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

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.

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

References

1a Dyke SF. Quessy SN. In The Alkaloids   Vol. 18:  Rodrigo RGA. Academic Press; New York: 1981.  p.1 

1b Tsuda Y. Sano T. In The Alkaloids   Vol. 48:  Cordell GA. Academic Press; San Diego: 1996.  p.249 

For recent synthetic studies, see:

2a Fukumoto H. Esumi T. Ishihara J. Hatakeyama S. Tetrahedron Lett.  2003,  44:  8047 

2b Shimizu K. Takimoto M. Mori M. Org. Lett.  2003,  5:  2323 

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2d Chikaoka S. Toyao A. Ogasawara M. Tamura O. Ishibashi H. J. Org. Chem.  2003,  68:  312 

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2g Padwa A. Waterson AG. J. Org. Chem.  2000,  65:  235 

2h Hosoi S. Nagao M. Tsuda Y. Isobe K. Sano T. Ohta T. J. Chem. Soc., Perkin Trans. 1  2000,  1505 

2i For asymmetric synthesis of erythrinan alkaloid, see: Sano T. Kamiko M. Toda J. Hosoi S. Tsuda Y. Chem. Pharm. Bull.  1994,  42:  1375 

2j Tsuda Y. Hosoi S. Isida K. Sangai M. Chem. Pharm. Bull.  1994,  42:  204 

2k Tsuda Y. Hosoi S. Katagiri N. Kaneko C. Sano T. Chem. Pharm. Bull.  1993,  41:  2087 

3 Throughout this work, the commonly accepted erythrinan numbering is used. See: Boekelheide V. Prelog V. In Progress in Organic Chemistry   Vol. 3:  Cook JW. Butterworths Scientific; London: 1955.  Chap. 5. see also ref. 1

4 Yasui Y. Koga Y. Suzuki K. Matsumoto T. Synlett  2004, DOI: 10.1055/s-2004-817753

For reviews, see:

5a Bringmann G. Breuning M. Tasler S. Synthesis  1999,  525 

5b Gant TG. Meyers AI. Tetrahedron  1994,  50:  2297 

5c For recent examples, see: Broutin P.-E. Colobert F. Org. Lett.  2003,  5:  3281 

5d Baudoin O. Décor A. Cesario M. Guéritte F. Synlett  2003,  2009 

5e See also: Anderson JC. Cran JW. King NP. Tetrahedron Lett.  2003,  44:  7771 

5f Kamikawa K. Sakamoto T. Tanaka Y. Uemura M. J. Org. Chem.  2003,  68:  9356 

5g Matsumoto T. Konegawa T. Nakamura T. Suzuki K. Synlett  2002,  122 

5h Shimada T. Cho Y.-H. Hayashi T. J. Am. Chem. Soc.  2002,  124:  13396 

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.

7a Miyaura N. Yanagi T. Suzuki A. Synth. Commun.  1981,  11:  513 

7b Watanabe T. Miyaura N. Suzuki A. Synlett  1992,  207 

7c For a review, see: Miyaura N. Suzuki A. Chem. Rev.  1995,  95:  2457 

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.

10a Tamura Y. Yakura T. Haruta J. Kita Y. J. Org. Chem.  1987,  52:  3927 

10b Lewis N. Wallbank P. Synthesis  1987,  1103 

10c For reviews on phenolic oxidation with hypervalent iodine reagents, see: Pelter A. Ward RS. Tetrahedron  2001,  57:  273 

10d Moriarty RM. Prakash O. Org. React.  2001,  57:  327 

10e For a review on synthetic uses of ortho-quinone monoacetals, see: Quideau S. Pouységu L. Org. Prep. Proced. Int.  1999,  31:  617 

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

13a Ghosal S. Majumdar SK. Chakraborti A. Aust.
J. Chem.  1971,  24:  2733 

13b Chou C.-T. Swenton JS.
J. Am. Chem. Soc.  1987,  109:  6898 

14

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