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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Synthesis of (-)-(S,S)-clemastine by invertive N --> C aryl migration in a lithiated carbamate
Anne M Fournier1, Robert A Brown, William Farnaby
1School of Chemistry, University of Manchester, Oxford Road, Manchester M13 9PL, UK.
Abstract:
The first enantioselective synthesis of the antihistamine agent clemastine, as its (S,S)-stereoisomer, has been achieved by ether formation between a proline-derived chloroethylpyrrolidine and an enantiomerically enriched tertiary alcohol. The tertiary alcohol was formed from the carbamate derivative of alpha-methyl-p-chlorobenzyl alcohol by invertive aryl migration on lithiation. The (S,S)-stereochemistry of the product confirms the invertive nature of the rearrangement.
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