The first and second cinchona rearrangement. Two fundamental transformations of alkaloid chemistry.
Stereochemistry, products, and driving forces of the "first and second Cinchona rearrangement" have been investigated and a unified theory is presented. The first cage expansion affords [3.2.2]azabicyclic alpha-amino ether and is formulated via a configurationally stable bridgehead iminium ion and quasiequatorial nucleophilic attack. The second cage expansion affords beta-functionalized [3.2.2]azabicycles. In this case a nonclassical nitrogen-bridged cation is postulated to account for retention of configuration and potential reversibility of the cage expansion. The second rearrangement is favored for the so-called cinch bases (6'-R = H) in trifluoroethanol. Stereoelectronic factors, electron demand at C9, ground state conformation, and solvent type are crucial in all cases. A two-step protocol for preparing 9-epi-configured Cinchona alkaloids from 9-nat precursors is described.
Franz
M Heiko
MH
Department of Organic Chemistry, University of Hannover, Schneiderberg 1 B, 30167 Hannover, Germany.
Röper
Stefanie
S
Wartchow
Rudolf
R
Hoffmann
H M R
HM
D000818:Animals; D001372:Aza Compounds / Q000737:chemistry; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry; D002929:Cinchona / Q000737:chemistry*; D002930:Cinchona Alkaloids / Q000737:chemistry*; D006868:Hydrolysis; D015394:Molecular Structure; D011803:Quinine / Q000737:chemistry; D012834:Silver / Q000737:chemistry; D013237:Stereoisomerism; D013644:Tartrates; D014270:Trifluoroethanol / Q000737:chemistry
D001372:Aza Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002930:Cinchona Alkaloids; D013644:Tartrates; D012834:Silver; D014270:Trifluoroethanol; D011803:Quinine; C029768:tartaric acid