Chelation with titanium

P-Diketone Chelates. P-Diketones, reacting as enols, readily form chelates with titanium alkoxides, Hberating in the process one mole of an alcohol. TYZOR AA [17927-72-9] (6) is the product mixture from TYZOR TPT and two moles of acetylacetone (acac) reacting in the enol form. The isopropyl alcohol is left in the product (87). The dotted bonds of stmcture (6) indicate electron... 

Lewis acids prefer to lie syn to the smaller substituent of the carbonyl, e.g. syn to H for aldehydes, anti to —OR for simple alkyl esters. In a, 3-unsaturated systems, Lewis acid coo ination syn to the double bond favors the s-trans conformation, but in two crystal structures, where coordination anti to the alkene occurs, s-cis complexes are observed. - " Finally, chelation with titanium and tin occurs readily and yields stable, crystalline complexes. 

The small quantities of titanium in water samples are concentrated by precipitation on iron hydroxide as carrier. Photometric determination is carried out with the aid of chromotropic acid, which forms a red chelate with titanium (IV) at pH 2 (8 approximately 17,000 at A = 70 nm). 

Cellulose has been converted into more reactive forms by chelation with titanium(m), iron(ni), tin(iv), vanadium(m), and zirconium(iv) salts. The unsubstituted ligands of the bound metals could be replaced by electron-donating groups of antibiotics e,g. ampicillin, gentamicin, kanamycin, neomycin, paro-mycin, etc.) to yield materials possessing antimicrobial activity the original chelated celluloses were inactive. The chelation procedure offers an easy way of rendering cellulose more resistant to microbial attack than that afforded by non-covalent adsorption of the antibiotic. 

A directed aldol reaction between two ketones affords thermodynamically unfavorable aldols in high yields, because of stabilization of the aldol adducts by their intramolecular chelation with titanium 42 or by their conversion to silyl ethers 43 (Eq. (22)). 

Enols and alkoxides give chelates with elimination of alcohol. For example, in the reaction of the enol form of acetylacetone [123-54-6] all four alkoxide groups attached to zirconium can be replaced, but only two of the four attached to titanium (Fig. 3). Acetoacetic esters react similarly. 

Sdanediols, eg, (CgH )2Si(OH)2 and H0Si(CgH )20Si(CgH )20H, yield four-and-six-membered rings with titanium alkoxides. Pinacols and 1,2-diols form chelates rather than polymers. The more branched the diol molecule, the more likely are its titanium derivatives to be soluble and even monomeric. 

The syn selectivity in the titanium(IV) chloride mediated reactions can be explained by an intermolecular chelation, with transition state 21A being sterically favored over 21B. On the other hand, nonchelation control governs the stereochemistry of the boron trifluoride mediated reactions. Thus, the sterically favored transition state 21 C leads to the observed anf/ -diastereo-mer12. 

Further upgrading by crystallization is possible. Presumably a highly diastereomerically enriched titanium intermediate is formed by chelation with the chiral urea moiety. 

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. 

Titanium enolates also can be prepared from /V-acyloxazolidinones. These Z-enolates, which are chelated with the oxazolidinone carbonyl oxygen,128 show syn stereoselectivity, and the oxazolidinone substituent exerts facial selectivity. 

Entries 4 and 5 are cases in which the oxazolidinone substituent is a 3-ketoacyl group. The a-hydrogen (between the carbonyls) does not react as rapidly as the y-hydrogen, evidently owing to steric restrictions to optimal alignment. The all -syn stereochemistry is consistent with a TS in which the exocyclic carbonyl is chelated to titanium. 

With titanium enolates it was found that use of excess (3 equiv.) of the titanium reagent reversed facial selectivity of oxazolidinone enolates.140 This was attributed to generation of a chelated TS in the presence of the excess Lewis acid. The chelation rotates the oxazolidinone ring and reverses the facial preference, while retaining the Z-configuration syn diastereoselectivity. 

The reactions of ligand exchange have frequently been applied to synthesize chelates with the coordination unit containing N,0-donor centers. The complexes of titanium [280], thorium, and uranium [281] tetrachlorides with fe(salicylidene)alkylene-amines, obtained in THF solution, are evidently formed through THF complexes of the type MX (THF). An example of such syntheses is the transformation (3.107) [280] ... 

Amongst some specific reactions used in regioselective syntheses, we note the cyclometallation processes [Sec. 2.2.5.1, reaction (2.8) Sec. 3.1.1.2, reactions (3.40)-(3.44) Sec. 3.3.2.3, reactions (3.226)-(3.228)]. In this respect, we note that C,N-donor ligands form, depending on the nature of Lewis acids, two types of complexes. In the case of immediate interaction (4.35) of azomethines 859 with titanium or tin tetrachlorides (MC14), the molecular complexes with M—N bond 860 [101] were obtained (route A), while the cyclometallation reaction with the use of palladium diacetate leads to binuclear chelates 861, in which the Pd — N, C metal-cycles are formed (4.35) [11,114-116] ... 

Up to pH 2, edta (LH4) forms (TiOHL)-, and (TiOL)2 above this pH.190 Ternary complex formation in the titanium-polyphenol-aminopolycarboxylic acid system has been studied.191 Tiron forms ternary chelates with nitrilotriacetic acid, edta, and [(H02CCH2)2NCH2CH2]2NCH2C02H. Pyrocatechol, dibromogallic acid, and gallic acid form mixed complexes only with nitrilotriacetic acid. Chromotropic acid forms a complex192 with Ti,v but not with the Ti -polyphenol system. 

The stereochemical outcome was rationalized by a Zimmerman-Traxler type transition state 45.64 Assuming the titanium enolate of 42 has a Z-geometry and forms a 7-membered metallacycle with a chairlike conformation, a model can be proposed where a second titanium metal coordinates to the indanol and aldehyde oxygens in a 6-membered chairlike conformation. The involvement of two titanium centers was supported by the fact that aldehydes that were not precomplexed with titanium tetrachloride did not react (Scheme 24.7).63 Ghosh and co-workers further hypothesized that a chelating substituent on the aldehyde would alter the transition state 46 and consequently the stereochemical outcome of the condensation, leading to. vyn-aldol products 47.64 Indeed, reaction of the titanium enolate of 42 with bidentate oxyaldehydes proceeded with excellent. s v -diastereo-selectivity (Scheme 24.8).65... 

The aldol reactions of the titanium Z-enolates proceeded smoothly with various aldehydes precomplexed with titanium chloride at -78° C. The diastereose-lectivity is high to excellent, with the single exception of benzaldehyde. The high degree of diastereoselection associated with this current asymmetric anti-aldol process can be rationalized by a Zimmerman-Traxler type of six-membered chairlike transition state Al9fl (Scheme 2.2r). The model is based on the assumptions that the titanium enolate is a seven-membered metallocycle with a chairlike conformation, and a second titanium metal is involved in the transition state, where it is chelated to indanolyloxy oxygen as well as to the aldehyde carbonyl in a six-membered chairlike transition-state structure. 

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. 

Variation of the Lewis acid from a titanium salt can alter the course of the reaction, i.e. either chelation or non-chelation path, to give different diastereoisomers this is exemplified in Eq. (75) [207]. With titanium halide the chelation intermediate is preferred, whereas with monodentate boron fluoride the reaction proceeds via a non-che-lation transition state to give another diastereoisomer. 

The lithiation of ethyl allyl sulfide followed by transmetallation with titanium isopropoxide engenders an allyltitanium reagent formulated as (26 Scheme 8). This and related reagents add to aldehydes or ketones to afford hydroxy sulfides, which are converted to epoxides as shown. The power of this method for the stereoselective generation of even trisubstituted epoxides is evident from Scheme 8 and equation (18). Reagent (26a), prepared as shown in Scheme 8a, undergoes addition to ketone (26b) to afford product exclusively resulting from chelation-controlled diastereofacial addition (as a mixture of epimers at the position shown). ... 

---