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A. Bouillon et al. / Tetrahedron 58 22002) 4369±4373
3.2.2. 2-Chloro-4-pyridylboronic acid 113a). White solid,
mp 2108C. IR <KBr): 3357, 3094, 1451, 1422, 1367, 1336,
3.4. General procedure for the synthesis of 2-halo-4-
pyridylboronic esters
1
1209, 1114, 1098, 1070, 1000, 845, 731, 664 cm21. H
NMR <d6-DMSO) d 8.69 <s, 2H), 8.39 <d, J4.7Hz, 1H),
7.72 <s, 1H), 7.64 <d, J4.7Hz, 1H). Anal. calcd for
C5H5BClNO2: C, 38.16; H, 3.20; N, 8.90. Found: C,
38.44; H, 3.41; N, 8.62.
To a slurry of freshly distilled tetramethylethylenediamine
<1.1 equiv.) in 150 mL of anhydrous ether cooled to 2108C
was added dropwise a 2.5 M solution of nBuLi <1.2 equiv.).
The mixture was allowed to react at this temperature over
20 min, and then cooled to 2608C. A solution of 2,4-dihalo-
pyridine <20 mmol, 1 equiv.) in anhydrous ether <50 mL)
was dropwise added, maintaining the temperature at
2608C. The resulting dark coloured <apricot) mixture was
allowed to react at this temperature over 30 min. After
cooling down to 2708C, a solution of triisopropylborate
<1.2 equiv.) in anhydrous ether <50 mL) was added in
10 min. The mixture was mixed at this temperature for
30 min, and allowed to warm to 108C <2 h). A solution of
anhydrous pinacol <1.3 equiv.) in 75 mL of anhydrous ether
was added and, after 10 min, a solution of glacial acetic acid
<1.05 equiv.) in anhydrous ether <50 mL). The mixture was
allowed to react for 4 h, then ®ltered through Celite, and
extracted by 4% aqueous NaOH solution <200 mL). The
resulting aqueous layer was collected and acidi®ed down
to pH 6 by dropwise addition of 3N HCl <<90 mL), keeping
the internal temperature below 58C. Extraction with Et2O,
evaporation of the ethereal layer and recrystallization gave
12b, 13b, and 14b.
3.2.3. 2-Fluoro-4-pyridylboronic acid 114a). White solid,
mp 2008C. IR <KBr): 3357, 1493, 1458, 1397, 1347, 1152,
1
1127, 1067, 1004, 897, 846, 733, 681, 755 cm21. H NMR
<d6-DMSO) d 8.66 <s, 2H), 8.22 <d, J4.7Hz, 1H), 7.59 <t,
J4.0 Hz, 1H), 7.37 <s, 1H). 13C NMR <d6-DMSO) d
163.1 <d, J236.1 Hz), 146.8 <d, J13.2 Hz), 126.3
<d, J4.1 Hz), 113.7<d, J33.7Hz). Anal. calcd for
C5H5BFNO2: C, 42.62; H, 3.58; N, 9.94. Found: C, 42.22;
H, 3.26; N, 9.62.
3.3. General procedure for the synthesis of 3-halo-4-
pyridylboronic acids
To a slurry of freshly distilled diisopropylamine <1.2 equiv.)
in 150 mL of anhydrous ether cooled to 2108C was added
dropwise a 2.5 M solution of nBuLi <1.25 equiv.). The
mixture was allowed to react at 2108C during 30 min,
and then cooled to 2608C <2958C for 17). A solution of
3-halopyridine <20 mmol, 1 equiv.) in 50 mL of anhydrous
ether was then added dropwise in order to keep the internal
temperature at 2608C <2958C for 17). The resulting
coloured mixture was allowed to react at this temperature
over 0.75 h. A solution of triisopropylborate <1.25 equiv.)
in 50 mL of anhydrous ether was then dropwise added,
keeping the internal temperature at 2608C <2958C for
17). The mixture was allowed to warm to room temperature
and left to react for an additional hour. The resulting
solution was quenched by slow addition of 4% aqueous
NaOH solution <150 mL). The resulting aqueous layer was
collected and acidi®ed to pH 5±6 by dropwise addition of
3N HCl <<70 mL), keeping the internal temperature below
58C. Extraction with ethyl acetate, evaporation of the
organic layer and crystallization from Et2O gave pure 18a,
19a, and 20a.
3.4.1. 2-[4-12-Bromo)pyridine]-4,4,5,5-tetramethyl-1,3-
dioxaborolane 112b). White solid, mp 1208C <acetonitrile).
IR <KBr): 2976, 2929, 1519, 1469, 1357, 1326, 1267, 1142,
1082, 964, 859, 718, 670 cm21. 1H NMR <d6-DMSO) d 8.43
<d, J4.6 Hz, 1H), 7.68 <s, 1H), 7.58 <d, J4.6 Hz, 1H),
1.29 <s, 12H). 13C NMR <d6-DMSO) d 150.5, 146.2,
132.4, 127.6, 84.8, 24.67. Anal. calcd for C11H15BBrNO2:
C, 46.53; H, 5.32; N, 4.93. Found: C, 46.65; H, 5.47; N,
4.88.
3.4.2. 2-[4-12-Chloro)pyridine]-4,4,5,5-tetramethyl-1,3-
dioxaborolane 113b). White solid, mp 688C <acetonitrile).
IR <KBr): 2976, 2926, 1472, 1371, 1329, 1267, 1143, 1088,
1
964, 864, 738, 674 cm21. H NMR <d6-DMSO) d 8.44 <d,
J4.6 Hz, 1H), 7.54 <bs, 2H), 1.29 <s, 12H). 13C NMR
<d6-DMSO) d 150.5, 149.9, 128.7, 127.4, 84.8, 24.6. Anal.
calcd for C11H15BClNO2: C, 55.16; H, 6.31; N, 5.85. Found:
C, 55.29; H, 6.41; N, 5.93.
3.3.1. 3-Fluoro-4-pyridylboronic acid 118a). White solid,
dec 2208C. IR <KBr): 3220, 1479, 1431, 1379, 1265, 1228,
1187, 1071, 837, 789 cm21. 1H NMR <d6-DMSO) d 8.69 <s,
2H), 8.58 <s, 1H), 8.38 <bs, 1H), 7.49 <bs, 1H). Anal. calcd
for C5H5BFNO2: C, 42.62; H, 3.58; N, 9.94. Found: C,
42.51; H, 3.38; N, 9.72.
3.4.3. 2-[4-12-Fluoro)pyridine]-4,4,5,5-tetramethyl-1,3-
dioxaborolane 114b). White solid, mp 608C <anhydrous
ether). IR <KBr): 3064, 2983, 2935, 1544, 1487, 1400,
1358, 1269, 1214, 1144, 1089, 966, 912, 850, 793,
1
689 cm21. H NMR <d6-DMSO) d 8.25 <d, J4.5 Hz, 1H),
3.3.2. 3-Chloro-4-pyridylboronic acid 119a). White solid,
mp .2508C. IR <KBr): 3105, 1411, 1371, 1298, 1262, 1182,
1163, 1077, 774, 695 cm21. 1H NMR <d6-DMSO) d 8.67<s,
2H), 8.52 <s, 1H), 8.43 <d, J4.1 Hz, 1H), 7.39 <d,
J4.1 Hz, 1H). Anal. calcd for C5H5BClNO2: C, 38.16;
H, 3.20; N, 8.90. Found: C, 38.44; H, 3.41; N, 8.62.
7.46 <bs, 1H), 7.19 <bs, 1H), 1.27 <s, 12H). 13C NMR <d6-
DMSO) d 162.9 <d, J237.0 Hz), 147.5 <d, J14.0 Hz),
126.2 <d, J3.3 Hz), 113.9 <d, J35.4 Hz), 84.7, 24.5.
Anal. calcd for C11H15BFNO2: C, 59.23; H, 6.78; N, 6.28.
Found: C, 59.35; H, 6.96; N, 6.42.
3.3.3. 3-Bromo-4-pyridylboronic acid 120a). White solid,
mp .2508C. IR <KBr): 3195, 1448, 1411, 1362, 1336, 1207,
3.5. General procedure for the synthesis of 3-halo-4-
pyridylboronic esters
1
1103, 1058, 840, 732, 661 cm21. H NMR <d6-DMSO) d
8.68 <s, 2H), 8.61 <s, 1H), 8.46 <d, J4.6 Hz, 1H), 7.34 <d,
J4.6 Hz, 1H). Anal. calcd for C5H5BBrNO2: C, 29.76; H,
2.50; N, 6.94. Found: C, 29.82; H, 2.37; N, 6.76.
To a slurry of freshly distilled diisopropylamine <1.2 equiv.)
in 150 mL of anhydrous ether cooled to 2108C was added
dropwise a 2.5 M solution of nBuLi <1.25 equiv.). The