4
03.2331). The second fraction contained the pure trans
(1S, 3S)-3-[(tert-Butyldimethylsilyloxy)methyl]-1-(2-methyl-1-
naphthyl)-1,2,3,4-tetrahydroisoquinoline 18a
22
diastereomer 16a (0.468 g, 58%) as an oil; [α] ϩ83.6 (c 1.46 in
CHCl ); ν
D
Ϫ1
(solution in CHCl )/cm 3320 (N–H), 2928
3
max
3
2
-Methyl-1-naphthyllithium was prepared by the dropwise add-
(
CH –OSi), 1598 (N–H); δH (250 MHz; CDCl ) Ϫ0.26 (3H, s,
2
3
ition, over 10 minutes, of 1-bromo-2-methylnaphthalene (0.442
Si(CH ) ), Ϫ0.10 (3H, s, Si(CH ) ), 0.56 (9H, s, (CH ) CSi), 2.65
3
2
3
2
3
3
t
g, 2 mmol) in Et O (3 mL) to BuLi (2.4 mL of a 1.7 M solution
2
(
1H, dd, J 16.2 and 10.4, CHHCHNH), 2.82 (1H, dd, J 16.2
in pentane, 4 mmol) in Et O (3 mL) under a nitrogen atmos-
2
and 4.0, CHHCHNH), 2.97–3.08 (1H, m, CHCH OSi), 3.50
2
phere at Ϫ78 ЊC. The resulting yellow slurry was stirred for an
additional 30 minutes before a solution of 13 (0.275 g, 1 mmol)
(
1H, dd, J 9.8 and 8.6, CHHOSi), 3.63 (1H, dd, J 9.8 and 4.0,
CHHOSi), 6.18 (1H, s, CCHNH), 6.76 (1H, d, J 7.0, Ar H),
.00 (1H, d, J 7.3, Ar H), 7.11–7.20 (1H, m, Ar H), 7.24–7.31
3H, m, Ar H), 7.49–7.64 (2H, m, Ar H), 7.74 (1H, d, J 8.3,
in Et O (4 mL) was added dropwise over 10 minutes at Ϫ78 ЊC.
2
7
(
The resulting mixture was stirred for 4 hours before warming
over one hour to Ϫ40 ЊC. Water (3 mL) was added dropwise
with stirring, and the reaction mixture warmed rapidly to room
temperature. The layers were separated, and a 50% aq. solution
of KOH (2 mL) was added to the aqueous layer. The aqueous
Ar H), 7.85 (1H, d, J 7.9, Ar H), 8.35 (1H, d, J 8.3, Ar H); δ (63
MHz; CDCl ) Ϫ5.7 (q), Ϫ5.6 (q), 17.8 (s), 25.4 (3 × q), 31.4 (t),
C
3
4
9.5 (d), 55.6 (d), 66.2 (t), 123.0 (d), 124.6 (d), 125.6 (d), 125.8
(
d), 126.6 (d), 126.7 (d), 127.0 (2 × d), 128.9 (d), 129.1 (2 × d),
layer was then extracted with Et O (3 × 20 mL). The combined
ϩ
2
1
1
31.4 (2 × s), 135.5 (s), 136.7 (s), 140.2 (s); m/z (EI) 403 (M ,
organic extracts were dried (MgSO ), filtered, and then concen-
4
7%), 258 (100), 216 (17), 130 (23), 83 (22), 71 (14), 57 (24)
trated in vacuo. Flash column chromatography (5% EtOAc–
ϩ
(
Found; M , 403.2333. C H NOSi requires 403.2331).
26
33
hexane) on SiO furnished pure 18a (0.340 g, 82%) as an oil;
2
2
2
Ϫ1
[
α] Ϫ4.4 (c 1.14 in CHCl ); ν
(solution in CH Cl )/cm
max 2 2
D
3
Two diastereomers of (3S)-3-[(tert-butyldimethylsilyloxy)-
methyl]-1-mesityl-1,2,3,4-tetrahydroisoquinoline 17a and 17b
3683 (N–H), 2858 (CH ), 1581 (N–H); δH (250 MHz; CDCl3)
3
0.07 (6H, s, Si(CH ) ), 0.89 (9H, s, (CH ) CSi), 2.11 (1H, br s,
3
2
3 3
NH), 2.67 (3H, s, CH ), 2.69 (1H, m, CHHCHNH), 3.53–
3
Mesityllithium was prepared by the dropwise addition, over 10
3
.65 (3H, m, CHHCHNH and CHHOSi), 3.93 (1H, dd, J 9.8
minutes, of 2-bromomesitylene (1.53 mL, 10.02 mmol) in Et O
2
and 9.8, CHHOSi), 5.97 (1H, s, CCHNH), 6.53 (1H, d, J 7.9,
Ar H), 6.88 (1H, dd, J 7.9 and 7.0, Ar H), 7.07–7.36 (5H, m,
Ar H), 7.70–7.75 (2H, m, Ar H), 7.98 (1H, d, J 8.5, Ar H);
t
(
15 mL) to BuLi (13.4 mL of a 1.5 M solution in pentane, 20.04
mmol) in Et O (15 mL) under a nitrogen atmosphere at Ϫ78 ЊC.
2
The resulting yellow slurry was stirred for an additional 30
δC (63 MHz; CDCl ) Ϫ5.24 (2 × q), 18.3 (s), 20.9 (q), 25.9
3
minutes before a solution of 13 (1.378 g, 5.01 mmol) in Et O (20
2
(
(
(
(
(
3 × q), 30.2 (t), 50.9 (d), 53.1 (d), 62.6 (t), 124.4 (d), 125.0
d), 125.8 (d), 126.0 (d), 126.1 (d), 127.3 (d), 127.6 (d), 128.2
d), 128.9 (d), 129.2 (d), 131.8 (s), 132.9 (s), 134.0 (s), 134.9
mL) was added dropwise over 10 minutes at Ϫ78 ЊC. The result-
ing mixture was stirred for 4 hours before warming over one
hour to Ϫ40 ЊC. Water (15 mL) was added dropwise with stir-
ring, and the reaction mixture warmed rapidly to room tem-
perature. The layers were separated, and a 50% aq. solution of
KOH (15 mL) was added to the aqueous layer. The aqueous
ϩ
s), 136.2 (s), 139.0 (s); m/z (EI) 417 (M , 10%), 358 (12), 272
ϩ
100), 229 (12), 130 (22), 84 (20) (Found; M , 417.2490.
C H NOSi requires 417.2488).
27
35
layer was then extracted with Et O (3 × 50 mL). The combined
2
(
3S)-1,2,3,4-Tetrahydro-3-isoquinolyl tetrahydro-1H-pyrrol-1-yl
organic extracts were dried (MgSO ), filtered, and then concen-
4
ketone 22
trated in vacuo. Flash column chromatography (5% EtOAc–
hexane) on SiO furnished the pure cis diastereomer 17b (0.212
To a solution of 10 (0.885 g, 5 mmol) in water (5 mL) and
BuOH (5 mL) was added NaOH (0.22 g, 5.5 mmol). To the
2
22
t
g, 11%) as a yellow oil; [α] ϩ59.2 (c 1.96 in CH Cl ); ν (solu-
D
2
2
max
Ϫ1
tion in CH Cl )/cm 3327 (N–H), 3019 (Ar H), 2858 (CH ),
reaction mixture was then added di-tert-butyl dicarbonate
(1.09 g, 5 mmol) dropwise to the clear solution. After a short
induction period, the temperature rose to about 30–35 ЊC.
The reaction was then brought to completion by stirring
overnight at room temperature, at which time, the clear solu-
tion had reached pH 7.5–8.5. The reaction mixture was
extracted with CH Cl (3 × 25 mL). The combined organic
2
2
3
1
610 (Ar H), 1579 (Ar H), 1274 (Si(CH ) ), 1252 (Si(CH ) );
3 2 3 2
δH (250 MHz; CDCl ) 0.06 (3H, s, Si(CH ) ), 0.07 (3H, s,
3
3 2
Si(CH ) ), 0.89 (9H, s, (CH ) CSi), 1.93 (3H, s, Ar CH ), 2.27
3
2
3
3
3
(
3H, s, Ar CH ), 2.47 (3H, s, Ar CH ), 2.70 (2H, br m,
3
3
CH CHNH), 3.23 (1H, br s, CHCH OSi), 3.60 (1H, dd, J 9.8
2
2
and 7.6, CHHOSi), 3.79 (1H, br m, CHHOSi), 5.62 (1H, s,
CCHNH), 6.64 (1H, d, J 7.6, Ar H), 6.78 (1H, s, Ar H), 6.89
2
2
layers were then extracted with saturated aq. NaHCO solu-
3
(
1H, s, Ar H), 6.99 (1H, m, Ar H), 7.10 (2H, d, J 3.7, Ar H);
tion (2 × 10 mL) before acidifying the combined aqueous
δ (63 MHz; CDCl ) Ϫ5.2 (2 × q), 18.4 (s), 19.9 (q), 20.7 (q),
layers to pH 1–1.5 by the addition of aq. KHSO (10 mL).
C
3
4
2
1.0 (q), 26.0 (3 × q), 32.1 (t), 56.2 (d), 57.7 (d), 67.3 (t), 125.7
The turbid reaction mixture was then extracted with CH Cl2
2
(
d), 125.8 (d), 126.2 (d), 128.7 (d), 128.9 (d), 131.3 (d), 134.4 (s),
(3 × 25 mL). The combined organic layers were washed with
ϩ
1
6
3
36.6 (s), 137.0 (2 × s), 138.5 (s), 139.4 (s); m/z (EI) 395 (M ,
water (2 × 25 mL), dried (MgSO ), filtered, and the solvent
4
ϩ
%), 250 (100), 147 (69), 130 (12), 119 (29) (Found; M ,
removed under reduced pressure. To a solution of crude 19
(1.591 g, 5.72 mmol) in DMF (30 mL) was added DCC
(1.413 g, 6.86 mmol), HOBT (0.926 g, 6.86 mmol), copper()
chloride (0.922 g, 6.86 mmol) and pyrrolidine (0.57 mL, 6.86
mmol). The reaction mixture was stirred at room temperature
for 24 hours, before evaporation of the solvent under reduced
95.2638. C H NOSi requires 395.2644). The second fraction
25
37
contained the pure trans diastereomer 17a (1.070 g, 54%) as a
white crystalline solid; mp 98–99 ЊC (EtOAc); [α] Ϫ10.3 (c 0.97
in CHCl ); ν
(
2
2
D
Ϫ1
(solution in CH Cl )/cm 3684 (N–H), 2858
3
max
2 2
CH ), 1580 (N–H); δH (250 MHz; CDCl ) 0.05 (6H, s,
3
3
Si(CH ) ), 0.89 (9H, s, (CH ) CSi), 1.94 (3H, s, Ar CH ), 2.27
pressure. The crude residue was then dissolved in CH Cl2
3
2
3
3
3
2
(
3H, s, Ar CH ), 2.46 (3H, s, Ar CH ), 2.56 (1H, d, J 15.9,
(50 mL) and to this was added trifluoroacetic acid (5.54 mL,
65 mmol) and triethylsilane (5.61 mL, 15 mmol). The reaction
mixture was left to stir at room temperature for 16 hours, and
the solvent evaporated in vacuo to afford the crude product.
3
3
CHHCHNH), 3.27–3.45 (2H, m, CHHNH/CHCH OSi), 3.53
(
CHHOSi), 5.64 (1H, s, CCHNH), 6.66 (1H, d, J 7.6, Ar H),
2
1H, dd, J 10.1 and 4.6, CHHOSi), 3.81 (1H, dd, J 10.1 and 9.8,
6
7
1
.80 (1H, s, Ar H), 6.87 (1H, s, Ar H), 6.95–7.04 (1H, m, Ar H),
.08 (2H, d, J 3.7, Ar H); δ (63 MHz; CDCl ) Ϫ5.3 (2 × q),
8.2 (s), 20.4 (q), 20.7 (q), 20.9 (q), 25.9 (3 × q), 30.1 (t), 50.5
Flash column chromatography on SiO (10% MeOH–EtOAc)
2
furnished pure 22 (0.713 g, 62%) as a white crystalline solid;
C
3
22
[α] Ϫ90.9 (c 0.33 in CH Cl ); mp 83–84 ЊC (EtOH) (Found;
D
2
2
(
(
1
d), 52.8 (d), 62.6 (t), 125.6 (d), 125.9 (2 × d), 128.6 (d), 128.9
C 72.77; H 8.05; N 12.06. C H N O requires C 73.01; H
14 18 2
Ϫ1
d), 131.2 (d), 133.3 (s), 136.4 (s), 136.9 (s), 137.4 (s), 138.7 (s),
7.88; N 12.16%); νmax (solution in CH Cl )/cm 3340 (N–H),
2 2
19
ϩ
38.8 (s); m/z (EI) 395 (M , 8%), 336 (5), 250 (100), 130 (20), 73
3049 (Ar C–H), 1638 (C᎐O), 1495 (Ar C–H) (lit., νmax
ϩ
Ϫ1
(
6) (Found; M , 395.2650. C H NOSi requires 395.2644).
(KBr)/cm 3350, 2930); δH (250 MHz; CDCl ) 1.83–2.04
25
37
3
J. Chem. Soc., Perkin Trans. 1, 1999, 2883–2889
2887