Kulinkovich reagent

Based on the Kulinkovich reagent (Ti(OiPr)4/iPrMgCl), a new route to allyltita-niums has been devised by Sato and coworkers and this has allowed the synthesis of chiral allylTi reagents which, by reaction with aldehydes and imines provide diverse polyfunctional chiral building blocks. Thus, while a number of versatile and dependable Ti-based allyl-transfer reagents are now available, the development and employment of chiral allyltitaniums appears to be poised for new application. 

Breit, B. Bis(alkoxy)titanacyclopropanes and -propenes (Kulinkovich reagents) Versatile reagents for carbon-carbon bond formation. J. Prakt. Chem. 2000, 342, 211-214. 

In general, esters, acid chlorides, and anhydrides are most reactive toward the Kulinkovich reagent. Carbonates and thioesters are of moderate reactivity, whereas carbonamides are least reactive. Case in point was made by chemoselective Kulinkovich reaction of succinic ester-amide 12. Cha observed that only the ester portion underwent the Kulinkovich reaction to afford cyclopropanol 13. Szymoniak demonstarted that nitriles are more reactive than ester and amides. 

The versatile Ti(II) chemistry available using preformed (alkene)Ti(OiPr)2 species was opened up by the discovery of the Kulinkovich cyclopropanation reaction [55]. Since 1995, Sato and collaborators have developed a wide range of elegant and synthetically useful reactions based on the Ti(OiPr)4/iPrMgCl reagent [56]. In particular, it was reported that the Ti(II) complex (q2-propene)Ti(OiPr)2, preformed from Ti(OiPr)4 and 2 equivalents of iPrMgCl, reacts with allylic compounds, such as halide, acetate, carbonate, phosphate, sulfonate, and aryl ether derivatives, to afford allyltitanium compounds as depicted in Scheme 13.27 [57]. 

The Kulinkovich cyclopropanation, in which an ester and two equivalents of a Grignard reagent are combined to make a cyclopropanol in the presence of a catalytic amount of Cp2TiCl2, is a useful variant of reductive coupling reactions. A cyclopropylamine can be obtained instead if a tertiary amide is substituted for the ester. 

Functionalized cyclopropanes. The reductive coupling of esters with 1-alkenes by a Grignard reagent and titanium alkoxide gives rise to cyclopropanols (the Kulinkovich reaction). With the use of ethylene carbonate, the condensation gives rise to 2-substituted cyclopropanone hemiacetals. An intramolecular version delivers bicyclic products. ... 

The Kulinkovich reaction is the titanium-catalysed synthesis of cyclo-propanols from carbo ylic esters and Grignard reagents. The reaction is very diastereoselective, and an asymmetric variant was described by Corey et al. in 1994, by using the spirotitanate 79 (Scheme 7.48). Since this work, only a few titanium-catalysed asymmetric syntheses of cyclopropanols were reported, with enantiomeric excesses never higher than 80%. ... 

Kulinkovich himself proposed that the dialkoxytitanacyclopropanes as the key intermediate in the Kulinkovich cyclopropanation. Extensive theoretical study on mechanism was published in 2001. Eisch also provided detailed exploration of the mechanism for the Kulinkovich reaction in 2003. In 2007, Kulinkovich proposed a modified ate complex mechanism for titanium-mediated cyclopropanation of carboxylic esters with Grignard reagents. 

The cyclopropylamine scaffold is a recurrent moiety in several natural products or drugs [24]. However, its preparation usually requires several steps [25]. Szy-moniak and Bertus have developed an amino version of the Kulinkovich [26] reaction for quicker access to these aminocyclopropanes from nitrile derivatives, Grignard reagents, and titanium isoproxide (Scheme 9.15) [27]. Starting from p- or... 

The Kulinkovich reaction is a unique reaction, in which cyclopropane derivatives are formed by a reaction between titanacyclopropanes and ester derivatives. The reaction was established by Kulinkovich in 1989 [273], and a recent review has been published [274, 275], Titanacyclopropanes were generated from a Grignard reagent and Ti(0-/-Pr)4, and the reaction with esters gave cyclopropanol in good yields. When amides are used instead, cyclopropane amine is formed. The mechanistic study on the Kulinkovich reaction was performed [276]. 

The preparation and reactions of titanium-olefm complexes vith a nonmetallocene structure have also been kno vn since the pioneering vork of Kulinkovich et al. for the preparation of cyclopropanols, starting vith an ester, Ti(OPr-i)4 and an ethyl Grignard reagent (Scheme 12.36) [55[. The reaction involves dialkoxytitanacyclopropane as an actual reagent effecting the active transformation (Scheme 12.48). 

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