Contrasting reactions of ketones and thioketones with alkyllithiums: a coordinated experimental and computational investigation

The reaction of ketones with organolithium reagents generally proceeds by addition of the organometallic to the electrophilic carbon of the C═O group to give the lithium salt of a tertiary alcohol. The seemingly analogous reaction of thioketones with organolithiums is a fundamentally different process: such reactions typically afford a variety of products, and addition of the organolithium to carbon of the C═S group to give a thiol is a relatively unimportant component. Reactions of the stable thioketone, adamantantanethione (1), with several alkyllithiums (MeLi, n-BuLi and t-BuLi) in a variety of solvents have been studied in the first comprehensive investigation of the reactions of organolithiums with a representative alkyl-substituted thione. Reactions of 1 with n-BuLi or t-BuLi afforded 2-adamantanethiol (2) as the major product. In an effort to explain the marked difference in behavior of ketones and thioketones in reactions with organolithiums, transition states for both the addition and reduction reactions have been located at the B3LYP/6-311+G* level using acetone and thioacetone as model substrates. The transition states for the addition of dimeric MeLi to the C═O and C═S carbons of acetone and thioacetone were significantly different as a result of the small bond angles preferred by divalent sulfur, and this accounts for the much slower addition to a C═S carbon vis-à-vis a C═O group. Transition states for reduction of acetone and thioacetone by EtLi were similar, but the greater exothermicity of the reduction of the thioketone results in an earlier transition state and lower activation energy for this process than that for the reduction of a ketone. The possible role of radical-mediated processes in this chemistry is also discussed.