The asymmetric addition of phenylacetylene to aldehydes

Enantioselective formation of C-C bonds is an area of intense research.Among them, the asymmetric addition of alkynyl reagents to aldehydes is very useful for the synthesis of chiral secondary propargyl alcohols, which are very important building blocks for many chiral organic compounds, and the acetylene and hydroxyl founctional group of propargyl alcohol can be easily transfered into many other structures.1Recently, many significant chiral ligands have been disclosed.2 Here, we report our r…     

Biocatalytic asymmetric formation of tetrahydro-β-carbolines

Strictosidine synthase triggers the formation of strictosidine from tryptamine and secologanin, thereby generating a carbon-carbon bond and a new stereogenic center. Strictosidine contains a tetrahydro-β-carboline moiety—an important N-heterocyclic framework found in a range of natural products and synthetic pharmaceuticals. Stereoselective methods to produce tetrahydro-β-carboline enantiomers are greatly valued. We report that strictosidine synthase from Ophiorrhiza pumila utilizes a range of simple achiral aldehydes and substituted tryptamines to form highly enantioenriched (ee >98%) tetrahydro-β-carbolines via a Pictet-Spengler reaction. This is the first example of aldehyde substrate promiscuity in the strictosidine synthase family of enzymes and represents a first step toward developing a general biocatalytic strategy to access chiral tetrahydro-β-carbolines.     

Amino acid-catalyzed asymmetric α-amination of carbonyls

Electrophilic amination of ketones and aldehydes in the presence of dibenzylazodicarboxylate in dichloromethane, using l-azetidine carboxylic acid as a catalyst, is described. Yields and ee are discussed in comparison with the corresponding l-proline-catalyzed reaction.     

Excited-state properties of asymmetric pentaazadentate expanded porphyrins

The research results of the excited-state properties of asymmetric pentaazadentate ex-panded-porphyrins are reported. The results show that the emission spectra appear in the 770-820 nm region in accord with the different substituents on the benzene ring. The quantum yield of fluorescence is less than 0.02, and the lifetime of the first singlet excited state (S1) is shorter than 1ns. There are excellent linear relationships between the energy of the S1 and the Hammett constants as well as the quantum yield of fluorescence and the electrophilic substituent constants σ+. The energies of the lowest excited triplet state (T1) of the complexes are in the range of 94 -130kJ/mol. The lifetime of T 1 is as long as tens of microseconds. The T1-Tn transient absorption spectra appear in 450-550 nm region. And the quantum yield of title compounds for generating singlet oxygen is as high as 0.9.     

Synthesis of (−)-benzolactam-V8 by application of asymmetric aziridination

(?)-Benzolactam-V8, an artificially-designed cyclic dipeptide with strong tumor-promoter activity, was synthesized from benzyl (S)-N-(2-formylphenyl)-N-methylvalinate by application of guanidinium ylide-participated asymmetric aziridination followed by the reductive ring-opening reaction of 3-arylaziridine-2-carboxylate formed.     

Catalytic, asymmetric synthesis of α-acetoxy amides

Non-racemic cyanohydrin acetates are readily available from aldehydes and potassium cyanide/acetic anhydride by use of bimetallic titanium (salen) catalyst 1. Treatment of the cyanohydrin acetates with a platinum(II) phosphinito catalyst 3 under neutral conditions results in chemoselective hydrolysis to the corresponding α-acetoxy amides in a racemization free process.     

Absolute asymmetric synthesis of tertiary α-amino acids

Frozen: the spontaneous crystallization of an achiral compound in a chiral conformation is used as the unique source of chirality in an absolute asymmetric synthesis of tertiary amino acids. The dynamic axial chirality of tertiary aromatic amides is frozen in a crystal and is responsible for the stereoselectivity of the deprotonation/alkylation. α-Amino acid derivatives are synthesized in up to 96 % ee.     

Ruthenium catalyzed asymmetric transfer hydrogenation of β-ketoesters

Chemoselective transfer hydrogenation of β-ketoesters to the corresponding alcohols is achieved in the presence of catalytic combinations of [RuCl₂(η⁶-arene)]₂ and ephedrine or diamino type chiral ligands with activities up to 190 h⁻¹ at 20°C and moderate to good enantiomeric excesses ranging from 36 to 94%.     

Application of chiral thiazolidine ligands to asymmetric hydrosilation

Seven chiral thiazolidines bound rhodium complexes were synthesized and their catalytic asymmetric hydrosilation properties were investigated It was found through investigation that the configuration of newly formed chiral centre C2 of substituted chiral thiazolidines prepared from L-cysteine or its esters has no effect on the final results of catalytic asymmetric hydrosilation.The direct reason for causing this phenomenon is reported by the present quantitative results for the first time:the rapid racemation of chiral center C2 of chiral thiazolidine ligands takes place under the catalysis of rhodium(Ⅰ) complex [Rh(COD)CI]2     

De novo asymmetric synthesis of (−)-nanaomycin A

The de novo asymmetric total synthesis of (?)-nanaomycin A is described. The entirely linear route required only 13 steps from commercially available starting materials (3% overall yield). Key transformations include a Claisen rearrangement, an asymmetric dihydroxylation, a regioselective tosylation, a diastereoselective intramolecular Friedel-Crafts alkylation and a nitrile hydrolysis. As the route relies on a Sharpless asymmetric dihydroxylation it is equally amenable for the synthesis of (+)-nanaomycin A.     

Catalytic asymmetric synthesis of γ-substituted vinyl sulfones

A fast new entry for the stereoselective construction of γ-substituted vinyl sulfones is presented. The key for success is the use of a readily available chiral secondary amine catalyst that allows the use of base-sensitive β-nitroethyl sulfones as masked β-sulfonyl vinyl anions in conjugate additions. The method performed in a three-step one-pot operation gives access to a great variety of vinyl sulfones in good yields and with excellent enantioselectivities. The method has also been extended to other relatively base-sensitive β-electron-withdrawing-substituted nitroalkanes to afford products with manifold functionality, providing a quick entry to very attractive synthetic intermediates for organic synthesis.     

A practical asymmetric synthesis of homochiral α-arylglycines

Enantioselective reduction of a series of substituted aryl trichloromethyl ketones with the CBS-catecholborane reagent afforded homochiral aryl trichloromethyl carbinols which have been elaborated to give homochiral α-arylglycines in high e.e.     

The applications of Schiff bases in Ti-catalyzed asymmetric alkynylation of aldehydes

Sciff bases 1 and 2, which were derived from chiral aminoalcohols, were used as ligands in Ti-catalyzed asymmetric alkynylation of aldehydes. Good enantioselectivities (up to 88% ee) and high chemical yields (80-90%) were obtained.     

Stereochemistry of the asymmetric alkylation of Δ9,10-octahydroquinolin-4-ones

The asymmetric character of the alkylation of a series of metallated bicyclic enaminoketones has been established and its stereoselectivity has been investigated. The enantiomers of (3S*)-methyl- and (3S*)- and (3R*)-3-methyl-3-butyl-^9,10-octahydroquinolin-4-ones have been obtained. The possibility of inducing chirality at the 3 position of the enaminoketone molecule during methylation in the presence of chiral lithium amides has been established in principle.M. V. Lomonosov Moscow State University, Moscow 119899. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1531–1542, November, 1995. Original article submitted November 10, 1995     

Catalytic asymmetric one-pot synthesis of α-methylene-γ-lactams

An organocatalytic enantioselective synthesis of α-methylene-γ-lactams has been developed. The reaction between protected 2-aminomalonates and Morita–Baylis–Hillman carbonates is catalyzed by chiral Lewis bases to afford the corresponding lactams in excellent yields and moderate to good enantioselectivities, after work-up.     

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.     

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).     

Peptide/laccase cocatalyzed asymmetric α-oxyamination of aldehydes

An asymmetric α-oxyamination could be successfully performed by a peptide catalyst and laccase. The combination of peptide catalysis and enzymatic air oxidation promoted the reaction smoothly in water without employing a metal reagent. The oxyaminated compounds could be obtained as both aldehyde and carboxylic acid products depending on the reaction conditions.     

Catalytic asymmetric aziridination of α,β-unsaturated aldehydes

The development, scope, and application of the highly enantioselective organocatalytic aziridination of α,β-unsaturated aldehydes is presented. The aminocatalytic azirdination of α,β-unsaturated aldehydes enables the asymmetric formation of β-formyl aziridines with up to >19:1 d.r. and 99% ee. The aminocatalytic aziridination of α-monosubstituted enals gives access to terminal α-substituted-α-formyl aziridines in high yields and up to 99% ee. In the case of the organocatalytic aziridination of disubstituted α,β-unsaturated aldehydes, the transformations were highly diastereo- and enantioselective and give nearly enantiomerically pure β-formyl-functionalized aziridine products (99% ee). A highly enantioselective one-pot cascade sequence based on the combination of asymmetric amine and N-heterocyclic carbene catalysis (AHCC) is also disclosed. This one-pot three-component co-catalytic transformation between α,β-unsaturated aldehydes, hydroxylamine derivatives, and alcohols gives the corresponding N-tert-butoxycarbonyl and N-carbobenzyloxy-protected β-amino acid esters with ee values ranging from 92-99%. The mechanisms and stereochemistry of all these catalytic transformations are also discussed.