Kulinkovich cyclopropanation refers to the reaction of esters, amides, and other carboxylic acid derivatives with Grignard reagents containing. Kulinkovich reaction: a facile method for cyclopropanol synthesis from esters Computational Study on Selectivity of Kulinkovich Reaction. An intermolecular Ti(IV)-mediated cyclopropanation reaction has been used to synthesize substituted 2-phenylcyclopropylamines and constrained analogues of .

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Kulinkovich reaction – Wikipedia

Despite the possibility of olefin exchange with the titanacyclopropane intermediate see Eq. The Kulinkovich-de Meijere Reaction is a modification of the Kulinkovich Reaction that allows the preparation of cyclopropylamines by the reaction of Grignard reagents substituted ethylmagnesium halides with N,N -dialkylamides and dialkylformamides in the presence of a stoichiometric amount of titanium IV isopropoxide or, even better, methyltitanium triisopropoxide. Brought to you by the Organic Reactions Wiki, the online kulinkpvich of organic reactions.

The presence of an alcohol in the target means that ketones may be used as electrophiles for intramolecular ring closing recation form cyclopropanols. Despite some operational difficulties associated with the need to reactiion introduce the Grignard reagent, the Kulinkovich reaction employs readily available reagents and provides access to synthetically useful cyclopropanols.

A recent review by de Meijere J. Complex VIa leads to the observed major cis diastereomer and is more favorable than the diastereomeric VIb due to unfavorable steric interactions between R and Ti OY 3 in the latter Eq. The formation of the initial titanacyclopropane intermediate from the Grignard reagent and the titanium IV isopropoxide has already been described in the article on the Kulinkovich Reaction.

The step that establishes the relative configuration reactin the product is the second migratory insertion of the carbonyl group into the titanium-carbon bond.


Together with the diverse chemistry of the cyclopropanol unit, it offers access to a wide range of functionalised unsaturated and saturated compounds. The Kulinkovich hydroxycyclopropanation reaction in natural product synthesis. Ku,inkovich other terminal alkenes, the bulkier cyclohexylmagnesium halides can be be used to retard the participation of the initially formed titanium II species in the alkylation reaction and to promote the reaction of the desired ligand with the ester.

This reaction was discovered by Oleg Kulinkovich and coworkers in The Kulinkovich cyclopropanation reaction provides a flexible and convenient method for the synthesis of cyclopropanols. Angewandte Chemie International Edition in English.

From Wikipedia, the free encyclopedia. The resulting mixture is stirred for an additional 3 h at room temperature. If you are the author of this article you still need to obtain permission to reproduce the whole article in a third party publication with the exception of reproduction of the whole article in a thesis or dissertation. Site Search any all words Main Categories. In the other modified procedure, described by de Meijere, MeTi O i Pr 3 is formed first, and a stoichiometric amount is used with only 1.

When Fischer carbenes are used, the reaction proceeds through a chair-like transition state Eq. Please enable JavaScript to access the full features of the site or access our non-JavaScript page.

Kulinkovich-de Meijere Reaction

Although the use of sub-stoichiometric amounts of the titanium reagent is readtion, yields are significantly better with stoichiometric amounts. The successful use in the synthesis of natural compounds is outlined in this perspective. Journal of the American Chemical Society.

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Kulinkovich Reaction

The use of methyl titanium IV isopropoxide 2 can be useful when the Grignard reagent starting material is precious. For reproduction of material from PPS: For more on the topic of 1, n -dicarbanionic titanium intermediates from monocarbanionic organometallics and their application in organic synthesis, see a recent review by Kulinkovich and de Meijere Chem.


A modification by Szymoniak allows the preparation of primary cyclopropylamines by the reaction of nitriles with Grignard reagents in the presence of titanium tetraisopropoxide and a Lewis acid. The insertion of metal carbenoids into electron-rich pi bonds is another method useful for the construction of the cyclopropanol skeleton. After the addition is complete, the resulting black reaction mixture is stirred for an additional 20 min.

The intramolecular reaction is also known: Crystallographic evidence indicates a carbon-carbon bond length between those of typical single and double bonds, and partial pyramidalization of the carbon atoms. Jump to site search.

Kulinkovich cyclopropanation

A 1 M solution of n -butylmagnesium chloride in ether 52 mL, 52 mmol is added over a kupinkovich of 6. The Journal of Organic Chemistry. Additionally, an olefin exchange process introduced in has enlarged the scope of possible products to include more highly substituted cyclopropanols.

The combination of both methods offers a broad synthetic potential for the synthesis of new cyclopropylamines:.

Contrary to the typical cis diastereoselectivity of the reaction, homoallylic alcohols may be cyclopropanated to afford trans -1,2-dialkylcyclopropanols. Complex 4 obtained is a tetraalkyloxytitanium compound able to play a part similar to that of the starting tetraisopropyloxytitanate, which closes the catalytic cycle.