October 1998
SYNLETT
1143
(13) For recent alternatives, see Evans, E. F.; Lewis, N. J.; Kapfer, I.;
Macdonald, G.; Taylor, R. J. K. Synth. Commun., 1997, 27, 1819;
Siro, J. G.; Martin, J.; Garcia Navio, J. L.; Remuinan, M. J.;
Vaquero, J. J. Synlett., 1998, 147; Jones, K. D.; Ellington, A. D.
Tetrahedron Lett., 1998, 39, 175 and references therein.
requires C, 67.25; H, 5.87; N, 12.55%].
A solution of the foregoing alcohol
ml) containing 5% palladium on charcoal (0.05 g) was vigorously
stirred under an atmosphere of hydrogen for 4 h at 20° C then
filtered through celite. The solid was washed with
dichloromethane and the combined filtrates evaporated to leave
(0.160 g) in methanol (11
12a
(14) Representative procedures:- General procedure for generation of
dianion 2:- Butyl lithium (2.2 equiv. of a 1.6M solution in
hexanes) was added to a stirred solution of tetraglyme (5 equiv.) in
the phenol
(0.078 g, 78%) as a colourless solid, m.p. 97-98°
13a
-1
C, ν /cm (CH Cl ) 3268 and 1723; δ (CDCl ; 323° K) 1.22-
max
2
2
H
3
t
-1
1.50 (9H, br s, BuO), 4.30-4.39 (2H, br s, CH Ar), 6.80-6.89 (2H,
tetrahydrofuran (10 ml mmol of N-Boc-aminobenzotriazole 1)
2
m), 6.99 (1H, d, J 7.5, Ar-H), 7.12 (1H, dd, J 7.5 and 7.5, 5-H),
7.19 (1H, d, J 7.5, 6-H), 7.25 (1H, dd, J 7.8 and 7.8, Ar-H), 7.81
(1H, br d, J 7.5, 4-H) and 8.75-8.82 (1H, br s, NH); δ (CDCl )
maintained at -78° C. After 0.5 h, a solution of the benzotriazole 1
(1 equiv.) in tetrahydrofuran (10 ml mmol ) was added dropwise
via syringe. The resulting deep purple solution was stirred at -78°
-1
C
3
28.4 (C(CH ) ), 30.3 (CH ), 84.3 (C(CH ) ), 116.3, 118.3, 121.0
C for 0.5 h. During this period, anhydrous cerium(III) chloride
(1.1 equiv.) was stirred in tetrahydrofuran (30 ml mmol ), the
3 3
2
3 3
-1
(all CH), 124.3 (C), 125.4 (CH), 125.7 (C), 128.6, 129.9, 131.2
(all CH), 131.4, 136.2, 144.8 (all C) and 154.4 (CO); m/z (APCI)
suspension cooled to -78° C and treated with butyl lithium (1.6M
solution in hexanes) until a faint orange colouration persisted
+
341 (M + 1, 100%).
-1
The foregoing phenol
(0.088 g) was dissolved in
13a
(typically 1 ml mmol ). The purple dianion solution was then
dichloromethane (2 ml) containing trifluoroacetic acid (0.2 ml)
and the resulting solution stirred at ambient temperature for 1.5 h.
The solution was then basified by the addition of aqueous 2M
sodium hydroxide (2 ml) and then the pH adjusted to ~5 by the
careful addition of 2M hydrochloric acid. The aqueous layer was
separated, saturated with sodium chloride and extracted with
dichloromethane (3 x 10 ml). The combined organic solutions
rapidly transferred via syringe into this suspension which was then
stirred at -78° C for 3 h before the addition of the benzaldehyde
-1
(1.1 equiv.) in tetrahydrofuran (1 ml mmol ). The resulting
mixture was stirred for 16 h without the addition of further coolant
then quenched with saturated aqueous ammonium chloride, made
acidic with 2M hydrochloric acid and the organic products
-1
extracted into ether (3 x 30 ml mmol ). The combined extracts
were washed with saturated brine, dried (MgSO ) and filtered. To
were washed with saturated aqueous sodium hydrogen carbonate
(10 ml mmol ), water (10 ml mmol ) and brine (10 ml mmol ),
4
-1
-1
-1
the stirred filtrate was added N-iodosuccinimide (0.090 g) in one
portion. When gas evolution had ceased, the solution was stirred
at 20° C for 0.5 h then washed with saturated aqueous sodium
thiosulfate (5 ml), water (5 ml) and brine (10 ml) then dried and
evaporated. Column chromatography of the residue using 40-60
dried (MgSO ) and evaporated. Column chromatography in 40-60
4
petrol/diethyl ether (7:3) was used to separate the pure products.
Condensation of benzotriazole with aldehyde
under these
1
11a
conditions give the alcohol
(1.145 g, 68%) as a beige solid,
12a
-1
petrol separated the xanthene
(0.066 g, 86%) as a colourless
14a
-1
m.p. 67-68 °C, ν /cm (CH Cl ) 3263 and 1744; δ (CDCl ;
max
2
2
H
3
t
solid, m.p. 56-59 °C, ν /cm (CH Cl ) 3062, 2962, 1926,
323K) 1.41-1.48 (9H, br s, BuO), 3.23 (1H, br d, J 4.4, OH), 4.98
(1H, d, J 11.1, CH H Ph), 5.05 (1H, d, J 11.1, CH H Ph), 6.62
max
2
2
1622, 1597, 1445, 1426, 1246, 1099, 891 and 754; δ (CDCl )
H
3
a
b
a b
3.95 (2H, s, CH ), 6.69 (1H, dd, J 7.7 and 7.7, 4-H), 6.99 (1H, dd,
(1H, d, J 4.4, CHOH), 7.02-7.06 (2H, m), 7.10 (1H, d, J 7.1, 6-H),
7.25-7.38 (8H, m), 7.80-7.85 (1H, br s, NH) and 7.99 (1H, dd, J
7.1 and 2.1, 4-H); δ (CDCl ) 28.4 (C(CH ) ), 70.7 (CH ), 84.0
2
J 7.6 and 7.6, Ar-H), 7.03-7.26 (4H, m) and 7.58 (1H, d, J 7.6, 5-
H); δ (CDCl ) 27.4 (CH ), 83.7 (CI), 115.8 (CH), 119.6, 120.8
C
3
2
C
3
3 3
2
(both C), 122.5, 123.4, 126.7, 127.5, 128.0, 136.5 (all CH), 150.1
(C(CH ) ), 112.1, 120.4, 121.8, 124.8 (all CH), 126.8 (C), 127.9,
3 3
+
128.0, 129.0, 129.3, 129.7 (all CH), 130.3, 136.4, 145.5, 154.2 (all
and 150.9 (both C); m/z (EI) 308 (M , 10%), 181 (32), 152 (41),
+
+
C) and 156.1 (CO); m/z (APCI) 447 (M + 1, 100%), 391 (9) and
139 (20), 127 (73) and 74 (100) [Found: M , 307.9693. C H IO
13
9
347 (12) [Found: C, 67.04; H, 5.63; N, 12.29. C
H
N O
4 4
requires M, 307.9700].
25 26