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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A recent review by de Meijere J. Site Search any all words Main Categories.
If you are not the author of this article and you wish to reproduce material from it in a third party non-RSC publication you must formally request permission using Copyright Clearance Center. From Wikipedia, the free encyclopedia. Angewandte Chemie International Edition in English.
The intramolecular reaction is also known: Previous Article Next Article. Kulijkovich addition, when the titanacyclopropane intermediate is prepared from cyclohexyl or cyclopentyl magnesium halide, ligand exchange with various alkenes mono- disubstituted, and cycloalkenes can be employed to expand the range of accessible kuulinkovich. An oxatitanacyclopentane intermediate is initially formed by insertion of the carbonyl group of the amide into the titanium-carbon reactjon of the titanacyclopropane.
The titanacyclopropane reacts with the ester as a 1,2-dicarbanion equivalent to produce a cyclopropanol after a 2-fold alkylation:.
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. For example, the final step in Eq. Significant 1,3-stereocontrol is also observed when chiral homoallylic alcohols are employed Eq.
The Kulinkovich reaction may be employed for cyclopropanation of a variety of carboxylic acid derivatives. If you are the author of this article you do not need to formally request permission kulinkovicj reproduce figures, diagrams etc. Back to tab navigation Download options Please wait Amidesprimary and secondary aminesmost carbamates are not stable to the reaction conditions, but tert-butyl carbamates N-Boc derivatives survive the transformation.
It should be noted that an anionic catalytic cycle involving a series of catalytic ate complexes has been proposed to explain the need for more than two equivalents of Grignard reagent under conditions that employ stoichiometric amounts of titanium.
Fetching data from CrossRef. Inthe team of Kulinkovich highlighted the aptitude of the titanacyclopropanes to undergo ligand exchange with olefins. Contrary to the typical cis diastereoselectivity of the reaction, homoallylic alcohols may be cyclopropanated to afford trans -1,2-dialkylcyclopropanols. This drawback kullnkovich 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.
Formation of the more stable monosubstituted titanancyclopropane from the disubstituted intermediate derived from cyclohexylmagnesium chloride drives the formation of the less substituted product Eq.
Back to tab navigation. The use of a syringe pump is advised when slow addition of the Grignard reagent is required. Site Search any all words. The Journal of Organic Chemistry.
Pages with citations lacking titles CS1 maint: In the transition state of this elementary stage, which is the limiting stage of kuljnkovich reaction, an agostic interaction stabilizing between the beta hydrogen and the R2 group and the titanium atom was called upon to explain the diastereoselectivity observed. The successful use in the synthesis of natural compounds is outlined in this perspective.
This page was last edited on 18 Julyat If ethylmagnesium bromide is used, the formation of ethane and a trace of ethene can be observed. The insertion of the carbonyl group of the ester in the weakest carbon-titanium bond leads to an oxatitanacyclopentane 2 being rearranged to ketone 3. Stereoselective construction of bicyclo[5. High yields are obtained from N,N -dialkylformamides, whereas amides with bulky groups consistently give products in lower yield. In addition, the reaction may be carried out in the presence of either a full equivalent or substoichiometric amount of titanium reagent, and the titanium reagent may be varied somewhat to optimize yields.
When the electrophile is part of the cyclopropanol, ring expansion may result Eq. The Kulinkovich hydroxycyclopropanation reaction in natural product synthesis. Kulinkovich reactions are typically carried out under an atmosphere of nitrogen or argon.
Site Search any all words. The Kulinkovich Reaction allows the preparation of cyclopropanol derivatives by the reaction of Grignard reagents ethyl or higher with esters in the presence of titanium IV isopropoxide as catalyst.
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.
Intermediate titanium complexes of the ate type were recently proposed by Kulinkovich. Carbon-carbon bond forming reactions Titanium Name reactions. Back to tab navigation Fetching data from CrossRef. Views Read Edit View history.
These pathways have not yet been distinguished experimentally. The Kulinkovich Reaction on Lactones. The step that establishes the relative configuration of the product is the kulijkovich migratory insertion of the carbonyl group kulinkvoich the titanium-carbon bond.
This intermediate may be depicted using either the titanacyclopropane resonance structure IIa or the titanium II -olefin structure IIb. For 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.
Retrieved from ” http: In all cases the Ref.
A cis relationship between substituents on the 1- and 2-positions of the cyclopropanol product is often observed in these reactions. The conversion of I to II may take place through two conceivable mechanisms Eq. At the end of the kulinkovifh, the product reactlon mainly in the shape of the magnesium alcoholate 5giving the cyclopropanol after hydrolysis by the reaction medium. The generally accepted reaction mechanism initially utilizes two successive stages of transmetallation of the committed Grignard reagentleading to an intermediate dialkyldiisopropyloxytitanium complex.