Titanium chelation

Titanium chelates are formed from tetraalkyl titanates or haUdes and bi- or polydentate ligands. One of the functional groups is usually alcohoHc or enoHc hydroxyl, which interchanges with an alkoxy group, RO, on titanium to Hberate ROH. If the second function is hydroxyl or carboxyl, it may react similarly. Diols and polyols, a-hydroxycarboxyflc acids and oxaUc acid are all examples of this type. P-Keto esters, P-diketones, and alkanolamines are also excellent chelating ligands for titanium. 

Ethyl Acetate. The esterification of ethanol by acetic acid was studied in detail over a century ago (357), and considerable Hterature exists on deterrninations of the equiUbrium constant for the reaction. The usual catalyst for the production of ethyl acetate [141-78-6] is sulfuric acid, but other catalysts have been used, including cation-exchange resins (358), a- uoronitrites (359), titanium chelates (360), and quinones and their pardy reduced products. 

The rheology of hydroxypropylguar is greatly complicated by the cross-linking reactions with titanium ions. A study to better understand the rheology of the reaction of hydroxypropylguar with titanium chelates and how the rheology depends on the residence time, shear history, and chemical... 

O. Barkat. Rheology of flowing, reacting systems The crosslinking reaction of hydroxypropyl guar with titanium chelates. PhD thesis, Tulsa Univ, 1987. 

Silyl enol ethers undergo reaction with carbonyl compounds promoted by Lewis acids, but especially titanium tetrachloride. The reaction is thought to proceed via a titanium chelate which inhibits the reverse aldol process and the regiochemical integrity of the starting silyl enol ether is retained (Scheme 102).373... 

Atkinson has extended the initial work of Rees, utilizing substituted acetoxyaminoquinazolinone as the aziridinat-ing species rather than the original family of A -aminoheterocycles <1996CC1935, 1998J(P1)2783>. Complete diastereoselectivity is obtained through titanium chelation of the pendent alcohol and N-1 of the quinazolinone 31... 

Prompted by the X-ray studies of the acryloyl lactate-TiCU complex (380a), commercially available pantolactone was chosen as an auxiliary aiming to facilitate entropically the formation of a seven-mem-bered titanium chelate (385). Indeed, using 0.1-0.75 mol equiv. of TiCU the acrylate and crotonate of (/ )-pantolactone (384) underwent smooth addition of cyclopentadiene, butadiene and isoprene to give adducts (386) and (387) in ratios of >93 <7 (Scheme 94, Table 24, entries a-d). Opposite product ratios were obtained using dienophiles (388) derived from (S)-pantolactone (entiy e) or (390) derived from the more readily available A -methyl-2-hydroxysuccinimide (entries f, g). The major products were purified by crystallization and saponified without epimerization (LiOH, THF/water, r.t.) to furnish the corresponding carboxylic acids. 

Ti-0-C3-C4 = 57.6 °). This out-of-plane coordination was proved by NOE experiments to persist in solution. Treatment of the diastereomeric /8-alkoxyketone with TiCU generates the titanium chelate with in-plane coordination geometry (Eq. 1) [31]. NMR study of these out-of-plane and in-plane complexes of the j8-alk-oxyketones revealed that the titanium portion in the former complex acts as a stronger Lewis acid than that of the latter [31,32]-... 

In addition to the aforementioned X-ray analysis to disclose the structure of a few crystalline titanium chelates, and NMR studies have been performed to provide evidence for the chelation structure of a- and /1-oxycarbonyl compounds in solution [33-35]. Approximate solution structures for -alkoxyaldehydes are as shown in Fig. 7 [34]. The mechanism of chelation-controlled reactions of organotitanium reagents has been investigated experimentally [5] and theoretically [36], and the subject has been reviewed [10]. The formation of a chelate structure with titanium metal at the center plays a pivotal role in determining the reactivity and selectivity [37] in many synthetic reactions as shown in the following discussion. 

There are many examples of the stereoselective addition of nucleophiles to carbonyl groups in which chelation to the titanium center should be critical—reported examples include the stereoselective hydride reduction of a- or /3-hydroxyketones (Eq. 305) [684-686], of a-phosphino ketones [687], of a-sulfonylketones [688], and of an a,/3-unsaturated carbonyl compound in a 1,4-fashion [689]. The stereoselective addition of organometallic compounds such as Grignard [669,690], zinc [691,692], copper [693], and other reagents [11] to carbonyl and related compoimds Ijy taking advantage of titanium chelation is a well established method in the stereoselective... 

The formation of a titanium chelate enables regiochemical control of the conjugate addition of a thiol to an a,/3,y,d-dienone, as shown in Eq. (307) [694]. Simple base-catalyzed reaction occurred selectively at the terminal (d) position of the substrate. When, however, a similar reaction was performed in the presence of TiCU, addition occurred exclusively at the position / to the carbonyl group, where the intermediate can take the chelate form, as depicted. The same observation was also noted for the corresponding conjugated trienone. A similar reaction has been applied to the cis —> trans isomerization of conjugated dienoates [695]. 

The titanium-chelated structure (18) forces the nucleophilic addition to occur from the less hindered si-face (i.e. syn to the lone pair of electrons) in contrast, the aluminum-based process proceeds via nonche-lated transition state (19). In this case, the less hindered re-face is syn to the electron pair. Unfortunately, a test of this transition state hypothesis would require an organoaluminum addition under chelation con-... 

A Schiff-base ligand, with a pendent phosphine donor bound to titanium, chelated to Pd affording the crystallographically characterized (Ti(/r-0)(PhCHNCHC6H30(PPh2))PdI2)2.865... 

A series of titanium chelate complexes with biologically active monofunctional bidentate semicarbazones having 0,N donors have been prepared by reacting Cp2TiCl2 with the appropriate ligand in 1 1 and 1 2 stoichiometries. The ligands were prepared by condensing heterocyclic ketones and semicarbazide hydrochlorides in presence of NaOAc.1583... 

Aldol and related reactions may also be chelation-controlled. Boron enolates of N-acyloxazolidinones 19 are chelated in the ground state. Their reactions with aldehydes will necessitate the coordination of the aldehyde with the boron atom at transition state, so that the initial bidentate chelate will be broken (Figure 1.26). However, the titanium atom of related titanium enolates can accommodate hexa-coordination so that the initial titanium chelate 20 does not need to be disrupted. In each case, the aldol reaction leads to different syn stereoisomers (Figure L26) via transition models 21 and 22. 

Titanium chelates of semi-salen 59 and salen 60 are used in asymmetric synthesis of a-cyanoalkyl ethyl carbonates from aldehydes and ethyl cyanoformate. By changing the metal atom to aluminum for complexing 60 a catalyst for elaborating a-acetoxy amides (Passerini reaction) is obtained (but enantioselectivity varies)/ ... 

A titanium chelate of dihydroxylamine 87 helps organization of the addends so that a-amino nitriles of the (/J)-conliguration ate generated. Thiourea 88 with a proximal salen unit offers multiple hydrogen bonding sites for an analogous purpose of acetylcyana-tion of aldimines. ... 

Nagy B, Pais I and Bokori J (1986) The application of titanium-chelate in pig-feeding. In Anke M, etal., ed. 5. Spurenelementsymposium New Trace Elements, pp. 1254-1259, University of Leipzig and Jena, Germany. 

Aldol condensation. Japanese investigators report that trimethylsilyl enol ethers of aldehydes or ketones react with carbonyl compounds in the presence of an equimolar amount of titanium tetrachloride to give the cross-aldol products in satisfactory yields. The success of the method probably depends on formation of an intermediate titanium chelate ... 

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