A Concise Synthesis of (-)-Deoxoprosopinine

Abstract

A simple and highly efficient approach to (-)-deoxo­prosopinine from racemic epoxide as a starting material is described employing a Jacobsen’s hydrolytic kinetic resolution (HKR) and Sharpless asymmetric dihydroxylation (AD) as key steps.

Jacobsen’s HKR - Sharpless AD - hydroboration-oxidation - piperidine alkaloids - total synthesis

References and Notes

For reviews that include piperidine alkaloids, see:

<A NAME="RG24507ST-1A">1a</A> Strunz GM. Findlay JA. In The Alkaloids   Vol. 26:  Brossi A. Academic Press; New York: 1985.  p.89 

<A NAME="RG24507ST-1B">1b</A> Foder GB. Colasanti B. The Pyridine and Piperidine Alkaloids: Chemistry and Pharmacology, In Alkaloids: Chemical and Biological Perspectives   Vol. 3:  Pelletier SW. Wiley; New York: 1985.  p.1 

<A NAME="RG24507ST-1C">1c</A> Numata A. Ibuka T. In The Alkaloids   Vol. 31:  Brossi A. Academic Press; New York: 1987.  p.193 ; and references therein

<A NAME="RG24507ST-1D">1d</A> Schneider MJ. Pyridine and Piperidine Alkaloids: An Update, In Alkaloids: Chemical and Biological Perspectives   Vol. 10:  Pelletier SW. Pergamon; Oxford: 1996.  p.155 

<A NAME="RG24507ST-1E">1e</A> Wang CJ. Wuonola MA. Org. Prep. Proced. Int.  1992,  24:  585 

<A NAME="RG24507ST-1F">1f</A> Laschat S. Dickner T. Synthesis  2000,  1781 

<A NAME="RG24507ST-1G">1g</A> Weintraub PM. Sabd JS. Kane JM. Borcherding DR. Tetrahedron  2003,  59:  2953 

Prosopis alkaloids from the leaves, stems, and roots of Prosopis africana:

<A NAME="RG24507ST-2A">2a</A> Ratle G. Monseur X. Das BC. Yassi J. Khuong-Huu Q. Goutarel R. Bull. Soc. Chim. Fr.  1966,  2945 

<A NAME="RG24507ST-2B">2b</A> Khuong-Huu Q. Ratle G. Monseur X. Goutarel R. Bull. Soc. Chim. Belg.  1972,  81:  425 

<A NAME="RG24507ST-2C">2c</A> Khuong-Huu Q. Ratle G. Monseur X. Goutarel R. Bull. Soc. Chim. Belg.  1972,  81:  443 

Previous asymmetric synthesis of deoxoprosopinine:

<A NAME="RG24507ST-3A">3a</A> Saitoh Y. Moriyama Y. Takahashi T. Tetrahedron Lett.  1980,  21:  75 

<A NAME="RG24507ST-3B">3b</A> Saitoh Y. Moriyama Y. Hirota H. Takahashi T. Khuong-Huu Q. Bull. Chem. Soc. Jpn.  1981,  54:  488 

<A NAME="RG24507ST-3C">3c</A> Ciufolini MA. Hermann CW. Whitmire KH. Byrne NE. J. Am. Chem. Soc.  1989,  111:  3473 

<A NAME="RG24507ST-3D">3d</A> Tadano K. Takao K. Nigawara Y. Nishino E. Takagi I. Maeda K. Ogawa S. Synlett  1993,  565 

<A NAME="RG24507ST-3E">3e</A> Takao K. Nigawara Y. Nishino E. Takagi I. Maeda K. Tadano K. Ogawa S. Tetrahedron  1994,  50:  5681 

<A NAME="RG24507ST-3F">3f</A> Yuasa Y. Ando J. Shibuya S. Tetrahedron: Asymmetry  1995,  6:  1525 

<A NAME="RG24507ST-3G">3g</A> Yuasa Y. Ando J. Shibuya S. J. Chem. Soc., Perkin Trans. 1  1996,  793 

<A NAME="RG24507ST-3H">3h</A> Kadota I. Kawada M. Muramatsu Y. Yamamoto Y. Tetrahedron Lett.  1997,  38:  7469 

<A NAME="RG24507ST-3I">3i</A> Kadota I. Kawada M. Muramatsu Y. Yamamoto Y. Tetrahedron: Asymmetry  1997,  8:  3887 

<A NAME="RG24507ST-3J">3j</A> Agami C. Couty F. Mathieu H. Tetrahedron Lett.  1998,  39:  3505 

<A NAME="RG24507ST-3K">3k</A> Agami C. Couty F. Lam H. Mathieu H. Tetrahedron  1998,  54:  8783 

<A NAME="RG24507ST-3L">3l</A> Comins DL. Sandelier MJ. Grillo TA. J. Org. Chem.  2001,  66:  6829 

<A NAME="RG24507ST-3M">3m</A> Wang Q. Sasaki NA. J. Org. Chem.  2004,  69:  4767 

<A NAME="RG24507ST-4A">4a</A> Pandey SK. Kandula SV. Kumar P. Tetrahedron Lett.  2004,  45:  5877 

<A NAME="RG24507ST-4B">4b</A> Pandey SK. Kumar P. Tetrahedron Lett.  2005,  46:  4091 

<A NAME="RG24507ST-4C">4c</A> Pandey SK. Kumar P. Tetrahedron Lett.  2005,  46:  6625 

<A NAME="RG24507ST-4D">4d</A> Kumar P. Naidu SV. J. Org. Chem.  2005,  70:  4207 

<A NAME="RG24507ST-4E">4e</A> Kumar P. Naidu SV. Gupta P. J. Org. Chem.  2005,  70:  2843 

<A NAME="RG24507ST-4F">4f</A> Kumar P. Bodas MS. J. Org. Chem.  2005,  70:  360 

<A NAME="RG24507ST-4G">4g</A> Kumar P. Gupta P. Naidu SV. Chem. Eur. J.  2006,  12:  1397 

<A NAME="RG24507ST-4H">4h</A> Kumar P. Naidu SV. J. Org. Chem.  2006,  71:  3935 

<A NAME="RG24507ST-4I">4i</A> Pandey SK. Kumar P. Tetrahedron Lett.  2006,  47:  4167 

<A NAME="RG24507ST-4J">4j</A> Pandey SK. Kumar P. Eur. J. Org. Chem.  2007,  369 

<A NAME="RG24507ST-5">5</A> Schaus SE. Brandes BD. Larrow JF. Tokunaga M. Hansen KB. Gould AE. Furrow ME. Jacobsen EN. J. Am. Chem. Soc.  2002,  124:  1307 

<A NAME="RG24507ST-6">6</A> Staudinger H. Meyer J. Helv. Chim. Acta  1919,  2:  635 

For reviews on the Swern oxidation, see:

<A NAME="RG24507ST-7A">7a</A> Tidwell TT. Synthesis  1990,  857 

<A NAME="RG24507ST-7B">7b</A> Tidwell TT. Org. React.  1990,  39:  297 

<A NAME="RG24507ST-8A">8a</A> Becker H. Sharpless KB. Angew. Chem., Int. Ed. Engl.  1996,  35:  448 

<A NAME="RG24507ST-8B">8b</A> Kolb HC. VanNieuwenhze MS. Sharpless KB. Chem. Rev.  1994,  94:  2483 

<A NAME="RG24507ST-8C">8c</A> Torri S. Liu P. Bhuvaneswari N. Amatore C. Jutand A. J. Org. Chem.  1996,  61:  3055 

<A NAME="RG24507ST-9">9</A>

The diastereoselectivity was determined from ¹H NMR and ¹³C NMR spectral data. Spectral data of compound 11: mp 137 °C; [α]_D ²⁵ +6.90 (c 1.00, CHCl₃). IR (CHCl₃): ν = 3434, 3018, 2927, 1719, 1508, 1216 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 0.89 (t, J = 5.95 Hz, 3 H), 1.26-1.70 (m, 29 H), 2.27 (br s, 2 H), 3.62-3.71 (m, 1 H), 3.91 (d, J = 6.45 Hz, 1 H), 4.06 (d, J = 1.61 Hz, 1 H), 4.29 (q, J = 6.72, 13.70 Hz, 2 H), 4.55 (d, J = 8.87 Hz, 1 H), 5.10 (s, 2 H), 7.32-7.38 (m, 5 H) ppm. ¹³C NMR (50 MHz, CDCl₃): δ = 14.0, 22.6, 25.8, 29.2, 29.6, 29.8, 31.4, 31.8, 35.5, 51.1, 61.8, 66.4, 72.3, 73.4, 127.9, 128.4, 136.5, 156.2, 173.4 ppm. ESI-MS: m/z = 516 [M + Na]⁺. Anal. Calcd (%) for C₂₈H₄₇NO₆: C, 68.12; H, 9.60; N, 2.84. Found: C, 68.17; H, 9.58; N, 2.82.

<A NAME="RG24507ST-10">10</A> Fleming PR. Sharpless KB. J. Org. Chem.  1991,  56:  2869 

<A NAME="RG24507ST-11">11</A>

Spectral data of compound 13: mp 96 °C; [α]_D ²⁵ +5.65 (c 0.60, CHCl₃). IR (CHCl₃): ν = 3583, 3436, 3019, 2928, 1725, 1519, 1455, 1215 cm^-1. ¹H NMR (200 MHz, CDCl₃): δ = 0.88 (t, J = 6.07 Hz, 3 H), 1.26-1.79 (m, 30 H), 2.11 (br s, 1 H), 2.65-2.74 (m, 1 H), 3.58 (d, J = 4.06 Hz, 1 H), 4.11-4.17 (m, 1 H) 4.21 (q, J = 7.12, 13.86 Hz, 2 H) ppm. ¹³C NMR (50 MHz, CDCl₃): δ = 14.0, 14.2, 22.6, 26.1, 28.0, 29.3, 29.5, 29.6, 31.8, 35.8, 51.6, 60.8, 61.5, 65.5, 172.2 ppm. ESI-MS: m/z = 342 [M + H]⁺. Anal. Calcd (%) for C₂₀H₃₉NO₃: C, 70.33; H, 11.51; N, 4.10. Found: C, 70.35; H, 11.48; N, 4.12.