A. Bouillon et al. / Tetrahedron 59 (2003) 10043–10049
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45 min. A solution of triisopropylborate (4.42 g, 24 mmol,
1.2 equiv.) was then added and the mixture was abandoned
at 2788C for 2 h, and then allowed to warm to room
temperature and stirred for an additional hour. The mixture
was quenched by slow addition of 3% aqueous NaOH
solution (200 mL). The resulting aqueous layer was
collected and acidified down to pH 5–6 by dropwise
addition of 3N HCl (<90 mL), keeping the internal
temperature below 58C. Extraction with ethyl acetate,
evaporation of the organic layer and crystallisation from
ether gave 3a; 4a; 7a.
3.3.2. 2-[2-(6-Chloro)pyridine]-4,4,5,5-tetramethyl-1,3-
dioxaborolane (4b). White solid, mp 1088C. IR (KBr):
2989, 1452, 1396, 1345, 1318, 1144, 1129, 860, 805 cm21
.
1H NMR (d6-DMSO) d 7.83 (dd, J¼7.0, 8.0 Hz, 1H), 7.69
(d, J¼7.0 Hz, 1H), 7.55 (d, J¼8.0 Hz, 1H), 1.29 (s, 12H).
13C NMR (d6-DMSO) d 151.0, 138.8, 129.7, 126.1, 84.4,
24.6. MS [m/z] 238–239–240–241, [m/z-Cl] 203–204.
Anal. calcd for C11H15BClNO2: C, 55.16; H, 6.31; N, 5.85.
Found: C, 55.28; H, 6.40; N, 5.92.
3.3.3. 2-[2-(5-Chloro)pyridine]-4,4,5,5-tetramethyl-1,3-
dioxaborolane (7b). White solid, mp 1078C. IR (KBr):
2974, 1460, 1405, 1382, 1191, 1167, 1146, 1043, 880, 821,
3.2.1. 6-Bromopyridin-2-yl-boronic acid (3a). White solid,
dec 2108C. IR (KBr): 3391, 1573, 1543, 1447, 1415, 1385,
1
762, 700 cm21. H NMR (d6-DMSO) d 8.62 (s, 1H), 8.52
1303, 1171, 1108, 987, 789, 681 cm21
.
1H NMR (d6-
(d, J¼4.4 Hz, 1H), 7.55 (d, J¼4.4 Hz, 1H), 1.31 (s, 12H).
13C NMR (d6-DMSO) d 148.7, 147.2, 135.3, 129.6, 84.7,
24.5. MS [m/z] 238–239–240–241, [m/z-Cl] 203–204.
Anal. calcd for C11H15BClNO2: C, 55.16; H, 6.31; N, 5.85.
Found: C, 55.29; H, 6.41; N, 5.93.
DMSO) d 7.95 (s, 2H), 7.84 (d, J¼7.2 Hz, 1H), 7.76 (dd,
J¼7.2, 7.9 Hz, 1H), 7.68 (d, J¼7.9 Hz, 1H). Anal. calcd for
C5H5BBrNO2: C, 29.76; H, 2.50; N, 6.94. Found: C, 29.81;
H, 2.39; N, 6.77.
3.2.2. 6-Chloropyridin-2-yl-boronic acid (4a). White
solid, dec 2008C. IR (KBr): 2989, 1452, 1396, 1345,
3.4. General procedure for the synthesis of
dioxazaborocanes
1
1318, 1144, 1129, 860, 805 cm21. H NMR (d6-DMSO) d
8.15 (s, 2H), 7.69–7.55 (m, 3H). Anal. calcd for C5H5-
BClNO2: C, 38.16; H, 3.20; N, 8.90. Found: C, 38.34; H,
3.42; N, 8.65.
To a solution of pyridin-2ylboronic acid and MgSO4 (ca. 1 g
per mmol) in freshly distilled CH2Cl2 (15 mL) is added
dropwise
a
solution of N-methyldiethanolamine
(1.05 equiv.) in CH2Cl2, The mixture is allowed to react
under strong stirring for 18 h. The mixture is then filtered
under reduced pressure. The filtrate is dried over MgSO4
and concentrated to dryness. The residue was pure enough
for further purpose but analytical samples could be prepared
by crystallisation from acetonitrile.
3.2.3. 5-Chloropyridin-2-yl-boronic acid (7a). Yellowish
solid, mp.2508C. IR (KBr): 3388, 3105, 1613, 1410, 1184,
1072, 774 cm21. 1H NMR (d6-DMSO) d 8.66 (s, 2H), 8.52
(s, 1H), 8.43 (d, J¼4.1 Hz, 1H), 7.39 (d, J¼4.1 Hz, 1H).
Anal. calcd for C5H5BClNO2: C, 38.16; H, 3.20; N, 8.90.
Found: C, 38.39; H, 3.40; N, 8.64.
3.4.1. 2-[2-(6-Bromo)pyridine]-1,3,6-dioxazaborocane
(3c). Cream solid (98%), mp 1608C. IR (KBr): 3076,
3053, 2966, 2878, 2848, 1572, 1535, 1468, 1424, 1380,
1224, 1151, 1106, 1085, 965, 852, 802, 737, 708 cm21. 1H
NMR (d6-DMSO) d 7.51 (m, 2H), 7.34 (dd, J¼8.6, 1.8 Hz,
1H), 3.88 (m, 4H), 3.25 (m, 2H), 2.99 (m, 2H), 2.34 (s, 3H).
Anal. calcd for C10H14BBrN2O2: C, 42.15; H, 4.95; N, 9.83.
Found: C, 42.10; H, 4.99; N, 9.88.
3.3. General procedure for the synthesis of halopyridin-
2-yl boronic esters (3b, 4b, 7b)
To a slurry of 2.5 M solution of n-BuLi (17 mL, 43 mmol,
1.2 equiv.) in dried tetrahydrofuran, cooled to 2788C, was
added a solution of 2-bromohalopyridine (1 equiv.) in THF.
The resulting dark coloured mixture was allowed to react at
this temperature over 45 min. A solution of triisopropyl-
borate (8.0 g, 43 mmol, 1.2 equiv.) was then added drop-
wise and the mixture allowed to warm to room temperature
and stirred for an additional hour. A solution of anhydrous
pinacol (5.65 g, 48 mmol, 1.35 equiv.) in THF was added
and, after 5 min, a solution of glacial acetic acid (2.3 g,
40 mmol, 1.05 equiv.). The mixture was filtered through
Celite, and extracted by 2.5% aqueous NaOH solution
(200 mL). The resulting aqueous layer was collected and
acidified down to pH 6–7 by dropwise addition of 3N HCl,
keeping the internal temperature below 58C. Extraction with
ether, evaporation of the ethereal layer and washing with
acetonitrile gave 3b; 4b; 7b.
3.4.2. 2-[2-(5-Chloro)pyridine]-1,3,6-dioxazaborocane
(7c). Beige solid, mp 1358C. IR (KBr): 3070, 3050, 2963,
1570, 1532, 1470, 1422, 1376, 1220, 1152, 1085, 965 cm21
.
1H NMR (CDCl3) d 8.39 (s, 1H), 8.31 (d, J¼4.7 Hz, 1H),
7.61 (d, J¼4.7 Hz, 1H), 4.10 (m, 4H), 3.19 (m, 4H), 2.52 (s,
3H). Anal. calcd for C10H14BClN2O2: C, 49.94; H, 5.87; N,
11.65. Found: C, 49.82; H, 5.79; N, 11.74.
3.5. General procedure for the palladium-assisted
coupling of pyridylboronic acid with halo compounds
A mixture of halopyridylboronic acid (1.2 equiv.), halo-
compound (bromobenzene, 2-iodo-4-nitrobenzene or
4-iodoanisole) (1 equiv.), tetrakis-(triphenylphosphine)pal-
ladium (0) (4% mol) and aqueous Na2CO3 (2.3 equiv.) in
DME was heated to reflux for 3–12 h (total consumption of
halocompound seen on TLC). Ethyl acetate and water were
then added to the mixture. The organic layer was separated,
dried over MgSO4 and concentrated to dryness. The residue
was chromatographied on silica gel (cyclohexane 80–ethyl
acetate 20).
3.3.1. 2-[2-(6-Bromo)pyridine]-4,4,5,5-tetramethyl-1,3-
dioxaborolane (3b). White solid, mp 1288C. IR (KBr):
2976, 2934, 1545, 1450, 1391, 1343, 1318, 1126, 858, 801,
710 cm21. 1H NMR (d6-DMSO) d 7.72–7.65 (m, 3H), 1.28
(s, 12H). 13C NMR (d6-DMSO) d 142.4, 138.6, 130.1,
129.8, 84.4, 24.7. MS [m/z] 283–284–285–286, [m/z-Br]
202–204. Anal. calcd for C11H15BBrNO2: C, 46.53; H,
5.32; N, 4.93. Found: C, 46.60; H, 5.45; N, 4.87.