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DOI: 10.1055/s-2006-926267
Concise Enantiospecific Synthesis of (+)-Calvine
Publication History
Publication Date:
06 February 2006 (online)
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Abstract
We report herein an efficient enantiospecific synthesis of (+)-calvine in nine steps from (R)-epichlorohydrine. The convergent synthesis is based on an olefin cross-metathesis (CM) reaction of a chiral homoallylamine and an enone. Subsequent reductive cyclization and lactonization of the cis-2,6-disubstituted piperidine intermediate furnished the product in good yield.
Key words
olefin cross-metathesis - hydrogenation - lactones - ruthenium catalyst - alkaloids
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References and Notes
The optical rotation of the product [α]D 20 +8.7 (c 1.4, CHCl3) was in agreement with the reported value {lit.11 [α]D 25 +8.3 (c 1.4, CHCl3)}.
13Preparation and Selected Data of Enone 2. [Ru] (11 mg, 18 µmol) was added to a solution of homoallylamine 4 (76 mg, 0.2 mmol) and enone ester 3 (60 mg, 0.4 mmol) in anhyd CH2Cl2 (4.7 mL) under a nitrogen atmosphere. The mixture was heated at reflux for 20 h. The solvent was evaporated and the residue was purified by column chromatography (SiO2, cyclohexane-EtOAc 3:2) to give 2 (70 mg, 70%, as keto-enol mixture) as a brown oil. [α]D 20 -8.0 (c 1, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 0.81 (br s, 3 H, H-12), 1.20 (br s, 8 H, H-9-11), 1.45-1.59 (m, 2 H, H-8), 2.20-2.68 (m, 2 H, H-6), 3.29 (br s, 2 H, H-13), 3.45 (s, H-2 keto), 3.50 (br s, 2 H, H-14), 3.68, 3.70 (s, 3 H, OCH 3), 4.05 (br s, 1 H, H-7), 4.96 (s, H-2 enol), 5.12 (s, 2 H, H-16), 5.69-5.85 and 6.05-6.20 (m, 1 H, H-4), 6.45-6.62 and 6.69-6.86 (m, 1 H, H-5), 7.21-7.41 (br s, 5 H, Ar), 11.75 (s, OH enol) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.0 (C-12), 22.6 (C-11), 26.1 (C-10), 31.6 (C-9), 33.1, 33.4 (C-8), 36.5, 37.0 (C-6), 46.4, 46.7 (C-13), 51.3 (C-7), 52.4 (OMe), 61.6, 62.6 (C-14), 67.2, 67.8 (C-15), 90.5 (C-2), 126.6 (C-4), 1276.9, 128.1, 128.3, 128.7, 131.3, 136.8 (Ar), 145.9, 147.0 (C-5), 155.6 (C-16), 173.3 (C-1), 191.7 (C-3) ppm.
18Preparation and Selected Data of Piperidine 1. Cross-metathesis product 2 (270 mg, 0.64 mmol) in isopropyl ether (20 mL) was hydrogenated over 10% Pd/C (68 mg, 60 µmol) at 3 bar and 40 °C for 3 d. After filtration over Celite® and evaporation, the residue was purified by column chromatography (SiO2, CH2Cl2-MeOH-NH3 97:3:0.1) to afford piperidine 1 (105 mg, 61%) and calvine (20 mg, 13%) as a light-yellow oil. [α]D 20 +8.5 (c 1.3, CH2Cl2). 1H NMR (200 MHz, CDCl3): δ = 0.88 (t, J = 7 Hz, 3 H, H-13), 1.10-1.80 (m, 14 H, H-3-5,9-12), 2.39 (dd, J = 15, 9 Hz, 1 H, H-7), 2.51-2.77 (m, 4 H, H-6,7,14), 3.09-3.25 (m, 1 H, H-2), 3.46 (t, J = 6 Hz, 2 H, H-15), 3.68 (s, 3 H, OCH 3) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1 (C-13), 21.7 (C-4), 22.7 (C-12), 26.2 (C-3), 27.0 (C-10), 27.3 (C-5), 32.1 (C-11), 34.1 (C-9), 39.3 (C-7), 48.4 (C-14), 51.7 (OMe), 58.3 (C-2), 60.5 (C-15), 61.9 (C-6), 173.0 (C-8) ppm.
20
Preparation and Selected Data of (+)-Calvine.
To a solution of 1 (12 mg, 44 µmol) in benzene (3 mL), p-TSA monohydrate (9.2 mg, 48 µmol) was added and the mixture was heated at reflux under a nitrogen atmosphere for 18 h. Then, CH2Cl2 (10 mL) and sat. aq NaHCO3 solution (10 mL) were added and the layers were separated. The aqueous layer was extracted with CH2Cl2 (3 × 10 mL), and the collected organic layers were evaporated to give neat calvine (7 mg, 66%) as a light-yellow oil. [α]D
20 +18.3 (c 0.35, CH2Cl2) {lit.2 [α]D
20 +18 (c 0.66, CH2Cl2)}. 1H NMR (200 MHz, CDCl3): δ = 0.88 (t, J = 7 Hz, 3 H, H-13), 1.15-1.81 (m, 14 H, H-3-5,9-12), 2.19-2.89 (m, 5 H, H-6,7,14), 3.23-3.37 (m, 1 H, H-2), 4.21-4.36 (m, 2 H, H-15) ppm. 13C NMR (125 MHz, CDCl3): δ = 14.1 (C-13), 21.5 (C-4), 22.7 (C-12), 24.6 (C-3), 25.2 (C-5), 32.3 (C-10, 11), 34.2 (C-9), 43.2 (C-7), 53.5 (C-14), 59.0 (C-2), 62.8 (C-6), 69.0 (C-15), 174.7 (C-8) ppm.