Asymmetric hydrogenation of enol esters

Although enol esters have a similar structure to enamides, they have proven more difficult substrates for asymmetric hydrogenation, which is evident from the significantly fewer number of examples. One possible explanation is the weaker coordinating ability of the enol ester to the metal center, as compared to the corresponding enamide. Some rhodium complexes associated with chiral phosphorous ligands such as DIPAMP [100, 101] and DuPhos [102] are effective for asymmetric hydrogenation of a-(acyloxy)acrylates. 

For example, a wide range of a-(acyloxy)acrylates have been hydrogenated with excellent enantioselectivity using the Et-DuPhos-Rh catalyst. High selectivities are also obtained for the asymmetric hydrogenation of the B/Z-isomeric mixtures of yS-substituted derivatives (Eq. 12). Asymmetric hydrogenation of enol phosphates with either Du-Phos-Rh or BPE-Rh catalyst provides moderate to excellent enantioselectivity (Eq. 13) 

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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... 

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... 

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

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. 

Reetz and Goossen et al. reported recently the asymmetric hydrogenation of a series of enol esters using monodentate phosphite ligands 17 and 24 based on a combination of BINOL and carbohydrates or simple alcohols the results of these studies are shown in Table 28.6. 

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

A chiral ligand system based on C2-symmetric chiral bis(phospholanes) (5 and 6) has shown to be a powerful ligand in the asymmetric hydrogenation of various substrates that include enamides, enol acetates, C=N bond reduction, and P-keto esters. Detailed discussions of this class of ligands are included Chapter 18. 

Freskos reported the synthesis of chiral succinate using Pd-catalyzed carbonylation of enol triflate 26 (Scheme 18) followed by asymmetric hydrogenation of resulting a,/3-unsaturated ester 27 using a ruthenium complex. - " In the absence of HCOOH, the yield was low (15-20%). Similarly, when water was substituted for formic acid, low product yields (15-20%) were observed. As one possible pathway to produce 27, reductive elimination from the palladium complex to yield a mixed anhydride derived from the product and triflic acid would be considered. 

The DKR processes for secondary alcohols and primary amines can be slightly modified for applications in the asymmetric transformations of ketones, enol esters, and ketoximes. The key point here is that racemization catalysts used in the DKR can also catalyze the hydrogenation of ketones, enol esters, and ketoximes. Thus, the DKR procedures need a reducing agent as additional additive to enable asymmetric transformations. 

Sodium borohydride (160) was found to serve as a hydrogen donor in the asymmetric reduction of the presence of an a,pi-unsaturated ester or amide 162 catalyzed by a cobalt-Semicorrin 161 complex, which gave the corresponding saturated carbonyl compound 163 with 94-97% ee [93]. The [i-hydrogen in the products was confirmed to come from sodium borohydride, indicating the formation of a metal enolate intermediate via conjugate addition of cobalt-hydride species (Scheme 2.17). 

Copper complexes derived from bis(-2,6-dichlorophenyle-dene)-( 15,25)-1,2-diaminocyclohexane (11) catalyze various reactions such as Diels-Alder reaction, aziridination (eq 20), cyclopropanation, and silyl enol ether addition to pyruvate esters. Although the scope of these reactions may be sometimes limited, enantioselectivities are generally high. The same complex (with copper(I) salts) catalyzes the asymmetric insertion of silicon- hydrogen bond into carbenoids. ... 

Recent developments tend to focus on the asymmetric aspects of stereoselective aldols but the diastereoselectivity is just as important. The cyclic ester 56 must of course form an E enolate and when the boron enolate -57 reacts with aldehydes the an//-aldol products 58 are formed with good stereoselectivity ranging from 4 1 to >20 1. The predominate isomer is that expected from the Zimmerman-Traxler transition state. The two benzylic-0 bonds can be cleaved by hydrogenation and the 2,3-dihydroxy acids anti-59 released in good yield.17... 

Other prochiral units that can be trapped in rings are enolates. One famous application is the alkylation of [3-hydroxy acid derivatives available from the chiral pool (chapter 23), by asymmetric aldol reactions (chapter 27) and by asymmetric reduction of P-keto-esters either by catalytic hydrogenation (chapter 26) or by enzymes (chapter 29). Frater found that the alcohol 55, from the baker s yeast reduction of the ketoester 54, formed the enolate 56 held in shape by chelation. Alkylation occurred on the top face.8 This is not so much because the OH is down in 55 as that the methyl group is down in 56. 

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