An attempt to access in an enantioselective fashion, a highly substituted cyclohexane
as required for the northeastern sector of okilactomycin is described. The application
of Oppolzer’s sultam chemistry, involving in particular an optically and chemically
efficient asymmetric conjugate addition of a functionalized allylic Grignard reagent
in tandem with ring closing metathesis forms the basis of a direct, highly stereocontrolled
route to the cyclohexenylmethanol 10. Ensuing Sharpless epoxidation very efficiently leads to construction of epoxide
11. This intermediate and its benzyl ether were found to undergo regiocontrolled oxirane
ring cleavage with cyanide and chloride ions. However, this precedence was not matched
when alternative carbon nucleophiles (particularly allyl) were brought into play.
Under no circumstances was a desired product detected. The all-equatorial array of
substituents on the cyclohexane is likely responsible for the lack of reactivity toward
organometallic reagents.
metathesis - sultams - cyanation - carbocupration - epoxide - asymmetric conjugate
addition
