title: A New Approach Towards Bicyclo[4.2.0]octan-1-ols: Synthetic and Mechanistic Studies
Creators: name: Rowen, Catherine Carmel
Publisher: name: Griffith University
Year: 2003
Subjects: subject: sulfoxides
subject: bicyclooctanol sulfoxides
subject: x-ray crystallography
subject: organic chemistry

description: The reaction between the lithium enolate of cyclohexanone and phenyl vinyl sulfoxide resulted in the formation of the novel bicyclooctanol sulfoxides 215-217 and the monoalkylated sulfoxide 218. The effects of variation in reaction time, temperature and concentration were studied. Under optimal conditions (10 minutes, -10°C and 0.085 M) the ratio of the bicyclooctanol sulfoxides 215-217 (75% yield) to the monoalkylated sulfoxide 218 was 95:5. The bicyclooctanol sulfoxides 215-217 were characterised as the sulfone derivatives, bicyclooctanol sulfones 219 and 220. X-ray crystal structures were used to determine the relative stereochemistry of the bicyclooctanol sulfoxides 215-217 and the bicyclooctanol sulfones 219 and 220. Bicyclo[4.2.0]octano-1-ol formation was determined to occur via an ionic mechanism. Mechanistic studies were carried out using variations in reaction lighting and reaction solvent, conducting the reaction in the presence of a radical trap and quenching the reaction with a deuterium label. The role of the counterion was determined to be important in the formation of the bicyclooctanol sulfoxides 215-217. Sequestering lithium ions with HMPA and substituting lithium with potassium favoured alkylation. Substituting the lithium enolate of cyclohexanone with the dimethylaluminium enolate of cyclohexanone resulted in a different distribution of the bicyclooctanol sulfoxides 215-217 and the formation of bicyclooctanol sulfoxide 243. Transition states to account for these differences have been proposed. The stability of the bicyclooctanol sulfoxides under conditions of acid, base and heating was studied. Thermal ring opening of the bicyclooctanol sulfoxides 215 and 216 to the monoalkylated sulfoxides 218A and 218B respectively occurred with retention of the configuration at sulfur. The relative stereochemistry of the individual bicyclooctanol sulfoxides 215-217 was considered to account for the observed stability in each case. The reaction between the lithium enolate of cyclohexanone and (R)-(+)-p-tolyl vinyl sulfoxide 193 gave the bicyclooctanol tolyl sulfoxides 246, 251 and 252 and the monoalkylated tolyl sulfoxide 247. This showed that both bond rotation in the side chain of the intermediate and epimerisation at sulfur occurred in the bicyclo[4.2.0]octan-1-ol forming process. The presence of the sulfoxide functionality in phenyl vinyl sulfoxide was determined to be crucial to the formation of bicyclo[4.2.0]octan-1-ols. In the reaction with the lithium enolate of cyclohexanone, phenyl vinyl sulfide gave no reaction, phenyl vinyl sulfone gave the bicyclic disulfones 260-265, ethyl acrylate gave the diesters 266-268 and diphenylvinylphosphine oxide gave the phosphine oxide 269. The cyclobutanol 270 and the ketone 271 were the products resulting from the reaction between the reaction between the lithium enolate of acetophenone and phenyl vinyl sulfoxide. This demonstrated potential scope for the cyclisation process using both cyclic and acyclic ketones.