ABSTRACT
Zinc salts have been shown to promote the Buchwald-Hartwig coupling of azaindoles and azaindazoles with heteroaryl chlorides to provide the corresponding 1-aryl-1H-azaindoles and 1-aryl-1H-azaindazoles. The substrate scope and mechanistic aspects of this reaction were explored.
ABSTRACT
We have developed highly enantioselective, copper-catalyzed alkynylations of benzopyranyl acetals. By using a copper(I) catalyst equipped with a chiral bis(oxazoline) ligand, high yields and enantioselectivities are achieved in the alkynylation of widely available, racemic isochroman and chromene acetals to deliver α-chiral oxygen heterocycles. This method demonstrates that chiral organometallic nucleophiles can be successfully used in enantioselective additions to oxocarbenium ions.
Subject(s)
Benzopyrans/chemistry , Copper/chemistry , Onium Compounds/chemistry , Organometallic Compounds/chemistry , Oxazoles/chemistry , Catalysis , Molecular Structure , StereoisomerismABSTRACT
We have developed a nickel-catalyzed cross coupling of benzylic ammonium triflates with aryl boronic acids to afford diarylmethanes and diarylethanes. This reaction proceeds under mild reaction conditions and with exceptional functional group tolerance. Further, it transforms branched benzylic ammonium salts to diarylethanes with excellent chirality transfer, offering a new strategy for the synthesis of highly enantioenriched diarylethanes from readily available chiral benzylic amines.
Subject(s)
Boronic Acids/chemistry , Ethane/chemical synthesis , Nickel/chemistry , Organometallic Compounds/chemistry , Quaternary Ammonium Compounds/chemistry , Catalysis , Crystallography, X-Ray , Ethane/analogs & derivatives , Ethane/chemistry , Models, Molecular , Molecular Conformation , Salts/chemistry , StereoisomerismABSTRACT
Controlling enantioselectivity in additions to oxocarbenium ions remains a challenge in asymmetric catalysis. By catalytically generating a chiral organometallic intermediate, a copper acetylide, we have developed a novel approach for additions of carbon nucleophiles to cyclic oxocarbenium ions in high enantioselectivities and yields.
ABSTRACT
We have developed an enantioselective, copper(I)-catalyzed addition of terminal alkynes to racemic isochroman acetals. This method is one of the first transition-metal-catalyzed approaches to enantioselective additions to prochiral oxocarbenium ions. In this reaction, TMSOTf is used to form the oxocarbenium ion in situ under conditions compatible with simultaneous formation of the chiral copper acetylide. By using a bis(oxazoline) ligand, good yields and enantioselectivities are observed for a variety of enantioenriched 1-alkynyl isochromans.
Subject(s)
Acetals/chemistry , Alkynes/chemistry , Alkynes/chemical synthesis , Chromans/chemistry , Copper/chemistry , Organometallic Compounds/chemistry , Ions/chemistry , Molecular Structure , StereoisomerismABSTRACT
The terphenyl structure has been proven to be an ideal scaffold mimicking side-chain functionalities of peptidic alpha-helices. The synthesis of 1,4-dipiperazino benzenes, using stepwise transition metal-catalyzed N-arylation of chiral piperazines to a central benzene core is reported. The structure determination by X-ray crystallography reveals a geometrical arrangement of the hydrophobic side chains resembling the orientation of key i, i + 3, and i + 7 positions in a peptidic alpha-helix or in terphenyl helix mimetics.
Subject(s)
Benzene Derivatives/chemical synthesis , Peptides/chemistry , Terphenyl Compounds/chemistry , Benzene Derivatives/chemistry , Crystallography, X-Ray , Molecular Conformation , Molecular Mimicry , Molecular Structure , Protein Structure, SecondaryABSTRACT
C(alpha)-tetrasubstituted alpha-amino acids are widely used to design and prepare peptides and peptide mimics with constrained conformations. Subcategories of these compounds are cyclic C(alpha)-tetrasubstituted alpha-amino acids, in which both alpha-substituents are covalently connected. This survey presents recent advances in the synthesis and application of cyclic C(alpha)-tetrasubstituted alpha-amino acids in a systematic order beginning with cyclopropane amino acids, continuing with four, five, six membered rings, and ring structures larger than six-membered. We discuss synthetic routes to the cyclic C(alpha)-tetrasubstituted alpha-amino acids and their use as conformation determining elements in peptides.
Subject(s)
Amino Acids, Cyclic/chemistry , Carboxylic Acids/chemistry , Oligopeptides/chemistry , Amino Acids, Cyclic/chemical synthesis , Carboxylic Acids/chemical synthesis , Cycloleucine/chemistry , Cyclopropanes/chemistry , Protein Structure, Secondary , StereoisomerismABSTRACT
The synthesis of tetrahydrofuran Calpha-tetrasubstituted amino acids (TAAs) and their effect on the conformation in small peptides are reported. The synthesis starts from the protein amino acid methionine, which is protected at the C and N terminus and converted into the corresponding sulfonium salt by alkylation. Simple base treatment in the presence of an aryl aldehyde leads to the formation of tetrahydrofuran tetrasubstituted Calpha-amino acids in a highly diastereoselective (trans/cis ratio up to 97:3) reaction with moderate to good yields (35-78%) depending on the aldehyde used. Palladium-catalyzed coupling reactions allow a subsequent further functionalization of the TAA. The R,S,S-TAA-Ala dipeptide amide adopts a beta-turn type I conformation, whereas its S,R,S isomer does not. The R,S,S-Gly-TAA-Ala tripeptide amide shows in the solid state and in solution a conformation of two consecutive beta-turn type III structures, stabilized by i+3-->i intramolecular hydrogen bonds.
