2.74 (1H, m, C(14)H), 3.15 (1H, d, J 19.3, C(10)HB), 3.47–3.50
(1H, m, C(9)H), 3.87 (3H, s, OMe), 4.20–4.22 (1H, m, C(6)H),
4.94–4.96 (1H, m, C(5)H), 5.30–5.34 (1H, m, C(8)H), 5.71–5.74
(1H, m, C(7)H), 6.89 (1H, s, C(2)H), 7.32–7.39 (3H, m, Ph),
7.51–7.54 (2H, m, Ph); δC (100 MHz, CDCl3) 20.3, 35.5, 40.5,
43.0, 43.1, 46.2, 56.2, 58.7, 66.5, 87.3, 91.9, 92.5, 113.9, 115.7,
123.4, 128.1, 128.2, 128.4, 131.1, 131.4, 133.4, 141.6, 142.2,
147.2; m/z (CIϩ) 400.2 (MHϩ, 100%).
19.4, 35.7, 40.3, 43.0, 46.3, 56.3, 58.8, 66.4, 91.6, 109.7, 112.9,
124.9, 128.2, 128.7, 131.0, 133.0, 133.5, 142.5, 146.6; m/z (EIϩ)
325 (Mϩ, 100%); HRMS (EIϩ) C20H23NO3 requires 325.1678,
found 325.1677.
Preparation of 3,6-di-O-tert-butyldimethylsilylmorphine 157
tert-Butyldimethylsilyl chloride (8.0 g, 53 mmol) was added to a
stirred solution of morphine (4.2 g, 14 mmol) and imidazole
(4.8 g, 71 mmol) in DMF (25 ml) and heated to 90 ЊC for four
hours. After cooling, the solution was diluted with DCM (200
ml), washed with H2O (2 × 100 ml), dried and concentrated
in vacuo. The residue was purified by column chromatography
(DCM–MeOH 25 : 1) to give 15 (6.2 g, 87%) as a white solid;
δH (300 MHz, CDCl3) 0.11, 0.14, 0.15, 0.22 (4 × 3H, s,
Preparation of 1-phenylcodeine 11
Following representative procedure 1, 2 (500 mg, 1 mmol),
phenyltributyltin (440 mg, 1.2 mmol), Pd(OAc)2 (5 mg, 2
mol%), PPh3 (25 mg, 8 mol%) and NEt3 (2 ml) gave, after
treatment with TBAF (0.64 g, 2 mmol) in THF (10 ml) accord-
ing to representative procedure 2, 11 (330 mg, 89%) as a white
solid; mp 162 ЊC; C24H25NO3 requires C, 76.8, H, 6.7, N, 3.4%;
found C, 76.6, H, 7.0, N, 3.7%; δH (300 MHz, CDCl3) 1.94–1.98
(1H, m, C(15)HB), 2.11–2.17 (2H, m, C(15)HA and C(10)HA),
2.45 (3H, s, NMe), 2.56 (1H, dd, J16B,16A 12.2, J16B,15B 3.4,
C(16)HA), 2.68–2.74 (2H, m, C(14)H and C(16)HB), 3.05 (1H,
d, J 19.0, C(10)HB), 3.33 (1H, m, C(9)H), 3.87 (3H, s, OMe),
4.21–4.24 (1H, m, C(6)H), 4.94–4.96 (1H, m, C(5)H), 5.30–5.34
(1H, m, C(8)H), 5.75–5.79 (1H, m, C(7)H), 6.64 (1H, s, C(2)H),
7.32–7.45 (5H, m, Ph); δC (75 MHz, CDCl3) 20.4, 35.6, 40.2,
43.3, 46.6, 56.3, 59.0, 66.3, 91.4, 114.4, 124.1, 126.8, 128.0,
128.3, 129.1, 131.2, 133.6, 134.1, 140.7, 142.0, 148.5; m/z (EIϩ)
375 (Mϩ, 100%).
t
t
Si(Me)2 Bu), 0.94, 0.98 (2 × 9H, s, Si(Me)2 Bu), 1.82–1.87 (1H,
m, C(15)HB), 2.13 (1H, td, J15A,15B;15A,16A 12.2, J15A,16B 3.5,
C(15)HA), 2.31 (1H, dd, J 18.6, J 6.1, C(10)HA), 2.46 (3H, s,
NMe), 2.38–2.48 (1H, m, C(16)HA), 2.54–2.65 (2H, m, C(16)HB
and C(14)H), 3.03 (1H, d, J 18.6, C(10)HB), 3.34 (1H, dd, J9,10A
6.1, J9,14 3.3, C(9)H), 4.19–4.25 (1H, m, C(6)H), 4.69 (1H, dd,
J 6.6, J 1.1, C(5)H), 5.24–5.28 (1H, m, C(8)H), 5.48–5.57 (1H,
m, C(7)H), 6.42, 6.58 (2 × 1H, d, J 8.1, C(1)H and C(2)H).
Preparation of 6-O-tert-butyldimethylsilylmorphine 16
TBAF (1.5 g, 4.7 mmol) in THF (5 ml) was added to a stirred
solution of 15 (2.4 g, 4.7 mmol) in THF (10 ml) at 0 ЊC and
stirred for one hour. The solution was diluted with DCM (100
ml), washed with H2O (2 × 30 ml), dried, and concentrated
in vacuo. The residue was purified by column chromatography
(DCM–MeOH 12 : 1) to give 16 (1.6 g, 89%) as a white solid;
mp 206 ЊC; C23H33NO3Si requires C, 69.1, H, 8.3, N, 3.5%;
found C, 69.1, H, 8.7, N, 3.1%; vmax (KBr) 3421 (OH), 2920,
2852 (C–H), 1248, 1126 (C–O); [α]2D2 Ϫ158.5 (c 0.53, CHCl3);
Preparation of 1-allylcodeine 13
Following representative procedure 1, 2 (500 mg, 1 mmol),
allyltributyltin (397 mg, 1.2 mmol), Pd(OAc)2 (5 mg, 2 mol%),
PPh3 (25 mg, 8 mol%) and NEt3 (2 ml) gave, after treatment
with TBAF (0.64 g, 2 mmol) in THF (10 ml) according to
representative procedure 2, 13 (250 mg, 73%) as a colourless oil;
C21H25NO3 requires C, 74.3, H, 7.4, N, 4.1%; found C, 74.1, H,
7.6, N, 3.8%; δH (300 MHz, CDCl3) 1.86–1.90 (1H, m,
C(15)HB), 2.11 (1H, td, J15A,15B;15A,16A 12.2, J15A,16B 5.0,
C(15)HA), 2.21 (1H, dd, J 18.7, J 6.3, C(10)HA), 2.38 (1H, td,
J16A,16B;16A,15A 12.2, J16A,15B 3.5, C(16)HA), 2.47 (3H, s, NMe),
2.64 (1H, dd, J16B,16A 12.2, J16B,15B 4.1, C(16)HB), 2.73–2.75 (1H,
m, C(14)H), 2.92 (1H, d, J 18.7, C(10)HB), 3.17–3.31 (2H, m,
t
δH (300 MHz, CDCl3) 0.13, 0.15 (2 × 3H, s, Si(Me)2 Bu), 0.95
t
(2 × 9H, s, Si(Me)2 Bu), 1.83–1.88 (1H, m, C(15)HB), 2.13 (1H,
td, J15A,15B;15A,16A 12.3, J15A,16B 5.1, C(15)HA), 2.31 (1H, dd,
J 18.5, J 6.1, C(10)HA), 2.45 (3H, s, NMe), 2.38–2.48 (1H, m,
C(16)HA), 2.58–2.67 (2H, m, C(16)HB and C(14)H), 3.03 (1H,
d, J 18.6, C(10)HB), 3.34 (1H, dd, J9,10A 6.2, J9,14 3.2, C(9)H),
4.23–4.27 (1H, m, C(6)H), 4.71 (1H, dd, J 5.9, J 1.2, C(5)H),
5.23–5.31 (1H, m, C(8)H), 5.59–5.63 (1H, m, C(7)H), 6.47, 6.63
(2 × 1H, d, J 8.0, C(1)H and C(2)H); δC (100 MHz, CDCl3)
Ϫ4.8, 18.4, 20.6, 25.9, 35.2, 40.5, 42.5, 43.6, 46.2, 58.5, 69.1,
92.6, 117.7, 119.0, 125.4, 128.3, 130.6, 133.7, 138.9, 147.3; m/z
(CIϩ) 400 (MHϩ, 70%).
CH CH᎐CH ), 3.42 (1H, dd, J9,10 6.3, J9,8 3.1, C(9)H), 3.83 (3H,
᎐
2
2
s, OMe), 4.16–4.20 (1H, m, C(6)H), 4.88 (1H, dd, J5,6 6.3, J5,7
3.1, C(5)H), 4.95 (1H, dq, J 17.2, J 1.6, CH CH᎐CHHtrans), 5.05
᎐
2
(1H, dq, J 10.1, J 1.6, CH CH᎐CHH ), 5.24–5.29 (1H, m,
᎐
2
cis
C(8)H), 5.69–5.74 (1H, m, C(7)H), 5.85–5.99 (1H, m,
CH CH᎐CH ), 6.51 (1H, s, C(2)H); δ (66 MHz, CDCl ) 19.0,
35.4, 36.1, 40.0, 42.8, 46.5, 56.4, 59.0, 66.2, 91.1, 113.9, 115.3,
124.8, 127.6, 129.8, 130.9, 133.6, 136.6, 142.1, 148.8; m/z (EIϩ)
339 (Mϩ, 100%).
᎐
2
2
C
3
Preparation of 3-O-trifluoromethylsulfonyl-6-O-tert-butyldi-
methylsilylmorphine 17
Trifluoromethanesulfonic anhydride (0.8 ml, 4.8 mmol) was
added dropwise to a stirred solution of 16 (1.6 g, 4.0 mmol) and
2,6-dimethylpyridine (0.46 ml, 4.0 mmol) in DCM (10 ml) at
0 ЊC and warmed to RT. After twenty hours, the solution was
diluted with DCM (100 ml), washed with H2O (2 × 30 ml),
dried, and concentrated in vacuo. The residue was purified by
column chromatography (DCM–MeOH 30 : 1) to give 17 (1.9
g, 89%) as a white solid; mp 75 ЊC; C24H32NF3O5SSi requires C,
54.2, H, 6.1, N, 2.6%; found C, 54.2, H, 6.3, N, 2.4%; vmax (KBr)
2960, 2852 (C–H), 1417, 1225, 1205, 1137 (C–O); [α]2D2 Ϫ127.7
(c 1.02, CHCl3); δH (300 MHz, CDCl3) 0.12, 0.15 (2 × 3H, s,
Preparation of 1-vinylcodeine 12
Following representative procedure 1, 2 (500 mg, 1 mmol),
vinyltributyltin (378 mg, 1.2 mmol), Pd(OAc)2 (5 mg, 2 mol%),
PPh3 (25 mg, 8 mol%) and NEt3 (2 ml) gave, after treatment
with TBAF (0.64 g, 2 mmol) in THF (10 ml) according to
representative procedure 2, 12 (260 mg, 73%) as a white solid;
mp 175 ЊC; δH (300 MHz, CDCl3) 1.85–1.90 (1H, m, C(15)HB),
2.07 (1H, td, J15A,15B;15A,16A 12.5, J15A,16B 5.1, C(15)HA), 2.27 (1H,
dd, J 18.7, J 6.2, C(10)HA), 2.39 (1H, td, J16A,16B;16A,15A 12.1,
J16A,15B 3.6, C(16)HA), 2.46 (3H, s, NMe), 2.60 (1H, dd, J16B,16A
12.3, J16B,15B 4.2, C(16)HB), 2.67–2.69 (1H, m, C(14)H), 3.03
(1H, d, J 18.7, C(10)HB), 3.41 (1H, dd, J9,10 6.2, J9,8 3.2, C(9)H),
3.87 (3H, s, OMe), 4.17–4.20 (1H, m, C(6)H), 4.90 (1H, dd, J5,6
t
t
Si(Me)2 Bu), 0.94 (2 × 9H, s, Si(Me)2 Bu), 1.84–1.89 (1H, m,
C(15)HB), 2.06 (1H, td, J15A,15B;15A,16A 12.3, J15A,16B 5.0,
C(15)HA), 2.27–2.41 (2H, m, C(10)HA and C(16)HA), 2.44 (3H,
s, NMe), 2.59 (1H, dd, J16B,16A 12.2, J16B,15B 4.5, C(16)HB),
2.66–2.68 (1H, m, C(14)H), 3.07 (1H, d, J 19.0, C(10)HB), 3.34
(1H, dd, J9,10A 6.0, J9,14 3.2, C(9)H), 4.25–4.28 (1H, m, C(6)H),
4.81–4.83 (1H, m, C(5)H), 5.23–5.28 (1H, m, C(8)H), 5.61–5.64
(1H, m, C(7)H), 6.57, 6.90 (2 × 1H, d, J 8.4, C(1)H and C(2)H);
δC (100 MHz, CDCl3) Ϫ4.9, Ϫ4.7, 21.2, 25.7, 35.6, 40.9, 43.0,
6.5, J5,7 1.1, C(5)H), 5.19 (1H, dd, J 11.1, J 1.1, CH᎐CHH ),
᎐
cis
5.27–5.32 (1H, m, C(8)H), 5.54 (1H, dd, J 17.4, J 1.1,
CH᎐CHHtrans), 5.70–5.74 (1H, m, C(7)H), 6.78 (1H, dd, J 17.4,
᎐
J 11.1, CH᎐CH ), 6.88 (1H, s, C(2)H); δ (66 MHz, CDCl3)
᎐
2
C
1418
J. Chem. Soc., Perkin Trans. 1, 2001, 1413–1420