KULINKOVICH Hydroxycyclopropanation

Dialkoxotitanacyclopropane derivatives Ti(CH2CR)(OPr1)2 react with esters to afford cycopropanols via a Kulinkovich hydroxycyclopropanation reaction, an efficient, fast, exothermic, and irreversible organic synthetic method. A detailed mechanism for this process has been explored with density functional theory calculations.286... 

Haym, L, Brunble, M. A. (2012). The Kulinkovich hydroxycyclopropanation reaction in natural product synthesis. Organic Biomolecular Chemistry, 10,7649-7665. 

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). 

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