Studies in Chemistry of the 8-Hetero Bicyclo[3.2.1]Octan-3-ones
Date
2008-10
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
ORCID
Type
Degree Level
Masters
Abstract
New processes that leads to formation of new carbon-carbon bond (the Michael reaction, the Mannich reaction and alkylation reaction) or carbon-heteroatom bond (á-halogenation, á-hydroxylation and á-amination) on bridged bicyclic ketones such as tropinone and TBON were investigated, utilizing LDA in the deprotonation step. All reactions, in which new carbon-heteroatom bond is formed, were not successful either due to low selectivity and/or yields. In case of new carbon-carbon bond forming processes, careful choice of electrophile (electrophile having the ester group in á-position to leaving group), allows for alkylation of tropinone with moderate yield and good selectivity.
Application of new conditions to the aldol reaction of TBON and tropinone (e.g. MgI2 catalyzed aldol reaction), gave new aldol products that were not detected from the lithium enolate chemistry of these ketones. Modification of reaction conditions in case of MgI2 catalyzed aldol reaction provides, in a ‘one pot’ process, bis-aldol product from TBON in good yield and high selectivity, as a single diastereoisomer.
Finally, TBON is used as a suitable scaffold for the synthesis of thiacocaine. The first known synthesis of racemic thiacocaine is presented, via deprotonation of TBON with LDA, as a key step.
Description
Keywords
8-hetero bicyclo[3.2.1]octan-3-ones, enolates, enantioselective deprotonation
Citation
Degree
Master of Science (M.Sc.)
Department
Chemistry
Program
Chemistry