TADDOL ligand

Seebach et al., who first developed the TADDOL ligands [53, 67], have also developed a number of polymer- and dendrimer-bound TiCl2-TADDOLate catalysts derived from the monomeric TADDOLs [68]. Application of 10mol% of this type of catalysts, derived from polymers and dendrimers of 27 and 28, respectively, in the... 

Seebach and co-workers copolymerized a dendritically modified TADDOL ligand with styrene (Figure 9). When associated with Ti(OiPr)4, the immobilized catalyst gave a very high ee (98%) for more than 20 runs in the enantioselective addition of diethylzinc to benzaldehyde95 96... 

TADDOL ligand over the competing (achiral) catalyst [Ti(OPr1)4]. The rate enhancement by the TADDOL ligands is due to an increase in the rate of ligand exchange in the TADDOL complex over the Ao-propoxyl complex because of the steric bulk of the TADDOL compared with two Ao-propoxides. 

Bidentate chiral auxiliaries have since been examined. While camphane-2,3-diol and (5-binaphthol gave disappointing results, tartrate-derived (TADDOL) ligands were found to be very promising as chiral inductors [44]. Particularly interesting results were obtained by using complex 21, readily available from natural (P,J )-(+)-tartaric acid (Scheme 13.21). 

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). 

Other chiral auxiliaries have been tested, such as those derived from TADDOL ligands, but, in these cases, better diastereocontrol was achieved using palladium acetate/diazomethane or using double differentiation with a chiral catalyst vide infra). 

Scheme 9 Dendronized TADDOL ligands which are cross-linked to form a dendritic network [58]...

One method has been employed in the reaction work-up. The reaction mixture is treated with aqueous 45% NH4F solution (or with water when silyl groups are present), stirred for 12 h at rt, filtered through Celite, and extracted twice with ether. The combined organic phases were washed with brine, dried overMgSOa, and concentrated. The solid residue was stirred with pentane. Subsequent filtration furnished the crystalline (/f,f )-Taddol or (S,S)-Taddol (ligand) which can be recycled after crystallization. The filtrate was evaporated and the residue was purified by chromatography to afford the homoallylic alcohol. 

Fhal and Renaud have examined the alkylation of a radical generated from the a-iodoimide 333 with a variety of Lewis acids, as shown in Sch. 42 [70]. The stereogenic step in this process would be hydrogen atom transfer from tin to a Lewis acid-com-plexed radical generated from 333. Initial screening was performed for the reaction of allyltributylstannane and imide 333, which was conducted by precomplexation of the imide with the Lewis acid and then addition of the stannane in the presence of AIBN under irradiation at 10 °C. The Lewis acid prepared from BINOL was ineffective whereas that prepared from the bis-sulfonamide 337 was slightly superior to that from the TADDOL ligand 339. 

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... 

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. 

The monodentate phosphonite ligands L18a-c (Fig. 8) modified by TADDOL ligands, which were derived from tartarates, were examined to show relatively high values of % ee 62-87% ees for acetophenone and 2-naphthyl methyl ketone with diphenylsilane [38]. 2-Naphthyl methyl ketone (K9) was reduced in 92% yield with 87% ee (R) by using a large excess of L18c (10-fold based on Rh) and [Rh(COD)Cl]2. 

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. 

Based on Frechefs work [20], Luis and coworkers [21] studied the influence of the mode of preparation of the polystyrene backbone functionalized with TADDOL (a,a,a, a -tetraaryl-l,3-dioxolane-4,5-dimethanol) 2. This immobilized ligand was loaded with titanium on the topicity of an asymmetric transformation. Here, the Diels-Alder reaction of cyclopentadiene with 3-crotonyl-l,3-oxazolidin-2-one was chosen as a model reaction. The TADDOL ligands were incorporated into the polymeric backbone either by polymerization using functionalized styrene derivative 1 or by grafting and coupling of phenol 2 to Merrifield-type resins (Scheme 7). 

Scheme 7 Preparation of monolithic and grafted materials functionalized with TADDOL ligands...

Markd and co-workers reported low levels of stereocontrol in the cycloaddition of 3-methoxycarbonyl-2-pyrone and butyl vinyl ether when TADDOL ligands are used in conjunction with YbfOTOj. ... 

The enantioselective a-chlorination of -keto esters was achieved with up to 88% ee using NCS with a commercially available TADDOL ligand. The chiral bisoxazoline copper(II) complexes have also been reported to induce the asymmetric a-chlorination of -keto esters when reacted with NCS. The asymmetric a-chlorination of aldehydes has been achieved using NCS and (2/ ,5/ )-diphenylpyrrolidine as a chiral catalyst. For example, the enantioselective chlorination of 3-methylbutanal with NCS proceeds in 95% yield and 94% ee (eq 17). ... 

The field of catalytic metallodendrimers has seen many advances, particularly in enantioselective catalysis. " Thanks to the early work of Seebach and coworkers, the synthesis of core-functionalised TADDOL dendrimers 40 has been achieved by using four Frechet dendrons (Figure 7.2). These dendrimers were used as ligands in the synthesis of titanium TADDOLates, which were evaluated as catalysts in the asymmetric addition of diethylzinc to benzaldehyde. In a general manner, the good stereoselectivities (89-97% enantiomeric excesses) detected were found to be comparable to those observed with the monomeric TADDOL ligand (98% enantiomeric excess). No attempt to recycle the catalyst or the ligand was mentioned by the authors. 

Figure 7.3 Polymer-supported TADDOL ligands and complexes. 

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