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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For more on the topic of 1, n -dicarbanionic titanium intermediates from monocarbanionic organometallics and rsaction application in organic synthesis, see a recent review by Kulinkovich and de Meijere Chem. Retrieved from ” https: Additionally, an olefin exchange process introduced in has enlarged the scope of possible products to include more highly substituted cyclopropanols.
Displacement of the product by two more equivalents of Grignard reagent restarts the catalytic cycle Eq. This reaction was discovered by Oleg Kulinkovich and coworkers in Contrary to the typical cis diastereoselectivity of the reaction, homoallylic alcohols may be cyclopropanated to afford trans -1,2-dialkylcyclopropanols.
Jump to site search. Easy Access to Various Substituted Azabicyclo[n. The bonds between the hydroxyl-bearing carbon of a cyclopropanol and the other ring carbons are susceptible to cleavage in the presence of electrophiles or acids.
For instance, amides may be cyclopropanated to afford cyclopropylamines in high yield and diastereoselectivity 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.
The exchange is fast for styrenes, and allows the use of EtMgBr as the Grignard reagent.
A 1 M solution of n -butylmagnesium chloride in ether 52 mL, 52 mmol is added over a period of 6. In the transition state of this elementary stage, which is the limiting stage of the reaction, an agostic interaction stabilizing between the beta hydrogen and the R2 group and the titanium atom was kulinkivich upon to explain the diastereoselectivity observed. For example, the final step in Eq.
If ethylmagnesium bromide is used, the formation of ethane and a trace of ethene can be observed. The mechanism of the prototypical Kulinkovich cyclopropanation begins with the displacement of alkoxides on titanium by two equivalents of Grignard reagent kulinkovixh form intermediate I. A titanacyclopropane intermediate is common to all Kulinkovich-type cyclopropanations. The Kulinkovich cyclopropanation reaction provides a flexible and convenient method for the synthesis of cyclopropanols.
Kulinkovich-de Meijere Reaction
Several methods exist for the synthesis of cyclopropanols. When the electrophile is part of the cyclopropanol, ring expansion may result Eq. Significant 1,3-stereocontrol is also observed when chiral homoallylic alcohols are employed Eq. Enantioselective versions of the Kulinkovich kulinkovicj are rare, and enantioselectivities are moderate.
Kulinkovich reaction – Wikipedia
Despite the possibility of olefin exchange with the titanacyclopropane intermediate see Eq. The Kulinkovich hydroxycyclopropanation reaction in natural product synthesis I. Two interesting modifications help to improve the atom economy for more specialized ligands. PrMgX leads to products with two stereocenters, and high diastereoselectivity can be had in the absence of any chelating substituents in the substrate:.
Complex 4 obtained is a tetraalkyloxytitanium compound able to play a part similar to that of the starting tetraisopropyloxytitanate, which closes the catalytic cycle.
The methodology has been extended to intramolecular reactions . 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. Retrieved from ” http: A cis relationship between substituents on the 1- and 2-positions of the cyclopropanol product is often observed in these reactions.
The reaction of higher alkylmagnesium halides e. The Kulinkovich Reaction on Lactones. This may take some time to load. Pages with citations lacking titles CS1 maint: Although the use of sub-stoichiometric amounts of the titanium reagent is possible, yields are significantly better with stoichiometric amounts. When Fischer carbenes are used, the reaction proceeds through a chair-like transition state Eq. In all cases the Ref. The use of a syringe pump is advised when slow addition of the Grignard reagent is required.