Titanium complexes cyclopropanation

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

Kulinkovich himself proposed that the dialkoxytitanacyclopropanes as the key intermediate in the Kulinkovich cyclopropanation. Extensive theoretical study on mechanism was published in 2001. Eisch also provided detailed exploration of the mechanism for the Kulinkovich reaction in 2003. In 2007, Kulinkovich proposed a modified ate complex mechanism for titanium-mediated cyclopropanation of carboxylic esters with Grignard reagents. 

Table 11.11. 2-Alkenyl-l-(N,N-dibenzylamino)cyclopropanes formed from N,N-dibenzylformamide (48) and titanium-diene complexes generated in situ by ligand exchange.

Although the reaction of a titanium carbene complex with an olefin generally affords the olefin metathesis product, in certain cases the intermediate titanacyclobutane may decompose through reductive elimination to give a cyclopropane. A small amount of the cyclopropane derivative is produced by the reaction of titanocene-methylidene with isobutene or ethene in the presence of triethylamine or THF [8], In order to accelerate the reductive elimination from titanacyclobutane to form the cyclopropane, oxidation with iodine is required (Scheme 14.21) [36], The stereochemistry obtained indicates that this reaction proceeds through the formation of y-iodoalkyltitanium species 46 and 47. A subsequent intramolecular SN2 reaction produces the cyclopropane. 

Fig. 3.34. Cyclopropanation with titanium carbene complexes generated in situ [33].

Experimental Procedure 3.2.2. Cyclopropanation with a Titanium Carbene Complex (E)-l-Hexyl-2-(2-phenylethenyl)cyclopropane [33]... 

Another broad class of compounds are the bridged carbene complexes. These compounds contain two identical or two different metal centers with the carbene centers bonded to both of the metal atoms in a bridging relationship. However, these binuclear complexes generally do not show classical carbene reactivity and will therefore not be discussed further, except to mention briefly the special case of the titanium-aluminum complex (3) developed by Tebbe and Grubbs and their coworkers.101 This, and related complexes, has proven to be particularly useful in organic synthesis, although its principal importance is in reactions other than cyclopropanations. 

Interestingly, the subsequent reactions of the titanium-alkylidene species 12 obtained from dithioacetals are not limited to carbonyl olefina-tions. When the carbene complex is prepared in the presence of olefins, the latter are smoothly cyclopropanated (Scheme 8 13) [14]. Furthermore, the reaction of symmetrically disubstituted acetylenes with dithioacetals containing a methylene unit provides the corresponding trisubsti-tuted 1,3-dienes 14 in a stereoselective fashion 115]. 

Other Lewis acids, such as boron trifluoride-diethyl ether complex, titanium(IV) fluoride, and triethyloxonium tetrafluoroborate, were far less effective. a, -Unsaturated esters and nitriles cannot be cyclopropanated in this manner. 

But-3-enyltrimethylsilanes undergo cyclodesilylation to give cyclopropanes 7 on reaction with acid chlorides activated by a Lewis acid. Titanium(IV) chloride was found to be the most effective activator of the Lewis acids studied. No reaction was observed for boron trifluoride-diethyl ether complex, zinc(II) chloride and iron(III) chloride. A variety of aliphatic, aromatic and alkenoyl chlorides were successfully utilized affording the corresponding cyclo-propylmethyl ketones in fairly good yields. It has been verified that the j8-chloro ketones 9 are secondary reaction products derived from the cyclopropyl ketones 7. The formation of these chloro ketones can be avoided by performing the reaction at low temperature. 

For the preparation of cyclopropanes from transition-metal complexes see Section 5.2.6., p 1849. Various transition-metal complexes are able to undergo addition to the exocyclic double bond of methylenecyclopropanes with formation of a (7 bond between the carbon and metal atoms. A variety of methylenecyclopropanes with one or two methyl groups in positions 1 and 2 were reacted with bis(cyclopentadienyl)titanium dichloride and isopropylmagnesium bromide to give the corresponding neutral bis(cyclopentadienyl)cyclopropylmethyltitanium(III) compounds 1 in yields ranging from 23 to The carbon-metal [Pg.1512]

Zirconium ester homoenolates 43 or 44 can be prepared from the triethyl orthoacrylate 42 with the zirconocene complex of but-l-ene 41 (Cp means cyclopentadiene). These resemble the zinc and titanium species we have been discussing but are not derived from cyclopropanes.11... 

CYCLOPROPANATION Copper-lsonitrile complexes. Cupric chloride. Diethylzinc-Bromoform-Oxygen. Palladium acetate. Titanium(IV) chloride-Lithium aluminum hydride. 

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