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Updated: Aug 24, 2026

Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
The first and second cinchona rearrangement. Two fundamental transformations of alkaloid chemistry
M Heiko Franz1, Stefanie Röper, Rudolf Wartchow
1Department of Organic Chemistry, University of Hannover, Schneiderberg 1 B, 30167 Hannover, Germany.
Abstract:
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.
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