BINOL-Ti 2 complex

Figure 6.25. Asymmetric allylation of benzaldehyde catalysed by a fluorinated Ti/BINOL complex under...

Since dienolates 1 and 2 represent diacetate synthons, the dienolate derived from 6-ethyl-2,2-dimethyldioxinone can be seen as a propionate-acetate syn-thon. The synthesis of the corresponding dienolate provides a mixture of the E and Z enolates in a 3 5 ratio. The reaction with Ti-BINOL complex 5 generates a 5 1 mixture with the syn isomer as the major diastereomer. After separation of the diastereomers, the enantiomeric excess of the syn isomer was determined to be 100%. The anti isomer was formed in 26% ee. The same transformation performed with boron Lewis acid 7 gave the anti isomer as the major compound, but only with 63% ee. The minor syn isomer was produced with 80% ee. The observed selectivity could be rationalized by an open transition state in which minimization of steric hindrance favors transition state C (Fig. 1). In all three... 

Inaba and coworkers reported that a Ti-BINOL complex is an effective catalyst for the desymmetrization of epoxide 44 using primary amines as nucleophiles. Of significant note is the efficiency of this reaction, with only 1 mol% catalyst necessary to attain high yields and selectivities [Eq. (10.11)]. Unfortunately, this epoxide is uniquely effective in this reaction. Cycloheptene oxide, dihydrofuran oxide, and an acyclic version of 44 each provided negligible yields under these reaction conditions ... 

The glyoxylate-ene reaction, promoted by the Ti-BINOL complex, produces chiral a-hydroxy esters, which provide an easy access to the corresponding carboxylic acid derivatives bearing a chiral center at the a position. The adduct between the glyoxylate and exo olefin is proposed as a key intermediate of the collagenase-selective inhibitor, Trocade (Hoffmann-La Roche) [20]. This remarkable process has been developed for large-scale production. 

Maruoka has documented a Ti-BINOL complex that promotes enantioselective cycloaddition reactions of diazoacetates and unsaturated aldehydes [94, 95]. The bridged structure 111 has been formulated as the active catalyst in this process (Scheme 18.21). A particularly attractive application involves the use of a-substituted acroleins in the reaction. These gave optically active pyrazolines with quaternary stereogenic centers such as 112 (95% ee). The procedure represents a substantive contribution to the area, additionally... 

Ti-BINOL-catalyzed reactions have been well established. When the Ti is replaced by Zr,92 the resulting complex 140 can also catalyze the addition of allyl-tributyltin to aldehydes (aldehydes allyl-tributyltin 140 = 1 2 0.2 mol ratio) in the presence of 4 A MS. Product l-alken-4-ols are obtained in good yield and high ee. The, Sz-face of the aldehyde is attacked if (S)-BINOL is used, and Re-face attack takes place when (K)-BINOL is used as the chiral ligand. For Zr complex-catalyzed reactions, the reaction proceeds much faster, although the... 

Ene reactions catalyzed by enantiopure (R)-9 can also be achieved with (7 )-BINOL as a chiral activator (Table 8.3). The reaction proceeds to give higher chemical yield (82.1 %) and enantioselectivity (96.8% ee) than those attained without the additional BINOL activator (19.8%, 94.5% ee) (entry 1 vs. 2). Kinetic studies indicate that the reaction catalyzed by (/f)-BESfOLato-Ti(0 Pr)2/(/f)-BESfOL complex ((/f,/ act)-9) is 25.6 times as fast as that catalyzed by (R)-9. These results imply that ( )-9 and a half-molar amount of (/f)-BINOL complex give (/f,/ act)-9, leaving (S)-9 uncomplexed. In contrast, (5)-BINOL activates (R)-9 to a smaller degree (entry 3), giving lower optical (86.0% ee) and chemical (48.0%) yields than with (K)-BINOL. 

The catalytic sulfoxidation system developed by Uemura and coworkers in 1993381,386 consisted of Ti(OPr-i)4, (f )-BINOL, H2O and TBHP in different compositions. The best results (highest ee) were obtained with low amounts of catalyst 0.025 eq. Ti(OPr-i)4, 0.05 eq. (f )-BINOL, 0.5 eq. H2O and 2 eq. TBHP. With this method sulfoxides could be obtained with excellent enantioselectivities (ee 96%), although yields were low (28-44%) due to kinetic resolution of the formed sulfoxides to give the corresponding sulfones. More detailed investigations by Uemura and coworkers showed that an enantiomeric excess of 50% of the sulfoxides is obtained at the initial stage of the reaction and that an increase in ee results the longer the reaction takes place . So the Ti-(i )-BINOL complex catalyzes... 

The vinylogous Mannich reaction of triisopyloxyfurans with aldimines prepared from aldehydes and 2-aminophenol proceeded with moderate selectivity in the presence of a catalytic amount of a Ti(IV)-BINOL complex [22]. 

For the same ene reaction, a possible activation of the enantiopure (R)-BINOL-Ti(OPr )2 [43] catalyst (R-2) by adding (R)-BINOL was investigated (Scheme 8C.16, Table 8C.4) [42a], In fact, the reaction in the presence of additional (R)-BINOL proceeded quite smoothly to provide the carbonyl-ene product in higher chemical yield (82%) and enantioselectivity (97% ee) than those without additional (R)-BINOL (20% yield, 95% ee). Based on the comparison of these results of enantiomer-selective activation of the racemic catalyst (90% ee, R) with those of the enantiopure catalyst with (97% ee, R) or without activator (95% ee, R), the reaction catalyzed by (R)-BINOL-Ti(OPr,)2/(/ )-BINOL complex (2 ) is calculated to be 27 times as fast as that catalyzed by (S)-BINOL-Ti(OPr )2 (S-2) in the reaction using racemic (+)-BINOL-Ti(OPr )2 ( 2) (Figure 8C.5a) [42a]. Indeed, kinetic studies indicated that the reaction catalyzed by the complex 2 is 26 times as fast as that catalyzed by the complex S-2 [42a], These results... 

CPrSSiMe3 catalyses the asymmetric allylation of aldehydes using (S)-BINOL-Ti(IV) complex (equation 8)15. 

Similarly, Keck [111] has used the Ti(0-i-Pr)4/BINOL complex (10 mol %) for the hetero Diels-Alder reaction of l-methoxy-3-trimethylsilyloxy-1,3-butadienes 2-10 and non-activated aldehydes. The lowest enantioselectivity was obtained with benzaldehyde and the best with phenylacetaldehyde and some aliphatic aldehydes to give the corresponding dihydropyrans with ee values ranging from 75 % up to 97%. 

These complexes are the first examples of multifunctional catalysts and demonstrate impressively the opportunities that can reside with the as yet hardly investigated bimetallic catalysis. The concept described here is not limited to lanthanides but has been further extended to main group metals such as gallium [31] or aluminum [32]. In addition, this work should be an incentive for the investigation of other metal-binaphthyl complexes to find out whether polynuclear species play a role in catalytic processes there as well. For example, the preparation of ti-tanium-BINOL complexes takes place in the presence of alkali metals [molecular sieve ( )]. A leading contribution in this direction has been made by Kaufmann et al, as early as 1990 [33], It was proven that the reaction of (5)-la with monobromoborane dimethyl sulfide leads exclusively to a binuclear, propeller-like borate compound. This compound was found to catalyze the Diels-Alder reaction of cyclopentadiene and methacrolein with excellent exo-stereoselectivity and enantioselectivity in accordance with the empirical rule for carbonyl compounds which has been presented earlier. 

Kureshy, R.I., Singh, S., Khan, N.H., Abdi, S.H.R., Agrawal, S., Mayani, V.J., and Jasra, R.V. 2006. Microwave-assisted asymmetric ring opening of meso-epoxides with aromatic amines catalyzed by a Ti-S-(-)-BINOL complex. Tetrahedron Letters, 47 5277-79. 

Yu, C.-M., Choi, H.-S., Jung, W.-H., Lee, S.-S. Catalytic asymmetric allylation of aldehydes with BINOL-Ti(IV) complex accelerated by I-PrSSiMes. Tetrahedron Lett. 1996, 37, 7095-7098. 

As part of a series of studies on the use of BINOL-Ti(IV) complex 53 as a catalyst in a number of C-C bond-forming reactions, Mikami has reported the aldol addition reactions of thioacetate-derived silyl ketene acetals 55, 56 to a collection of highly functionalized aldehydes (Eq. (8.13)) [28]. As little as 5 mol% of the catalyst mediates the addition reaction and furnishes adducts 57 in excellent yields and up to 96% ee. One of the noteworthy features of the Mikami process is the fact that aldehyde substrates containing polar substituents can be successfully employed, a feature exhibited by few other Lewis-acid-catalyzed aldehyde addition reactions. 

Nonracemic Ti-BINOLate (BINOL = l,l -bi-2-naplilli()l) and Ti-TADDOLate (TADDOL = a,a,a, a -tetraaryl-2,2-dimethyl-l,3-dioxolan-4,5-dimethanol) complexes are also effechve chiral catalysts for the asymmetric alkylation of aldehydes [9-11]. Seebach developed polystyrene beads with dendritically embedded BINOL [9] or TADDOL derivatives 11 [10, 11]. As the chiral ligand is located in the core of the dendritic polymer, less steric congeshon around the catalyhc center was achieved after the treatment with Ti(OiPr)4. This polymer-supported TiTADDOLate 14 was then used for the ZnEt2 addition to benzaldehyde. Chiral 1-phenylpropanol was obtained in quantitahve yield with 96% ee (Scheme 3.3), while the polymeric catalyst could be recycled many times. 

New work on the asymmetric hetero DA reaction as a route to 2,3-dihydropyran-4-ones includes the use of axially chiral biaryl-based diols <05JA1336> and chiral Bronsted acids <05TL6355> which work through hydrogen bonding. Polymer-bound Danishefsky s diene derived from acetoacetate has been used in the hetero DA reaction with aldehydes. With a chiral BINOL-Ti(IV) complex, good yields of 2-aryl-5-methoxycarbonyl-5,6-dihydropyran-... 

Uemura described use of a Ti(OiPr)4/(i )-BINOL complex for the oxidation of alkyl aryl sulfides with aqueous ferf-butyl hydroperoxide as stoichiometric oxidant [22]. At room temperature p-tolyl methyl sulfide was converted into the corresponding sulfoxide with 96% ee in 44% yield with as little as 5 mol % of the chiral ligand. The reaction is insensitive to air, while the presence of water seems to be essential for the formation of the catalytically active species, long catalyst lifetime, and high asymmetric induction. The authors observed a large positive non-linear effect which indicates that the actual catalyst consists of a titanium species with more than one (K)-BINOL ligand (11) coordinated to the metal. 

A study on the time course of the enantiomeric excess of the sulfoxide revealed that it was highly dependent on the reaction time. In addition, as the reaction proceeded, the formation of sulfone was observed. With the gradually increasing amounts of sulfone the ee of the sulfoxide was raised. This dependence of the enantiomeric excess on time and sulfone formation indicated that a kinetic resolution process of the newly formed sulfoxide took place. Chiral recognition of the (S)-sulfoxide by the Ti(OiPr)4/(i )-BINOL complex led preferably to consumption of this enantiomer and thereby raised the enantiomeric excess of the fi j-sulfoxide. 

Mukaiyama and coworkers have utilized complexes prepared from (R)- or (S)-l,T-2,2 -binaphthol (BINOL) and Ti(IV) precursors generated upon treating Ti(0 Pr)4 with an equivalent of H2O in benzene [87,88]. The catalytically active species is suggested to be a BIN0L Ti=0 complex 138. However, given the proclivity of related Ti(IV)=0 complexes to exist as dimers centered about a (Ti(p-... 

A related Mukaiyama aldol catalyst system reported by Keck prescribes the use of a complex that is prepared in toluene from (R)- or (S)-BINOL and Ti(0 Pr)4 in the presence of 4 A molecular sieves. In work preceding the aldol addition reaction, Keck had studied this remarkable catalyst system and subsequently developed it into a practical method for enantioselective aldehyde allylation [95a, 95b, 95c, 96]. Because the performance of the Ti(IV) complex as an aldol catalyst was quite distinct from its performance as a catalyst for aldehyde allylation, a careful examination of the reaction conditions was conducted. This meticulous study describing the use of (BINOL)Ti(OiPr)2 as a catalyst for aldol additions is noteworthy since an extensive investigation of reaction parameters, such as temperature, solvent, and catalyst loading and their effect on the enantiomeric excess of the product was documented. For example, when the reaction of benzal-dehyde and tert-butyl thioacetate-derived enol silane was conducted in dichlo-romethane (10 mol % catalyst, -10 °C) the product was isolated in 45% yield and 62% ee by contrast, the use of toluene as solvent under otherwise identical conditions furnished product of higher optical purity (89% ee), albeit in 54% yield. For the reaction in toluene, increasing the amount of catalyst from 10 to 20 mol %... 

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