Reaction of Kulinkovich

The reaction of Kulinkovich is a reaction of cyclopropanation of carboxylic esters, leading diastéréosélectivement to cyclopropanols.

Stoechiometric version

The first examples of reactions of Kulinkovich , described in 1989, employed a stoechiometric quantity of tétraisopropyloxytitane. Three equivalents of Hard grindstone reagent were necessary to obtaining good outputs (1).

Catalytic version

It is into 1991 that Kulinkovich showed that a catalytic quantity of tétraisopropyloxytitane was enough with obtaining to good outputs. It proved even possible, under these conditions, to reduce the committed quantity of Hard grindstone reagent to two equivalents (2).

Asymmetrical version of the reaction of Kulinkovich

The reaction of Kulinkovich being catalytic out of titanium, Corey and its team published an asymmetrical version of it. They obtained enantiomeric excesses being able to reach 78% while resorting to a ligand of the type Taddol (3).

Mechanism

The usually called upon mechanism utilizes initially two successive stages of transmetallation of the committed organomagnésien, leading to an intermediate complex dialkyldiisopropyloxytitane. This one undergoes a dismutation to give an alkane molecule and a titanacyclopropane 1 . The insertion of carbonyl of ester in the connection carbon-titanium the most released from this species leads to a oxatitanacyclopentane 2 being rearranged out of ketone 3 . Lastly, the insertion of the carbonyl group of 3 in the residual connection carbon-titanium farm cyclopropane. In the state of transition from this elementary stage, which is the limiting stage of the reaction, a agostic interaction stabilizing between hydrogen in α grouping R ² and the titanium atom was called upon to explain the diastereoselectivity observed. The complex 4 obtained is a tétraalkyloxytitane able to play a part similar to that of the starting tétraisopropyloxytitane, which closes the catalytic cycle. At the end of the reaction, the product is mainly in the shape of the magnesium alcoholate 5 , giving the cyclopropanol at the time of the hydrolysis of the reactional medium.

The mechanism of the reaction of Kulinkovich was the subject of thorough calculations published in 2001 (4). Certain points remain nevertheless obscure and according to any probability, the mechanism of this reaction is actually not also simple. Intermediate titanium complexes of type “ate” were recently proposed by Kulinkovich (5).

Reactions of exchange of ligands with olefins

Since 1993, the team of Kulinkovich highlighted the aptitude of the titanacyclopropanes to undergo exchanges of ligands with the olefins (6). This discovery was important, because it gave access to cyclopropanols more functionalized by making the economy of the preparation of magnesian corresponding, whose at least two equivalents should have been committed to obtain good outputs.
Cha and its team introduced the use of cyclic Hard grindstone reagents, particularly adapted to these reactions of exchange of ligands (7).

Intramolecular reactions of Kulinkovich

An interesting application of the reactions of exchange of ligands consists in carrying out intramolecular reactions at the ester beginning carrying a function olefin (8).

Related reactions

Several extensions of the reaction of Kulinkovich were developed:

the reaction of Kulinkovich-in Meijere , leading to aminocyclopropanes starting from amides.
the reaction of Kulinkovich-Szymoniak , leading to aminocyclopropanes starting from nitriles.
See also: F. Sato, H. Urabe and S. Okamoto, Pure Appl. Chem. , 1999 , 71 , 1511-1519.

Complementary information sources

Several articles summaries are been published:

O.G. Kulinkovich and A. of Meijere, Chem. Rev. , 2000 , 100 , 2789-2834.
F. Sato and Al, Synlett , 2000 , 753-775.
A. of Meijere, S.I Kozhushkov and AD INTERIM Savchenko in Titanium and Zirconium in Organic Synthesis (ED.: I. Marek), Wiley-VCH, Weinheim, 2002 , PPP 390-434.
O.G. Kulinkovich, Chem. Rev. , 2003 , 103 , 2597-2632.
O.G. Kulinkovich, rus. Chem. Bull., Int. ED. , 2004 , 53 , 1065-1086.
O.G. Kulinkovich, Eur. J. Org. Chem. , 2004 , 4517-4529.

For a procedure with discussion, to see:

A. of Meijere, S.I Kozhushkov, T. Späth, '' Organic Syntheses '', vol. ''' 78 ''', p.142

Quoted bibliographical references

(1) O.G. Kulinkovich, S.V. Sviridov, D.A. Vasilevsky and T.S. Prityckaja, Zh. Org. Khim. , 1989 , 25 , 2244-2245.
(2) O.G. Kulinkovich, S.V. Sviridov and D.A. Vasilevski, Synthesis , 1991 , 234.
(3) E.J. Corey, S. Achyutha Rao and Mark C. Noah, J. amndt Chem. Plowshare , 1994 , 116 , 9345-9346.
(4) There. - D. Wu and Z. - X. Yu, J. amndt Chem. Plowshare , 2001 , 123 , 5777-5786.
(5) O.G. Kulinkovich and D.G. Kananovich, Eur. J. Org. Chem. , 2007 , 2121-2132.
(6) O.G. Kulinkovich, AD INTERIM Savchenko, S.V. Sviridov and D.A. Vasilevski, Common Mendeleev. , 1993 , 230-231.
(7) J. Lee, H. Kim and J.K. Cha, J. amndt Chem. Plowshare , 1996 , 118 , 4198-4199
(8) A. Kasatkin and F. Sato, Tetrahedron Lett. , 1995 , 36 , 6079-6082.

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