Enantioselective Alkylation Research Articles

ChemInform Abstract: Catalytic Asymmetric Synthesis of 1,1‐Disubstituted Tetrahydro‐β‐carbolines by Phase‐Transfer Catalyzed Alkylations.

Efficient catalytic asymmetric synthesis of 1,1-disubstituted tetrahydro-β-carbolines has been achieved via asymmetric alkylation of 1-cyanotetrahydro-β-carbolines using a binaphthyl-modified N-spiro-type chiral phase-transfer catalyst. This is a valuable example of hitherto difficult highly enantioselective alkylations at α-carbon of the cyano group under phase-transfer conditions.

Asymmetric synthesis of α-keto esters via Cu(II)-catalyzed aerobic deacylation of acetoacetate alkylation products: an unusually simple synthetic equivalent to the glyoxylate anion synthon.

A simple and efficient method for the preparation of β-stereogenic α-keto esters is described using a copper(II)-catalyzed aerobic deacylation of substituted acetoacetate esters. The substrates for the title process arise from catalytic, enantioselective conjugate additions and alkylation reactions of acetoacetate esters. The mild conditions do not induce racemization of the incipient enolizable α-keto ester. The reaction is tolerant of esters, certain ketones, ketals, and nitro groups and utilizes inexpensive, readily available materials.

Pd-Catalyzed Asymmetric Allylic Alkylation of Indoles and Pyrroles by Chiral Alkene-Phosphine Ligands

A variety of chiral binaphthyl-based terminal-alkene-phosphine hybrid ligands were synthesized in four steps with (S)-BINOL as a starting material and utilized for the Pd-catalyzed enantioselective allylic alkylations of indoles and pyrroles to afford the desired products in high yields with good to excellent ee's.

Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts: Enantioselective Propargylic Alkylation of Propargylic Alcohols Bearing an Internal Alkyne with Aldehydes (Eur. J. Org. Chem. 12/2011)

AbstractThe cover picture shows that both wings are necessary for a butterfly to fly. Likewise, both a Lewis acid and an organocatalyst contribute cooperatively to the catalytic enantioselective propargylic alkylation of proparglylic alcohols bearing an internal alkyne moiety with aldehydes. Details are discussed in the article by Y. Nishibayashi et al. on p. 2239 ff.

Graphical Abstract: Eur. J. Org. Chem. 12/2011

AbstractThe cover picture shows that both wings are necessary for a butterfly to fly. Likewise, both a Lewis acid and an organocatalyst contribute cooperatively to the catalytic enantioselective propargylic alkylation of proparglylic alcohols bearing an internal alkyne moiety with aldehydes. Details are discussed in the article by Y. Nishibayashi et al. on p. 2239 ff.

Catalytic Enantioselective Friedel-Crafts Alkylation of Indoles with β,γ-Unsaturated α-Keto Phosphonates in the Presence of Chiral Palladium Complexes

The catalytic enantioselective Friedel-Crafts alkylation reaction promoted by chiral palladium complexes is described. The treatment of indoles with β,γ-unsaturated α-keto phosphonates under the mild reaction conditions afforded the corresponding Friedel-Crafts alkylation adducts with excellent enantioselectivities (up to 99% ee).

Enantioselective Friedel−Crafts Alkylation of Indoles with Trifluoroethylidene Malonates by Copper−Bis(oxazoline) Complexes: Construction of Trifluoromethyl-Substituted Stereogenic Tertiary Carbon Center

An enantioselective alkylation of indoles with trifluoroethylidene malonates catalyzed by copper(II)-bis (oxazoline) complexes has been developed. The expected adducts with a stereogenic tertiary carbon center bearing a trifluoromethyl group were obtained in excellent yields (up to 99%) and ee values (up to 96% ee). The synthetic utility of this asymmetric catalytic reaction was demonstrated by the preparation of β-CF(3)-tryptophan and 4-CF(3)-β-carboline in high ee.

Cooperative Catalytic Reactions Using Lewis Acids and Organocatalysts: Enantioselective Propargylic Alkylation of Propargylic Alcohols Bearing an Internal Alkyne with Aldehydes

AbstractThe enantioselective propargylic alkylation of propargylic alcohols bearing an internal alkyne moiety with aldehydes in the presence of a metal salt as the Lewis acid and an optically active secondary amine as the co‐catalyst has been found to give the corresponding propargylic alkylated products in high yields as a mixture of two diastereoisomers with high enantioselectivity.

Ring-contraction strategy for the practical, scalable, catalytic asymmetric synthesis of versatile γ-quaternary acylcyclopentenes.

Contraction action! A simple protocol for the catalytic asymmetric synthesis of highly functionalized γ-quaternary acylcyclopentenes (see schematic) in up to 91 % overall yield and 92 % ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions.

Enantioselective alkylation of β-keto esters promoted by dimeric Cinchona-derived ammonium salts as recoverable organocatalysts

Financial support from the Spanish Ministerio de Ciencia e Innovacion (projects CTQ2007-62771/BQU and Consolider Ingenio 2010, CSD2007-00006), the Generalitat Valenciana (Prometeo/2009/039), FEDER and the University of Alicante.

ChemInform Abstract: Copper‐Catalyzed Regio‐ and Enantioselective Synthesis of Chiral Enol Acetates and β‐Substituted Aldehydes.

The in situ transformation of α,β-unsaturated aldehydes into α-chloroallylic acetates and subsequent copper-catalyzed regio- and enantioselective (up to 94% ee) allylic alkylation with Grignard reagents provides chiral enol acetates and chiral β-substituted aldehydes in a one-pot protocol.

ChemInform Abstract: Catalytic Highly Enantioselective Alkylation of Aldehydes with Deactivated Grignard Reagents and Synthesis of Bioactive Intermediate Secondary Arylpropanols.

Because of the high reactivity of Grignard reagents, a direct, highly enantioselective Grignard reaction with aldehydes has rarely been disclosed. In this report, Grignard reagents were introduced with bis[2-(N,N′-dimethylamino)ethyl] ether (BDMAEE) to effectively deactivate their reactivity; thus, a highly enantioselective alkylation of aldehydes with Grignard reagents resulted from catalysis by (S)-BINOL-Ti(OiPr)2. It is thought that BDMAEE chelates the in situ generated salts MgBr2 from a Schlenk equilibrium of RMgBr and Mg(OiPr)Br from transmetalation of RMgBr with Ti(OiPr)4. The Mg salts can actively promote the undesired background reaction to give the racemate. The chelation definitely inhibits the catalytic activity of the Mg salts, suppresses the unwanted background reaction, and enables the highly enantioselective addition catalyzed by (S)-BINOL-Ti(OiPr)2. Consequently, the Mg salt byproducts were not removed, less Ti(OiPr)4 than RMgBr was used, and extremely low temperature was avoided in this ...

Cooperative Catalytic Reactions Using Organocatalysts and Transition Metal Catalysts: Enantioselective Propargylic Alkylation of Propargylic Esters with Aldehydes

The enantioselective propargylic alkylation of propargylic esters with aldehydes in the presence of a copper complex and an optically active secondary amine as cocatalysts has been found to give the corresponding propargylic alkylated products in good yields as a mixture of two diastereoisomers with a high enantioselectivity.

Chiral 1,2,3-Triazoliums as New Cationic Organic Catalysts with Anion-Recognition Ability: Application to Asymmetric Alkylation of Oxindoles

Chiral 1,2,3-triazoliums have been designed, and the rational structural modification based on their unique anion-binding abilities has led to the establishment of the highly enantioselective alkylation of 3-substituted oxindoles.

Enantioselective organocatalytic asymmetric allylic alkylation. Bis(phenylsulfonyl)methane addition to MBH carbonates

The highly enantioselective asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with bis(phenylsulfonyl)methane is presented. The reaction is simply catalyzed by cinchona alkaloid derivatives affording the final alkylated products in good yields and enantioselectivities.

The versatile roles of ammonium salt catalysts in enantioselective reduction and alkylation of α,β-unsaturated aldehydes: iminium catalysis, enamine catalysis and acid catalysis

A novel strategy for highly efficient utilization of chiral ammonium salt catalysts has been described in this paper. Three kinds of catalytic functions including iminium catalysis, enamine catalysis, and acid catalysis of chiral ammonium salt catalysts, have been achieved in the enantioselective reduction and alkylation reaction of α,β-unsaturated aldehydes with alcohols.

Enantioselective Friedel–Crafts alkylation of indole derivatives catalyzed by new Yb(OTf)3-pyridylalkylamine complexes as chiral Lewis acids

New Yb(OTf)(3)-pyridylalkylamine complexes have been employed as chiral Lewis acids in the enantioselective Friedel-Crafts alkylation of indole derivatives with trifluoropyruvates. The influence of the substituents as well as the configuration of the ligands have been studied and allowed us to reach enantiomeric excesses up to 83%.

Catalytic asymmetric synthesis of 1,1-disubstituted tetrahydro-β-carbolines by phase-transfer catalyzed alkylations

Efficient catalytic asymmetric synthesis of 1,1-disubstituted tetrahydro-β-carbolines has been achieved via asymmetric alkylation of 1-cyanotetrahydro-β-carbolines using a binaphthyl-modified N-spiro-type chiral phase-transfer catalyst. This is a valuable example of hitherto difficult highly enantioselective alkylations at α-carbon of the cyano group under phase-transfer conditions.

Catalytic enantioselective alkyl and aryl addition to aldehydes and ketones with organozinc reagents derived from alkyl Grignard reagents or arylboronic acids

A highly practical, catalytic enantioselective alkyl and aryl addition to aldehydes and ketones with organozinc reagents, which were prepared in situ from commercially available Grignard reagents or arylboronic acids, was developed. A chiral phosphoramide ligand was essential for promoting the addition reactions in high yields with high enantioselectivities.

Enantioselective α- and γ-Alkylation of α,β-Unsaturated Aldehydes Using Dienamine Activation

The enantioselective alkylation of α,β-unsaturated aldehydes with stabilized carbocations as electrophiles via the activation as dienamine intermediates is described. This unique application of dienamine catalysis allows for the first enantioselective γ-alkylation of linear α,β-unsubstituted enals.