Toward a Total Synthesis of Okilactomycin. 2. A Metathesis-Based Approach to the Heavily Functionalized Cyclohexane Ring

Abstract

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.

Key words

metathesis - sultams - cyanation - carbocupration - epoxide - asymmetric conjugate addition

References and Notes

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7

Boulet, S. L.; unpublished findings.