Diastereoselective [3,2]-Stevens and Sommelet-Hauser Rearrangements in the Dihydromethanodibenzoazocine Series

Abstract

Bridged tricyclic dihydroazocines, readily available from α-amino acids were subjected to a series of diastereoselective [3,2]-Stevens and Sommelet-Hauser rearrangements via the corresponding ‘azocinium’ salts. The enantiopure rearrangement products have functionalities that can be used in preparing diversely substituted heterocyclic scaffolds.

Key words

sigmatropic rearrangements - nitrogen ylides - tetrahydroisoquinoline

References

• See for example:
• 1a Burger’s Medicinal Chemistry and Drug Discovery   Vol. 1-5:  Wolff ME. Wiley-Interscience; New York: 1995-1997. 
• 1b Gringauz A. In Introduction to Medicinal Chemistry, How Drugs Act and Why   Wiley-VCH; New York: 1997. 
• For pertinent reviews, see:
• 2a Gözler B. In The Alkaloids   Vol. 31:  Roberts MF. Wink M. Plenum; New York: 1981.  p.317-389  
• 2b Ruzwadowska MD. Heterocycles  1994,  39:  903 
• 2c Kametani T. The Chemistry of the Isoquinoline Alkaloids   Phillipson JD. Roberts MF. Zenk MH. Springer-Verlag; New York: 1985.  p.205-289  
• 3 Hanessian S. Mauduit M. Demont E. Talbot C. Tetrahedron  2002,  58:  1485 
• 4a Reetz MT. Drewes MW. Schmitz A. Angew. Chem., Int. Ed. Engl.  1987,  26:  1141 
• 4b Reetz MT. Chem. Rev.  1999,  99:  1121 
• 5 Casadio S. Pala G. Crescenzi E. Marazzi-Uberti E. Coppi G. Turba C. J. Med. Chem.  1968,  11:  97 
• 6a Takayama H. Nomoto T. Suzuki T. Takamoto M. Okamoto T. Heterocycles  1978,  9:  1545 
• 6b Hanessian S. Mauduit M. Angew. Chem. Int. Ed.  2001,  40:  3810 
• 7a Monn JA. Schoepp DD. Ann. Rep. Med. Chem.  1994,  29:  53 
• 7b Gee KR. Barmettler P. Rhodes MR. McBurney RN. Reddy NL. Hu L.-Y. Cotter RE. Hamilton PN. Weber E. Keana JFW. J. Med. Chem.  1993,  36:  1938 
• 7c Webber E, Keana JWF, and Barmettler P. inventors; Patent WO  9012575.  ; Chem. Abstr. 1991, 115, 106019
• 7d Kemp JA. Foster AC. Wong EHF. Trends Neurosci.  1987,  10:  294 
• 7e Russell JH. inventors; British Patent GB  1146109.  ; Chem. Abstr. 1969, 71, 30370
• 7f Waldmann E. inventors; German Patent DE  1035141.  ; Chem. Abstr. 1958, 56, 1436
• 8 Hanessian S. Saravanan P. Mauduit M. J. Med. Chem.  2003,  46:  34 
• 9a Stevens TS. Creighton EM. Gorden AB. MacNicol M. J. Chem. Soc.  1928,  3193 
• 9b Pine SH. Org. React.  1970,  18:  403 
• 10 Markó IE. In Comprehensive Organic Synthesis   Vol. 3:  Trost BM. Fleming I. Pattenden G. Pergamon; Oxford: 1991.  p.913-917 
• 11a Jamieson RW. Laird T. Ollis WD. Sutherland IO. J. Chem. Soc., Perkin Trans. 1  1980,  1436 
• 11b Jamieson RW. Laird T. Ollis WD. Sutherland IO. J. Chem. Soc., Perkin Trans. 1  1980,  1450 
• 13 Hanessian S. Talbot C. Mauduit M. Saravanan P. Gone JR. Heterocycles  2006,  67:  205 
• 14a Sommelet M. Kantor CR. C. R. Acad. Sci.  1937,  205:  56 
• 14b Kantor M. Hauser CR. J. Am. Chem. Soc.  1951,  73:  4122 
• 14c Jones FN. Hauser CR. J. Org. Chem.  1962,  27:  1542 
• 14d Puterbaugh WH. Hauser CR. J. Am. Chem. Soc.  1964,  86:  1108 
• 14e Tanaka T. Shirai N. Sugimori J. Sato Y. J. Org. Chem.  1992,  57:  5034 
• 15 Ollis WD. Rey M. Sutherland IO. J. Chem. Soc., Perkin Trans. 1  1983,  1009 

12

To ascertain the relative stereochemistry of the major and minor products of the [3,2]-Stevens rearrangement products, 2D-NOESY was used in order to look for 1,3-pseudo-diaxial spatial correlations between protons marked as α and β in the case of the minor product 4 and between the proton marked as γ and the methyl group in the case of the major product 3 (Figure [1] ).

16

CCDC 286054 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

17

CCDC 286055 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.