ACCEPTED MANUSCRIPT
(d, J = 11.9 Hz, 1H), 2.76 (m, 3H), 2.49 (m, 2H), 1.65 (m, 1H), 1.55 (td, J1 = 12.7 Hz and J2 = 5.2
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Hz, 1H) 1.16 (s, 9H, t-Bu), 1.13 (s, 9H, t-Bu). C NMR (CDCl3, 101 MHz):
δ ppm 207.2 (CO),
206.9*, 155.6*, 155.4 (NCO) 148.4, 138.1, 136.4, 136.4, 135.8, 135.8, 134.9, 134.9, 133.9, 133.5,
132.6, 132.4, 130.2, 130.1, 128.8, 128.0, 127.9, 127.8, 126.5*, 126.4, 122.3, 119.9, 89.4, 73.6, 72.6,
53.0, 50.1, 49.8* 47.9, 41.2, 37.3*, 37.1, 36.0*, 35.7, 29.3, 29.1*, 27.0, 26.8, 19.7, 19.6. HRMS
calcd for C50H55NO7NaSi2. [M+23]+ 860.3415 found 860.3417.
N-methyl
3,6-bis[[(1,1-dimethyl)-t-butylsilyl]oxy]-4,5-epoxy-7-hydroxy-8-oxo-(5α,6α,7β)-
morphinan carbamate (21). Compound 21 was prepared according to the general procedure
described above under the reaction conditions described on Table S1, Entry 12. The reaction time
50 min. Purification with automated column chromatography by eluting with an n-heptane/ethyl
acetate gradient (5 → 20% EtOAc) gave compound 21 as a white solid (100 mg, 34%). Mp 167-169
1
°C; FTIR-ATR 3431 (OH), 1690 (C=O), 1495, 1444, 1254, 1127, 998, 837, 778 cm-1. H NMR
(CDCl3, 400 MHz):
δ ppm 6.69 (d, J = 8.1 Hz, 1H, aromatic-H), 6.48 (d, J = 8.1 Hz, 1H, aromatic-
H), 5.32 (m, 1H), 4.76 (d, J = 4.7 Hz, 1H), 4.02 (m, 2H), 3.74 (brs, 3H, NCOOCH3), 3.43 (d, J =
11.7 Hz, 1H), 2.90 (m, 2H), 2.77 (d, J = 3.3 Hz, 1H), 2.71 (brs, 1H), 2.67 (m, 2H), 1.88 (m, 2H),
0.99 (s, 9H, t-Bu), 0.95 (s, 9H (t-Bu), 0.22 (s, 3H, SiCH3), 0.19 (s, 3H, SiCH3), 0.16 (s, 3 H,
SiCH3), 0.13 (s, 3 H, SiCH3). 13C NMR (CDCl3, 101 MHz):
δ ppm 206.7 (CO), 206.5* 155.7*,
155.6 (NCO), 148.4, 137.7, 128.9, 126.8*, 126.6, 123.6, 120.3, 89.9, 73.6, 72.3, 53.1, 50.4, 50.1*,
48.1, 41.4, 37.5*, 37.3 36.3*, 36.0, 29.4, 29.3* 26.0, 25.9, 18.5, 18.6, -4.2 (SiCH3), -4.4 (SiCH3), -
4.4 (SiCH3), -4.7 (SiCH3). HRMS calcd for C30H48NO7Si2. [M+1]+ 590.2969 found 590.2970.
N-Methyl 4,5-epoxy-7-hydroxy-3,6-dimethoxy-8-oxo-(5α,6α,7β)-morphinan carbamate (22).
Compound 22 was prepared according to the general procedure described above under the reaction
conditions described on Table S1, Entry 12. The reaction time 1 h. Purification with automated
column chromatography by eluting with n-heptane/ethyl acetate (1:5) gave compound 22 as a
colorless solid (29 mg, 15%). Mp 125 °C (decomp.); FTIR-ATR 3396 (OH), 1690 (C=O), 1503,
1
1444, 1274, 1098, 1030, 753, 731 cm-1. H NMR (CDCl3, 400 MHz):
δ ppm 6.75 (d, J = 8.3 Hz,
1H, aromatic-H), 6.57 (d, J = 8.3 Hz, 1H, aromatic-H), 5.35 (m, 1H), 5.07 (d, J = 4.1 Hz, 1H), 4.03
(m, 1H), 3.86 (s, 3H, OCH3), 3.74 (brs, 3H, NCOOCH3), 3.62 (s, 3H, OCH3), 3.52 (m, 2H), 2.91
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(m, 3H), 2.77 (d, J = 3.5 Hz, 1H), 2.65 (d, J = 18.6 Hz, 1H), 1.92 (m, 2H). C NMR (CDCl3, 101
MHz):
δ ppm 205.8 (CO), 205.6*, 155.6*, 155.4 (NCO), 146.1, 142.6, 128.5, 125.9*, 125.7, 120.6,
115.4, 86.1, 78.9, 72.9, 58.1 (OCH3), 56.6 (OCH3), 53.0 (NCOOCH3), 50.1, 49.8* 48.0, 41.3,
37.3*, 37.2, 35.9*, 35.7, 29.1, 28.9*. HRMS calcd for C20H24NO7. [M+1]+ 390.1553 found
390.1557.
N-Methyl 4,5-epoxy-3,6,7-trihydroxy-8-oxo-(5α,6α,7β)-morphinan carbamate (23). Compound
12 (297 mg, 0.667 mmol) was dissolved in a mixture of methanol: chloroform (4:1, 10 mL). A 0.1
M aqueous solution of NaOH (4.5 mL) was added and the resulting white suspension was stirred at
room temperature for 2.5 h. The organic solvents were evaporated and the pH of the residue was
adjusted to 6 with a 1 M aqueous solution of HCl. The aqueous phase was extracted with a mixture
of chloroform: isopropanol 4:1 (3 × 20 mL) and the combined organic phases were washed with
brine (18 mL), dried with anhydrous Na2SO4, filtered and concentrated in vacuo to give a light
brown solid. The crude product was purified with automated column chromatography by eluting
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