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

Abstract

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 Et 2 Ti(OiPr) 2 or iPr 2 Ti(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 Et 2 Ti(OiPr) 2 but not with iPr 2 Ti(OiPr) 2 . As to the role of two other potential intermediates, Ti(OiPr) 2 and R 2 Ti(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 titanacy-

Analysis of Interactions between the Epidermal Growth Factor Receptor and Soluble Ligands on the Basis of Single‐Molecule Diffusivity in the Membrane of Living Cells

“…A direct comparison with the kinetic stability of R 2 Ti(O i Pr) 2 (R = c C 3 H 5 , c C 4 H 7 , c C 5 H 9 , CHMe 2 , CHEt 2 ) is not possible, because isolation and structural characterisation of the parent dialkyltitaniums have not been described 1b,24,26. It has been postulated that the synthesis of the Kulinkovich reagent from Ti(O i Pr) 4 and i PrMgBr involves the formation of ( i Pr) 2 Ti(O i Pr) 2 as intermediate,27 which apparently suffers β‐H elimination already at low temperatures 28…”

A Novel Approach to Monobenzannulated Spiroketals Using Styrenes in the Kulinkovich Reaction

“…12b Thus, cyclohexylmagnesium chloride was added to a solution of Ti(Oi-Pr) 4 in THF at -78°C over 20 minutes in order to form the titanacyclopropane complex. 19 After addition of 11, the suspension was stirred for 1 hour, followed by the addition of 12 with subsequent warming to room temperature. Cyclopropanol 13 was only obtained in 16% yield in this case (entry 3).…”

5.34 Early Transition Metal Mediated Reductive Coupling Reactions

“…[6][7][8][9][10] Rather, this chapter is presented in a manner that simply accepts that the fate of R 2 Ti(OR) 2 can be manipulated to generate new organometallic complexes of alkynes, imines, and alkenes by net transfer epititanation -the reactive intermediates that are central to the powerful organic transformations discussed in this chapter.…”