First Cinchona Rearrangement

As yet, the l-azabicyclo[3.2.2]nonane scaffold has been encountered in nature only rarely, for example, in tronoharine, vincathicine, and communesin B, in contrast to the l-azabicyclo[2.2.2]octane moiety of cinchona alkaloids. A short and simple access to this particular bicyclic system is thus ofhigh interest for exploring its biological and chemical properties. 

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The first cinchona rearrangement is also feasible without Ag +, provided stringent stereochemical and experimental conditions are fulfilled. In the preferred conformation of epi-la-OMs, the C9-OMs leaving group and migrating C7-C8 0-bond are antiperiplanar (Scheme 12.41). Under optimized conditions with NaOBz as a buffer (for the liberated methanesulfonic acid), a-amino ether 107-OMe was formed in 81%... 

The [2.2.2]azabicyclic cage of the alkaloids is not immutable. The first and second cage expansions have been discovered only during the past decade. A general cinchona alkaloid solvolysis and rearrangement scheme and a unified theory have been presented. Classical solvolysis chemistry with conventional hydrocarbon substrates is complemented. The resulting azabicyclo[3.2.2]nonanes have hardly been studied. 

In 2008, Jorgensen et al. reported the first organocatalysed enantioselective [l,3]-sigmatropic O- to A -rearrangement reactions. These reactions took place under regio- and enantioselective control, and were catalysed by cinchona alkaloids, such as [DHQD]2PHAL derived from dihydroquinidine. A first... 

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