Tartaric acid derivatives

Several structures of the transition state have been proposed (I. D. Williams, 1984 K. A. Jorgensen, 1987 E.J. Corey, 1990 C S. Takano, 1991). They are compatible with most data, such as the observed stereoselectivity, NMR measuiements (M.O. Finn, 1983), and X-ray structures of titanium complexes with tartaric acid derivatives (I.D. Williams, 1984). The models, e. g., Jorgensen s and Corey s, are, however, not compatible with each other. One may predict that there is no single dominant Sharpless transition state (as has been found in the similar case of the Wittig reaction see p. 29f.). 

The enantioselectivity a is defined as the distribution ratio of one single enantiomer over the two chiral phases and has been determined experimentally for a variety of compounds (Table 5-1). It has been known from work by Prelog [66, 67] that tartaric acid derivatives show selectivities towards a-hydroxyamines and amino acids. However, from Table 5-1 it is obvious that tartaric acid derivatives show selectivity for many other compounds, including various amino bases (e.g. mirtazapine (10)) and acids (e.g. ibuprofen (11)). The use of other chiral selectors (e.g. PLA)... 

Addition reactions to aldehydes in the presence of the tartaric acid derived chiral auxiliaries (.S ..S )-l,2,3,4-tetramethoxybutane (5), (S,.S)-2,3-dimethoxy-A%V,/V, A,, -tctramethyl-l,4-bu-tanediamine (6) and (5,5)-2,3-bis[2-(dimethylamino)ethoxy]-Af,yV,A. iV -tetramethyl-l,4-bu-tanediamine (7) have been studied in detail9" u. Again there was low enantioselection (generally 10-55% ee). 

Addition of the analogous methyltitanium reagent to bcnzaldchydc afforded the addition product with only 59% ee34. Use of the methyltitanium reagent obtained via chiral modification by the tartaric acid derived diol 43, did not lead to an improvement of the enantioselectivity42. 

Reagent 7 is easily prepared from commercially available diacetone-D-glucose and trichloro(cyclopentadienyl)titanium35 (Section 1.3.3.3.8.1.). The monomeric structure of reagent 7 was confirmed by an X-ray crystal structure analysis1 7. Complex 9 is obtained36 analogously from (7 .7 )-tartaric acid derived (R,7 )-2,3-CMsopropylidene-l,l,4,4-tetraphenyl-1,2,3,4-butanetetrol. 

The (acyloxy)borane complex 9, readily available from tartaric acid derivative 8, also catalyzes aldol additions of silyl enol ethers34 and silylketene acetals3 5 in an enantioselective manner. Thus,. u -ketones 10 and /Thydroxy esters 12 are available34, as well as a-unsubstituted ketones 1135. 

L-Tartaric acid-derived disulfonamide ligand for additions of ZnEt2 to aldehydes. 

Chiral modifiers were screened in the zinc chemistry. Once again, in the case of aniline ketone 36, chichona alkaloids, binaphthol, and tartaric acid derivatives gave very poor selectivity and ephedrine derivatives provided good selectivity. The results are summarized in Table 1.8. 

Saito and coworkers have used C2-symmetrical alkenes derived from a variety of tartaric acid derivatives, for controller in discriminating 71 faces of dipolarophile in nitrone cycloaddition. Excellent endolexo and diastereofacial selectivity (de) are obtained. Endo transition state assembly shown in Eq. 8.50 could be responsible for the formation of preferred distereoisom-... 

A patent procedure for formation of compounds 19 from simple tartaric acid derivatives has appeared <06USP047129> and various new routes to chiral dioxolanones include synthesis of dioxolan-2-ones either by transition metal-mediated asymmetric synthesis <06T1864> or enzyme-mediated kinetic resolution <06H(68)1329> and a new synthesis of the chiral dioxolan-4-ones 21 from lactic or mandelic acid involving initial formation of intermediates 20 with trimethyl orthoformate in cyclohexane followed by reaction with pivalaldehyde <06S3915>. 

High stereoselective addition of vinylmagnesium bromide to L-tartaric acid-derived nitrone was used as a key step in the synthesis of (+ )-lentiginosine and its structural analogs (653). 

The most common chiral auxiliaries are diphosphines (biphep, binap and analogues, DuPhos, ferrocenyl-based ligands, etc.) and cinchona and tartaric acid-derived compounds. It is clear that the optimal chiral auxiliary is determined not only by the chiral backbone (type or family) but also by the substituents of the coordinating groups. Therefore, modular ligands with substituents that can easily be varied and tuned to the needs of a specific transformation have an inherent advantage (principle of modularity). 

Chiral titanium catalysts have generally been derived from chiral diols. Narasaka and colleagues251 developed an efficient catalyst, 406, prepared from TiCl2(OPr- )2 and a (+)-tartaric acid derived 1,4-diol. These authors found that Af-crotonyl-l,3-oxazolidin-2-one (404) reacted with cyclopentadiene in the presence of 10 mol% of 406 to give cycloadduct 405 with up to 91% ee (equation 120)252. 

For these and similar reactions recently a variety of Lewis acidic aluminium, rare earth metals, and titanium alkoxides have been applied. Alkoxides have the additional advantage that they can be made as enantiomers using asymmetric alcohols which opens the possibility of asymmetric catalysis. Examples of asymmetric alcohols are bis-naphtols, menthol, tartaric acid derivatives [28], Other reactions comprise activation of aldehydes towards a large number of nucleophiles, addition of nucleophiles to enones, ketones, etc. 

Saito et al. (32) developed a tartaric acid derived chiral nitrone 18. In the reaction of 18 with methyl crotonate 19, the 1,3-dipolar cycloaddition product 20 was obtained in an endo/exo ratio of 10 1 and with high diastereofacial induction to give the endo-isomer (Scheme 12.9). 

Saito et al. (32,121) developed a variety of tartaric acid derivatives, including Ci-symmetric chiral alkenes such as 76. The 1,3-dipolar cycloaddition between 76 and 77 gave primarily endo-1%. (Scheme 12.26) The diastereofacial selectivity of the reaction is excellent, as endo-1% is obtained with >98% de. Other cyclic and acyclic nitrones have been employed in reactions with 76, and in all cases, moderate to excellent endo/exo-selectivities and excellent diastereofacial selectiv-ities were obtained (32,121). Three other research groups have applied various y-hydroxylated ot,p-unsaturated carbonyl compounds in related reactions with nitrones (122-124). However, the selectivities were somewhat lower than those obtained by Saito and et al. (32,121). 

Enantioselective epoxidation of allylic alcohols using hydrogen peroxide and chiral catalysts was first reported for molybdenum 7B) and vanadium 79) complexe. In 1980, Sharpless 80) reported a titanium system. Using a tartaric acid derivative as chiral auxiliary it achieves almost total stereoselection in this reaction. 

The development of a large scale manufacturing route to Esomeprazole is described by Federsel and Larsson ° using the titanium catalyst originally described by Kagan and Luukas. Employment of a tartaric acid derived chiral auxiliary, with the addition of a base such as diisopropylethylamine to the reaction mixture, resulted in a full-scale catalytic process capable of delivering multi-ton quantities of product with optical yields well above 90 %, a figure which could be raised to 99.5 % ee by recrystallization from methyl isobutyl ketone. 

V(C104)2 or-Keto adds Tartaric acid derivatives 10... 

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