X. Li et al. / Tetrahedron 57 (2001) 1175±1182
1181
1
99; MS m/z 247 (M1H ) . Anal. Calcd for C H NBrO :
1
7
C, 43.92; H, 4.91. Found: C, 44.04; H, 4.90.
cooling to room temperature, the mixture was quenched
with water, and then basi®ed with 10% aqueous K CO .
9
12
2
2
3
The crude product was then partitioned between CHCl3
and water, the aqueous layer was washed twice with
CHCl , and the organic layers combined and dried with
4
1
.3.7. Bis(2-(6-pyridylcarbinol ethoxymethyl ether)ketone
8. 2.35 g (9.55 mmol) of 17 was dissolved in 40 mL of
3
THF and the resulting solution cooled to 2788C. A solution
of n-BuLi in hexanes (10.5 mmol, 8.75 mL of a 1.2 M solu-
tion) was added dropwise to the cooled solution. After a
anhydrous MgSO . Column chromatography (mobile
4
phase 10% acetone in hexane), and removal of the solvent
under reduced pressure, gave the desired product as color-
1
less oil in 82% yield: H NMR (400 MHz, CD CN) d 1.10
period of 5 min,
(
a
4.78 mmol, 580 mL in 16 mL diethyl ether) was slowly
solution of diethyl carbonate
3
(t, 9H, J7.0 Hz) 3.17 (s, 3H) 3.53 (q, 6H, J7.0 Hz) 4.50
added to the solution of the lithiate. After stirring for 2 h
at 2788C, the reaction was allowed to warm to ca. 08C, and
quenched with water. The resulting mixture was basi®ed
with 10% aqueous K CO , and the crude product partitioned
(s, 6H) 4.69 (s, 6H) 7.29 (d, 3H, J7.3 Hz) 7.49 (d, 3H,
1
3
J7.3 Hz) 7.69 (pseudo t, 3H, J7.3 Hz); C NMR
(75 MHz) d 15.3, 53.3, 63.6, 70.6, 88.6, 95.1, 119.4,
2
1
123.2, 136.3, 157.0, 161.0; IR (®lm) cm 2997, 2947,
2887, 1606, 1581, 1462, 1407, 1372, 1193, 1158, 1118,
1068, 799, 764; MS m/z 542 (M1H ) . Anal. Calcd for
2
3
between CHCl and water. The aqueous layer was washed
3
twice with CHCl , and the organic layers combined, dried
3
1
1
with anhydrous MgSO , and the solvent removed under
4
C H N O : C, 64.31; H, 7.26. Found: C, 64.28; H, 7.35.
29 39
3
7
reduced pressure. Column chromatography (mobile phase
4% acetone in hexane), and removal of the solvent under
reduced pressure gave the product as a pale yellow oil in
4.3.10. Tris(2-(6-pyridylcarbinol)methanol methyl ether
21. 500 mg of ether 20 was dissolved in 30 mL of methanol
containing 1 mL of 37% aqueous HCl. The reaction was
warmed to 608C for 15 min. The solvent was removed
under reduced pressure and the crude product partitioned
1
4
3
2
9% yield: H NMR (400 MHz) d 1.22 (t, 6H, J7.0 Hz),
.65 (q, 4H, J7.0 Hz), 4.79 (s, 4H), 4.84 (s, 4H), 7.66 (d,
H, J7.8 Hz) 7.87 (pseudo t, 2H, J7.8 Hz), 8.00 (d, 2H,
1
3
J7.8 Hz); C NMR (75 MHz) d 15.1, 63.6, 70.1, 95.1,
between CHCl
layer was then washed twice with CHCl
layers combined and dried with anhydrous MgSO .
4
3
and 10% aqueous K
CO
2
3
. The aqueous
2
1
123.9, 124.3, 137.1, 153.4, 158.4, 192.6; IR (®lm) cm
2997, 2947, 2897, 1696, 1596, 1457, 1402, 1372, 1337,
1237, 1197, 1168, 1128, 1058, 854, 814, 764; MS m/z 361
3
, and the organic
Removal of the solvent under reduced pressure gave the
essentially pure product as a colorless oil in 99% yield. H
1
1
1
(M1H ) . Anal. Calcd for C H N O : C, 63.32; H, 6.71.
1
Found: C, 63.30; H, 6.77.
9
24
2
5
NMR (400 MHz) d 3.26 (s, 3H) d 4.00 (broad s, 3H) 4.64 (s,
6
H) 7.09 (d, 3H, J7.3 Hz) 7.54 (d, 3H, J7.3 Hz) 7.67
1
3
4
.3.8. Tris(2-(6-pyridylcarbinol ethoxymethyl ether)-
methanol 19. 0.26 g (1.07 mmol) of 17 was dissolved in
0 mL diethyl ether and the resulting solution cooled to
788C. A solution of n-BuLi in hexanes (1.18 mmol,
.98 mL of a 1.2 M solution) was then added dropwise to
the cooled solution. After a period of 5 min, a solution of 18
0.95 mmol, 340 mg in 5 mL) in ether was slowly added to
(pseudo t, 3H, J7.3 Hz); C NMR (75 MHz) d 53.3, 63.6,
2
1
88.3, 119.0, 122.5, 136.8, 157.4, 159.7; IR (®lm) cm
3356 (broad), 2927, 2857, 1606, 1581, 1462, 1227, 1093,
1
2
0
1
1
1008, 784; MS m/z 368 (M1H ) . Anal. Calcd for
.1/2 H O: C, 63.80; H, 5.98. Found: C, 63.79;
H, 5.81.
C
H
20
N
3
O
4
21
2
(
the lithiate solution. After stirring for 2 h at 2788C, the
reaction was allowed to warm to ca. 08C, and quenched
with water. The resulting mixture was basi®ed with 10%
aqueous K CO , and the crude product partitioned between
4.3.11. Tris(2-(picolinic acid)methanol methyl ether 6.
To a suspension of 0.18 g (0.49 mmol) of 11 and 0.06 g of
NaOH (1.47 mmol) in 20 mL H
(4.41 mmol) KMnO . The mixture was stirred at room
O, was added 0.70 g
2
2
3
4
CHCl and water. The aqueous layer was washed twice
3
with CHCl , the organic layers combined and dried with
3
temperature for 12 h. An excess of methanol was then
added to quench the reaction and the mixture was stirred
anhydrous MgSO , and the solvent removed under reduced
4
for a further 10 min. The MnO precipitate was ®ltered off,
2
pressure. Flash chromatography (mobile phase, hexane to
chloroform gradient), and removal of the solvent under
reduced pressure gave the product as colorless oil in 55%
and the ®ltrate acidi®ed with 10% aqueous HCl. Removal of
the solvent under reduced pressure gave the crude product
as a white solid. The pure triacid was isolated as a white
solid in 69% yield by washing the solid with THF and
1
yield: H NMR (400 MHz, CD CN) d 1.11 (t, 9H,
3
J7.0 Hz) 3.55 (q, 6H, J7.0 Hz) 4.55 (s, 6H) 4.71 (s,
recrystallization from methanol: mp .4008C, decompo-
sition at 1508C. H NMR (400 MHz, DMSO-d ) d 3.24 (s,
1
6
H) 7.08 (s, 1H) 7.33 (d, 3H, J7.3 Hz) 7.54 (d, 3H,
6
1
3
J7.3 Hz) 7.72 (pseudo t, 3H, J7.3 Hz); C NMR
3H) 7.81 (dd, 3H, J7.6 Hz, 2.0 Hz) 7.96 (m, 6H) d 13.00
21
1
(broad s, 3H); C NMR (75 MHz) d 53.2, 88.2, 123.8,
3
(
75 MHz) d 15.4, 63.7, 70.3, 81.1, 95.1, 119.8, 122.0,
2
37.0, 156.4, 162.2; IR (®lm) cm 3326, 3007, 2947,
1
1
2
1
127.8, 137.8, 147.2, 161.1, 166.3; IR (®lm) cm 3475
(broad), 2947, 2867, 1716, 1691, 1591, 1572, 1472, 1392,
907, 1606, 1586, 1472, 1407, 1377, 1197, 1163, 1113,
058, 794, 769; MS m/z 528 (M1H ) . Anal. Calcd for
1
1
1 1
1322, 1282, 1098, 1033, 1013, 779; MS m/z 410 (M1H ) ,
1
442 (M1Na ) , 819 (2M1H ) . Anal. Calcd for
1
1 1
C H N O : C, 63.74; H, 7.07. Found: C, 63.46; H, 7.10.
7
2
8
37
3
C H N O ´H O: C, 56.21; H, 4.00. Found: C, 56.47; H,
2
0
15
3
7
2
4
.3.9. Tris(2-(6-pyridylcarbinol ethoxymethyl ether)-
methanol methyl ether 20. 310 mg (7.80 mmol) of a
0% oil dispersion of NaH was washed twice with pentane
and added to 60 mL THF. To this stirring mixture was added
.82 g (1.56 mmol) of alcohol 19, and 490 mL (7.80 mmol)
of MeI. The reaction was stirred at 608C for 16 h. After
4.13.
6
Acknowledgements
We are grateful to Richard B. Cole of the New Orleans
0