ABSTRACT
Propargylamines are popular substrates for triazole formation, but tetrasubstituted variants have required multistep syntheses involving stoichiometric amounts of metal. A recent cyclohexanone-amine-silylacetylene coupling forms silyl-protected tetrasubstituted propargylamines in a single copper-catalyzed step. The development of the tandem silyl deprotection-triazole formation reported herein offers rapid access to alpha-tetrasubstituted triazoles. A streamlined two-step approach to this uncommon class of hindered triazoles will accelerate exploration of their therapeutic potential. The superior activity of copper(II) triflate in the formation of triazoles from sensitive alkyne substrates extends to simple terminal alkynes.
ABSTRACT
A one-step catalytic synthesis of 6-substituted 4-phenyl-2-(2'-pyridyl)quinolines provides electronically differentiated ligands without solvent, inert atmosphere, metal contamination, or chromatography. Gold(III) complexes formed from these bidentate PyQuin ligands were characterized and studied by single-crystal X-ray diffraction. The cationic gold(III) chloride synthesized from 6-methoxy-4-phenyl-2-(2'-pyridyl)quinoline has a distorted square-planar ligand environment. Diamagnetic neutral gold(III) complexes from methoxy-, methyl-, and phenyl-PyQuin ligands exhibit a long axial Au-N2 interaction.
Subject(s)
Gold Compounds/chemistry , Organogold Compounds/chemistry , Pyridines/chemistry , Quinolines/chemistry , Antineoplastic Agents/chemistry , Catalysis , Crystallography, X-Ray , Models, Molecular , Molecular StructureABSTRACT
Difficult-to-access alkyl-substituted quinolines are formed directly from commercially available anilines, aldehydes, and alkynes bearing a variety of substituents. Copper(II) triflate catalyzes this three-component coupling without ligand, cocatalyst, solvent, or inert atmosphere. In addition, a two-component Povarov reaction forms 2,3-dialkyl quinolines under the same green conditions that enable the selective three-component synthesis of 2-alkyl quinolines as well as more common aryl quinolines.
Subject(s)
Mesylates/chemistry , Quinolines/chemical synthesis , Aldehydes/chemistry , Alkynes/chemistry , Aniline Compounds/chemistry , Catalysis , Ligands , Molecular Structure , Quinolines/chemistrySubject(s)
Alkynes/chemistry , Amines/chemistry , Copper/chemistry , Ketones/chemistry , Titanium/chemistry , Alkynes/chemical synthesis , Amines/chemical synthesis , Carbon , Catalysis , Cyclohexanones/chemical synthesis , Cyclohexanones/chemistry , Ketones/chemical synthesis , Pargyline/analogs & derivatives , Pargyline/chemical synthesis , Pargyline/chemistry , Propylamines/chemical synthesis , Propylamines/chemistryABSTRACT
A single Cu(II) catalyst without the addition of ligand or base couples a diverse range of nitrogen sources with alkynes and aldehydes bearing alkyl, halogenated, silyl, aryl, and heteroaryl groups. The first example of a copper-catalyzed alkynylation involving p-toluenesulfonamide provides high yields of N-Ts-protected propargylamines. The superior activity of copper(II) triflate also allows this three-component alkynylation to incorporate a ketone.
Subject(s)
Aldehydes/chemistry , Alkynes/chemistry , Copper/chemistry , Nitrogen/chemistry , Catalysis , Imines/chemistry , Molecular StructureABSTRACT
A highly efficient Cu-catalyzed tandem C-N bond-forming reaction of 1,4-dihalo-1,3-dienes has been developed. The transformation allows the synthesis of pyrroles and heteroarylpyrroles with a wide variety of functional groups and substitution patterns from readily available precursors.
Subject(s)
Copper/chemistry , Pyrroles/chemical synthesis , Alkenes/chemical synthesis , Catalysis , Heterocyclic Compounds/chemical synthesis , Hydrocarbons, Halogenated/chemical synthesisABSTRACT
A new strategy for organocatalysis based on the biochemical blueprints of biosynthesis has enabled a new laboratory approach to cascade catalysis. Imidazolidinone-based catalytic cycles, involving iminium and enamine activation, have been successfully combined to allow a large diversity of nucleophiles (furans, thiophenes, indoles, butenolides, hydride sources, tertiary amino lactone equivalents) and electrophiles (fluorinating and chlorinating reagents) to undergo sequential addition with a wide array of alpha,beta-unsaturated aldehydes. These new cascade catalysis protocols allow the invention of enantioselective transformations that were previously unknown, including the asymmetric catalytic addition of the elements of HF across a trisubstituted olefin. Importantly, these domino catalysis protocols can be mediated by a single imidazolidinone catalyst or using cycle-specific amine catalysts. In the latter case, cascade catalysis pathways can be readily modulated to provide a required diastereo- and enantioselective outcome via the judicious selection of the enantiomeric series of the amine catalysts. A central benefit of combining multiple asymmetric organocatalytic events into one sequence is the intrinsic requirement for enantioenrichment in the second induction cycle, as demonstrated by the enantioselectivities obtained throughout this study (>/=99% ee in all cases).
Subject(s)
Biological Products/chemical synthesis , Organic Chemicals/chemical synthesis , Aldehydes/chemistry , Amines/chemistry , Catalysis , Imidazoles/chemistry , Imines/chemistry , Models, Chemical , Oxidation-Reduction , StereoisomerismABSTRACT
The factors controlling the highly alpha-selective C-glycosylation of ribose derivatives were determined by examining the stereoselective reactions of 18 ribose analogues differing in substitution at C-2, C-3, and C-4. The lowest energy conformers of the intermediate oxocarbenium ions display the C-3 alkoxy group in a pseudoaxial orientation to maximize electrostatic effects. To a lesser extent, the C-2 substituent prefers a pseudoequatorial position, and the alkyl group at C-4 has little influence on conformational preferences. In all cases, the product was formed by stereoelectronically preferred inside attack on the lowest energy conformer.
