Carbonyl compound-TiCl

The McMurry reaction (the reductive dimerization of carbonyl compounds giving olefins after treatment with the low-valent titanium reagents TiCla/Mg and TiCla/Zn in THF at 40°C) (CR891513) is a key step in the synthesis of photochromic cyclopentene derivatives. Later, it has been shown that TiCU, which is easier to handle than TiCls, can be used. The cyclization products are formed in 50-60% yields (98S1092,03EJO155). The advantages of this method are that the reactions can be scaled and inexpensive starting materials can be used. 

Heterosubstituted cyclopropanes can be synthesized from appropriate olefins and car-benes. Since cyclopropane resembles olefins in its reactivity and is thus an electron-rich car bo-cycle (p. 76ft). it forms complexes with Lewis acids, e.g. TiCL, and is thereby destabilized This effect is even more pronounced in cydopropanone ketals. If one of the alcohols forming the ketal is a silanol, the ketal is stable and distillable. The O—Si-bond is cleaved by TiCl4 and a d3-reagent is formed. This reacts with a -reagents, e.g. aldehydes or ketals. Various 4-substituted carboxylic esters are available from 1-alkoxy-l-siloxycyclopropanes in this way (E. Nakamura, 1977). If one starts with l-bromo-2-methoxycyclopropanes, the bromine can be selectively substituted by lithium. Subsequent treatment of this reagent with carbonyl compounds yields (2-methoxycyclopropyl)methanols, which can be transformed to /7,y-unsaturated aldehydes (E.J. Corey, 1975B). 

Isoprenylation of carbonyl compounds. In the presence of TiCl, 1 can react as an allylsilane with acetals and acid chlorides (7, 370-371) to give isoprenylated compounds in generally satisfactory yields. Yields with aldehydes tend to be low. Isoprenylation of carbonyl groups is best effected with catalysis with tetrabutylammonium fluoride or io-dotrimethylsilane (10, 216). 

Phenylthioalkylation of silyl enol ethers. Silyl enol ethers of ketones, aldehydes, esters, and lactones can be alkylated regiospecifically by a -chloroalkyl phenyl sulfides in fhe presence of a Lewis acid. Zinc bromide and titanium(IV) chloride are the most effective catalysts. The former is more satisfactory for enol ethers derived from esters and lactongs. ZnBr2 and TiCL are about equally satisfactory for enol ethers of ketones. The combination of TiCL and Ti(0-f-Pr)4 is more satisfactory for enol ethers of aldehydes. Since the products can be desulfurized by Raney nickel, this reaction also provides a method for alkylation of carbonyl compounds. Of more interest, sulfoxide elimination provides a useful route to a,B-unsaturated carbonyl compounds. 

Alkylation of carbonyl compounds. The presence of two metallic centers in reagent 1 makes it easy to attain a six-center transition state therefore, much more efficient transfer of an alkyl group to aldehydes is noted. In comparison with the 2,6-dimethylphenoxy (dialkylaluminum) reagents the improvement is remarkable (e.g., 84% vs 0%, 52% vs 10%, the latter seems to be the best case for the mononuclear phenoxide). Contrary to TiCl which promotes ionization of dimethylacetal unit, 1 activates a carbonyl group preferentially toward nucleophiles such as allyltributylstannane and silyl ketene acetals. ... 

Although the mechanism of the Mukaiyama reaction is not yet fully understood, several points have now been firmly established (a) a Lewis acid enolate is not involved (b) the Lewis acid activates the carbonyl group for the nucleophilic addition and (c) the Si—O bond is cleaved by nucleophilic attack of the anionic species, generally halide, on silicon. Point (a) has been established by the use of INEPT-29Si NMR spectroscopy.5 Moreover, trichlorotitanium enolates have been synthesized, characterized and shown to give a completely different stereochemical outcome than the TiCL-mediated reactions of silyl enol ethers.6 Complexes between Lewis acids and carbonyl compounds have been isolated and characterized by X-ray crystallography7 and recently by NMR spectrometry.8 On the basis of these observations closed transition structures will not be considered here open transition structures with no intimate involvement between the silyl enol ether and the Lewis acid offer the best rationale for the after the fact interpretation of the stereochemical results and the best model for stereochemical predictions. 

Cleavage of 2,4-dinitrophenylhydrazones. Carbonyl compounds can be regenerated in high yield (80-95%) from the 2,4-DNP derivatives by treatment in DME with a 20% aqueous solution of TiCls at reflux temperature (N2). McMurry and Sylvestri consider that titanous ion reduces the nitro groups to amino groups and then cleaves the hydrazone N—N bond to generate an imine, which is then hydrolyzed readily to the carbonyl compound. 

This reagent [M] reacts with carbonyl compounds in the ratio TiCls 3THF/ Mg/RiR2C=0 = 1 2.5 2 to form olefins or coupled vic-diols, often in high yield. Compare Tungsten hexachloride, 4, 569-570. 

Chiral aziridine-2-carboxylates. The generation of enolates and their subsequent cyclization occur when P-benzyloxyamino carbonyl compounds are treated with TiCl -EtjN. Since the chiral substrates are readily available, this reaction realizes a valuable synthesis of chiral aziridines. 

The allylation of a carbonyl compound, or equivalent thereof (aldehydes, ketones, acetals, ketals, enones, acid chlorides, epoxides, etc.), performed with an allylsilane 39 promoted by a Lewis acid (TiCl, SnCl, BF3-OEt2, AICI3, EtjAlCl, etc.) is known as Hosomi-Sakurai reaction (Scheme 12.11, Eq. 1) [68, 69]. This reaction was first described in 1976, allowing the synthesis of homoallylic alcohols 43 from aldehydes and ketones 40 [70]. A year later, the authors extended the method to ketals 41, which provide homoallylic ethers 44 (Scheme 12.11, Eq. 2) [71], and to a,p-unsaturated ketones 42 (Scheme 12.11, Eq. 3) [72]. 

Reactions of carbonyl compounds with these gem-dizinc species gave the corresponding heteroatom-substituted alkenes. In these reactions, the addition of a titanium salt was necessary. jS-TiCls was used, except in the case of reaction of a-boryl-substituted gem-dizinc, where TiCU was used instead (Table 5.4). 

The stereospecific polymerization of alkenes is catalyzed by coordination compounds such as Ziegler-Natta catalysts, which are heterogeneous TiCl —AI alkyl complexes. Cobalt carbonyl is a catalyst for the polymerization of monoepoxides several rhodium and iridium coordination compounds... 

Epoxides can also be reductively opened to form a radical. An example of an intramolecular cyclization of such a radical has recently been reported <06TL7755>. Treatment of 40 with Cp TiCl generates an intermediate alkoxy radical, which then adds to the carbonyl of the formate ester. The product, 41, is formed as a 2 1 mixture of isomers at the anomeric carbon. This reaction is one of the first examples of a radical addition to an ester. The major byproduct of this reaction is the exo-methylene compound, 42, arising from a P-hydrogen elimination. 

A reduced anthracene complex has been prepared by reaction of TiCL dmpe) (dmpe= l,2-bis(dimethyl)phos-phinoethane 9 with NajCuHio], furnishing 10 (Scheme 2).8 The reaction of Cp TiCl3 11 with anthracenium anion results in the formation of compound 12 where one arene is -coordinated while the other adopts if hapticity. Reaction of the anthracene complexes with CO induces formation of the known carbonyl complexes, Ti(CO)3(dmpe)9 and [Cp Ti(CO)3], respectively.10... 

In our work on Cp2TiR compounds vide supra) we noticed that hydrogen abstraction from the cyclopentadienyl ligands is the exclusive route followed in thermal decomposition. It was expected that introduction of pentamethylcyclopentadienyl instead of cyclopentadienyl ligands would improve the thermal stability of the alkyl and aryl derivatives and moreover, by steric and electronic induction, would modify the reactions with unsaturated substrates, such that they could be studied under moderate reaction conditions. For these reasons we started to explore CpJTiR chemistry a few years ago. Some of the preliminary results on synthesis and carbonylation of Cp TiCl have been published [27]. 2... 

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