H), 7.99 (m, 1H); 13C NMR (75 MHz, CD3OD): d
(ppm) 111.9, 123.3, 135.3, 153.2, 162.9, 166.2; HR-EIMS:
m/z calcd for C6H5BFNO4, 185.0296. Found, 185.0292.
Compound 2e: white solid, mp 256–258 ꢁC; 1H NMR
(300 MHz, DMSO-d6): d (ppm) 2.41 (s, 3H), 7.36 (m, 2H),
8.03 (d, J = 8.3 Hz, 1H), 8.13 (s, 2H); 13C NMR (75 MHz,
CD3OD): d (ppm) 124.3, 131.8, 133.6, 147.8, 150.0; HR-
EIMS: m/z calcd for C7H8BNO4, 181.0546. Found,
In conclusion, we have developed a facile and conve-
nient method for the preparation of functionalized
ortho-nitrophenylboronic acids, complementing existing
synthesis of aryl boronic acids. All reagents used in this
procedure are commercial available and were used with-
out further purification. The combined reaction and
purification time of about an hour allows for rapid
access to these analogs. The ortho-nitrophenylboronic
acids prepared by our methods are potentially useful
building blocks in organic synthesis.
Acknowledgements
We thank Drs. Brian T. Gregg and William G. Earley
for their help and encouragement.
References and notes
1. Cadogan, J. I. G.; Cameron-Wood, M. Proc. Chem. Soc.
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2. For an example, see: Kilic, E.; Tuezuen, C. Org. Prep.
Proced. Int. 1990, 22, 485.
3. For an example, see: Gronowitz, S.; Timari, G. J.
Heterocycl. Chem. 1990, 27, 1159.
4. Badger, G. M.; Seidler, J. H.; Thomson, B. J. Chem. Soc.
1951, 3207.
5. (a) William, D. H.; Bardsley, B. Angew. Chem., Int. Ed.
1999, 38, 1172; (b) Nicolaou, K. C.; Boddy, C. N. C.;
Brase, S.; Winssinger, N. Angew. Chem., Int. Ed. 1999, 38,
2096.
6. David, B.; Sevenet, T.; Morgat, M.; Guenard, D.; Moi-
sand, A.; Tollon, Y.; Thoison, O.; Wright, M. Cell Motil.
Cytoskeleton 1994, 28, 317.
7. (a) Ratcliffe, A. H.; Smith, G. N. Tetrahedron Lett. 1973,
52, 5179; (b) Johnson, J. A.; Sames, D. J. Am. Chem. Soc.
2000, 122, 6321.
8. Husain, A.; Galopin, C. C.; Zhang, S.; Pohnert, G.;
Ganem, B. J. Am. Chem. Soc. 1999, 121, 2647.
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1995, 60, 7508; (b) Ishiyama, T.; Itoh, Y.; Kitano, T.;
Miyaura, N. Tetrahedron Lett. 1997, 38, 3447.
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1997, 62, 6458; (b) Murata, M.; Oyama, T.; Watanabe, S.;
Masuda, Y. J. Org. Chem. 2000, 65, 164; (c) Baudoin, O.;
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1
181.0543. Compound 2f: white solid, mp 282–284 ꢁC; H
NMR (300 MHz, CD3OD): d (ppm) 7.84 (d, J = 8.1 Hz,
1H), 8.60 (d, J = 8.1 Hz, 1H), 8.98 (s, 1H); 13C NMR
(75 MHz, CD3OD): d (ppm) 119.6, 130.1, 135.1, 150.5,
152.5; HR-EIMS: m/z calcd for C6H5BN2O6, 212.0241.
Found, 212.0240. Compound 2g: white solid, mp 169–
171 ꢁC; 1H NMR(300 MHz, CD3OD): d (ppm) 7.31
(d, J = 7.9 Hz, 1H), 8.13 (d, J = 7.9 Hz, 1H), 8.57 (s,
1H); 13C NMR (75 MHz, CD3OD): d (ppm) 95.0, 133.2,
134.7, 144.9, 152.4; HR-EIMS: m/z calcd for C6H5BINO4,
292.9356. Found, 292.9361. Compound 2i: pale yellow
solid, mp 130–132 ꢁC; 1H NMR (300 MHz, CD3OD): d
(ppm) 3.90 (s, 3H), 7.35 (dd, J = 2.3, 8.1 Hz, 1H), 7.43
(d, J = 8.1 Hz, 1H), 7.74 (d, J = 2.3 Hz, 1H); 13C NMR
(75 MHz, CD3OD): d (ppm) 109.1, 122.6, 134.3, 153.3,
162.6; HR-EIMS: m/z calcd for C7H8BNO5, 197.0496.
Found, 197.0501. Compound 2j: off-white solid, mp 274–
1
276 ꢁC; H NMR (300 MHz, CD3OD): d (ppm) 7.51 (d,
J = 7.9 Hz, 1H), 7.96 (dd, J = 1.9, 7.9 Hz, 1H), 8.30 (d,
J = 1.9 Hz, 1H); 13C NMR (75 MHz, CD3OD): d (ppm)
124.4, 127.4, 134.9, 139.0, 152.8; HR-EIMS: m/z calcd for
C6H5BBrNO4, 244.9495. Found, 244.9490. 2k: white solid,
mp 328–330 ꢁC (dec); 1H NMR (300 MHz, CD3OD): d
(ppm) 7.76 (d, J = 7.9 Hz, 1H), 8.11 (d, J = 7.9 Hz, 1H),
8.62 (s, J = 1H); 13C NMR (75 MHz, CD3OD): d (ppm)
115.4, 118.3, 128.2, 134.8, 138.8, 152.1; HR-EIMS: m/z
calcd for C7H5BN2O4, 192.0372. Found, 192.0344. Com-
pound 2l: off-white solid, mp 125–127 ꢁC; 1H NMR
(300 MHz, CD3OD): d (ppm) 4.68 (s, 2H), 7.54 (d,
J = 7.5 Hz, 1H), 7.83 (dd, J = 1.3, 7.5 Hz, 1H), 8.30 (d,
J = 1.3 Hz, 1H); 13C NMR (75 MHz, CD3OD): (ppm)
32.2, 124.7, 133.8, 136.5, 142.6, 152.3; HR-EIMS: m/z
calcd for C7H7BBrNO4, 258.9651. Found, 258.9647.