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DOI: 10.1055/s-2008-1078021
A Practical Asymmetric Synthesis of the ACNO Fragment of Morphine Alkaloids
Publication History
Publication Date:
31 July 2008 (online)
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Abstract
Asymmetric total synthesis of the ACNO skeleton of morphine alkaloids has been achieved in excellent overall yields and optical purities using the Ru-catalyzed asymmetric transfer hydrogenation, Pd-catalyzed cyclization, and Pt-catalyzed hydrogenation as key steps.
Key words
asymmetric catalysis - total synthesis - transition metals - hydrogenation - Heck reaction
- Supporting Information for this article is available online:
- Supporting Information
-
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References and Notes
Chiral HPLC Analysis: The free base of the sample was dissolved in 1% isopropanol (IPA) in n-hexane. Then the sample solution (10 µL) was eluted using 1.5% [for compound (+)-4], 2.5% [for compounds (-)-3 and (-)-6], or 8% [for compound (-)-10] IPA in n-hexane in the presence of 0.2% diethylamine as mobile phase on the CHIRALCEL OD column (250 × 4 mm, DAICEL). The ee values were calculated based on the UV absorption (λ = 254 nm) areas of the two enantiomers.
10Microwave Experiments: The reactions under microwave irradiation were conducted in sealed heavy-walled Pyrex tubes. Microwave heating was carried out with a single mode cavity Discover Microwave Synthesizer (CEM Corporation, P.O. Box 200, Matthews, NC 28106, USA), producing continuous irradiation at 2.45 GHz. The reaction temperature was measured and feedback controlled with an infrared device under the reaction vessel.
11
Spectral Data:
Compound (-)-10: pale yellow solid; [α]D
²
4 -31.1
(c = 1.00, MeOH); ee = 96.3%. ¹H
NMR (300 MHz, CDCl3): δ = 1.61-1.74
(m, 2 H), 1.85-2.03 (m, 2 H), 2.57-2.61 (m, 2
H), 4.59 (t, J = 5.9 Hz, 1 H),
5.30 (s, 1 H), 7.32 (d, J = 5.0
Hz, 1 H), 8.07 (s, 1 H), 8.11 (d, J = 5.0
Hz, 1 H). ¹³C NMR (75 MHz, CDCl3): δ = 19.2,
25.8, 31.8, 66.6, 122.3, 132.4, 146.2, 148.8, 149.2. HRMS (EI): m/z [M]+ calcd
for C9H11NO: 149.0841; found: 149.0839.
Compound
(+)-9: yellow oil; [α]D
²
0 +60.0
(c = 0.10, MeOH). ¹H
NMR (400 MHz, CDCl3): δ = 1.37-1.41
(m, 1 H), 1.43-1.49 (m, 1 H), 1.54-1.66 (m, 4
H), 1.82-1.88 (m, 1 H), 2.12 (s, 3 H), 2.27-2.37
(m, 3 H), 2.56 (s, 2 H), 3.69 (s, 1 H), 4.12 (s, 1 H). ¹³C
NMR (100 MHz, CDCl3): δ = 18.3, 26.8,
27.5, 32.3, 45.2, 52.2, 57.9, 67.0, 128.9, 129.2. HRMS (EI): m/z [M]+ calcd
for C10H17NO: 167.1310; found: 167.1317.
Compound
(-)-6: pale yellow oil; [α]D
²
0 -51.1
(c = 1.90, MeOH); ee = 92%. ¹H
NMR (200 MHz, CDCl3): δ = 1.39-1.62
(m, 2 H), 1.89-1.91 (m, 2 H), 1.96-2.20 (m, 2
H), 2.29 (m, 1 H), 2.31 (s, 3 H), 2.35-2.39 (m, 1 H), 2.60-2.73
(m, 3 H), 2.91 (d, J = 15.7
Hz, 1 H), 3.76 (s, 3 H), 4.66 (s, 1 H), 6.69 (t, J = 8.0
Hz, 1 H), 6.82 (dd, J = 1.5,
8.2 Hz, 1 H), 7.31 (dd, J = 1.6,
7.8 Hz, 1 H). ¹³C NMR (50 MHz, CDCl3): δ = 18.4,
27.80, 27.84, 28.3, 45.6, 52.5, 55.3, 58.4, 77.5, 93.5, 112.4, 124.9,
126.4, 130.9, 132.6, 147.4, 152.5. HRMS (FAB): m/z [M + H]+ calcd
for C17H23INO2: 400.0774; found:
400.0783.
Compound (+)-4:
pale yellow oil; [α]D
²
0 +105.0
(c = 0.92, MeOH); ee = 92.5%. ¹H
NMR (200 MHz, CDCl3): δ = 1.10-1.26
(m, 1 H), 1.35-1.47 (m, 1 H), 1.50-1.68 (m, 1
H), 1.84-1.93 (m, 4 H), 2.00-2.17 (m, 1 H), 2.62
(s, 3 H), 2.71-2.82 (m, 2 H), 3.88 (s, 3 H), 4.46 (dd, J = 6.1, 9.4 Hz, 1 H), 5.91 (s,
1 H), 6.74-6.90 (m, 3 H). ¹³C
NMR (50 MHz, CDCl3):
δ = 22.7,
29.3, 29.7, 37.1, 43.0, 45.9, 46.7, 55.9, 90.8, 106.8, 111.4, 116.8,
120.6, 134.2, 138.2, 145.2, 146.2. HRMS (EI): m/z [M]+ calcd
for C17H21NO2: 271.1572; found:
271.1569.