TADDOL catalysis

Taddol catalysis of cycloadditions can be extended to other reactive dienes. Ding and coworkers showed in 2004 that taddol 1 was capable of catalyzing the cycload-dition of Brassard s diene with various aromatic aldehydes to give 5-lactone products directly on reaction workup (Scheme 10.5) [61]. The products were obtained in good yields (up to 85%) and good to high enantioselectivities (68-91% ee). The methodology was applied to the synthesis of the natural product (S)-(-l-)-dihydroka-... 

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... 

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. 

R. Hilgraf, A. Pfaltz, Chiral Bis(N-tosylamino)phosphine-and TADDOL-Phosphite-Oxazolines as Ligands in Asymmetric Catalysis, Synlett, 1999,11,1814-1816. 

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-... 

The role of multicomponent ligand assembly into a highly enantioselective catalyst is shown in the enantioselective catalysis for the carbonyl-ene reaction (Table 8.9). The catalyst is prepared from an achiral precatalyst, Ti(0 Pr)4 and a combination of BINOL with various chiral diols such as TADDOL and 5-Cl-BIPOL in a molar ratio of 1 1 1 (10mol% with respect to the olefin and glyoxylate) in... 

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. 

A similar Diels-Alder reaction was investigated at DFT-level by Houk and co-workers [57]. Instead of using TADDOL, they selected one methanol molecule, two methanol molecules and 1,4-butanediol in cooperative and bifurcated coordination as catalysts. It was found that cooperative catalysis is generally the favored route. 

Since the pioneering studies of asymmetric catalysis with core-functionalized dendrimers reported by Brunner (88) and Bolm (89), several noteworthy investigations have been described in this field. Some examples of the dendritic effects observed in enantioselective catalysis with dendrimers having active sites in the core were discussed in Section II, such as the catalytic experiments with TADDOL-cored dendrimers described by Seebach et al. (59) the asymmetric addition of Et2Zn to aldehydes catalyzed by core-functionalized phenylacetylene-containing dendrimers reported by Hu et al (42)-, the asymmetric hydrogenation investigations with (R)-BINAP core-functionalized dendrimers synthesized by Fan et al. (36) or the results... 

The last few years have witnessed major advances in the use of small organic molecules as organic acid catalysts in asymmetric catalysis [1], Selected examples of such organic acid catalysts include urea and thiourea [2], TADDOL [3], BINOL [4], and phosphoric acid derived from BINOL [5] (Figure 2.1). 

Because a comprehensive discussion of the transition state of hydrogen-bond catalysis will be presented by Berkessel in Chapter 3, the hydrogen bond catalyzed hetero Diels-Alder reaction of butadiene with carbonyl compounds will be discussed briefly here. Huang and Rawal reported that the hetero Diels-Alder reaction of aminodiene with aldehyde exhibited significant solvent effects (Scheme 2.7) [15]. The reaction in CHCfi was accelerated 30 times in comparison with that in THF, while that in i-PrOH was accelerated 630 times. They proposed that the Diels-Alder reaction was promoted by the hydrogen-bond activation of aldehyde. This finding resulted in the development of TADDOL catalyst [3]. 

TADDOL-Promoted Enantioselective Hetero-Diels-Alder Reaction of Danishefsky s Diene with Benzaldehyde-Another Example for Catalysis by Cooperative Hydrogen Bonding... 

The Rawal group next applied diol catalysis to the enantioselective vinylogous Mukaiyama aldol (VMA) reaction of electron-deficient aldehydes [105]. Screening of various known chiral diol derivatives, including VANOL, VAPOL, BINOL, BAMOL, and TADDOL, revealed that 38a was the only catalyst capable of providing products in acceptable levels ofenantioselection (Scheme 5.55). Subsequent to this work, Scettri reported a similar study of TADDOL-promoted VMA reactions with Chan s diene [106]. 

In the following sections, progress made in asymmetric phase-transfer catalysis using chiral crown ethers, taddolates, Nobin and metal(salen) complexes is surveyed. Each section is further subdivided according to the reaction being catalyzed. 

Taddol has been widely used as a chiral auxiliary or chiral ligand in asymmetric catalysis [17], and in 1997 Belokon first showed that it could also function as an effective solid-liquid phase-transfer catalyst [18]. The initial reaction studied by Belokon was the asymmetric Michael addition of nickel complex 11a to methyl methacrylate to give y-methyl glutamate precursors 12 and 13 (Scheme 8.7). It was found that only the disodium salt of Taddol 14 acted as a catalyst, and both the enantio- and diastereos-electivity were modest [20% ee and 65% diastereomeric excess (de) in favor of 12 when 10 mol % of Taddol was used]. The enantioselectivity could be increased (to 28%) by using a stoichiometric amount of Taddol, but the diastereoselectivity decreased (to 40%) under these conditions due to deprotonation of the remaining acidic proton in products 12 and 13. Nevertheless, diastereomers 12 and 13 could be separated and the ee-value of complex 12 increased to >85% by recrystallization, thus providing enantiomerically enriched (2S, 4i )-y-methyl glutamic add 15. 

A. HECKELand D. Seebach, Immobilization of TADDOL with a high degree of loading on porous silica gel and first applications in enantioselective catalysis, Angew. Chem.,... 

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