|
The Kulinkovich reaction describes the organic synthesis of cyclopropanols via reaction of esters with dialkyldialkoxytitanium reagents, generated in situ from Grignard reagents bearing hydrogen in beta-position and titanium(IV) alkoxides such as titanium isopropoxide. This reaction was discovered by Oleg Kulinkovich and coworkers in 1989. The titanium reagent can be used catalytically. Titanium catalysts are ClTi(OiPr)3 or Ti(OiPr)4, ClTi(OtBu)3 or Ti(OtBu)4, Grignard reagents are EtMgX, PrMgX or BuMgX. Solvents can be Et2O, THF, Toluol. Tolerated Functional Groups: Ethers R–O–R, R–S–R, Imines RN=CHR. Amides, primary and secondary amines, most carbamates are not stable to the reaction conditions, but tert-butyl carbamates (N-Boc derivatives) survive the transformation. An asymmetric version of this reaction is also known with a TADDOL-based catalyst. ==Reaction mechanism== The generally accepted reaction mechanism initially utilizes two successive stages of transmetallation of the committed Grignard reagent, leading to an intermediate dialkyldiisopropyloxytitanium complex. This complex undergoes a dismutation to give an alkane molecule and a titanacyclopropane 1. 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. Lastly, the insertion of the carbonyl group of 3 in the residual carbon-titanium connection forms a cyclopropane ring. 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 called upon to explain the diastereoselectivity observed. Complex 4 obtained is a tetraalkyloxytitanium compound able to play a part similar to that of the starting tetraisopropyloxytitanate, 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 after hydrolysis by the reaction medium. The reaction mechanism of the Kulinkovich reaction was the subject of thorough calculations published in 2001. Certain points remain nevertheless obscure and the mechanism of this reaction is actually not so simple. Intermediate titanium complexes of the ate type were recently proposed by Kulinkovich. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Kulinkovich reaction」の詳細全文を読む スポンサード リンク
|