Titanium BINOL ligands

It has also been shown by Mikami et al. that a BINOL-titanium(IV) complex in which the 6,6 position of the BINOL ligand is substituted with bromine catalyzes... 

Other use of the functionalized chiral BINOL includes the 5,5, 6,6, 7, 7, 8,8 -octahydro derivative developed by Chan and coworkers, the titanium complex of which is more effective than BINOL in the enantioselective addition of triethylaluminum and diethylzinc a 4,4, 6,6 -tetrakis(perfluorooctyl) BINOL ligand developed for easy separation of the product and catalyst using fluorous solvents for the same zinc reaction an aluminum complex of 6,6 -disubstituted-2,2 -biphenyldiols used by Harada and coworkers in the asymmetric Diels-Alder reaction a titanium complex of (5 )-5,5, 6,6, 7,7, 8,8 -octafluoro BINOL employed by Yudin and coworkers in the diethylzinc addition, in the presence of which the reaction of the enantiomeric (/f)-BINOL is promoted . 

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. 

Tridentate BINOL catalysts can be derived from titanium tetra(isopropoxide), BINOL ligands, and hindered amine bases. These catalysts have also been shown to provide good yields and ee s for the aldol reactions at low temperatures of 2-methoxypropene with several aldehydes to the P-hydroxyketones, but an acid workup of the products is required. 

Immobilization of chiral ligands to effect asymmetric induction in alkylation of aromatic aldehydes by diorganozinc reagents promoted by PEG-im-mobilized ligands 54-57 can also be promoted by soluble polystyrene-bound species. A recent example of this is work where a polystyrene-bound BINOL was prepared [ 105]. This polymer 69 was used to form titanium-BINOLate and AlLibis(binaphthoxide) catalysts for Et2Zn reaction with benzaldehyde and for asymmetric Michael additions of stabilized carbanions to cyclohexenone. While good stereoselectivities were obtained with these catalysts, the synthetic yields were modest. 

Three new substituted BINOL ligands, (i )-3-[4,6-bis(dimethylamino)-l,3,5-triazin-2-yl]-l,10-bi-2-naphthol (R)-(72), (i )-3,3 -bis[4,6-bis(dimethylamino)-l,3,5-triazin-2-yl]-l,10-bi-2-naphthol (R)- 73), and 2,4-bis(2,2 -dihydroxy-1,10-binaphthalen-3-yl)-6-(/i-tolyl)-l,3,5-triazine iR,R)-74), have been obtained by directed ort o-lithiation and a Suzuki cross-coupling process (Scheme 10) <2005TA3667>. The titanium complex of (R)-72 was found to be an effective catalyst in the asymmetric addition of diethylzinc to a variety of aromatic aldehydes. 

It is relatively rare for the interactions with the polymeric support to be beneflcial to catalytic performance. However, one example of this was observed upon the deliberate positioning of a binol ligand in close proximity to polystyrene via amide linkages [15], which resulted in enhanced performance in the titanium-catalyzed addition of diethylzinc to aldehydes (Figure 5.2b). 

Another approach to facilitate the recovery of catalytic systems relies on the use of fluorinated analogues of classic chiral ligands. The recycling options offered by the fluorous catalysts have been explored in the field of asymmetric addition of dialkylzinc reagents to aldehydes in presence of titanium tetraisopropoxide. In 2000, the groups of Chan ° and Curran reported independently the synthesis of perfluoroallqrl-substituted BINOL ligands and their evaluation in the titanium-mediated enantioselective addition of diethylzinc to aromatic aldehydes in fluorous biphasic system (Scheme 7.27). 

BINOL ligands 41a-c bearing dendritic wedges at the 6,6 positions were used in titanium-catalysed reaction of tributylallyl stannane and benzaldehyde (Scheme 7.33). Whereas the yield was low, the enantioselectivity was similar to the reaction with BINOL (87% enantiomeric excess), whatever the size of the dendritic moieties. However, no attempt to recycle the catalyst or the ligand was described by the authors. 

Self-supported titanium complexes with linked bis-BINOL ligands were used as an alternative approach for the immobilisation of catalysts, as shown in enantioselective sulfide oxidation (see Section 7.2.2). The same ligands were used with success in asymmetric carbonyl ene reactions. The chiral metal-bridged polymer 76, derived from ent-lOa, titanium tetraisopropoxide and water (Scheme 7.45), catalysed the ene reaction between 68b and 71, to give R)-72 in 88% yield and 88% enantiomeric excess. The catalyst can be reused at least five times without affecting its efficiency. 

To facilitate catalyst recovery, polymeric and dendrimeric TADDOL, and BINOL ligands have been used for the titanium-catalyzed diethylzinc addition reaction [49]. Moreover, ionic liquids and fluorous solvents have also been used as the reaction media to facilitate the separation of ligands [50]. The microporous metal-organic frameworks prepared from BINOL derivatives were applicable to heterogeneous diethylzinc addition to aldehydes in the presence of excess amount of Ti(O Pr)4 [51]. 

Mikami found that the ene reaction of 1,1-di- and trisubstituted olefins with glyoxylate ester can be catalyzed by the titanium complexes prepared from BINOL and Ti(O Pr)2Cl2, Ti(O Pr)2Br2, or Ti(O Pr)4 [128]. The remarkable level of enan-tioselectivity and rate acceleration observed with these BINOL-Ti catalysts stems from the favorable infiuence of the inherent C2 symmetry and the higher acidity of BINOL ligands compared with aliphatic diols. The reaction is applicable to a variety of 1,1-disubstituted olefins and furnishes the ene products with excellent enantiomeric excesses (Scheme 14.48). However, no reaction occurs when mono-and 1,2-disubstituted olefins were adopted as the reactants. 

A one-pot titanium-catalyzed tandem sulfoxidation-kinetic resolution process was developed by Chan using TBHP as the oxidant This process combines asymmetric sulfoxidation (at 0°C) and kinetic resolution (at room temperature). Excellent enantiomeric excesses (up to >99.9%) and moderate to high chemical yields of sulfoxides were obtained [270] (Scheme 14.113). The effect of fluorine substitution at the backbone of BINOL on the catalytic activity in titanium-catalyzed sulfide oxidation with TBHP or cumyl hydrc en peroxide (CHP) was studied by Yudin [271]. Introduction of fluorines into the BINOL scaffold was found to increase the electrophilic character of the Lewis acidic titanium center of the catalyst The most intriguing difference between the FsBINOL and BINOL systems is the reversal in the sense of chiral induction upon fluorine substitution. A steroid-derived BINOL ligand has also been used for the same reaction [272]. 

Bicyclic meso-N-ary aziridines are ring-opened by anilines, giving trans-1,2-diamines in the presence of a Ti(0-Bu-t)4/(l )-BlN0L catalyst in CH2Cl2." The reactions occur in yields between 65 and 96% with 57-99% ee. Lower enantioselectivities were found when electron-withdrawing and orifto-substituents were on the aniline. Alkyl amines failed to react. ESI-MS experiments indicate that the catalyst contains two titanium and two linked bis-BINOL ligands. 

The elements of the 4b transition group were also stabilized by triflates. Titanium is among the most moisture-sensitive elements. Air- and moisture-stable titanium(IV) triflates were prepared by its co-complexation with organic ligands. Reported examples referred to Cj-symmetric amine tris(phenolate) [36] or Binol ligands [37]. These compounds demonstrated efficiency as Lewis acid catalysts for formal a a-Diels-Alder (Equation (8.15)) and the homoaldol (the addition of silyloxycyclopropanes to aldehydes) (Equation (8.16)) reactions. 

Effect of Alkoxy Ligand. Since the modification of the chiral diol in the titanium complex affected the enantioselectivity, we studied the effect of the alkoxide ligand in (/ )-BINOL-Ti(OR)2 and prepared several complexes by treatment of lithium (/ )-binolate with TiCl2(OR)2. Although a primary alkoxide ligand led to minimal asymmetric induction, a secondary alkoxide resulted in reasonable ee s. A tertiary butoxide or binolate ligand decreased the ee considerably. Thus, the bulk of the alkoxide ligand on the titanium complex appears to be extremely important to create an appropriate size of the reaction site. 

A remarkable change in reaction course is notable when changing the metal from aluminum to titanium for cydoaddition reactions using BINOL as the chiral ligand. When the chiral aluminum(III) catalyst is applied the cydoaddition product is the major product, whereas for the chiral titanium(IV) catalyst, the ene product is the major product. The reason for this significant change in reaction course is not fully understood. Maybe the glyoxylate coordinates to the former Le-... 

In 2008, the titanium complex of a novel BINOL-based thiazole thioether ligand was found by Li et al. to be an efficient catalyst in the enantioselective... 

In 2001, Scettri and coworkers could show that titanium-catalyzed asymmetric sulfoxidation with a tertiary furyl hydroperoxide 188a can be achieved under catalytic conditions by a modification of Uemura s approach employing (R)-BINOL as chiral ligand (equation 57). Under these conditions sulfoxides could be isolated in medium to good... 

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