The First and Second Cinchona Rearrangement. Two Fundamental Transformations of Alkaloid Chemistry

Journal of Organic Chemistry

Volumn 69, Issue 9, 2004, Pages 2983-2991

  Franz, M Heiko ^a   Röper, Stefanie ^a   Wartchow, Rudolf ^a   Hoffmann, H M R ^a  

^a LEIBNIZ UNIVERSITY HANNOVER   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; CONFORMATIONS; ETHERS; GROUND STATE;

ALKALOIDS; NITROGEN-BRIDGED CATIONS; NUCLEOPHILIC ATTACK; STEREOELECTRONIC FACTORS;

STEREOCHEMISTRY;

1 AZABICYCLO[3.2.2]NONANE; [3.2.2]AZABICYCLIC ALPHA AMINO ETHER; ALKALOID; BASE; BICYCLO COMPOUND; CATION; ETHER DERIVATIVE; IMINE; NITROGEN; SOLVENT; TRIFLUOROETHANOL; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; CHEMICAL STRUCTURE; CINCHONA; CONFORMATIONAL TRANSITION; ELECTRON; HYDROLYSIS; METHANOLYSIS; REACTION ANALYSIS; SOLVOLYSIS; STEREOCHEMISTRY;

ANIMALS; AZA COMPOUNDS; BICYCLO COMPOUNDS, HETEROCYCLIC; CINCHONA; CINCHONA ALKALOIDS; HYDROLYSIS; MOLECULAR STRUCTURE; QUININE; SILVER; STEREOISOMERISM; TARTRATES; TRIFLUOROETHANOL;

EID: 11144358642     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo030363s     Document Type: Article

References (35)

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21. Thus, even quinine (6′-R = OMe) undergoes the second rearrangement, although in much lower yield. See also Scheme 3.
22. 2OH were roughly equal (Schemes 6 and 7). Inspection of the X-ray crystal structure suggests that generation of a silver dication is feasible from 3-Br. Complexation of the bridgehead nitrogen is expected to slow migration of nitrogen.
23. X-ray crystal structure of quininium hydrogen (S,S)-tartrate hemihydrate: Ryttersgard, C.; Larsen, S. Acta Crystallogr. Sect. C 1998, C54, 1701. Quinine has three hydrogen bond acceptors excluding the quinoline nitrogen. Tartaric acid is present in an extended chain configuration and has four hydrogen bond donor and six potential acceptor atoms. Cooperative binding seems feasible, in the presence of 6′-R = OMe more so than in 6′-R = H.
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26. For reactivity in an aqueous environment see: Candler, D. Nature 2002, 417, 491. Ball, P. Nature 2003, 423, 25. See also: Grieco, P. A. Organic Synthesis in Water; Blackie Academic; London, UK, 1998. Li, C.-J.; Chan, T.-H. Organic Reactions in Aqueous Media; Wiley: New York, 1997. Breslow, R. Acc. Chem. Res. 1991, 6, 159.
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30. As another route to 9-epi configured cinch bases with intact cage the Mitsunobu reaction can be used with moderate success (ca. 50% by standard protocol). See: Hughes, D. L. Org. React. 1992, 42, 335-656. Castro, B. R. Org. React. 1983, 29, 1-162.
31. As another route to 9-epi configured cinch bases with intact cage the Mitsunobu reaction can be used with moderate success (ca. 50% by standard protocol). See: Hughes, D. L. Org. React. 1992, 42, 335-656. Castro, B. R. Org. React. 1983, 29, 1-162.
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33. See the X-ray crystal structure.
34. 2 as intermediate; see: King, J. F. Acc. Chem. Res. 1975, 8, 10 and references therein.
35. N2-like attack by water; see: Braje, W. M.; Holzgrefe, J.; Wartchow, R.; Hoffmann, H. M. R. Angew. Chem., Int. Ed. 2000, 39, 2085.