ABSTRACT
A general protocol for the palladium-catalyzed dearomative trimethylenemethane [3+2] cycloaddition reaction with simple nitroarene substrates is described. This methodology leads to the exclusive formation of the dearomatized alicyclic products without subsequent rearomatization. The reaction is tolerant toward a broad range of heterocyclic and benzenoid substrates. The use of chiral bisdiamidophosphite ligands enabled the development of an enantioselective variant of this transformation, representing one of the rare examples of an asymmetric catalytic dearomatization process.
Subject(s)
Hydrocarbons, Aromatic/chemistry , Methane/analogs & derivatives , Palladium/chemistry , Catalysis , Cycloaddition Reaction , Ligands , Methane/chemistry , Molecular Structure , Nitroquinolines/chemistry , StereoisomerismABSTRACT
The marcfortines are complex secondary metabolites that show potent anthelmintic activity and are characterized by the presence of a bicyclo[2.2.2]diazaoctane fused to a spirooxindole. Herein, we report the synthesis of two members of this family. The synthesis of marcfortine B utilizes a carboxylative TMM cycloaddition to establish the spirocyclic core, followed by an intramolecular Michael addition and oxidative radical cyclization to access the strained bicyclic ring system. In addition, the first asymmetric synthesis of (−)-marcfortine C is described. The key step involves a cyano-substituted TMM cycloaddition, which proceeds in nearly quantitative yield with high diastereo- and enantioselectivity. The resulting chiral center was used to establish all remaining stereocenters in the natural product.
Subject(s)
Alkaloids/chemical synthesis , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Indole Alkaloids/chemical synthesis , Indoles/chemical synthesis , Indolizines/chemical synthesis , Methane/analogs & derivatives , Palladium/chemistry , Spiro Compounds/chemical synthesis , Alkaloids/chemistry , Catalysis , Crystallography, X-Ray , Cyclization , Heterocyclic Compounds, 4 or More Rings/chemistry , Indole Alkaloids/chemistry , Indoles/chemistry , Indolizines/chemistry , Methane/chemistry , Models, Molecular , Molecular Structure , Oxindoles , Spiro Compounds/chemistryABSTRACT
ß,ß-Disubstituted nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. The reaction provides access to heavily substituted cyclopentanes containing up to three contiguous stereocenters, and the products may be converted to both cyclopentylamines and cyclopentenones. A rare dependence of the sense of chirality of the cycloadducts was observed to be exclusively dependent on the structure of the palladium-bound trimethylenemethane intermediate.
Subject(s)
Alkenes/chemistry , Alkenes/chemical synthesis , Cyclopentanes/chemistry , Cyclopentanes/chemical synthesis , Methane/analogs & derivatives , Nitro Compounds/chemistry , Nitro Compounds/chemical synthesis , Palladium/chemistry , Catalysis , Cycloaddition Reaction , Methane/chemistry , Molecular Structure , StereoisomerismABSTRACT
Nitroalkenes readily undergo palladium-catalyzed [3 + 2] cycloaddition with trimethylenemethane to generate nitrocyclopentanes in excellent yield and enantioselectivity. Furthermore, the products thus formed are highly versatile synthetic intermediates and provide convenient access to both cyclopentylamines and cyclopentenones.
Subject(s)
Alkenes/chemistry , Methane/analogs & derivatives , Nitrogen/chemistry , Palladium/chemistry , Catalysis , Cyclization , Ligands , Methane/chemistry , Models, Molecular , Molecular Structure , StereoisomerismABSTRACT
The palladium-catalyzed [3 + 2] cycloaddition of trimethylenemethane (TMM) with aldehydes is a direct and efficient route to methylenetetrahydrofurans. Herein we describe the first asymmetric synthesis of methylenetetrahydrofurans utilizing a palladium-TMM complex in the presence of a novel phosphoramidite ligand possessing a stereogenic phosphorus. The method allows for the formation of chiral disubstituted tetrahydrofurans in good yields and enantioselectivities.
Subject(s)
Aldehydes/chemistry , Methane/analogs & derivatives , Palladium/chemistry , Catalysis , Chromatography, High Pressure Liquid , Ligands , Methane/chemistryABSTRACT
The Bergman cyclization has long been known to produce polymers as side products. More recently, this attribute has been harnessed for the production of conjugated materials. However, the structures of these polymers have not been established. To resolve this question, the metal-catalyzed polymerization of 1,4-dibromonaphthalene and thermal polymerization of o-diethynylbenzene were conducted. Two distinct polymers were obtained. Comparison of IR spectroscopy, MALDI-TOF MS, solid-state NMR spectroscopy, UV-vis reflectance spectroscopy, and pyrolysis GC-MS data indicates that only one of the polymers is consistent with poly(1,4-naphthalene).
