TADDOL titanium complex

Narasaka et al. demonstrated the utility of titanium-ligand complexes in the resolution of chiral a-aryl esters [52]. Ti(Oi-Pr)4-ligand 56 complex resolves 2-pyridine thioesters with high selectivities (fcrei=26-42, see Scheme 13). Seebach and co-workers have examined titanium-TADDOLate complexes as reagents for the ring opening of meso anhydrides, dioxolanones, and azalactones [53]. Addition of an achiral isopropoxide source renders the desymmetrization of meso... 

On use as homogeneous catalysts in the asymmetric reductive alkylation of benzaldehyde with diethylzinc to form secondary alcohols, the corresponding dendritic titanium-TADDOL complexes having either chiral or achiral dendrons gave enantiomeric excesses (ee) of up to 98.5 1.5 at a conversion of 98.7% (for the catalyst with GO dendrons). With larger dendrons the reduction of the ee to 94.5 5.5 (G4) remained within reasonable limits, while the drop in conversion to 46.8% (G4) proved to be drastic. In comparison, the unsubstituted Ti-TAD-DOL complex gave an ee of 99 1 with complete conversion. This negative den-... 

Comparable selectivity can be obtained in the alkylation of ben-zaldehyde 3 with diethylzinc using the titanium TADDOL complex 20 (>99 1 er) or 3-exo-(dimethylamino)isoborneol, 21 (>99 1 er), although both methods employ higher catalyst loadings. While benzaldehyde is illustrative, the substrate scope is equally broad in the case of these two catalysts. 

Scheme 2.95 Asymmetric electrophilic fluorination of j8-ketoesters, catalyzed by chiral titanium TADDOL complexes (Np = 1-naphthyl, R = Et, R = 2,4,6-(/Pr)3C6H2-CH2) pH].

Table 6.6. Asymmetric cycloadditions of crotyloxazolidinones and cyclopentadiene catalyzed by titanium TADDOLate complexes.

The titanium TADDOLATE complex was also used efficiently in the asymmetric addition of dimethyl zinc to 3-trimethylsilyl-2-propynal with and e.e. values over 90% (Schane 21.13). 

The Simmons-Smith reaction is the conversion of olefins to cyclopropanes by the use of halomethylzinc halides or related agents. Charette et al. found that a catalytic amount of chiral titanium-TADDOLate complex 78 was able to induce an enantioselective cyclopropanation of allylic alcohols. After optimisation of the catalytic structure, good yields and enantioselec-tivities were obtained, especially when 3-aryl and 3-heteroaiyl substituted allylic alcohols were used (Scheme 7.47). However, the reaction required the use of a high catalyst loading (25 mol%). 

Charette and co-workers reported a chiral Lewis acid-catalysed Simmons-Smith reaction, using a titanium TADDOL complex, although in general this system shows limited substrate scope compared to the Kobayashi system. ... 

A number of promising methods for catalytic enantioselective halogena-tions of enolates have recently emerged [26, 27). Togni documented the use of titanium-TADDOL complexes such as 232 for a-halogenations of -ke-toesters (Scheme 3.34) [126-128]. High enantioselectivity was observed both... 

A chiral titanium(IV) complex has also been used by Wada et al. for the intermole-cular cycloaddition of ( )-2-oxo-l-phenylsulfonyl-3-alkenes 45 with enol ethers 46 using the TADDOL-TiX2 (X=C1, Br) complexes 48 as catalysts in an enantioselective reaction giving the dihydropyrans 47 as shown in Scheme 4.32 [47]. The reaction depends on the anion of the catalyst and the best yield and enantioselectivity were found for the TADDOL-TiBr2 up to 97% ee of the dihydropyrans 47 was obtained. 

Several titanium(IV) complexes are efficient and reliable Lewis acid catalysts and they have been applied to numerous reactions, especially in combination with the so-called TADDOL (a, a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) (22) ligands [53-55]. In the first study on normal electron-demand 1,3-dipolar cycloaddition reactions between nitrones and alkenes, which appeared in 1994, the catalytic reaction of a series of chiral TiCl2-TADDOLates on the reaction of nitrones 1 with al-kenoyloxazolidinones 19 was developed (Scheme 6.18) [56]. These substrates have turned out be the model system of choice for most studies on metal-catalyzed normal electron-demand 1,3-dipolar cycloaddition reactions of nitrones as it will appear from this chapter. When 10 mol% of the catalyst 23a was applied in the reaction depicted in Scheme 6.18 the reaction proceeded to give a yield of up to 94% ee after 20 h. The reaction led primarily to exo-21 and in the best case an endo/ exo ratio of 10 90 was obtained. The chiral information of the catalyst was transferred with a fair efficiency to the substrates as up to 60% ee of one of the isomers of exo3 was obtained [56]. 

The phosphino-oxazoline copper(II) complex (55) has also been found to be an effective catalyst[136] as have some titanium complexes, such as the extensively researched titanium-TADDOL system (56)[137]. A modified Ti(IV)-TADDOL compound is the catalyst of choice to promote Diels-Alder cycloaddition reactions between cyclopentadiene and alk-2-enyl phenylsulfonylmethyl ketones[138]. 

The tartrate (or TADDOL) derived approach to catalyst design has also been applied to the enantioselective a-hydroxylation of p-ketoesters. In this case, an enantiospecihc titanium(IV) complex combines with a sulfonyloxaziridine as the... 

Convergent dendrimers, with their versatile three-dimensional scaffold, may be tailored to mimic, perhaps crudely, some elements of enzymatic structures. Numerous catalytic moieties, including manganese porphyrins,253,254 bis(oxazoline) copper complexes,304 305 tertiary amines,306 binaphthol titanium complexes,285 307 titanium taddolates,292,308 thiazolio-cyclophanes,309 and fullerene-bound bisoxazoline copper complexes,310 have been incorporated at the core of dendritic molecules to determine the effect of dendritic encapsulation on their catalytic activity. 

A newer approach toward the enantioselective electrophilic fluorination of jS-ketoesters is based on enolization of the substrate under neutral conditions by coordination to a chiral titanium catalyst [211]. The catalyst, a chiral titanium TADDOLato complex (TADDOL = a,a,a, a -tetraaryl-2,2-dimethyl-1,3-dioxolan-4,5-dimethanol) [212, 213], coordinates to the -ketoester, enolizes it, and thus renders it susceptible to electrophilic fluorination (Scheme 2.95). One face of the prochiral enolate substructure is covered by a bulky naphthyl substituent from the TADDOL ligand, impeding electrophilic attack of F-TEDA. 

There are many examples of asymmetric addition of organo-metallic reagents to aldehydes (chapter 27) and the one that works here uses Seebach s TADDOL 51 as a ligand for zinc.8 The TAD-DOL 51 is prepared from tartaric acid and used as its titanium (IV) complex to catalyse the addition of the organozinc compound to acrolein. After photochemical cyclisation in the presence of Cu(I), the bicyclic alcohol 53 was isolated in good yield and >98% ee. 

Titanium(IV)-TADDOL complexes are competent catalysts for intramolecular Diels-Alder reactions as well (Scheme 40) [ 111 ]. While a highly functionalized product is obtained, reaction times are on the order of days (68-257 h). The presence of the dithiane in the alkyl tether appears to be necessary not only for reasonable reactivity but also for high diastereoselectivity the latter apparently results from unfavorable interactions between the dithiane and the diene in the... 

Figure 6.21. Titanium TADDOLate - crotyloxazolidinone complexes. The dioxolane ring of the chiral ligand (Figure 6.18h) is deleted for clarity, and the phenyl groups are labelled as axial (ax) or equatorial (eq). (a) Symmetrical complex found by NMR to be the predominant species in solution [237], and also characterized crystallographically [238]. (b) Complex judged to be most likely to be responsible for the asymmetic cycloaddition [228,237]. (c) This complex is probably less reactive, since approach of the dienophile is hindered by the axial phenyl [228].

This explanation is described as a mnemonic rule [228], which can only be taken as a first approximation of reality. The same rule can be used to rationalize the topicity of other asymmetric Diels-Alder reactions, such as those employing titanium BINOLate catalysts (Figure 6.18i, [230]), or iron bisoxazoline catalysts (Figure 6.18j,k [206,215]). Although the explanation seems reasonable, the picture is not complete, since it does not account for a number of observations, including the fact that the dioxolane substituents exert an extraordinary effect on catalyst efficiency (c/ Table 6.6, entries 2 and 5). Additionally, both titanium TADDOLate [228] and BINOLate [230] complexes show a nonlinear relationship between enantiomeric purity of the catalyst and that of the product, which suggests that some sort of dimerization phenomenon is involved. 

The widely used chiral auxiliaries, tetraaryl-l,3-dioxolane-4,5-dimethanols (TADDOLs), developed by Seebach and co-workers, have found applications in several fields of asymmetric synthesis (75). From their transition metal complexes, the titanium-containing ones (titanium-TADDOLates) are the most successful ones (see titanium complexes). 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

An X-ray structure of the complex formed between 3-cinnamoyl-l,3-oxazohdin-2-one and a chiral TADDOL-Ti(IV) complex (see Chapters 1 and 6 by Hayashi and Gothelf, respectively) has been characterized [16]. The structure of this complex has the chiral TADDOLate and cinnamoyloxazohdinone ligands coordinated to titanium in the equatorial plane and the two chloride ligands in the axial plane and is similar to A in Fig. 8.8. The chiral discrimination was proposed to be due to... 

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