Synthesis of optically active α-hydroxy ketones by enantioselective oxidation of silyl enol ethers with a fructose-derived dioxirane

Optically active α-hydroxy ketones 3 have been prepared in moderate to high enantioselectivities by the asymmetric oxidation of the silyl enol ethers 2 with in situ generated dioxirane from the fructose-derived ketone 1. Best results (ee values up to 82%) for this novel non-transition metal mediated asymmetric α-hydroxylation may be obtained, when an excess of the fructose-derived ketone 1 is employed at pH ca. 8 and short reaction times. Valuable mechanistic information on the spiro versus planar transition states for the oxygen-transfer process has been aquired through the absolute configuration of the resulting α-hydroxy ketone 3 products.     

Asymmetric oxidation of enol phosphates to α-hydroxy ketones using Sharpless reagents and a fructose derived dioxirane

The asymmetric oxidation of a variety of differently substituted, acyclic and cyclic enol phosphates using the Sharpless AD-reagents AD-mix-α and AD-mix-β, and a fructose derived chiral ketone as a catalyst, afforded the corresponding α-hydroxy ketones in high enantioselectivity and good yield. The influence of steric and electronic factors of the substrates on the facial stereoselectivity in the reported oxidations was studied.     

Oxidation of enamines to α-hydroxy ketones and α-amino ketones using N-sulfonyloxaziridines

Tri-substituted enamines are oxidized to α-hydroxy ketones by N-sulfonyloxaziridines while di-substituted enamines are oxidized to α-amino ketones. A unified mechanism for the formation of both α-hydroxy ketones and α-amino ketones is proposed.     

Synthesis of optically active α-sulfinylacetaldehyde

Optically active α-sulfinylacetaldehyde is prepared by formylation of the (R)-methyl p-tolylsulfoxide anion with N-formylpiperidine.     

Enantioselective α-benzoyloxylation of ketones promoted by primary amine catalyst

A mixture of 9-amino-(9-deoxy)epi-dihydroquinidine and salicylic acid was able to promote the direct reaction of various cyclohexanones with dibenzoyl peroxide, thus affording the corresponding protected α-hydroxy carbonyl compounds in high yield and enantioselectivity. Interestingly the same catalytic salt was found to be active when 1-indanones derivatives were directly employed in the reaction with dibenzoyl peroxide furnishing chiral 1-oxo-2,3-dihydro-1H-inden-2-yl benzoates in high yields and enantioselectivity. Furthermore their treatment with NaBH(4) gives easy access to the corresponding enantioenriched 1,2-diols in high yields and without any loss of stereoselectivity.     

Enantioselective organocatalytic α-fluorination of cyclic ketones

The first highly enantioselective α-fluorination of ketones using organocatalysis has been accomplished. The long-standing problem of enantioselective ketone α-fluorination via enamine activation has been overcome via high-throughput evaluation of a new library of amine catalysts. The optimal system, a primary amine functionalized Cinchona alkaloid, allows the direct and asymmetric α-fluorination of a variety of carbo- and heterocyclic substrates. Furthermore, this protocol also provides diastereo-, regio-, and chemoselective catalyst control in fluorinations involving complex carbonyl systems.     

A highly stereoselective conversion of α,β-epoxy esters to α-hydroxy esters. An efficient route to optically active α-hydroxyesters

α,β-Epoxy esters were cleanly converted to α-hydroxy esters with retention of the configurations at the α-carbon atoms via MgI₂-promoted regioselective oxirane ring-opening followed by tributyltin hydride-reduction.     

Enantioselective synthesis of β-hydroxy amines and aziridines using asymmetric transfer hydrogenation of α-amido ketones

A rapid, expedient and enantioselective method for the synthesis of β-hydroxy amines and monosubstituted aziridines in up to 99% e.e., via asymmetric transfer hydrogenation of α-amido ketones, is described.     

NBS-assisted an efficient conversion of styrenes to α-hydroxy ketones in water

An expedient, mild and environmentally benign method for the oxidation of styrenes to α-hydroxy ketones has been developed. This conversion has been achieved by employing water as a solvent as well as an oxygen source. This facile and efficient tandem process provides α-hydroxy ketones in moderate to good yields from easily accessible styrenes.     

Microwave-assisted synthesis of α-hydroxy aromatic ketones from α-bromo aromatic ketones in water

A reaction ofα-bromo aromatic ketones in water with microwave irradiation gave the correspondingα-hydroxy aromatic ketones in good yields.The use of microwaves was found to significantly improve yields and shorten the reaction time.This reaction afforded a very clean,convenient method for the synthesis ofα-hydroxy aromatic ketones.     

Lead(IV) acetate oxidative ring-opening of 2,3-epoxy primary alcohols: a new entry to optically active α-hydroxy carbonyl compounds

The treatment of 2,3-epoxy primary alcohols with lead(IV) acetate (LTA) leads to α-acetoxy aldehydes or α-acetoxy ketones, through the nucleophilic ring-opening of an intermediate oxonium and the subsequent carbon-carbon bond cleavage. This reaction represents a new route to optically active α-hydroxy carbonyl compounds.     

Enantioselective synthesis of optically pure β-amino ketones and γ-aryl amines by Rh-catalyzed asymmetric hydrogenation

A series of optically pure β-amino ketones have been synthesized in high enantioselectivities (ee > 99%) by Rh-DuanPhos-catalyzed asymmetric hydrogenation of readily prepared β-keto enamides. Further reduction of these β-amino ketones with hydrogen and Pd/C leads to the formation of a variety of protected enantiomerically pure γ-aryl amines (ee > 99%), which are key building blocks in many bioactive molecules.     

Enantioselective organocatalytic conjugate addition of α-nitroacetate to α,β-unsaturated ketones in water

The catalytic enantioselective conjugate addition reaction of α-nitroacetate to α,β-unsaturated ketones promoted by chiral bifunctional organocatalysts is described. The treatment of α-nitroacetate to α,β-unsaturated ketones under aqueous-phase reaction conditions afforded the corresponding Michael adducts with high enantioselectivity. The conjugate addition adducts are easily converted to chiral δ-keto nitroalkanes and δ-keto esters.     

Enantioselective aldol reactions of α,β-unsaturated ketones with trifluoroacetophenone catalyzed by a chiral primary amine

Chiral primary amine catalyzed direct asymmetric aldol reactions of ketones with trifluoroacetophenone, afforded trifluoromethylated β-hydroxycarbonyl aldol products bearing a quaternary carbon stereogenic center in high yields (up to 93% yield) and with high to excellent enantioselectivities of up to 99% ee.     

Enantioselective N-heterocyclic carbene-catalyzed Michael addition to α,β-unsaturated aldehydes by redox oxidation

Enantioselective N-heterocyclic carbene-catalyzed Michael addition reactions to α,β-unsaturated aldehydes by redox oxidation were realized. With 10 mol % of camphor-derived triazolium salt D, 15 mol % of DBU, 5 mol % of NaBF(4), and 100 mol % of quinone oxidant, the reactions of various dicarbonyl compounds with α,β-unsaturated aldehydes led to 3,4-dihydro-α-pyrones in good yields and excellent ee's.     

Synthesis of optically active α-bromohydrins via reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase

Enantiomerically pure (S)-α-bromohydrins were prepared by the reduction of α-bromoacetophenone analogues catalyzed by an isolated carbonyl reductase from Candida magnolia with high yield and excellent enantiomeric excess when methyl tert-butyl ether was employed as the co-solvent, while avoiding the formation of by-products. This provides a new approach to access these chiral α-bromohydrins which are of pharmaceutical importance.     

Enantioselective sulfa-Michael addition of thioacids to α,β-unsaturated ketones with bifunctional organocatalyst

Organocatalytic conjugate addition of thioacids to α,β-unsaturated ketones has been studied in the presence of cinchona alkaloid derived urea catalyst. Both the enantiomers of products are accessible with the same level of enantioselectivity using pseudoenantiomeric quinine/quinidine derived catalysts. The catalytic process provides optically active thioesters with high chemical yields (up to 99%) and useful enantioselectivity (up to 83% ee). The reaction was performed with 1 mol % of catalyst in toluene at room temperature. A transition state model has been proposed to explain the stereochemical outcome of the reaction.     

Asymmetric Michael addition of silyl nitronates to cyclic α,β-unsaturated ketones catalyzed by chiral quaternary ammonium bifluorides: isolation and selective functionalization of enol silyl ethers of optically active γ-nitro ketones

Highly enantioselective Michael addition of silyl nitronates to cyclic α,β-unsaturated ketones has been accomplished by the utilization of N-spiro C₂-symmetric chiral quaternary ammonium bifluoride 1 as an efficient catalyst, offering a new route to the enol silyl ethers of optically active γ-nitro ketones. The synthetic utility of this transformation has been demonstrated by the diastereoselective derivatizations of the optically active enol silyl ethers to the corresponding α-substituted cyclic ketones having three consecutive stereochemically defined stereocenters.     

Enantioselective synthesis of β-hydroxy ketones from heterocyclic aldehydes in water catalyzed by a recyclable organocatalyst bearing an ionic liquid moiety

The aldol reactions of cyclic (heterocyclic) ketones and heterocyclic aldehydes catalyzed by (4R,S)-4-hydroxyproline modified with a ionic liquid moiety proceed with high yields and diastereo- and enantioselectivity in the presence of water. The catalyst retained its activity and selectivity for at least five cycles.     

Organoselenium-mediated reduction of α,β-epoxy ketones to β-hydroxy ketones: A new access to inter- and intramolecular aldols

The organoselenium-mediated reduction of α,β-epoxy ketones has been demonstrated to be a promising entry to a variety of cyclic and acyclic aldols.