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 .

Author: Akinom Faugis
Country: Andorra
Language: English (Spanish)
Genre: Software
Published (Last): 16 October 2018
Pages: 265
PDF File Size: 4.17 Mb
ePub File Size: 6.32 Mb
ISBN: 194-1-74225-510-6
Downloads: 73593
Price: Free* [*Free Regsitration Required]
Uploader: Todal

The Kulinkovich reaction describes the organic synthesis of cyclopropanols via reaction of esters with dialkyldialkoxytitanium reagents, kilinkovich in situ from Grignard reagents bearing hydrogen in beta-position and titanium IV alkoxides such as titanium isopropoxide. Titanium II is reoxidized to titanium IV over the course of this addition process.

A wide variety of esters may be cyclopropananted using the Kulinkovich reaction. In other projects Wikimedia Commons. Together with the diverse chemistry of the cyclopropanol unit, it offers access to a wide range of functionalised unsaturated and saturated compounds.

Kulinkovich-de Meijere Reaction

The olefin exchange procedure is not generally useful when monosubstituted olefins are employed, unless more substituted Grignard reagents such as cyclohexylmagnesium chloride are used as starting materials.

Brought to you by the Organic Reactions Wiki, the online collection of organic reactions. The use of methyl titanium IV isopropoxide 2 can be useful when the Grignard reagent starting material is precious. With amides instead of esters the reaction product is an aminocyclopropane in the de Meijere variation [15] [16]. Some years after the development of the Kulinkovich Reaction, a highly versatile preparation of cyclopropylamines from amides was worked out by de Meijere and a conversion of nitriles into primary cyclopropylamines was developed by Szymoniak.


A cis relationship between substituents on the 1- and 2-positions of the cyclopropanol product kulinkivich often observed in these reactions. Retrieved from ” http: 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 oulinkovich N,N -dialkylamides and dialkylformamides in the presence of a stoichiometric amount of titanium IV isopropoxide or, even better, methyltitanium triisopropoxide.

For example, samarium-mediated reductive ring closure provides cyclopropanols in high yield Eq. Here, the disproportionation produces methane as a gaseous side product and allows the Grignard reagent to be fully utilized:.

Angewandte Chemie International Edition in English.

Kulinkovich-de Meijere Reaction

Additionally, an olefin exchange process introduced in has enlarged the scope of possible products to include more highly substituted cyclopropanols. They may serve as iminium ion equivalents in the presence of a nucleophile. Jump to site search. Carbon-carbon bond forming reactions Titanium Name reactions. The mechanism of the prototypical Kulinkovich cyclopropanation begins with the displacement of alkoxides on titanium by two equivalents of Grignard reagent to form intermediate I.

The conversion of I to II may take place through two conceivable mechanisms Eq. High yields are obtained from N,N -dialkylformamides, whereas amides with bulky groups consistently give products in lower yield. This complex undergoes a dismutation to give an alkane molecule and a titanacyclopropane 1.

The Journal of Organic Chemistry. Cyclopropanation of carbonates provides access raection synthetically useful cyclopropanone hemiacetals Eq.

The production of ethene has been attributed to a side reaction of the titanacyclopropane with additional titanium IV isopropoxide to afford 2 equivalents of titanium III isopropoxide Kulinkovich, Synlett Reactions of carbonyl derivatives and nitriles”. The original Kulinkovich reaction discovered in employed esters and ethyl Grignard and yielded mono- or disubstituted cyclopropanols Eq. The use of a syringe pump is advised when slow addition of the Grignard reagent is required.


Kulinkovich cyclopropanation – Organic Reactions Wiki

Amidesprimary and secondary aminesmost carbamates are not stable to the reaction conditions, but tert-butyl carbamates N-Boc derivatives survive the transformation. 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 reaction mechanism of the Kulinkovich reaction was the subject of thorough calculations published in XX is the XXth reference in the list of references. Although 2 is prepared from methylmagnesium bromide, only one equivalent of Grignard reagent is needed for the Kulinkovich reaction because methane evolves as the reaction proceeds Eq.

Thus, titanium IV isopropoxide can be used in catalytic amounts:. The intramolecular reacgion is also known: Please enable JavaScript to access the full features of the site or access our non-JavaScript page. This drawback seems to limit the scope of the reaction significantly; however, it is possible for the intermediate titanacycle II to exchange with a more substituted olefin to afford more highly substituted cyclopropanols in high yield Eq.

Complex 4 obtained is a tetraalkyloxytitanium compound able to play a part similar to that of the starting tetraisopropyloxytitanate, which kulinoovich the catalytic cycle.