Enamides Noyori

Complexes containing one binap ligand per ruthenium (Fig. 3.5) turned out to be remarkably effective for a wide range of chemical processes of industrial importance. During the 1980s, such complexes were shown to be very effective, not only for the asymmetric hydrogenation of dehydroamino adds [42] - which previously was rhodium s domain - but also of allylic alcohols [77], unsaturated acids [78], cyclic enamides [79], and functionalized ketones [80, 81] - domains where rhodium complexes were not as effective. Table 3.2 (entries 3-5) lists impressive TOF values and excellent ee-values for the products of such reactions. The catalysts were rapidly put to use in industry to prepare, for example, the perfume additive citronellol from geraniol (Table 3.2, entry 5) and alkaloids from cyclic enamides. These developments have been reviewed by Noyori and Takaya [82, 83]. 

Although the Rh-catalyzed asymmetric hydrogenations of prochiral enamides have been extensively studied and excellent results have been frequently achieved, the catalytic asymmetric hydrogenations of 2-arylacrylic acids have been less successful. Until recently most catalyst systems gave only moderate optical yields for the 2-arylpropionic acid products (77). An important breakthrough in the study of these reactions was reported by Noyori et al. By using Ru(BINAP)(OAc)2 as a catalyst precursor, these researchers obtained excellent optical yields in the asymmetric hydrogenation of 2-(6 -methoxy-2 -naphthyl)acrylic acid (72). 

The use of a chiral hydride complex has been central to the asymmetric reduction of ketones such as acetophenone (58). A number of excellent chiral metal hydride complexes have been introduced by many researchers, including Noyori (59,60), Meyers (61), Mukaiyama (62,63), Terashima (64,65), and others (58). It is apparent that there is a close similarity in structure between acetophenone and the proposed intermediate in enamide photocyclization, therefore suggesting the possibility of undergoing photocyclization in an asymmetric manner. 

Another example of how catalysis plays a key role in enabling our lives is in the synthesis of pharmaceuticals. Knowles s development, at Monsanto in the early 1970s, of the enantioselective hydrogenation of the enamide precursor to L-DOPA (used to treat Parkinson s disease), using a Rh-chiral phosphine catalyst (Section 3.5), led to a share in the Nobel prize. His colaureates, Noyori and Sharpless, have done much to inspire new methods in chiral synthesis based on metal catalysis. Indeed, the dramatic rise in the demand for chiral pharmaceutical products also fuelled an intense interest in alternative methodologies, which led to a new one-pot, enzymatic route to L-DOPA, using a tyrosine phenol lyase, that has been commercialized by Ajinomoto. 

Noyori asymmetric hydrogenation Formation of enantio-enriched carboxylic acids, alcohols and amino acids from unsaturated carboxylic acids, allylic alcohols and enamides, respectively. 316... 

BINAP was first introduced by Noyori [80]. It has been particularly explored for reduction with ruthenium catalysts. BINAP is an atropisomeric ligand because rotation aroimd the central C-C bond is blocked. Accordingly BINAP exists in two enantiomers. Complexes of Ru(II) with BINAP are extremely powerful catalysts for enantioselective hydrogenations of prochiral a,p- and P,Y-unsaturated carboxylic acids, enamides, allylic and homoallylic alcohols, imines etc. [83]. In many cases, the hydrogenation is quantitative with enantiomeric excesses of over 95%. A wide variety of vitamins, terpenes, P-lactam antibiotics, etc. are accessible by the use of catalysts containing the BINAP stereogenic element. An example for 3-oxo carboxylic esters is shown in reaction (1) of Fig. 6.32. 

In 1986, Noyori reported a hexa coordinate BINAP Ru(II) complex that can efficiently catalyze the asymmetric hydrogenation of (Z) N acyl 1 alkylidenete tra hydroisoquinolines (70) in the presence of 0.5 1 mol% of the catalyst loadings in a 5 1 mixture of ethanol and dichloromethane under 1 4 atm of hydrogen at 23 °C (Scheme 9.18) [63]. However, the corresponding E enamide substrates were inert to this catalytic system under the same hydrogenation conditions. 

NOYORI Chiral homogeneous hydrogenation Homogeneous chiral hydrogenation of unsaturated alcohols, or carboxylic acids, enamides. ketones in the presence of BINAP Ru or Rh complex 8 as catalyst. 

Knowles and co-workers reported that DiPAMP, the most well-known P-stereogenic phosphine, gave 12 with an outstanding (at that time) 96% ee. With this phosphine many other enamides, enol esters and similar compounds could be hydrogenated in high ee. This work can be considered a milestone in the field of enantioselective homogeneous catalysis and have been profusely cited. William S. Knowles was awarded (along with Ryoji Noyori and Barry Sharpless) the Nobel Prize in Chemistry for the year 2001 for his contributions to enantioselective catalysis. ... 

Recent work by several research groups has shown that supercritical fluids can be superior to other solvents for several chemical processes. For example, DeSimone has demonstrated the ability of supercritical CO2 to replace Freons in the free radical polymerization of fluorinatkl acrylate monomers. 34) Noyori has shown that significant rate enhancements can be achieved in supercritical carbon dioxide relative to other solvents for the homogeneous catalytic hydrogenation of carbon dioxide to either formic acid or its derivatives in the presence of triethylamine or triethylamine/methanol respectively, (equation 1). (55-57) As discussed below, we have recently demonstrated that improved enantioselectivities can be achieved in supercritical carbon dioxide for the catalytic asymmetric hydrogenation of several enamides. 5 8)... 

Mechanistic insight into Noyori asymmetric hydrogenations of enamides, allylic alcohols, Q, )S-unsaturated carboxylic acids, o ,jS-keto esters, and aromatic ketones using Ru(OAc)2[(5)-binap], (3), as the catalyst has been highlighted ... 

These precursors to the morphine alkaloids can also be obtained by the hydrogenation of the related enamide structures in which the R group is joined to the ring system by a C=C bond. The preferred route depends largely on the substrate synthesis. The synthesis of the enamides can be more flexible, and Noyori has published the synthesis of the optically active tetrahydroquinolines from the enamide (Equation 15.80). ... 

Kitamura M, Hsiao Y, Ohta M, Tsukamoto M, Ohta T, Takaya H, Noyori R (1994) General asymmetric synthesis of isoquinoline alkaloids. Enantioselective hydrogenation of enamides catalyzed by BINAP-ruthenium(II) complexes. J Oig Chem 59 297-310... 

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