Mechanism of the Kulinkovich Cyclopropanol Synthesis: Transfer-Epititanation of the Alkene in Generating the Key Titanacyclopropane Intermediate

An investigation of the Kulinkovich cyclopropanol synthesis, the interaction of esters with 2:1 or 3:1 mixtures of alkyl Grignard reagents and Ti(OiPr)4 at low temperatures, has been conducted, in order to ascertain which reactive intermediates are involved and how they are interconverted. Because of the nature of the ultimate product, one of the most obvious intermediates is the 1,1‐diisopropoxy‐1‐titanacyclopropane stemming from the epititanation of the alkene set free from the alkyl Grignard reagent employed. A search for the formation of such a titanocycle by warming an ethereal solution of either Et2Ti(OiPr)2 or iPr2Ti(OiPr)2 between −78 °C and +25 °C was attempted by chemical trapping with either an ester or nitrile. In this manner it was shown that such a titanocycle was formed in the case of Et2Ti(OiPr)2 but not with iPr2Ti(OiPr)2. As to the role of two other potential intermediates, Ti(OiPr)2 and R2Ti(OiPr)2, it was demonstrated that preformed Ti(OiPr)2 in the presence of ethylene and an ester does not form the corresponding cyclopropanol. Thus, under the reaction conditions Ti(OiPr)2 cannot perform the direct epimetallation necessary to produce the requisite titanacyclopropane. On the other hand, either iPr2Ti(OiPr)2 or Et2Ti(OiPr)2 can achieve the transfer‐epititanation of ethylene at low temperatures and hence with methyl benzoate yield 1‐phenyl‐1‐cyclopropanol. In contrast, neither iPr2Ti(OiPr)2 nor Et2Ti(OiPr)2 can at low temperatures transfer‐epititanate propylene. This difference in alkene reactivity can be ascribed to steric factors operating in the proposed octahedral transition state for transfer‐epimetallation. Finally, by introducing free ethylene into such Kulinkovich reaction mixtures, either by ethylene gas itself or a third equivalent of EtMgX, the isolated yields of cyclopropanols were more than doubled over those obtained with a 1:2 ratio of Ti(OiPr)4/EtMgX. From this observation one can conclude that free ethylene catalytically initiates the Kulinkovich reaction by coordinating with Et2Ti(OiPr)2 and undergoes transfer‐epititanation to produce the requisite titanacyclopropane and thereby liberates ethylene, which perpetuates the reaction. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)