Stereoselective Synthesis of Quaternary Benzylic Carbons
J . Org. Chem., Vol. 63, No. 23, 1998 8115
NMR δ 27.7, 34.2, 34.4, 42.2, 55.9, 58.8, 58.9, 69.8, 80.1, 110.1,
110.9, 111.2, 126.3, 127.3, 128.6, 133.4, 143.9, 144.4, 148.2,
168.2; MS, m/z 473 (100), 315 (21); HRMS, m/z 472.2725
(C30H36N2O3, requires 472.2726).
[5RS,5(4′R*,5′R*)]-7-ter t-Bu t oxy-5-(4′,5′-d ih yd r o-4′,5′-
diph en yl-1H-im idazol-2′-yl)-5-ph en ylh eptan -1-ol (24a) was
obtained from 14a as colorless amorphous solid (81%, 7.8:1
mixture of two diastereoisomers): Rf 0.41 (dichloromethane
saturated with ammonia); IR (neat, cm-1) 3368 (b), 2969, 1600;
1H NMR (250 MHz) (major isomer) δ 1.05 (9H, s), 1.45 (2H,
tt, J ) 6.0 Hz, J ) 5.9 Hz), 1.60 (2H, q, J ) 6.3 Hz), 2.28 (2H,
m), 2.48 (2H, m), 3.41 (2H, t, J ) 6.5 Hz), 3.61 (2H, td, J ) 6.0
Hz, J ) 3.0 Hz), 4.78 (2H, s), 7.18-7.50 (15H, m); 13C NMR
(major isomer) δ 20.5, 27.6, 32.4, 35.9, 36.2, 47.4, 58.3, 62.2,
126.3, 126.4, 126.7, 126.9, 127.x, 127.9, 128.7, 129.0, 143.6,
170.6; MS m/z 485 (100), 412 (12), 384 (15); HRMS, m/z
484.3077 (C32N40N2O2 requires 484.3090).
[2(1′RS),4R*,5R*]-4,5-Dih yd r o-4,5-d ip h en yl-2-(1′-p h e-
n ylp en t-4-en -1-yl)-1H-im id a zole (15) was obtained from 8a
and 4-bromobutene 13 as white crystals (85%, mixture of two
diastereoisomers): mp 175-176 °C (ether); Rf 0.60 (dichlo-
romethane saturated with ammonia/pentane 1:2); IR (KBr,
1
cm-1) 3028, 2920, 1599; H NMR (250 MHz) δ 2.03 (3H, m),
2.32 (1H, 2q, J ) 6.3 Hz), 3.61 (1H, 2t, J ) 7.8 and 6.4 Hz),
4.60 (2H, d, J ) 7.7 Hz), 4.98 (2H, m), 5.78 (1H, m,), 7.05-
7.45 (15H, m); 13C NMR δ 31.6, 31.8, 32.4, 45.6, 74.5, 115.4,
125.7-129.0, 138.0, 143.5, 168.1; MS (FAB technique), m/z
(relative intensity) 339 ([M - C2H4]+•, 100%); HRMS, m/z
366.2096(M+) (C26H26N2, requires 366.2096).
[5RS,5(4′R*,5′R*)]-7-ter t-Bu t oxy-5-(4′,5′-d ih yd r o-4′,5′-
dip h en yl-1H-im ida zol-2′-yl)-5-(3,4-d im eth oxyp h en yl)h ep -
ta n -1-ol (24b) was obtained from 14b as a colorless viscous
oil (77%, 6.3:1 mixture of two diastereoisomers): Rf 0.31
(7RS,2R*,3R*)-7-(2,3-Dim eth oxyp h en yl)-2,3-d ip h en yl-
2,3,4,5,6,7-h exa h yd r o-p yr r olo[1,2-a ]im id a zole (16) was
obtained from 8c and chlorobromoethane 12b as a pale yellow
amorphous solid (81%, mixture of two diastereoisomers): Rf
0.70 (dichloromethane saturated with ammonia/pentane 1:2);
mp 87-96 °C; IR (KBr, cm-1) 3361, 2937, 1628; 1H NMR (250
MHz) δ 2.45 (1H, m), 2.87 (2H, m), 3.10 (1H, m), 3.22 (1H, t,
J ) 7.1 Hz), 3.85 and 3.89 (3H, 2s), 3.95 and 3.99 (3H, 2s),
4.29 and 4.40 (1H, 2d, J ) 9.7 Hz, J ) 7.1 Hz), 5.22 and 5.31
(1H, 2d, J ) 9, 4 Hz, J ) 7.8 Hz), 6.85-7.40 (13H, m); 13C
NMR δ 35.7, 35.9; 40.7, 41.3, 42.9, 44.9, 55.9, 73.9, 75.8, 85.5,
85.9, 111.0, 111.3, 111.6, 119.6, 119.9, 126.6, 126.8, 127.1,
127.2, 127.7, 127.8, 128.2, 128.3, 128.6, 128.8, 133.2, 139.8,
140.3, 142.4, 147.9, 149.0, 175.5; MS (FAB technique) m/z 398
(80), 91 (100%); HRMS, m/z 398.1992 (C26H26N2O2, requires
398.1994).
Gen er a l P r oced u r e for th e Alk yla tion of Ar yl-Su bsti-
tu ted Im id a zolin es w ith THF . Into a degassed solution of
imidazoline (2.5 mmol) in THF (7.5 mL) was added sec-
butyllithium (2.4 mL, 2.5 M solution in hexane) at -25 °C and
under an Ar atmosphere. After 25 min the mixture was cooled
to -100 °C, and 9-BBN triflate (7.5 mL, 0.5 M solution in
hexane) was slowly added via syringe. The progress of the
reaction could be monitored simply by following the change
in the color of the mixture which turned from dark red to
orange. The mixture was quenched after 3 min with some
drops of water and allowed to reach room temperature. Then
H2O2 (1.0 mL, 35%, 10.3 mmol) and NaOH (2.5N, 3.0 mL, 7.5
mmol) were added, and the mixture was stirred for 1 h at room
temperature. The solution was extracted twice with water,
and then the aqueous layer was extracted three times with
dichloromethane. The unified organic phases were dried over
Na2SO4, concentrated in a vacuum, and chromatographied on
preparative TLC using a mixture of dichloromethane saturated
with ammonia and hexane (1:1) as eluents.
[5S-5(4′S,5′S)]-5-(4′,5′-Dih yd r o-4′,5′-d ip h en yl-1H-im id a -
zol-2′-yl)-5-p h en ylh exa n -1-ol (22) was obtained from (-)-
8b as a colorless viscous oil (86%, 9.8:1 mixture of two
diastereoisomers): Rf 0.31 (dichloromethane saturated with
ammonia); [R]D ) -130 (c ) 1.05, MeOH); IR (KBr, cm-1) 3248
(b), 3060, 3028, 2931, 1600; 1H NMR (400 MHz) (major
diastereomer) δ 1.45 (4H, m), 1.62 (3H, s), 1.96 (1H, m), 2.20
(1H, td, J ) 10.8 Hz J ) 2.1 Hz), 3.52 (2H, td, J ) 7.1 Hz, J
) 7.1 Hz), 4.66 (2H, bs), 7.02-7.48 (15H, m); 13C NMR δ 21.1,
24.5, 32.7, 39.0, 44.9, 61.9, 74.7 (broad), 126.4, 126.6, 127.1,
127.6, 128.7, 169.1; MS m/z 399 (13), 167 (36), 150 (100);
HRMS, m/z 398.2367 (C27H30N2O, requires 398.2358).
[1RS,1(4′R*,5′R*)]-1-(4′,5′-Dih yd r o-4′,5′-d ip h en yl-1H -
im id a zol-2′-yl)-1-(4-h yd r oxybu tyl)in d a n (23) was obtained
from 11 as a colorless viscous oil (77%, 6.5:1 mixture of two
diastereoisomers): Rf 0.30 (dichloromethane saturated with
ammonia); IR (KBr, cm-1) 3274 (b), 3028, 2929, 1594; 1H NMR
250 MHz) (major isomer) δ 1.48, (4H, m), 2.15 (2H, m), 2.49
(1H, m), 2.65 (1H, apparent td, J ) 15.8 Hz, J ) 8.8 Hz), 3.02
(2H, m), 3.50 (2H, apparent t, J ) 5.6 Hz), 4.60 (2H, s), 6.95-
7.30 (14H, m); 13C NMR (major isomer) δ 21.3, 31.0, 32.0, 36.6,
37.7, 53.9, 61.6, 74.5 (broad), 124.3, 125.3, 126.3, 126.7; 127.6,
127.8; 128.7, 143.5, 170.7; MS m/z 411 (97), 337 (83), 106 (100);
HRMS, m/z 410.2357 (C28H30N2O requires 410.2358).
(dichloromethane saturated with ammonia); IR (KBr, cm-1
)
3392 (b), 2931, 1602; 1H NMR (400 MHz) (major isomer) δ 1.00
(9H, s), 1.41 (2H, m), 1.51 (4H, m), 1.28 (2H, m), 2.28 (1H, dt,
J ) 12.8 Hz, J ) 3.0 Hz), 2.40 (1H, dt, J ) 13.1 Hz, J ) 2.8
Hz), 3.38 (1H, tt, J ) 7.8 Hz, J ) 2.8 Hz), 3.52 (2H, m), 3.69
(1H, tt, J ) 8.3 Hz J ) 2.1 Hz), 3.73 (6H, s), 4.93 (2H, s), 6.82-
7.35 (13H, m); 13C NMR (major isomer) δ 20.4, 27.5, 32.6, 35.7,
36.0, 46.8, 55.9, 58.2, 62.2, 73.1 (broad), 110.3, 110.8, 118.8,
126.5, 127.4, 128.6, 136.1, 143.6, 170.7; MS m/z 544 (8), 488
(27), 472 (48), 385 (100); HRMS, m/z 544.3318 (C34N44N2O4
requires 544.3301).
[5RS,5(4′R*,5′R*)]-5-(4′,5′-Dih yd r o-4′,5′-d ip h en yl-1H -
im id a zol-2′-yl)-5-p h en yln on -8-en -1-ol (25) was obtained
from 15 as a colorless viscous oil (84%, 15:1 mixture of two
diastereoisomers): Rf 0.32 (dichloromethane, saturated with
ammonia); IR (KBr, cm-1) 3222 (b), 2941, 1594; 1H NMR (250
MHz) (major isomer) δ 1.31 (1H, td, J ) 14.0 Hz Hz, J ) 6.9
Hz), 1.45 (1H, td, J ) 14.5 Hz, J ) 6.3 Hz), 1.88 (1H, apparent
q, J ) 7.6 Hz), 1.95 (1H, apparent q, J ) 7.2 Hz), 2.11 (4H,
apparent q, J ) 8.1 Hz), 3.45 (2H, apparent t, J ) 6.2 Hz),
4.61 (2H, bs), 4.91 (2H, m), 5.72 (1H, m), 7.10-7.45 (15H, m);
13C NMR (major isomer) δ 20.4, 28.3, 32.8, 34.5, 47.9, 62.1,
114.6, 126.2, 16.6, 126.8, 127.0, 127.1, 127.2, 127.4, 127.5,
127.6, 128.2, 128.3, 128.4, 128.6, 128.7, 128.8, 128.9, 138.4,
143.2, 143.5, 170.8; MS m/z (relative intensity) 439 (100), 282
(42), 161 (99); HRMS, m/z 438.2660 (C30H34N2O requires
438.2671).
[5R*,5(3a ′R*,7a ′R*)]-5-(3a ′,4′,5′,6′,7′,7a ′-h exa h yd r o-1H-
ben zim id a zol-2′-yl)-5-p h en ylh exa n -1-ol (33) was obtained
from 32 as a colorless viscous oil (68%): Rf 0.30 (dichlo-
romethane, saturated with ammonia); IR (KBr, cm-1) 2942,
1
1594; H NMR (250 MHz) δ 1.22 (2H, m), 1.40 (1H, m), 1.51
(3H, s), 1.71 (2H, m), 1.90 (1H, m), 2.10 (1H, m), 2.68 (2H, m),
3.6 (2H, m), 5.30 (1H, bs), 7.20-7.35 (5H, m); 13C NMR δ 20.5,
23.1, 25.0, 30.7, 31.2, 38.3, 45.2, 60.7, 125.9, 126.9, 127.4, 128.7,
129.2, 145.2, 174.1; MS m/z (relative intensity) 301 (100);
HRMS (HCl salt), m/z 301.2287 (C19H29N2O requires 301.2287).
(7RS,2′R*,3′R*)-[7-(2,3-Dim eth oxyph en yl)-2′,3′-diph en yl-
2′,3′,4′,5′,6′,7′-h exa h yd r op yr r olo[1′,2′-a ]im id a zol-7′-yl]-4-
bu ta n -1-ol (26). Into a degassed solution of 18 (0.995 mg,
2.5 mmol) in THF (7.5 mL) was added sec-butyllithium (1.2
mL, 2.5 M solution in hexane) at -78 °C and under Ar. After
15 min of incubation, 9-BBN triflate (7.5 mL, 0.5 M solution
in hexane) was slowly introduced via syringe, and shortly (3
min) some drops of water were added. A mixture of H2O2 (1.0
mL, 35%, 10.3 mmol) and NaOH (2.5N, 3.0 mL, 7.5 mmol) was
added to the reaction at room temperature, and the solution
was stirred for 2 h more. The solution was washed twice with
water; then the aqueous layer was extracted with dichlo-
romethane. The unified organic phases were dried over Na2-
SO4, concentrated in a vacuum, and chromatographed on
preparative TLC using 1:1 dichloromethane-hexane as eluant
saturated with ammonia. The alcohol 26 (1.032 g, 88%) was
isolated as a colorless viscous oil (3:4 mixture of two diaste-
reoisomers): Rf 0.41 (dichloromethane saturated with am-
1
monia); IR (neat, cm-1) 3389 (b), 2937, 1624; H NMR δ 1.45
(2H, m), 2.00 (2H, m), 2.70 (4H, m), 3.50 (2H, s), 3.90 (6H, 2s),
4.28 and 4.30 (1H, 2d, J ) 7.8 Hz, J ) 6.9 Hz), 5.15 and 5.32