Enantioselective Hydrogenation of Enol Esters

Enol esters have a similar structure as enamides. However, in contrast to many highly enantioselective examples on enantioselective hydrogenation of enamides, only a few successful results have been reported for the hydrogenation of 

Catalyst R R Geometry Reaction conditions % ee of product (config.) Refer- ence 

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The rhodium-catalyzed enantioselective hydrogenation of enol esters is an alternative to the asymmetric reduction of ketones. Although enol esters are accessible both from ketones and alkynes, the number of studies reporting successful asymmettic hydrogenation has been limited. It appears that, compared... 

Rubio M, Suarez A, Alvarez E et al (2005) Highly enantioselective hydrogenation of enol ester phosphonates catalyzed by rhodium phosphine-phosphite complexes. Chem Commun... 

Asymmetric Hydrogenation of Enol Esters. Prochiral ketones represent an important class of substrates. A broadly effective and highly enantioselective method for the asymmetric hydrogenation of ketones can produce many useful chiral alcohols. Alternatively, the asymmetric hydrogenation of enol esters to yield a-hydroxyl compounds provides another route to these important compounds. 

The asymmetric hydrogenation of enol esters can also be catalyzed by chiral amidophosphine phosphinite catalysts derived from chiral amino acids, but the enantioselectivity of these reactions has thus far been only moderate.35... 

The asymmetric hydrogenation of enol esters is an alternative to asymmetric ketone hydrogenation. The precursors can be prepared from the ketones but also via ruthenium-catalyzed addition of the carboxylic acids to the 2-postion of terminal alkynes. This latter method allows the study of the effect of the carboxylate on the enantioselectivity of the asymmetric hydrogenation. A remarkable study by Reetz and colleagues established that it is possible to hydrogenate enolate... 

Hydrogenation of Enol Esters. In addition to the high activity and excellent enantioselectivity being obtained in the asymmetric... 

Table 28.6 Enantioselective hydrogenation of aliphatic enol esters. R2...

Table 3 Enantioselective hydrogenation of various enol Rh[(S,S)-ethyl-DuPHOS](cod) +OTr complex (MeOH, 25 MPaH2,48 h, S/C = 500 1) esters with °C, 0.4-0.6...

We have found that the Et-DuPHOS-Rh catalysts are capable of effecting smooth and highly enantioselective hydrogenation of E/7. mixtures of enol esters 26 (R = Me, Ph, etc.) [31]. As delineated in Table 3, a wide substrate scope has been demonstrated with enantioselectivities of > 95% ee. Products 27 thus obtained may be directly converted to a-hydroxy esters 28 through mild acidic hydrolysis in alcohol, or alternatively 27 may be reduced to the corresponding 1,2-diols 29 by the use of reagents such as LiAlH4, with no loss of enantiomeric purity. 

One of the standard methods for preparing enantiomerically pure compounds is the enantioselective hydrogenation of olefins, a,/3-unsaturated amino acids (esters, amides), a,/3-unsaturated carboxylic acid esters, enol esters, enamides, /3- and y-keto esters etc. catalyzed by chiral cationic rhodium, ruthenium and iridium complexes ". In isotope chemistry, it has only been exploited for the synthesis of e.p. natural and nonnatural H-, C-, C-, and F-labeled a-amino acids and small peptides from TV-protected a-(acylamino)acrylates or cinnamates and unsaturated peptides, respectively (Figure 11.9). This methodology has seen only hmited use, perhaps because of perceived radiation safety issues with the use of hydrogenation procedures on radioactive substrates. Also, versatile alternatives are available, including enantioselective metal hydride/tritide reductions, chiral auxiliary-controlled and biochemical procedures (see this chapter. Sections 11.2.2 and 11.3 and Chapter 12). 

In the early 1990s, Burk introduced a new series of efficient chiral bisphospholane ligands BPE and DuPhos.55,55a-55c The invention of these ligands has expanded the scope of substrates in Rh-catalyzed enantioselective hydrogenation. For example, with Rh-DuPhos or Rh-BPE as catalysts, extremely high efficiencies have been observed in the asymmetric hydrogenation of a-(acylamino)acrylic acids, enamides, enol acetates, /3-keto esters, unsaturated carboxylic acids, and itaconic acids. 

While Rh-DuPhos mediated asymmetric hydrogenation of acyclic enol esters shows high levels of enantioselectivity, it does not provide the same high... 

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