NHC-copper-catalyzed asymmetric conjugate silylation of access chiral α-aminosilanes

Chiral α-aminosilane and its derivatives have found potential applications in pharmaceuticals. Yet there are rare examples have been reported for the synthesis of these molecules. Herein we report a catalytic asymmetric conjugate silylation reactions of β-amido-acrylonitriles and β-amido-acrylates for the first time in the presence of catalytic amount of chiral N-heterocyclic carbene (NHC)/Copper(I) complex. A variety of functionalized chiral α-aminosilanes were obtained at room temperature in good yields with high enantioselectivities in the presence of NHC (10 mol%), CuCl (10 mol%), NaOtBu or NaOMe (20 mol%), and MeOH (2 equivalents).     

Organocatalytic asymmetric α-benzoyloxylation of α-branched aldehydes and enals: a useful approach to oxygenated quaternary stereocenters

Direct asymmetric α-benzoyloxylation of α-branched aldehydes and α-branched enals via enamine and dienamine catalysis was used to construct quaternary oxygenated stereocenters with good yields and moderate to good enantioselectivity. This method uses an inexpensive and readily available cinchona alkaloid-derived primary amine as the catalyst, benzoyl peroxide as the oxygen source, and stoichiometric amounts of the aldehyde substrates, providing simple metal-free access to valuable protected 2-hydroxyaldehyde derivatives.     

beta-peptides as catalysts: poly-beta-leucine as a catalyst for the Juliá-Colonna asymmetric epoxidation of enones

Poly-beta-leucines have been evaluated as catalysts for the Juliá-Colonna asymmetric epoxidation of enones; the beta 3-isomer was found to be an effective catalyst for the epoxidation of chalcone (70% ee) and some analogues.     

A novel and effective chiral phosphoramide catalyst for the borane-mediated asymmetric reduction of prochiral α-halo ketones

The novel chiral phosphoramide, 1,4-bis[(5S)-1,3-diaza-2-phospha-2-oxo-3-phenylbicyclo(3.3.0)octan-2-yl]piperazine, was synthesised and successfully employed as a catalyst in the borane-mediated asymmetric reductions of prochiral α-halo ketones, providing the corresponding α-halo alcohols in 90–95% enantiomeric purities.     

Enantioselective α-alkylation of unsaturated carboxylic acids using a chiral lithium amide

The regio- and stereochemistry of the alkylation of dienediolates from unsaturated carboxylic acids with benzylic halides, which often results in mixtures of isomers, can be controlled by means of changes in the lithium amide, allowing the α-regioisomer to be obtained as the major diastereoisomer. In addition, when chiral amines are used, moderate enantiomeric excesses can be attained.     

Highly asymmetric Michael additions of α,α-disubstituted aldehydes to β-nitroalkenes promoted by chiral pyrrolidine-thiourea bifunctional catalysts

A series of secondary amine-thiourea catalysts derived from l-proline and chiral diamine were prepared and first applied to the Michael addition of α,α-disubstituted aldehydes to trans-β-nitroalkenes. Moderate yields (47-75%) and excellent enantioselectivities (up to 96% ee) were obtained for a variety of aryl and heteroaryl nitroalkenes.     

Catalytic asymmetric syntheses II. Hydrogenation of α,β-unsaturated ketones using chiral ruthenium complexes

α,β-Unsaturated ketones have been hydrogenated inthe presence of HRuCl-(TBPC)₂ (TBPC = (−)-trans-1,2-bis(diphenylphosphinomethyl)cyclobutane) to give ketones with a maximum optical purity of 62%. Factors affecting the stereoselectivity of the catalytic reaction are discussed.     

Studies on the rhodium- and ruthenium-catalyzed asymmetric hydrogenation of α-dehydroamino acids using a family of chiral dipyridylphosphine ligand (P-Phos)

The applications of the chiral dipyridylphosphine ligand P-Phos and its derivatives Tol-P-Phos and Xyl-P-Phos in Ru- and Rh-catalyzed hydrogenations of the methyl esters of a variety of (Z)-2-acetamido-3-arylacrylic acids have been studied systematically. The results show that the electronic and steric properties of these ligands have significant influences on the enantioselectivity of the reduction. Rh and Ru complexes of the same dipyridylphosphine ligand family exhibit different trends in enantioselectivity toward the same substrate.     

Catalytic asymmetric borane reduction of prochiral ketones using chiral camphor-derived mercapto-alcohols

Easily available D-(+)-camphor-derived chiral mercapto-alcohols 2 and 3 were employed for catalytic asymmetric borane reduction of aromatic ketones. Moderate enantioselectivities with e.e. 20.2-72.1% were obtained with 10 mol% catalyst. Opposite asymmetric induction was achieved when mercapto-alcohols 2 and 3 were used.     

Novel and practical asymmetric synthesis of β2,3-amino esters using asymmetric Michael addition of chiral amine

A practical method for the synthesis of chiral β^2,3-amino esters having various substituents was developed, which is characterized by an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,β-unsaturated esters. We found that a highly face-selective protonation occurred by the quick addition of water to the enolate intermediate derived from the Michael addition reaction to afford N-protected β^2,3-amino esters in moderate to excellent yields. This finding was made possible by the facile preparation of geometrically pure trisubstituted (E)-α,β-unsaturated esters, which was established recently by our group. The subsequent deprotection of the amino group in the Michael adduct by using N-iodosuccinimide (NIS) efficiently provided β^2,3-amino esters having various substituents.     

Importance of the nature of α-substituents in pyrrolidine organocatalysts in asymmetric Michael additions

The fundamental factors contributing toward the stereoselectivity in organocatalyzed asymmetric Michael reaction between aldehydes (propanal and 3-phenyl propanal) and methyl vinyl ketone (MVK) are established by using density functional theory methods. Three of the most commonly employed α-substituted pyrrolidine organocatalysts are examined. Several key stereochemical modes of addition between (i) a model enamine or (ii) pyrrolidine enamines derived from aldehydes and secondary amine to MVK are examined. Among these possibilities, the addition of (E)-enamine to cis-MVK is found to have a lower activation barrier. The stereochemical outcome of the reaction is reported on the basis of the relative energies between pertinent diastereomeric transition states. Moderate selectivity is predicted for the reaction involving pyrrolidine catalysts I and II, which carry relatively less bulky α-substituents dimethylmethoxymethyl and diphenylmethyl, respectively. On the other hand, high selectivity is computed in the case of catalyst III having a sufficiently large α-substituent (diarylmethoxymethyl or diphenylprolinol methyl ether). The enantiomeric excess in the case of 3-phenyl propanal is found to be much higher as compared to that with unsubstituted propanal, suggesting potential for improvement in stereoselectivity by substrate modifications. The computed enantiomeric excess is found to be in reasonable agreement with the reported experimental stereoselectivities. A detailed investigation on the geometries of the crucial transition states reveals that apart from steric interactions between the α-substituent and MVK, various other factors such as orbital interactions and weak stabilizing hydrogen-bonding interactions play a vital role in stereoselectivity. The results serve to establish the importance of cumulative effects of various stabilizing and destabilizing interactions at the transition state as responsible for the stereochemical outcome of the reaction. The limitations of commonly employed qualitative propositions, relying on the steric protection of one of the prochiral faces of enamines offered by the bulky α-substituent, are presented.     

Synthesis of new α-aminophosphonates using nanoscale nickel-based metal–organic framework as a heterogeneous catalyst and their antibacterial activity

An elegant approach was presented for the synthesis of novel α-aminophosphonates: a three-component one-pot condensation of 3-(trifluoromethyl)aniline, substituted aromatic aldehydes, and diethyl phosphite using a nickel-based metal–organic framework (Ni-MOF). The Ni-MOF was synthesized using 4,4′-biphenyldicarboxylic acid and further characterized using various techniques such as X-ray diffraction, Fourier-transform infrared, thermogravimetry/differential thermal analysis, Brunauer–Emmett–Teller, and field-emission scanning electron microscopy analyses. Ni-MOF seems to be an eco-friendly, an easily recyclable, and heterogeneous catalyst up to the eighth run with minimal reduction in its catalytic activity. The synthesized α-aminophosphonates were also investigated for antibacterial and antioxidant activities. In few cases, compounds 4a–4x show similar as well as higher antibacterial activity. Among the synthesized α-aminophosphonates, 4a–4x had more potent antibacterial activity against pathogenic bacteria while compounds 4h, 4m, 4n, 4q, 4u, 4v, and 4w exhibited significant antioxidant activity.     

Synthesis of α-aminonitriles using silica-bonded N-propylpiperazine sulfamic acid as a recyclable catalyst

<正>α-Aminonitriles were synthesized via a one-pot three-component condensation of aldehydes,amines,and trimethylsilyl cyanide using silica-bonded N-propylpiperazine sulfamic acid(SBPPSA) as a recyclable solid acid at room temperature.SBPPSA showed much the same efficiency when used in consecutive reaction runs.     

Solvent free,fast and asymmetric Michael additions of ketones to nitroolefins using chiral pyrrolidine–pyridone conjugate bases as organocatalysts

New chiral organocatalysts are envisaged based on a pyrrolidine–pyridone conjugate and synthesized from commercially available proline employing standard protocols. These catalysts were found to be useful for asymmetric Michael additions of ketones to nitroolefins to afford the desired products in very good yields (up to 98%) with excellent diastereo- and enantioselectivities (>97:3 syn/anti and up to 98% ee) in very short reaction time compared with the existing reports.     

Enantioselective preparation of cis-β-azidocyclopropane esters by cyclopropanation of azido alkenes using a chiral dirhodium catalyst

A diastereo- and enantiocontrolled preparation of the conformationally restricted cis-β-azidocyclopropane esters have been developed. The Rh(2)(S-DOSP)(4) was found to be an efficient catalyst in hexane for the cyclopropanation of azido alkenes with diazo esters, and 19 cis-β-azidocyclopropane esters were prepared in excellent yields. The value of the diastereomer ratio was up to 99:1, and the enantiomeric excess was up to 95%. Furthermore, the relative and absolute configuration was confirmed by X-ray analysis.     

New one pot synthesis of a chiral α-hydroxy-γ-butyrolactone via sequential asymmetric hydrogenation of an α,γ-diketoester

The hydrogenation of ethyl 2,4-dioxovalerate in the presence of chiral rhodium or ruthenium catalysts provides direct access to 2-hydroxy-4-methyltetrahydrofuran-2-one 4 with syn:anti ratios of up to 84:16 and with up to 98% and 94% e.e. in the syn and anti form, respectively.     

Efficient asymmetric protonation of enolates with readily accessible chiral α-sulfinyl alcohols

The efficient asymmetric protonation of lithium enolates of 2-alkylcycloalkanones (87–96% ee) with readily accessible chiral α-sulfinyl alcohols is described. Optimal stereoselection is achieved for each lithium enolate at a different reaction temperature in the range −40 to −100°C.     

The asymmetric synthesis of chiral cyclic α-hydroxy phosphonates and quaternary cyclic α-hydroxy phosphonates

A highly practical, catalytic enantioselective cyclic phosphite addition to aldehydes and ketones was developed. The reaction rate of the asymmetric hydrophosphonylation was significantly enhanced by the addition of silver carbonate. Particularly, significant improvement has been achieved on the asymmetric hydrophosphonylation of unactivated ketones, giving quaternary α-hydroxy phosphonates with excellent enantioselectivity (up to 99% ee).     

Iron-catalyzed asymmetric epoxidation of β,β-disubstituted enones

The combination of Fe(OTf)(2) and novel phenanthroline ligands enables the catalytic asymmetric epoxidation of acyclic β,β-disubstituted enones, which have been a heretofore inaccessible substrate class. The reaction provides highly enantioenriched α,β-epoxyketones (up to 92% ee) that can be further converted to functionalized β-ketoaldehydes with an all-carbon quaternary center.