1,3-Dioxolane-4,5-dimethanol TADDOL

Seebach, D., Hayakawa, M., Sakaki, J. and Schweizer, W.B. (1993) Derivatives of tetraaryl-2,2-dimethyl-1,3 -dioxolane-4,5 -dimethanol (TADDOL) containing nitrogen, sulfur, and phosphorus atoms. New ligands and auxiliaries for enantioselective reactions. Tetrahedron, 49, 1711-1724. 

The procedure described here is a typical one tor the preparation of a,a,a ,a -tetraaryl 2,2-disubstituted 1,3-dioxolane-4,5-dimethanols (TADDOLs, 1), a class of diols of which ca. 50 representatives have been synthesized.7 They have become useful chiral auxiliaries for the preparation of enantiomerically enriched or pure compounds and for analytical purposes. The diols themselves have been employed... 

The a,a,a,a-tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) chiral ligands have also been the basis of enantioselective catalysis of the D-A reaction. In a study using 2-methoxy-6-methylquinone as the dienophile, evidence was found that the chloride-ligated form of the catalysts was more active than the dimeric oxy-bridged form.117... 

Chiral titanium complexes with a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands are versatile auxiliaries in the Lewis acid catalyzed alcoholysis of racemic 4-(arylmethyl)-2-phenyl-5(477)-oxazolones 234, providing the corresponding enantiomerically enriched N-protected amino acid esters 235 (Scheme 7.73). The enantioselectivity of the reaction is dependent on the solvent, temperature, and chiral ligand. Selected examples of the alcoholysis of saturated 5(477)-oxazolones are shown in Table 7.21 (Fig. 7.23). 

Various tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands have been employed in the syntheses of a series of Ti-TADDOL derivatives578 such as TiCl2(TADDOL),579 TiCl2(TAD-DOL)(THF)2 (54),515 and Ti(OC(Ph)CHC(Ph)0)(TADDOL)(THF)2.580 Much of this chemistry has been reviewed.383,386,581 Ti complexes of these ligands have been extensively used in asymmetric synthesis.515,582-591... 

Tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) ligands synthesized from tartaric acid have been extensively employed by Narasaka as the chiral control element in selective Diels-Alder reactions. Initial experiments were conducted with simple dienes and a,P-unsaturated imides using complex 44 (Scheme 36) [104,105]. Several rather subtle features have contributed to the success of these endeavors 1) the use of the acetophenone-derived dioxolane rather than the ac-etonide resulted in an increase of 20% ee 2) the use of alkyl-substituted benzenes as solvent augmented enantioselectivities relative to more common organic solvents e.g., CH2CI2, THF) [106] 3) use of 4 A molecular sieves was typically required to achieve maximum enantioselectivity. 

Asymmetric PTC is an important method in the synthesis of a-alkyl and a-amino acids. Belokon et al. [7] reported that the compound (47 ,57 )-2,2-dimethyl-Q ,Q ,Q , Q -tetra-phenyl-l,3-dioxolane-4,5-dimethanol (TADDOL) was used to catalyze the C-alkylation of C-H acids with alkyl halides to the asymmetric synthesis of a-methyl-substituted a-amino acids under PTC conditions. The alkylations of the substrate C-H acids with benzyl bromide or allyl bromide were conducted in dry toluene at ambient temperature with NaH or solid NaOH as base and TADDOL as a chiral promoter. The type of base is important in the asymmetric C-alkylation of C-H acids. 

The dienophile may also be activated by hydrogen bonding of the carbonyl oxygen with suitable protic molecules and it has been observed that Diels-Alder reactions are accelerated when performed in protic solvents such as 2-butanol. Thus the opportunity exists for the development of an enantioselective alcohol-catalysed asymmetric Diels-Alder reaction. Indeed, Rawal and coworkers have recently discovered that the use of catalytic amounts of the enantiomerically pure diol a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) (8.113) in the Diels-Alder reaction of aminosilyloxydiene (8.114) with 2-substituted acroleins such as (8.24), results in the formation of the cycloadduct (8.115) with high ee. Simiharly, the strong Bronsted acid (8.116) effectively catalyses the Diels-Alder reaction of sUyloxydienes such as (8.117) with a,P-enone (8.105). ... 

Wu and his co-workers reported an experimental and theoretical study on the hydrogen-bond-promoted enantioselective hetero-Diels-Alder reaction (HAD) of Danishefsky s diene 105 with benzaldehyde 106, Scheme 3.37 [52], The reaction was achieved catalytically by a series of a,ct,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol (TADDOL) derivatives through hydrogen-bonding activation and afforded 2-phenyl-2, 3-dihydro-4H-pyran-4-one 108 in good enantioselectivity. 

Both (—)-(4R,5R)- or (+)(4S,5S)-2,2-dimethyl-a,a,a, a -tetraphenyl-l,3-dioxolane-4,5-dimethanol (TADDOL) and l,l -bi-2-naphthol (BINOL) ligands were investigated as chiral Ugands in this process to establish an enantioselective aldol-Tishchenko reaction based upon this concept. However, only moderate enantioselectivities of up to 60% ee were obtained [19]. 

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). 

As mentioned earlier, much less efficient methods are available for allylation of imines than for allylation of aldehydes. Accordingly, the pincer-complex-catalyzed allylation of imines attracted considerable attention. In particular, the asymmetric version of this process is very important, as it grants access to chiral homoal-lylamines. The Szabo group [81j,l] developed a,Q ,a, a -tetraaryl-l,3-dioxolan-4,5-dimethanol (TADDOL-), l,l -bi-2-naphthol (BINOL-) and bisphenantrole-based chiral pincer complexes to achieve asymmetric allylation reactions (Scheme 6.28). 

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 use of TADDOL-based ligands offers an important alternative for copper-catalyzed asymmetric 1,4-additions. TADDOLs (a, a, a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol compounds), introduced by Seebach, are among the most successful currently known ligands in asymmetric catalysis. Seebach also developed the first copper-catalyzed 1,4-addition of a Grignard reagent using a TADDOL derivative as a chiral ligand (see Scheme 7.2) [17]. We have reported TADDOL-based... 

Another chiral ligand which plays an increasingly important role in asymmetric catalysis is TADDOL (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) [63]. Various attempts have been made to immobilize this chiral system to various solid sup-... 

In the catalytic system shown in Scheme 9, a hydrogen bond between one hydroxy function of the diol catalyst and the carbonyl group of the substrate is regarded as the driving force of catalysis. Here, the spatial orientation of the bulky a-1-naphthyl substituents of the TADDOL (a,a,a, a -tetraaryl-l,3-dioxolan-4,5-dimethanol) scaffold generates the chiral environment controlling the enantioselectivity of the reaction. 

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