Stereochemical consequences of 6- and 8-substitution in reactions of bicyclo[4.2.0]octan-7-ones

Article abstract of DOI:10.1021/jo00085a031

Reduction (zinc/copper couple) of each epimer of 8-chloro-8-methylbicyclo[4.2.0]oct-2-en-7-one (6 and 7) gives the same product mixture containing 95% of the 8-endo-methyl compound 8. Ketalization of 8 catalyzed by TMSOTf gives the endo-methyl cyclic ethylene ketal 10 at -78°C and the exo-methyl epimer 11 (90:10) at 25°C, in contrast to β-naphthalenesulfonic acid-catalyzed reactions. Wittig olefination of both the functionalized 8-endo- and 8-exo-methyl ketones gives only the 8-endo-methyl olefin, whereas introduction of a 6-methoxy or 6-methyl substituent favors the 8-exo configuration. A rationale for these observations is proposed.