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Synlett 2004(4): 619-622  
DOI: 10.1055/s-2004-817754
LETTER
© Georg Thieme Verlag Stuttgart · New York

Transmission of Axial Chirality to Spiro Center Chirality, Enabling Enantiospecific Access to Erythrinan Alkaloids

Yoshizumi Yasui, Keisuke Suzuki, Takashi Matsumoto*
Department of Chemistry, Tokyo Institute of Technology and CREST-JST Agency, 2-12-1, O-okayama, Meguro-ku, Tokyo 152-8551, ­Japan
Fax: +81(3)5734-3531; e-Mail: tmatsumo@chem.titech.ac.jp;
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Publication History

Received 28 December 2003
Publication Date:
10 February 2004 (online)

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Abstract

Synthesis of O-methylerysodienone in enantiomerically pure form is described, where the axial chirality of the intermediate biphenyl is stereospecifically transmitted to the spiro center ­chirality of the erythrinan skeleton.

Key words

erythrinan alkaloid - biphenyl compound - axial chirality - spiro center chirality

6

All new compounds were fully characterized by 1H and 13C NMR, IR and combustion analysis. Data for the selected compounds follow. [*The specific rotation is shown for (+)-6 and for each isomer derived from (+)-6. See ref. 9 and ref. 14] Compound 6: [α]D 28 +20.5 (c 1.12, CHCl3)*. 1H NMR (CDCl3): δ = 7.46-7.36 (m, 5 H), 6.97 (s, 1 H), 6.86 (s, 1 H), 6.54 (s, 1 H), 6.01 (s, 1 H), 5.15 (s, 2 H), 3.93 (s, 3 H), 3.82 (s, 3 H), 3.73-3.55 (m, 4 H), 2.60-2.45 (m, 4 H), 1.35 (br, 1 H), 0.97 (s, 21 H). 13C NMR (CDCl3): δ = 148.4, 147.3, 145.2, 141.8, 135.9, 134.2, 131.8, 130.0, 128.8, 128.5, 128.4, 127.9, 113.5, 113.2, 112.4, 111.5, 71.4, 63.8, 62.6, 55.8, 55.7, 37.6, 36.2, 17.9, 11.8. IR (NaCl): 3515, 2940, 2865, 1605, 1515, 1490, 1465, 1255, 1215, 1165, 1110, 1045, 755 cm-1. Anal. Calcd for C34H47BrO6Si: C, 61.90; H, 7.18. Found: C, 61.98; H, 7.45. HPLC (Daicel CHIRAL-PAK AD-H, φ0.46 × 250 mm × 2, hexane:i-PrOH = 85:15, 1.0 mL/min) retention time: 10.9 min for (+)-6, 12.8 min for (-)-6. Compound 9: Colorless needles (hexane), mp 194.0-194.5 °C; [α]D 24 +16 (c 1.1, CHCl3)*. 1H NMR (CDCl3): δ = 6.95 (s, 1 H), 6.78 (s, 1 H), 6.55 (s, 1 H), 5.48 (s, 1 H), 4.45 (s, 1 H), 3.92 (s, 3 H), 3.82 (s, 3 H), 3.81 (s, 3 H), 3.60 (t, 2 H, J = 6.8 Hz), 3.30-3.18 (m, 2 H), 2.50-2.39 (m, 3 H), 2.34 (ddd, 1 H, J 1 = J 2 = 6.8 Hz, J 3 = 13.2 Hz), 1.42 (s, 9 H), 0.95 (s, 21 H), -0.1 (s, 9 H). 13C NMR (CDCl3): δ = 155.8, 151.1, 148.2, 147.1, 146.6, 138.5, 134.1, 133.5, 132.0, 129.5, 119.1, 114.3, 111.4, 79.2, 64.1, 61.3, 55.9, 55.7, 40.1, 36.9, 33.1, 28.4, 17.9, 11.9, 1.7. IR (KBr): 3325, 2940, 2865, 1685, 1515, 1465, 1245, 1170, 1110, 880 cm-1. Anal. Calcd for C36H61NO7Si2: C, 63.96; H, 9.09; N, 2.07. Found: C, 64.26; H, 9.38; N, 2.06. HPLC (Daicel CHIRALCEL OD-H, φ0.46 × 250 mm × 2, hexane:i-PrOH = 98:2, 1.0 mL/min) retention time: 20.5 min for (+)-9, 25.6 min for (-)-9. Compound 10: [α]D 24 -24 (c 0.99, CHCl3)*. 1H NMR (CDCl3): δ = 6.81 (s, 1 H), 6.61 (s, 1 H), 6.10 (s, 1 H), 4.59 (br, 1 H), 3.92 (s, 3 H), 3.85 (s, 3 H), 3.72-3.61 (m, 2 H), 3.42-3.33 (m, 2 H), 3.35 (s, 3 H), 3.24 (s, 3 H), 2.61 (t, 2 H, J = 7.7 Hz), 2.16 (ddd, 1 H, J 1 = J 2 = 7.2 Hz, J 3 = 14.5 Hz), 2.03 (ddd, 1 H, J 1 = J 2 = 5.6 Hz, J 3 = 14.5 Hz), 1.43 (s, 9 H), 0.99 (s, 21 H), -0.11 (s, 9 H). 13C NMR (CDCl3): δ = 196.7, 155.7, 153.9, 153.2, 148.8, 148.3, 146.8, 130.1, 129.3, 125.2, 113.3, 111.3, 94.5, 79.3, 61.3, 55.9, 55.8, 50.3, 50.2, 39.8, 37.4, 33.2, 28.3, 17.9, 11.8, 1.6. IR (NaCl): 3385, 2945, 2865, 1715, 1665, 1510, 1465, 1250, 1165, 1090, 1070 cm-1. Anal. Calcd for C37H63NO8Si2: C, 62.94; H, 8.99; N, 1.98. Found: C, 62.65; H, 9.18; N, 1.94. HPLC (Daicel CHIRALCEL OD-H, φ0.46 × 250 mm, hexane:i-PrOH = 98:2, 1.0 mL/min) retention time: 7.4 min for (-)-10, 12.6 min for (+)-10. Compound 11: [α]D 27 +52.0 (c 1.73, CHCl3)*. 1H NMR (CDCl3): δ = 6.56 (s, 1 H), 6.49 (s, 1 H), 6.05 (s, 1 H), 4.15 (ddd, 1 H, J 1 = J 2 = 5.1 Hz, J 3 = 13.2 Hz), 3.85 (s, 6 H), 3.76 (ddd, 1 H, J 1 = 5.1 Hz, J 2 = 8.9 Hz, J 3 = 13.2 Hz), 3.66 (s, 3 H), 3.63 (ddd, 1 H, J 1 = 6.2 Hz, J 2 = 8.1 Hz, J 3 = 9.7 Hz), 3.49 (ddd, 1 H, J 1 = 6.2 Hz, J 2 = 8.1 Hz, J 3 = 9.7 Hz), 3.03 (ddd, 1 H, J 1 = 5.1 Hz, J 2 = 8.9 Hz, J 3 = 16.1 Hz), 2.93 (ddd, 1 H, J 1 = J 2 = 5.1 Hz, J 3 = 16.1 Hz), 2.31 (ddd, 1 H, J 1 = J 2 = 6.2 Hz, J 3 = 12.3 Hz), 2.11 (ddd, 1 H, J 1 = J 2 = 8.1 Hz, J 3 = 12.3 Hz), 1.37 (s, 9 H), 0.94 (s, 21 H), 0.0 (s, 9 H). 13C NMR (CDCl3): δ = 181.6, 167.4, 157.1, 154.9, 148.7, 148.5, 147.7, 126.3, 124.3, 123.5, 111.0, 109.8, 81.1, 66.3, 61.3, 59.8, 55.8, 55.7, 40.1, 34.7, 28.3, 27.9, 17.9, 11.7, 1.4. IR (NaCl): 2940, 2865, 1695, 1660, 1515, 1365, 1260, 1225, 1165, 1090, 860 cm-1. Anal. Calcd for C36H59NO7Si2: C, 64.15; H, 8.82; N, 2.08. Found: C, 64.01; H, 9.02; N, 1.93. HPLC (Daicel CHIRAL-CEL OD-H, φ0.46 × 250 mm, hexane:i-PrOH = 99:1, 0.5 mL/min) retention time: 14.3 min for (+)-11, 17.1 min for (-)-11. Compound 1: Pale yellow needles (CHCl3), mp 90.5-91.0 °C; [α]D 24 +46 (c 0.86, CHCl3)*. HPLC (Daicel CHIRALPAK AD-H, φ0.46 × 250 mm, hexane:i-PrOH = 80:20, 1.0 mL/min) retention time: 31.6 min for (+)-1, 25.3 min for (-)-1.

8

Attempts to remove the MOM group from alcohol 4 led to concomitant desilylation.

9

We converted both isomers of 6 to O-methyleryso-dienone(1). The absolute configuration of each intermediate was not determined. In Scheme [2] and Scheme [3] , one of the enantiomers was tentatively drawn for convenience.

11

The enantiomeric purity was determined by HPLC analysis. For the analytical conditions and retention times, see ref. 6.

12

We were afraid of racemization in the oxidation of 9 and in the cyclization of 10. If the reaction process involved dienone i as a transient intermediate, generated by the intermolecular attack of a nucleophile at the C(5), the change in the C(5) hybridization into sp3 might have caused racemization due to the lowered rotational barrier about the C(5)-C(13) bond (Figure [2] ).

Figure 2

14

The specific rotation of O-methylerysodienone has not been reported.