Synthesis of α-amino ketones

Summary A new method is described for synthesizing aromatic -amino ketones with the general formula , which is based on the condensation of azlactones with benzene in the presence of aluminum chloride.     

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.     

Synthesis of cyclic α-amino ketones

Summary A simple method is described for synthesizing cyclic -amino ketones by intramolecular cyclization of azlactones under the action of aluminum chloride.     

Asymmetric α-oxyacylation of cyclic ketones

Reaction of cyclic ketones with chiral N-alkyl-O-acyl hydroxylamines leads to the corresponding α-oxyacylated carbonyl compound in up to 89% ee. The levels of asymmetric induction were influenced by solvent polarity, acid strength and, to a lesser extent, temperature. Increasing the steric bulk around the nitrogen atom of the hydroxylamine reagent led to increased levels of asymmetric induction, which was also found to be detrimental to the yield observed for the transformation. Examination of N- and O-substituents along with substrates revealed the scope and limitations of the procedure.     

Synthesis of fluorinated α-amino ketones part I: α-benzamidoalkyl mono- di- and trifluoromethyl ketones

2-Phenyl-5(4H)-oxazolones, obtained from α-amino acids, are reacted with di- and trifluoro acetic anhydride by a modified Dakin-West procedure to yield in a one-pot reaction α-benzamidoalkyl-di- and trifluoromethyl ketones in good yields. The monofluoromethyl analogues were also prepared from α-amino acids, however the use of the highly toxic fluoroacetic anhydride was avoided. The key step is the halogen exchange reaction on the corresponding bromomethyl ketone.     

Copper-catalyzed synthesis of α-ketothioamides from ketones

In this paper, the conversion of acetophenone to α-ketothioamide was reported in the presence of CuI as the catalyst and S₈/DMF as the coupling partners. The presence of both KF and NaOH was found to be necessary to achieve the high yield of the product. Propiophenone and butyrophenone also reacted in the presence of phenylboronic acid as an additive. Willgerodt-Kindler products were not observed in these reactions.     

Stereoelectronic structure of α-bromoalkenyl trifluoromethyl ketones

The results of quantum-chemical calculations at the B3LYP/6-311G** level of theory showed that (Z)-α-bromo-β-arylalkenyl trifluoromethyl ketones are more stable than the corresponding E isomers by 4–5 kcal/mol. Relatively large positive charge on the olefinic β-carbon atom and strong polarization of the C=C bond in both Z-s-cis and Z-s-trans conformers makes bromoalkenyl trifluoromethyl ketones the most potent Michael acceptors among α,β-unsaturated carbonyl compounds. The calculated data are very consistent with the experimental IR spectra.     

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.     

One-pot asymmetric synthesis of α-trifluoromethylated amines from α-trifluoromethyl ketones

Diastereoselective reduction of (Rs)-N-tert-butanesulfinyl α-trifluoromethyl ketimines formed in situ from the corresponding α-trifluoromethyl ketones and N-tert-butanesulfinamide has been achieved, and either diastereomer of N-tert-butanesulfinyl α-trifluoromethyl amines was obtained in good yields with excellent diastereoselectivities (up to 99:1 dr) using NaBH₄ and L-Selectride as the reductants, respectively.     

Highly diastereoselective chelation-controlled additions to α-silyloxy ketones

The polar Felkin-Anh, Cornforth-Evans, and Cram-chelation models predict that the addition of organometallic reagents to silyl-protected α-hydroxy ketones proceeds via a nonchelation pathway to give anti-diol addition products. This prediction has held true for the vast majority of additions reported in the literature, and few methods for chelation-controlled additions of organometallic reagents to silyl-protected α-hydroxy ketones have been introduced. Herein, we present a general and highly diastereoselective method for the addition of dialkylzincs and (E)-di-, (E)-tri-, and (Z)-disubstituted vinylzinc reagents to α-silyloxy ketones using alkyl zinc halide Lewis acids, RZnX, to give chelation-controlled products (dr ≥18:1). The compatibility of organozinc reagents with other functional groups makes this method potentially very useful in complex molecule synthesis.     

Lipase-catalyzed kinetic resolution of α,β-unsaturated α′-acetoxy ketones

The lipase-catalyzed kinetic resolutions of the α,β-unsaturated α′-acetoxy ketones 3a,b have been investigated. Of the lipases examined, CAL-B from Candida antarctica (fraction B) has been shown to be an efficient biocatalyst, which may be used effectively in preparative scale reactions.     

Highly diastereoselective addition of allyltitanocenes to α-chiral ketones

The addition of allyltitanium reagents, generated by the desulfurizative titanation of allylic sulfides with the titanocene(II) reagent Cp₂Ti−1-butene, to α-chiral ketones produced tertiary homoallylic alcohols bearing three adjacent chiral centers with high diastereoselectivity.     

Regiospecific synthesis of α-arylsulfonoxy ketones from ketone derivatives

Isomeric enol ester, enamine, and silyl enol ether derivatives of unsymmetrical ketones are converted regiospecifically to α-arylsulfonoxy ketones with arylsulfonyl peroxides.     

Synthesis of α-amino ketone hydrochlorides via chemoselective hydrogenation of α-nitro ketones

Chemoselective hydrogenation of various α-nitro ketones was accomplished with 5% Pt sulfide on carbon as a catalyst to afford α-amino ketone hydrochlorides in good yields.     

Efficient ruthenium-catalyzed α-alkylation of ketones using pyridyl methanols

By employing an easily available [Ru(p-cymene)Cl₂]₂/Xantphos/t-BuOK catalyst system, the α-alkylation of ketones was demonstrated by using pyridyl methanol as the alkylating reagents. The synthetic protocol allows synthesizing a wide range of α-pyridyl methylated ketones in reasonable to excellent isolated yields with high atom-efficiency. The transformation is operationally simple, the substrate scope is wide, and the starting materials are readily-available. There is no need for addition of alkenes as the hydrogen receptors or the use of stoichiometric amount of base.     

Calcium-mediated stereoselective reduction of α,β-epoxy ketones

The development of a calcium-mediated stereoselective reduction of α,β-epoxy ketones is reported. The corresponding α,β-epoxy alcohols are obtained in very good anti diastereoselectivity using Ca(OTf)₂ and NaBH₄. Furthermore, we have shown that our method can diastereoselectively reduce α,β-aziridinyl ketones.     

Generation and Dienophilic reactivity of α-oxoselenoaldehydes and ketones

The reaction of elemental selenium with sulfur ylides stabilized by electron-withdrawing substituent(s) affords a facile method for generation of functionalized selenocarbonyl compounds, which can be effectively trapped by Diels-Alder reaction with 1,3-dienes.