A general preparative method for carbonyl-protected γ-lithioketones via reductive lithiation. Synthetic uses of the bishomoenolate equivalents

Abstract

The mixed cuprates, generated by reductive lithiation of bis(phenylthio)acetals using lithium 4,4′-di- tert-butylbiphenylide (LDBB), followed by addition of cuprous bromide - dimethyl sulfide complex, undergo conjugate addition to enones in the presence of trimethylsilyl chloride to produce γ-(phenylthio)ketones. Protection of the ketone as its dioxolane, and reductive lithiation with LDBB provides carbonyl-protected γ-lithioketones. Primary, secondary, tertiary, and vinylic organolithiums have been prepared in this way and the protected ketone function can be in a ring. Previously, only primary straight chain γ-lithioketone equivalents were known. This method is the most versatile and general available for the production of such carbanions, which behave as bishomoenolate equivalents. The organometallics react with aldehydes to yield alcohols. The vinyllithiums react with N,N-dimethylformamide to produce an enal containing a protected ketone group. The mixed cuprates, formed upon treatment of the organolithiums with cuprous bromide - dimethyl sulfide complex, undergo allylation with allyl bromide, conjugate addition to enals and enones in the presence of trimethylsilyl chloride to produce monoprotected 1,7-dicarbonyl compounds, and acetylation to yield monoprotected 1,5-diketones. The monoprotected dicarbonyl compounds are readily deprotected and in a number of cases the resulting diketones can be induced to undergo base induced intramolecular aldol condensations to enones.