Asymmetric hydrogenation unsaturated acids, esters

Prochiral organic acids were hydrogenated on clay-supported Rh-chiral phosphine complexes.205,206 Hectorite-supported chiral Rh(I)-phosphine complexes were used for the asymmetric hydrogenation of a,P-unsaturated carboxylic acids.207 It was found that the interaction between the a-ester group of itaconates and phenyl groups of phosphine can play an important role in the determination of the configuration of products. 

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. 

The broad range of alkenes undergoing asymmetric hydrogenation using ruthenium-based systems as catalysts has attracted the attention of chemists engaged in the synthesis of chiral biologically active natural products (Scheme 13)[60] and other pharmaceuticals (Scheme 14)[61]. a, (3-Unsaturated phosphoric acids and esters have also proved to be suitable substrates for Ru(II)-catalysed asymmetric hydrogenation [62]. 

This ligand, MeO-BIPHEP (96a), has shown similar reactivities and enantioselectivities to catalysts that contain BINAP.117 Ruthenium catalysts that contain MeO-BIPHEP have been used in several asymmetric hydrogenations from bench scale to multi-ton scale, which include the large-scale preparation of a P-keto ester, an aryl ketone, allylic alcohol, and several oc,P-unsaturated carboxylic acid substrates, which are shown in Figure 12.5. 

Ruthenium and rhodium complexes that contain TMBTP have shown utility in the asymmetric hydrogenation of allylic alcohols,155,156 P-keto esters,155,157 and a,P-unsaturated carboxylic acids.155... 

Hypothesizing that primary amine catalysts, due to their reduced steric requirements, might be suitable for the activation of ketones, we studied various salts of a-amino acid esters. (For pioneering use of primary amine salts in asymmetric iminium catalysis involving aldehyde substrates, see Ishihara and Nakano 2005 Sakakura et al. 2006 for the use of preformed imines of a, 3-unsaturated aldehydes and amino acid esters in diastereoselective Michael additions, see Hashimot et al. 1977.) We have developed a new class of catalytic salts, in which both the cation and the anion are chiral. In particular, valine ester phosphate salt 35 proved to be an active catalyst for the transfer hydrogenation of a variety of a, 3-unsaturated ketones 36 with commercially available Hantzsch ester 11 to give saturated ketones 37 in excellent enantiose-lectivities (Scheme 28 Martin and List 2006). 

A considerable success has been realized for asymmetric hydrogenation of functionalized alkenes since the discovery of BINAP-Ru complexes in the mid-1980s [5]. The details are described in each of the following substrates, enamides, alkenyl esters and ethers, a,/3- and /3,y-unsaturated carboxylic acids, a,/3-unsaturated esters and ketones, and allylic and homoallylic alcohols. 

Two ruthenium complexes, binap 3.43-Ru(OCOR)2(R = Me,CF3) [892] and binap 3.43-RuX2 (X = Cl, Br, I) [893, 894], are quite useful. The acetate and trifluoroacetate complexes of 3.43 induce selective asymmetric hydrogenations of classes of prochiral olefins that are poorly selective with rhodium complexes. These classes include a,(3- or fcy-unsaturated acids and esters, ally alcohols, j3-acylaminoacrylates and enamide precursors of isoquinoline alkaloids [752, 853, 859, 881, 883, 895]. 

Other atropisomeric phosphines 3.45 have been recommended as ligands in rhodium-catalyzed asymmetric hydrogenations of prochiral a,[3-unsaturated acids or esters [892, 904] when R = c-CgHj or in rhodium-catalyzed asymmetric isomerization of allylamines 3.44 [905] when R = Ph. These phosphines 3.45 (R = Ph or c- CgHj j) are interesting ruthenium ligands in asymmetric hydrogena-... 

ASYMMETRIC HYDROGENATION OF 2-OXOCARBOXYLIC ACID ESTERS AND UNSATURATED CARBOXYLIC ACIDS ON MODIFIED PT AND PD CATALYSTS... 

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 ... 

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