Catalysts TADDOL

Hyperbranched and dendritic macromolecules have recently been the subject of considerable interest. Bolm developed chiral hyperbranched macromolecules 57 that catalyzed the enantioselective addition of diethylzinc to benzaldehyde [75]. The enan-tiocontrol of the hyperbranched chiral catalysts was slightly lower than for the low-molecular-weight catalyst. TADDOLs linked with dendritic molecules have been synthesized [59]. For example, use of the first generation dendrimer 58 with six terminal TADDOL units resulted in high enantioselectivity. 

I would like to thank Professors E. J. Corey and K. Narasaka for giving me a chance to work with super-reactive chiral catalyst 9 and TADDOL-based chiral titanium catalyst 31, respectively. 

A chiral titanium(IV) complex has also been used by Wada et al. for the intermole-cular cycloaddition of ( )-2-oxo-l-phenylsulfonyl-3-alkenes 45 with enol ethers 46 using the TADDOL-TiX2 (X=C1, Br) complexes 48 as catalysts in an enantioselective reaction giving the dihydropyrans 47 as shown in Scheme 4.32 [47]. The reaction depends on the anion of the catalyst and the best yield and enantioselectivity were found for the TADDOL-TiBr2 up to 97% ee of the dihydropyrans 47 was obtained. 

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]. 

In most TiCl2-TADDOLate-catalyzed Diels-Alder and 1,3-dipolar cycloaddition reactions oxazolidinone derivatives are applied as auxiliaries for the alkenoyl moiety in order to obtain the favorable bidentate coordination of the substrate to the catalyst... 

In a more recent study on 1,3-dipolar cycloaddition reactions the use of succi-nimide instead of the oxazolidinone auxiliary was introduced (Scheme 6.19) [58]. The succinimide derivatives 24a,b are more reactive towards the 1,3-dipolar cycloaddition reaction with nitrone la and the reaction proceeds in the absence of a catalyst. In the presence of TiCl2-TADDOLate catalyst 23a (5 mol%) the reaction of la with 24a proceeds at -20 to -10 °C, and after conversion of the unstable succinimide adduct into the amide derivative, the corresponding product 25 was obtained in an endojexo ratio of <5 >95. Additionally, the enantioselectivity of the reaction of 72% ee is also an improvement compared to the analogous reaction of the oxazolidinone derivative 19. Similar improvements were obtained in reactions of other related nitrones with 24a and b. 

Tab. 6.2 Application of TiX2 between la and 19a TADDOLate as catalyst for the 1,3-dipolar cycloaddition reaction...

The TiX2-TADD0Late-catalyzed 1,3-dipolar q cloaddition reactions were extended to include an acrylate derivative [66]. In the absence of a catalyst, the reaction between nitrones 1 and acryloyl oxazolidinone 19b proceeded to give a mixture all eight regio-and stereoisomers (Scheme 6.23). However, application of in this case only 10 mol% of Ti(OTs)2-TADDOLate 23d as catalyst for the reaction of various nitrones 1 with alkene 19b, led to complete regioselectivity and high endo selectivity in the reaction and the endo products 21 were obtained with 48-70% ee (Scheme 6.23) [66]. 

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... 

The normal electron-demand principle of activation of 1,3-dipolar cycloaddition reactions of nitrones has also been tested for the 1,3-dipolar cycloaddition reaction of alkenes with diazoalkanes [71]. The reaction of ethyl diazoacetate 33 with 19b in the presence of a TiCl2-TADDOLate catalyst 23a afforded the 1,3-dipolar cycloaddition product 34 in good yield and with 30-40% ee (Scheme 6.26). 

It was our delight that the reactions catalyzed were activated even at -40 °C in the presence of a catalytic amount of achiral titanium catalysts (10 mol%) to afford the desilylacetylated 2-pyrazoline cycloadduct Na, l-acetyl-4-methyl-5-(2-oxo-3-oxazolidinylcarbonyl)-2-pyrazoline, in high yields as the far major product (Scheme 7.35). Although some chiral titanium TADDOlate catalysts were successfully applied to activate these reactions leading to the moderate enantioselectivities (up to 55% ee), the chemical yields were not satisfactory. 

The exo selecdvity of the TiCL-TADDOLate-catalyzed 1,3-thpolar cycloadthdon is improved by the tise of sticcinimide instead of oxazoiidinone as attxiliary for the a,fi-imsatitrated carbonyl moiety (Eq. 8.55). A strong bidentate coo rdinadon of the alkenyl moiety to the metal catalyst is impcrtant in these re... 

Since catalysts immobilised on hydrophilic silica gel often give superior performances to their polymer-bound or polymer-incorporated analogues for multiple applications, Heckel and Seebach have immobilised TADDOL derivatives on hydrophobic controlled-pore glass (CPG) silica gel. Indeed, CPG is... 

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... 

Entry 9 uses the oxaborazolidine catalysts discussed on p. 505 with 2-bromopropenal as the dienophile. The aldehyde adopts the exo position in each case, which is consistent with the proposed TS model. Entry 10 illustrates the use of a cationic oxaborazolidine catalyst. The chirality is derived from trans-1,2-diaminocyclohcxanc. Entry 12 shows the use of a TADDOL catalyst in the construction of the steroid skeleton. Entry 13 is an intramolecular D-A reaction catalyzed by a Cu-Ws-oxazoline. Entries 14 and 15 show the use of the oxazaborolidinone catalyst with more complex dienes. 

The Ti(IV) TADDOL catalyst Q leads to moderate enantioselectivity in nitrone-alkene cycloaddition.158... 

Fig. 31. Selectivity comparison for the enantioselective addition of Et2Zn to benzaldehyde using different dendritic and non-dendritic homogeneous and heterogeneous Ti-TADDOLates as chiral catalysts [107,110], (S)-.(R) ratios refer to the 1-phenyl-propanol formed...

The rate for the simple polymer-bound TADDOLate published in [107] was taken from [110]. Newer results show a similar rate for both polymer-bound catalysts described herein. 

Seebach has developed immobilization of TADDOL with a high degree of loading on porous silica gel and applications in enantioselective addition of Eq. 8.54. This catalyst leads to 85%... 

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... 

Figure 9 Supported Ti-TADDOLate catalyst for enantioselective addition of diethylzinc to benzaldehyde...

A PHOX analogue containing a P-O bond, the TADDOL-derived phosphite oxa-zoline catalyst 20a (Fig. 29.8) has been used in the hydrogenation of a number of substituted styrenes, as well as in asymmetric allylic alkylation [19]. However,... 

The diamine and TADDOL-derived catalysts 44 were tested on substrates 36-39, giving good enantioselectivities however, high catalyst loadings of 4 mol% were required for full conversion [34]. 

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. 

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. 

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]. 

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