Asymmetric hydrogenation PennPhos

TABLE 6-8. Asymmetric Hydrogenation of Simple Ketones Catalyzed by Rh-PennPhos... 

A Rh complex with (/f.S. /f.S -Me-PennPhos efficiently catalyzes asymmetric hydrogenation of simple ketones (Figure 1.22). Addition of catalytic amounts of 2,6-lutidine is crucial to achieve high enantioselectivity. This catalyst is also... 

The asymmetric hydrogenation of unfunctionalized ketones is a much more challenging task than that of functionalized ketones [3 j, 115]. Many chiral catalysts which are effective for functionalized ketones do not provide useful levels of enantioselectivity for unfunctio-nalized ketones, due to a lack of secondary coordination to the metal center. Zhang demonstrated the enantioselective hydrogenation of simple aromatic and aliphatic ketones using the electron-donating diphosphane PennPhos, which has a bulky, rigid and well-defined chiral backbone, in the presence of 2,6-lutidine and potassium bromide [36]. 

Aromatic Ketones The DIOP-Rh [116] and DBPP-Rh [117] complexes, in conjunction with a tertiary amine, have been employed in the asymmetric hydrogenation of acetophenone, albeit with moderate enantioselectivity (80 and 82% respectively Tab. 1.10). The asymmetric hydrogenation of aromatic ketones was significantly improved by using the Me-PennPhos-Rh complex, with which enantioselectivities of up to 96% ee were achieved [36]. Interestingly, the additives 2,6-lutidine and potassium bromide were again found to be crucial for optimum selectivity, although their specific role has not been determined. 

Aliphatic Ketones The asymmetric hydrogenation of simple aliphatic ketones remains a challenging problem. This may be attributed to the difficulty with which the chiral catalyst differentiates between the two-alkyl substituents of the ketone. Promising results have been obtained in asymmetric hydrogenation of aliphatic ketones using the PennPhos-Rh complex in combinahon with 2,6-lutidine and potassium bromide (Tab. 1.11) [36]. For example, the asymmetric hydrogenation of tert-butyl methyl ketone affords the requisite secondary alcohol in 94% ee. Similarly, isopropyl, Butyl, and cyclohexyl methyl ketones have been reduced to the corresponding secondary alcohols with 85% ee, 75% ee, and 92% ee respectively. 

Enantioselective Hydrogenation of Alkenes. (R,S,R,S)-Mc-PennPhos has been employed as catalyst in combination with Rh(I) for enantioselective hydrogenation of alkene carbon-carbon double bonds in a variety of substrates. A representative sampling of these asymmetric hydrogenations is shown in Table 1 Chang-... 

Table 1 Asymmetric hydrogenations of prochiral alkenes catalyzed by a (/ ,S,/f,S)-Me-PennPhos-Rh(I) complex...

Scheme 9.14 Asymmetric hydrogenation of cyclic enamides using the Rh/Me PennPhos or...

The asymmetric hydrogenation of cyclic enol acetate has also proven to be a challenging problem. In this respect, Me-PennPhos 125 was shown to be an effective ligand in the rhodium-catalyzed asymmetric hydrogenation of five- or six-membered cyclic enol acetates such as 172. " In addition, Tang et al. found that the TangPhos-Rh catalyst system provided good-to-excellent (92%-99%) enantioselectivities for a diverse set of aryl enol acetates. ... 

The asymmetric hydrogenation of unfiinctionalized ketones still remains a challenging problem. High levels of asymmetric induction have been achieved in the hydrogenation of acetophenone 182 using Me-PennPhos ligand in the presence of 2,6-lutidine and potassium bromide as additives. ... 

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