Catalysis BINAP

BINAP was introduced by Noyori [18], It has been particularly explored for reduction with ruthenium catalysts. While the first generation rhodium catalysts exhibited excellent performance with dehydroamino acids (or esters), the second generation of hydrogenation catalysts, those based on ruthenium /BINAP complexes, are also highly enantioselective for other prochiral alkenes. An impressive list of rather complex organic molecules has been hydrogenated with high e.e. s. 

Firstly, the system will also hydrogenate enamides with high e.e., provided that the amide substituent and the one substituent at the other carbon are cis to one another. Secondly, the Ru(BINAP)(RC02)2 catalyst gives enantioselective hydrogenation of acrylic derivatives, see the examples below for Naproxen and the like. 

Noyori using ruthenium complexes of the ligand BINAP has successfully accomplished asymmetric hydrogenation of molecules of this type. With this system a high enantioselectivity can be achieved (97%) albeit at rather high pressures (135 bar). 

Asymmetric catalysis involving metal catalysed hydrogenations and isomerisations is becoming increasingly important in the production of pharmaceuticals, agrochemicals and flavours and fragrances. More examples of 

In summary, we have encountered five types of asymmetric phosphine ligands  

Secondly, the BINAP-Ru(D)(02CR)2 catalyst gives enantioselective hydrogenation of acrylic derivates. See Fig. 6.31 for the synthesis of Naproxen. 

Finally, ketones and aldehydes containing another polar group can be hydrogenated. Although the pressures needed for quantitative conversion are high the use of the BINAP-Ru(II) has the advantage that enantiomeric excesses are 

The success of this so-called second-order stereoselectivity hydrogenation depends on the fact that (a) the rate of racemization has to be fast with respect to the rate of hydrogenation (b) the diastereotopic face discrimination by the chiral 

6 — HOMOGENEOUS CATALYSIS WITH TRANSITION METAL COMPLEXES 

BINAP-Ru(II) catalyst must be efficient and (c) a unique difference between syn-and antidiastereoisomeric transition states must exist in the hydrogenation step. 

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Scheme 10 Proposed catalytic cycle of the CuF-Tol-BINAP catalysis...

In the practice of homogeneous asymmetric catalysts, we must solve such problems as high cost of chiral auxiliaries and difficulties in the handhng of sensitive catalysts. For industrial applications, the consumption of chiral auxiliaries should be kept to a minimum by improving TON as much as possible. When first discovered, the TON of the Rh-BINAP catalysis in Eq. (1) was only 100 as usual laboratory works. A feasibility study indicated that the TON must be more than... 

It is essential to remove isomers 5 and 9 from 1 for the asymmetric reaction, because the former reduces the enantiomeric purity while the latter acts as a strong catalyst poison (see Chapter 23). As the volatility of 9 is very close to that of 1, a distillation column with 80 theoretical plates is applied to furnish 1 in the purity of 99.98% for the Rh-BINAP catalysis. 

The reaction of aromatic aldehydes with the silyl dienolate 27 under Binap catalysis yields S,6-disubstituted dihydropyran-2-ones with excellent dia- and enantio- stereoselectivities (Scheme 29). Aliphatic aldehydes show similar stereoselectivity but a linear aldol product is also formed <010L3807>. 

Table 3.12 surveys current industrial applications of enantioselective homogeneous catalysis in fine chemicals production. Most chiral catalyst in Table 3.12 have chiral phosphine ligands (see Fig. 3.54). The DIP AMP ligand, which is used in the production of L-Dopa, one of the first chiral syntheses, possesses phosphorus chirality, (see also Section 4.5.8.1) A number of commercial processes use the BINAP ligand, which has axial chirality. The PNNP ligand, on the other hand, has its chirality centred on the a-phenethyl groups two atoms removed from the phosphorus atoms, which bind to the rhodium ion. Nevertheless, good enantio.selectivity is obtained with this catalyst in the synthesis of L-phenylalanine. 

The preparation of BINAP reported in 1980 has marked a landmark in asymmetric catalysis and has illustrated the peculiar stereorecognitive properties inherent with the axially chiral 1,1 -binaphthalene framework. Since then, a great deal of work has been devoted to the preparation of binaphthalene-templated ligands of related design. These efforts have resulted in the... 

Many enantioselective catalysts have been developed for reduction of functional groups, particularly ketones. BINAP complexes of Ru(II)C12 or Ru(II)Br2 give good enantioselectivity in reduction of (3-ketoesters.49 This catalyst system has been shown to be subject to acid catalysis.50 Thus in the presence of 0.1 mol % HC1, reduction proceeds smoothly at 40 psi of H2 at 40° C. 

Annual Volume 71 contains 30 checked and edited experimental procedures that illustrate important new synthetic methods or describe the preparation of particularly useful chemicals. This compilation begins with procedures exemplifying three important methods for preparing enantiomerically pure substances by asymmetric catalysis. The preparation of (R)-(-)-METHYL 3-HYDROXYBUTANOATE details the convenient preparation of a BINAP-ruthenium catalyst that is broadly useful for the asymmetric reduction of p-ketoesters. Catalysis of the carbonyl ene reaction by a chiral Lewis acid, in this case a binapthol-derived titanium catalyst, is illustrated in the preparation of METHYL (2R)-2-HYDROXY-4-PHENYL-4-PENTENOATE. The enantiomerically pure diamines, (1 R,2R)-(+)- AND (1S,2S)-(-)-1,2-DIPHENYL-1,2-ETHYLENEDIAMINE, are useful for a variety of asymmetric transformations hydrogenations, Michael additions, osmylations, epoxidations, allylations, aldol condensations and Diels-Alder reactions. Promotion of the Diels-Alder reaction with a diaminoalane derived from the (S,S)-diamine is demonstrated in the synthesis of (1S,endo)-3-(BICYCLO[2.2.1]HEPT-5-EN-2-YLCARBONYL)-2-OXAZOLIDINONE. 

According to Chen et ah, alkali cation co-catalysis kinetics cannot be distinguished from classic ideas (proton instead of alkali) for the asymmetric hydrogenation of acetophenone with the Noyori-catalyst trans-RuC12[(S)-BINAP]... 

One of the first applications of the then newly developed Ru-binap catalysts for a,/ -unsaturated acids was an alternative process to produce (S)-naproxen. (S)-Naproxen is a large-scale anti-inflammatory drug and is actually produced via the resolution of a racemate. For some time it was considered to be one of the most attractive goals for asymmetric catalysis. Indeed, several catalytic syntheses have been developed for the synthesis of (S)-naproxen intermediates in recent years (for a summary see [14]). The best results for the hydrogenation route were obtained by Takasago [69] (Fig. 37.15), who recently reported that a Ru-H8-binap catalyst achieved even higher activities (TON 5000, TOF 600 h 1 at 15 °C, 50 bar) [16]. 

Isomerization of allylic amines is another example of the application of the BINAP complex. Rh BINAP complex catalyzes the isomerization of N,N-diethylnerylamine 40 generated from myrcene 39 with 76-96% optical yield. Compound (R)-citronellal (R)-42. prepared through hydrolysis of (R)-41, is then cyclized by zinc bromide treatment.49 Catalytic hydrogenation then completes the synthesis of (—)-menthol. This enantioselective catalysis allows the annual production of about 1500 tons of menthol and other terpenic substances by Takasago International Corporation.50... 

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