Hydrogenation diastereoselective asymmetric

Asymmetric induction is used in the stereoselective synthesis of silanes via the hvdrosilyla-tion of a,/l-unsaturated esters30. The addition of the tris(trimethylsilyl)silyl radical to the double bond is highly regioselective. yielding an ester-substituted radical that abstracts hydrogen diastereoselectively. 

Fig. 22 Diastereoselective asymmetric transfer hydrogenation of cyclic substrates with dynamic kinetic resolution...

Asymmetric synthesis is a method for direct synthesis of optically active amino acids and finding efficient catalysts is a great target for researchers. Many exceUent reviews have been pubHshed (72). Asymmetric syntheses are classified as either enantioselective or diastereoselective reactions. Asymmetric hydrogenation has been appHed for practical manufacturing of l-DOPA and t-phenylalanine, but conventional methods have not been exceeded because of the short life of catalysts. An example of an enantio selective reaction, asymmetric hydrogenation of a-acetamidoacryHc acid derivatives, eg, Z-2-acetamidocinnamic acid [55065-02-6] (6), is shown below and in Table 4 (73). 

In the case of tri-substituted alkenes, the 1,3-syn products are formed in moderate to high diastereoselectivities (Table 21.10, entries 6—12). The stereochemistry of hydrogenation of homoallylic alcohols with a trisubstituted olefin unit is governed by the stereochemistry of the homoallylic hydroxy group, the stereogenic center at the allyl position, and the geometry of the double bond (Scheme 21.4). In entries 8 to 10 of Table 21.10, the product of 1,3-syn structure is formed in more than 90% d.e. with a cationic rhodium catalyst. The stereochemistry of the products in entries 10 to 12 shows that it is the stereogenic center at the allylic position which dictates the sense of asymmetric induction... 

In entry 15 of Table 21.10, it is noted that even a remote hydroxyl group directed hydrogenation by the cationic [Rh(diphos-4)(nbd)]+ catalyst to afford a moderate diastereoselectivity (80 20) [23]. This is an interesting example of long-range 1,5-asymmetric induction. 

As described hitherto, diastereoselectivity is controlled by the stereogenic center present in the starting material (intramolecular chiral induction). If these chiral substrates are hydrogenated with a chiral catalyst, which exerts chiral induction intermolecularly, then the hydrogenation stereoselectivity will be controlled both by the substrate (substrate-controlled) and by the chiral catalyst (catalyst-controlled). On occasion, this will amplify the stereoselectivity, or suppress the selectivity, and is termed double stereo-differentiation or double asymmetric induction [68]. If the directions of substrate-control and catalyst-control are the same this is a matched pair, but if the directions of the two types of control are opposite then it is a mismatched pair. 

Another possibility to increase the diastereoselectivity in an asymmetric synthesis can arise from different thermodynamic stabilities of the diasteieoisomeric products. If the thermodynamic stabilities of these are different enough, then, under conditions of equilibrium, a complete conversion of the less stable into the more stable can be achieved. For example, the diastereoselective hydrogenation of naphthalene derivates over Pd/C catalyst leads to a mixture of dihydronaphtalenes in which the cA-isomer predominates. The conversion of this isomer into the tram occurs by changing the properties of the reaction medium, namely by equilibration with a base. For such a purpose, NaOMe in IHF can be used [263], Generally, such an increase in stability in the six-membered rings can result from a rearrangement of the substituents from an axial to an equatorial position. 

The chiral auxiliaries anchored to the substrate, which is subjected to diastereoselective catalysis, is another factor that can control these reactions. These chiral auxiliaries should be easily removed after reduction without damaging the hydrogenated substrate. A representative example in this sense is given by Gallezot and coworkers [268], They used (-)mentoxyacetic acid and various (S)-proline derivates as chiral auxiliaries for the reduction of o-cresol and o-toluic acid on Rh/C. A successful use of proline derivates in asymmetric catalysis has also been reported by Harada and coworkers [269,270], The nature of the solvent only has a slight influence on the d.e. [271],... 

Since the discovery and development of highly efficient Rh catalysts with chiral diphosphites and phosphine-phosphites in the 1990s, the enantioselectivity of asymmetric hydroformylation has reached the equivalent level to that of asymmetric hydrogenation for several substrates. Nevertheless, there still exist substrates that require even further development of more efficient chiral ligands, catalyst systems, and reaction conditions. Diastereoselective hydroformylation is expected to find many applications in the total synthesis of complex natural products as well as the syntheses of biologically active compounds of medicinal and agrochemical interests in the near future. Advances in asymmetric hydrocarboxylation has been much slower than that of asymmetric hydroformylation in spite of its high potential in the syntheses of fine chemicals. 

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