Concise Total Synthesis of (±)-Crinine

Abstract

The concise total synthesis of (±)-crinine was accomplished in 24% overall yield and eleven steps starting from an easily available allylic alcohol. The key step of the current synthesis involved the NBS-promoted semipinacol rearrangement reaction of allylic alcohols. The hydroindole skeleton with the sterically congested quaternary carbon center was established concisely by utilizing this semipinacol rearrangement followed by a combination of intramolecular aldol and aza-Michael reactions.

Key words

aldol reaction - alkaloids - aza-Michael reaction - semi­pinacol rearrangement - total synthesis

References and Notes

• 1a Martin SF. The Amaryllidaceae Alkaloids, In The Alkaloids   Vol. 30:  Academic Press; New York: 1987.  p.251 
• 1b Hoshino O. The Amaryllidaceae Alkaloids, In The Alkaloids   Vol. 51:  Academic Press; New York: 1998.  p.323 
• For reviews, see:
• 2a Hoshino O. In The Alkaloids   Vol. 51:  Coedell GA. Academic Press; New York: 1998.  p.362 
• 2b Alarcon M. Cea G. Weigert G. Bull. Environ. Contam. Toxicol.  1986,  37:  508 
• 2c Pacheco P. Silva M. Steglich W. Watson WH. Rev. Latinoam. Quim.  1978,  9:  28 
• 3a Wang BM. Song ZL. Fan CA. Tu YQ. Chen WM. Synlett  2003,  1497 
• 3b Wang M. Wang BM. Shi L. Tu YQ. Fan C.-A. Wang SH. Hu XD. Zhang SY. Chem. Commun.  2005,  5580 
• 3c Yuan D.-Y. Tu Y.-Q. Fan C.-A. J. Org. Chem.  2008,  73:  7797 
• 3d Zhang E. Tu Y.-Q. Fan C.-A. Zhao X. Jiang Y.-J. Zhang S.-Y. Org. Lett.  2008,  10:  4943 
• 3e Fan C.-A. Tu Y.-Q. Song Z.-L. Zhang E. Shi L. Wang M. Zhang S.-Y. Org. Lett.  2004,  6:  4961 
• 3f Hu X.-D. Tu Y.-Q. Zhang E. Gao S.-H. Wang S.-H. Wang A.-X. Fan C.-A. Wang M. Org. Lett.  2006,  8:  1823 
• 3g Zhang F.-M. Tu Y.-Q. Liu J.-D. Fan X.-H. Shi L. Hu X.-D. Wang S.-H. Zhang Y.-Q. Tetrahedron  2006,  62:  9446 
• 4a Muxfeldt H. Schneider RS. Mooberry JB. J. Am. Chem. Soc.  1966,  88:  3670 
• 4b Whitlock HW. Smith GL. J. Am. Chem. Soc.  1967,  89:  3600 
• 4c Overman LE. Mendelson LT. J. Am. Chem. Soc.  1981,  103:  5579 
• 4d Overman LE. Jacobsen EJ. Tetrahedron Lett.  1982,  23:  2741 
• 4e Overman LE. Sugai S. Helv. Chim. Acta  1985,  68:  745 
• 4f Martin SF. Campbell CL. J. Org. Chem.  1988,  53:  3184 
• 4g Pearson WH. Lovering FE.
  J. Org. Chem.  1998,  63:  3607 
• 4h Bru C. Guillou C. Tetrahedron  2006,  62:  9043 
• 4i Tam NT. Cho C.-G. Org. Lett.  2008,  10:  601 
• 5 Bräse S. Wertal H. Frank D. Vidović D. de Meijere A. Eur. J. Org. Chem.  2005,  4167 
• 6 D’hooghe M. Mangelinckx S. Persyn E. Brabandt WV. Kimpe DN. J. Org. Chem.  2006,  71:  4232 
• 7 Ito Y. Hirao T. Saegusa T. J. Org. Chem.  1978,  43:  1011