Similarity TADDOL

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. 

An X-ray structure of the complex formed between 3-cinnamoyl-l,3-oxazohdin-2-one and a chiral TADDOL-Ti(IV) complex (see Chapters 1 and 6 by Hayashi and Gothelf, respectively) has been characterized [16]. The structure of this complex has the chiral TADDOLate and cinnamoyloxazohdinone ligands coordinated to titanium in the equatorial plane and the two chloride ligands in the axial plane and is similar to A in Fig. 8.8. The chiral discrimination was proposed to be due to... 

A comparison of the rates showed that the polymer-bound Ti-TADDOLate 88 and the dendritic polymer 89 catalyze the Et2Zn-to-PhCHO addition at a similar fast rate as the monomeric TADDOLate 86 and the dendritic TADDOLate 87 in homogeneous solution [107,112]. Further experiments also with other ligands are being carried out in our laboratories. 

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. 

So far, few data are available which allow the comparison of differences in efficacy and selectivity of one catalytic system attached to different supports. As far as the TADDOLate complexes are concerned, no clear rules can be drawn. Polystyrene-based catalysts derived from (8) and (10) show similar enantioselectivities and reaction rates. Differences appear, however, when comparing them with a polystyrene-embedded dendritic ligand system, generated by co-polymerization from TADDOL-derivative (32) (Scheme 4.18) which is described in Section 4.3.2.1. Re-cydabihty seems to be easier for the dendritic catalyst and the enantioselectivity. 

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. 

Exclusive formation of the M-nitroso aldol product from similar starting materials was observed in the presence of 1-naphthyl TADDOL (30 mol%) in toluene (63-81%, 65-91% ee-, n=, 2). 

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]. 

Seebach et al. (350), who first developed the TADDOL ligands, have also developed a number of polymer- and dendrimer-bound TiCl2-TADDOLate catalysts derived from the monomeric TADDOLs (361). The use of catalysts derived from polymers and dendrimers of 249 and 250, respectively, in the reactions between the nitrone 225a and the alkene 241a led to endo/exo-ratios of between 18 82 and 8 92, and enantioselectivities of up to 56% ee (Scheme 12.78). The enantioselectivities are thus slightly decreased compared to the similar reactions of... 

More recently, a Ti-TADDOLate catalyst was found useful for a similar asymmetric transformation, and this reaction has been successfully applied to the asymmetric synthesis of the potent, non-peptidic, NKl-selective, substance P antagonist RPR 107880 [59] (Eq. 8A.35). 

Similar to the success achieved with TADDOLs (see Chapter 8) [17], many chiral catalysts and chiral ligands were synthesized from tartaric add, which provides a proper C2-symmetric framework and structural diversity. TaDiAS 1 has remarkable structural diversity because a wide variety of catalysts can be easily synthesized by changing the acetal moieties (R1 and R2), aromatic parts (Ar), and counter anions (X ), making it possible to fine-tune, three-dimensionally, the catalyst (vide infra). Other candidates, such as 2, 3, and 4 (Figure 6.3), produced unsatisfactory results (<10% ee) during preliminary catalyst screening of the N-substituents [4a]. Thus,... 

Conversions and enanhoselechvihes of CPG-immobilized Ti-TADDOLates match the results observed with unsupported catalysts under similar but homogeneous condihons, a finding also observed in other situations (for references, see the next section) ... 

The power of this methodology lies in the ability to prepare unnatural amino acid derivatives by asymmetric alkylation of prochiral enolates. Several asymmetric alkylations of the alanine derivative 7, catalysed by the C2-symmetrical quaternary ammonium salt 6d, have been reported these reactions yield unnatural amino acids such as 8 in high enantiomeric excess (Scheme 2) [7]. The chiral salen complex 9 has also been shown to be an effective catalyst for the preparation of a,a-dialkyl a-amino acids [8, 9]. For example, benzylation of the Schiff base 10 gave the a-methyl phenylalanine derivative 11 in 92% ee (Scheme 3) [8]. Similar reactions have been catalysed by the TADDOL 12, and also give a,a-dialkyl a-amino acids in good enantiomeric excess [10]. 

Catalytic Michael additions of a-nitroesters 38 catalyzed by a BINOL (2,2 -dihydroxy-l,r-bi-naphthyl) complex were found to yield the addition products 39 as precursors for a-alkylated amino acids in good yields and with respectable enantioselectivities (8-80%) as shown in Scheme 9 [45]. Asymmetric PTC (phase transfer catalysis) mediated by TADDOL (40) as a chiral catalyst has been used to synthesize enantiomeri-cally enriched a-alkylated amino acids 41 (up to 82 % ee) [46], A similar strategy has been used to access a-amino acids in a stereoselective fashion [47], Using azlactones 42 as nucleophiles in the palladium catalyzed stereoselective allyla-tion addition, compounds 43 were obtained in high yields and almost enantiomerically pure (Scheme 9) [48]. The azlactones 43 can then be converted into the a-alkylated amino acids as shown in Scheme 4. 

This method is comparable to similar, catalytic Sim-mons-Smith-type methods employing the titanium TADDOL catalyst 20 (95 5 er) or the Ci-symmetric bis-sulfonamide catalyst 32 (93 7 er) for the cyclopropanation of the allylic alcohol 22 (eq 6). However, due to the preliminary nature of these earlier investigations, substrate scope and generality have not been extensively documented. All of the aforementioned methods are limited by their dependence on the allylic alcohol functionality. Only one method for Simmons-Smith-type cyclopropanation of other substrate classes has been developed. Use of a stoichiometric, chiral dioxaborolane [CAS 161344-85-0] additive allows for selective cyclopropanation of allylic ethers, homo-ally lie alcohols and allylic carbamates. ... 

Polymer-supported TADDOL-Ti catalyst 79 prepared by chemical modification was poorly active in the Diels-Alder reaction of 3-crotonoyloxazolidinone with cyclo-pentadiene (Eq. 24) whereas polymeric TADDOL-Ti 81 prepared by copolymerization of TADDOL monomer 80 with styrene and divinylbenzene had high activity similar to that of the soluble catalyst. In the presence of 0.2 equiv. 81 (R = H, Aryl = 2-naphthyl) the Diels-Alder adduct was obtained in 92 % yield with an endolexo ratio of 87 13. The enantioseleetivity of the endo product was 56 % ee. The stability and recyclability of the catalyst were tested in a batch system. The degree of conversion, the endolexo selectivity, and the enantioseleetivity hardly changed even after nine runs. Similar polymer-supported Ti-TADDOLate 82 was prepared by the chemical modification method [99]. Although this polymer efficiently catalyzed the same reaction to give the (2R,2S) adduct as a main product, asymmetric induction was less than that obtained by use of a with similar homogeneous species. 

Free-radical and anionic polymerizations of TAD-DOL—MA (30) proceed exclusively via a cyclization mechanism, and the obtained polymer seems to have a helical conformation with an excess helicity.92-94 The main chain structure of poly(TADDOL—MA) with cyclized units (poly-30) is different from that of all other polymethacrylates discussed here. Similar monomers have been synthesized and polymerized.95... 

Based on this concept, Seebach et al. developed the first example of TADDOL-cored dendrimers (Figure 4.41) immobilized in a PS matrix [116]. The resultant internally dendrimer-functionalized polymer beads were loaded with Ti(OiPr)4, leading to a new class of supported Ti-TADDOLate catalysts for the enantioselective addition of diethylzinc to benzaldehyde. Compared to the conventional insoluble polymer-supported Ti-TADDOLate catalysts, these heterogeneous dendrimer catalysts gave much higher catalytic activities, with turnover rates close to those of the soluble analogues. The polymer-supported dendrimer TADDOLs were recovered by simple phase separation and reused for at least 20 runs, with similar catalytic efficiency. 

Tartaric acid derivatives (TADDOLs) and a hexamethoxy substituted l,l -bi-phenol give rise to reagents having similar potential [BD3, RMl]. 

Cycloaddition reactions proceeded at room temperature with a 2.5-fold excess of cyclopentadiene. Conversions depended very much on the resin type and ranged from 30-100%. Endolexo selectivity amounted to about 4 1 (88 89) which is similar to the one reported for the homogeneous phase reaction showing that the polymer-supported TADDOLs 86 indeed possessed... 

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