Kulinkovich cyclopropanol synthesis

Eisch, J. J., Adeosun, A. A., Gitua, J. N. Organic chemistry of subvalent transition metal complexes, 27. Mechanism of the kulinkovich cyclopropanol synthesis Transfer-epititanation of the alkene in generating the key titanacyclopropane intermediate. Eur. J. Org. Chem. 2003,4721-4727. 

Kulinkovich cyclopropanol synthesis, also known as Kulinkovich reaction or Kulinkovich cyclopropanation, is titanium-catalyzed transformation of esters... 

Kulinkovich, O. G., Sviridov, S. V., Vasilevskii, D. A. Titanium(IV) isopropoxide-catalyzed formation of 1-substituted cyclopropanols in the reaction of ethylmagnesium bromide with methyl alkanecarboxylates. Synthesis 1991, 234. 

More detailed isotopic labeling studies have also been performed. Hydroxycyclopropanation of trans-f.3-deutero-styrene 273 under Kulinkovich conditions furnishes m-2-phcny 1-1 -cyclopropanol, 274, indicating retention of configuration at the carbon bound to titanium and is consistent with frontside attack of the Ti-C bond on a titanium-bound carbonyl.220 For the related de Meijere cyclopropylamine synthesis, the opposite outcome has been observed where a 3 1 mixture of A, Wdimethyl-W(/ra t-3-deutero-/ra j-2-phenylcyclopropyl)amine 278 and -dim ethyl-. V-((7.i-dcutcro-t7r-2-phony Icyclopropy I )amine 277 is produced. These products require inversion of configuration at the carbon bound to titanium and are consistent with a W-shaped transition structure for ring closure (Scheme 46). 

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%. ... 

Corey employed the Kulinkovich reaction in the total synthesis of P-arianeosene (48). Ester 46 was converted to cyclopropanol 47, which served as the substrate to make cyclobutanone by treating 47 with Al(Me)3. 

The ester Kulinkovich reaction was used to prepare a key allylic bromide 5333 in a synthesis of neolauh-malide and isolaulimalide (Scheme 5.88). The cyclopropanol 5.332 produced by the Kulinkovich reaction of ester 5.331, as its mesylate, was subjected to ring opening with magnesium bromide. This is likely to involve electrocyclic ring opening of the cyclopropyl carbocation, followed by bromide trapping. 

---