Titanium-TADDOL system

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]. 

Seebach et al. have comprehensively examined the use of a chiral diol (TAD-DOL) derived from tartaric acid as a chiral ligand [22]. The titanium-TADDOL system also catalyzes the asymmetric addition of diethylzinc to various aldehydes (Scheme 8) [23,24]. This system is applicable to the alkylation of various... 

The titanium-TADDOL system is notable for its breadth of reacting partners. Fumaroyl [104b] andacryloyl [107] imidedienophiles maybe employed with substituted and unsubstituted butadienes to afford cyclohexenes in high enantiomeric excess (Scheme 37). In the case of 2-thioethylbutadiene, the lower yield is accounted for by the intervention of a competing [2-1-2] cycloaddition pathway. 

It has been observed that enantioselective polymer-bound catalysts prepared by copolymerization produce in some cases better asymmetric inductions than systems prepared by grafting [175]. After much optimization, a monolithic polymer catalyst 51 suitable for a titanium-TADDOLate catalyzed Diels-Alder reaction was developed (Scheme 4.77). The monolith was applied in a flow system both under one pass and 24 h recirculation conditions, the latter producing the best yield (55%) and ee (23%) however, this contrasts poorly with the homogeneous batch reaction although the ee is comparable with the heterogeneous batch process. The reversal of topicity was also... 

Seebach s group demonstrated the utility of polymer-bound, chiral titanium TADDOLates in preparing chiral secondary alcohols (Figure 3.24).The polymeric catalyst 37 was contained inside a mesh tea bag, and was reused by simply charging fresh reagents and solvent. The ruggedness of the system was shown when the product enantioselectivity dropped from 96% (S) to only 92% (S) over 20 successive runs, and the average yield was 90% [50]. 

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. ... 

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 self-assembly of a chiral Ti catalyst can be achieved by using the achiral precursor Ti(OPr )4 and two different chiral diol components, (R)-BINOL and (R,R)-TADDOL, in a molar ratio of 1 1 1. The components of less basic (R)-BINOL and the relatively more basic (R,R)-TADDOL assemble with Ti(OPr )4 in a molar ratio of 1 1 1, yielding chiral titanium catalyst 118 in the reaction system. In the asymmetric catalysis of the carbonyl-ene reaction, 118 is not only the most enantioselective catalyst but also the most stable and the exclusively formed species in the reaction system. 

Bernardi and Scolastico have reported the use of chiral Ti complexes, prepared in situ from TiCl2(Ot-Pr)2 and a,a,a, a -[4R, 51 )-tetraaryl-l,3-dioxolane-4,5-dimefha-nol (TADDOLs), for Michael addition of KSA to a-enone 93 [245]. The reaction is only modestly enantioselective (up to 47% ee), however, even with stoichiometric use of the titanium complex. Chiral Cu(II)-box complex (P,P)-70d has also been used for the same reaction (Scheme 10.89) [246]. The catalyst system is more enantioselective, and a catalytic quantity of 70d can be used. 

Asymmetric catalysis of ene reactions was initially explored in the intramolecular cases, since the intramolecular versions are much more facile than their intermolecular counterparts. The first example of an enantioselective 6-(3,4) car-bonyl-ene cyclization was reported using a BINOL-derived zinc reagent [55]. However, this was successful only when using an excess of the zinc reagent (at least 3 equivalents). Recently, an enantioselective 6-(3,4) olefin-ene cyclization has been developed using a stoichiometric amount of a TADDOL-derived chiral titanium complex (Scheme 17) [56]. In this ene reaction, a hetero Diels-Alder product was also obtained, the ratio depending critically on the solvent system... 

As a final cautionary note regarding mechanistic interpretation of this system, Seebach has noted positive non-linear effects for the Diels-Alder reaction using Ti(IV)-TADDOL, indicating the possibility of either an aggregated transition state or the formation of catalytically inactive 1 1 (i ,i )/(S,S)-titanium complexes [119]. 

Titanium isopropoxide-TADDOLate, 99, system was used by Charette et al. for asymmetric cyclopropanation of allylic alcohols, 100, (reaction 7.18) with acceptable yield and enantioselectivity [68]. 

An enantioselective 6-(3,4) olefin-ene cyclization could be achieved using a stoichiometric amount of a TADDOL-derived chiral titanium complex [127]. In this ene reaction, a HDA product was also obtained, where the periselectivity depends critically on the solvent system employed. In both cases, geminal disubstitution is required for good enantiocontrol (Scheme 14.47). 

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