Iridium-catalyzed asymmetric hydrogenation of β-keto esters with f-amphox ligands

The iridium-catalyzed asymmetric hydrogenation of β-keto esters with chiral tridentate P,N,N-ligands (f-amphox) has been developed. Under the optimized conditions, a wide range of β-keto esters can be hydrogenated smoothly, affording the corresponding β-hydroxy esters in good to excellent enantioselectivities (up to 95% ee).     

Ru-catalyzed asymmetric hydrogenation of γ-heteroatom substituted β-keto esters

A series of enantiomerically pure γ-heteroatom substituted β-hydroxy esters were synthesized with high enantioselectivities (up to 99.1% ee) by hydrogenation of γ-heteroatom substituted β-keto esters in the presence of Ru-(S)-SunPhos catalyst. These asymmetric hydrogenations provide key building blocks for a variety of naturally occurring and biologically active compounds.     

Dynamic kinetic resolution of α-keto esters via asymmetric transfer hydrogenation

The dynamic kinetic resolution of β-aryl α-keto esters has been accomplished using a newly designed (arene)RuCl(monosulfonamide) transfer hydrogenation catalyst. This dynamic process generates three contiguous stereocenters with remarkable diastereoselectivity through a reduction/lactonization sequence. The resulting enantioenriched, densely functionalized γ-butyrolactones are of high synthetic utility, as highlighted by several secondary derivatizations.     

Enantioselective synthesis of anti-β-hydroxy-α-amido esters by asymmetric transfer hydrogenation in emulsions

Herein, we present two methods for an asymmetric transfer hydrogenation through the dynamic kinetic resolution of α-amido-β-ketoesters. These procedures yield the corresponding anti-β-hydroxy-α-amido esters in good yields and with good diastereo- and enantioselectivities. First, the scope of the reduction of α-amido-β-ketoesters by using triethylammonium formate azeotrope is examined. Then, an emulsion technology with sodium formate is explored, which allows for broader substrate scope, faster reaction times, and lower catalyst loading. Furthermore, these reactions are operationally simple and can be set up in air.     

SPANamine derivatives in the catalytic asymmetric α-fluorination of β-keto esters

The use of C₂-symmetric enantiopure nitrogen ligands in the asymmetric catalytic α-fluorination of β-ketoesters is described. SPANamine 1 in the presence of nickel salts gives up to 63% ee in the fluorination of tert-butyl 2-oxocyclopentanecarboxylate with N-fluorosuccinimide (NFSI). The same enantioselectivity is obtained when SPANamine 1 is used as an organocatalyst, although the reaction is much slower.     

The setereoselective preparation ofβ-keto esters using baker's yeast in the presence of rice wine koji

By the addition of rice wine koji,enhancement of the reactivity was observed for the baker's yeast reduction ofβ-keto esters into (S)-β-hydroxy esters with high enantiomeric purity (73-98%).     

Cu(I)-catalyzed asymmetric α-hydroxylation of β-keto esters in the presence of chiral phosphine-Schiff base-type ligands

Chiral phosphine-Schiff base-type ligand L1 prepared from (R)-(?)-2-(diphenylphosphino)-1,1′-binaphthyl-2′-amine was found to be a fairly effective ligand for Cu(I)-promoted enantioselective α-hydroxylation of β-keto esters using oxaziridine 2a as the oxidant to give the corresponding products in high yields along with moderate enantioselectivities.     

Iridium-catalyzed asymmetric hydrogenation of β-keto esters with new phenethylamine-derived tridentate P,N,N-ligands

A new class of phenethylamine-derived tridentate P,N,N-ligands has been successfully developed. These ligands exhibited good performance in the Ir-catalyzed asymmetric hydrogenation of β-keto esters, affording the corresponding β-hydroxy esters in moderate to good enantioselectivities.     

Enantioselective synthesis of anti-β-amido-α-hydroxy esters via asymmetric transfer hydrogenation coupled with dynamic kinetic resolution

The asymmetric transfer hydrogenation of β-amido-α-keto esters providing the corresponding anti-β-amido-α-hydroxy esters via dynamic kinetic resolution is reported. The use of a commercially available, or simply prepared, chiral ruthenium catalyst results in good yields as well as high diastereoselectivities and enantioselectivities.     

Selective reduction of α,β-unsaturated esters in the presence of olefins

Several α,β-unsaturated esters containing also isolated olefins or other functionalities subject to saturation were selectively reduced to the corresponding saturated esters by magnesium in methanol.     

Catalytic asymmetric chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones

Highly efficient catalytic chloroamination reaction of α,β-unsaturated γ-keto esters and chalcones has been developed via a chloronium-based mechanism to deliver anti-regioselective vicinal chloroamines instead of the aziridinium intermediates delivered aminochlorides. The combination of TsNCl(2) and TsNH(2) as reagents made the transformation highly efficient, delivering the γ-carbonyl-β-chloro-α-amino acid derivatives and α-chloro-β-amino-ketone derivatives in nearly quantitative yields with up to 99% ee and 99:1 dr under 0.05-0.5 mol % catalyst loading. TsNHCl was demonstrated to act as the key reactive species to form a bridged chloronium ion intermediate in the presence of a chiral scandium complex. The method might provide useful information for further realization of other haloamination reactions.     

Synthesis of α-fluoro-β-hydroxy esters by an enantioselective Reformatsky-type reaction

The first enantioselective Reformatsky-type reaction of ethyl iodofluoroacetate has been accomplished with alkyl aryl ketones. High diastereoselectivities and excellent enantioselectivities for the major diastereomer (93-95% ee) were achieved with large alkyl groups. For smaller alkyl groups the diastereoselectivities were moderate, but excellent enantioselectivities were obtained for both diastereomers (79-94% ee).     

Catalytic enantioselective chlorination of cyclic β-keto esters in the presence of chiral Pd(II) complexes

The catalytic enantioselective electrophilic chlorination promoted by chiral palladium complexes is described. The treatment of β-keto esters with 2,3,4,5,6,6-hexachlorocyclohex-2,4-dienone as chlorine source under mild reaction conditions afforded the corresponding α-chlorinated β-keto esters with excellent enantioselectivities (up to 94% ee).     

Dynamic kinetic resolution of α-chloro β-keto esters and phosphonates: hemisynthesis of Taxotere® through Ru-DIFLUORPHOS asymmetric hydrogenation

The dynamic kinetic resolution (DKR) of racemic α-chloro β-ketoesters and α-chloro β-ketophosphonates through ruthenium-mediated asymmetric hydrogenation is reported. The corresponding α-chloro β-hydroxyesters and α-chloro β-hydroxyphosphonates were obtained in good to high enantio- and diastereomeric excesses using, in particular, the atropisomeric ligand DIFLUORPHOS. This methodology allowed an efficient preparation of the anti phenylisoserine side chain of Taxotere® which has been used for the hemisynthesis of the cancer therapeutic agent itself. In addition, ¹³C NMR in chiral oriented solvents was used to investigate the DKR effect.     

A mild,chemoselective, one-pot synthesis of δ-keto α-cyano esters by organocatalysis

A sequential condensation of α-cyano esters, aldehydes, and ketones with catalytic amount of pyrrolidine/HOAc at room temperature has been developed. This method offers a chemoselective, one-pot cascade access to δ-keto α-cyano esters with moderate to good yields under mild conditions.     

BINOL-derived phosphoramidites in asymmetric hydrogenation: can the presence of a functionality in the amino group influence the catalytic outcome?

In discovering the remarkable catalytic properties of BINOL-derived phosphoramidites (binoP-NR(2)), Dutch researchers recently achieved a long-awaited breakthrough in asymmetric catalysis. For the first time, easily accessible monodentate chiral P(III) ligands turned out to provide high enantioselectivities when used in rhodium-catalysed olefin hydrogenation. The simplest ligand representative of this family is MonoPhos, which can be made straightforwardly from BINOL and hexamethylphosphorous triamide. Since the first publication dealing with such catalysts (J. Am. Chem. Soc., 2000), a variety of binoP-NRR' ligands have been reported in which the amino group bears a functional substituent or a stereogenic centre. This critical review examines the impact of the presence of such a functionality in the amino group on catalytic olefin hydrogenation reactions.     

Synthesis of novel chiral oxazoline-Schiff base ligands for the catalytic asymmetric chlorination of β-keto esters

A series of novel monooxazoline-Schiff base ligands 1 has been successfully synthesized. The Cu(I)–1a complex showed excellent catalytic activities with up to 83% ee for the asymmetric α-chlorination of β-keto esters.     

The setereoselective preparation of β-keto esters using baker＇s yeast in the presence of rice wine koji

By the addition of rice wine koji, enhancement of the reactivity was observed for the baker＇s yeast reduction of β-keto esters into （S）-β-hydroxy esters with high enantiomeric purity （73-98%）.     

Asymmetric synthesis of β-amino alcohols by the transfer hydrogenation of α-keto imines

The asymmetric transfer hydrogenation of representative aryl and benzofuranyl 2-tert-butylaminoethanones with formic acid–triethylamine, catalyzed by RhCl[(R,R)-TsDPEN](C₅Me₅), produced the corresponding β-tert-butylamino alcohols in 97–99% ee. A short asymmetric synthesis of (R)-bufuralol, a potent β-adrenergic receptor antagonist, is described. This approach to β-amino alcohols from ketones circumvents the halogenation–reduction–amination sequence.