Kulinkovich reaction
The Kulinkovich reaction is a name of reaction in organic chemistry for the preparation of derivatives of cyclopropanol. It was 1989 by Kulinkovich et al. developed.
Survey
The reactants of the reaction Kulinkovich serve a carboxylic acid ester, a Grignard compound and a titanium (IV ) alkoxide. It thereby formed in situ titanium reagents with a hydrogen atom at the β - position. The titanium reagent can be used in catalytic Megen.
Titanium catalysts as, for example, ClTi (OiPr ) 3, Ti (OiPr ) 4, ClTi (OtBu ) 3, Ti ( OtBu) 4 are used. Typical solvents Et2O, THF or toluene. Tolerated functional groups are ethers R -O -R, thioethers R -S -R and imines RN = CHR. Amides, primary and secondary amines, carbamates, and most can not be tolerated under the usual reaction conditions.
Reaction mechanism
The widely accepted reaction mechanism is based on two successive transmetalation with Grignard reagents. The resulting titanium complex disproportionates to an alkane and Titanacyclopropan 1 Insertion of the carbonyl group of the ester to the weakest bond is the carbon- titanium Oxatitanacyclopentan 2, which then can migrate to the ketone 3. Lastly, the carbonyl group of 3 pushes further into the remaining carbon- titanium bond, making the cyclopropanol 4 is formed. The stabilization of the transition state of this step, which is also the rate-limiting, by an agostic interaction of the β - hydrogen and titanium is suspected as the reason for the observed diastereoselectivity. Transmetalation of 4 leads to the large extent the observed product 5 - a magnesium from which by hydrolysis of the desired Cyclopropanolat is formed.
DeMeijere variant
Armin deMeijere et al. developed a variant with amides instead of esters, where now the main product is a aminocyclopropane:
Intramolecular variants are also known:
Szymoniak variant
In the of Szymoniak et al. developed variant, the substrate is a nitrile, and the main product of a cyclopropane by a primary amine group:
The reaction mechanism is analogous to that of the normal Kulinkovich reaction.