ABSTRACT
Electrooxidation has emerged as an increasingly viable platform in molecular syntheses that can avoid stoichiometric chemical redox agents. Despite major progress in electrochemical C-H activations, these arene functionalizations generally require directing groups to enable the C-H activation. The installation and removal of these directing groups call for additional synthesis steps, which jeopardizes the inherent efficacy of the electrochemical C-H activation approach, leading to undesired waste with reduced step and atom economy. In sharp contrast, herein we present palladium-electrochemical C-H olefinations of simple arenes devoid of exogenous directing groups. The robust electrocatalysis protocol proved amenable to a wide range of both electron-rich and electron-deficient arenes under exceedingly mild reaction conditions, avoiding chemical oxidants. This study points to an interesting approach of two electrochemical transformations for the success of outstanding levels of position-selectivities in direct olefinations of electron-rich anisoles. A physical organic parameter-based machine learning model was developed to predict position-selectivity in electrochemical C-H olefinations. Furthermore, late-stage functionalizations set the stage for the direct C-H olefinations of structurally complex pharmaceutically relevant compounds, thereby avoiding protection and directing group manipulations.
Subject(s)
Oxidants , Palladium , Palladium/chemistry , Oxidation-ReductionABSTRACT
Enantioselective C-H activation has surfaced as a transformative toolbox for the efficient assembly of chiral molecules. However, despite of major advances in rhodium and palladium catalysis, ruthenium(II)-catalyzed enantioselective C-H activation has thus far largely proven elusive. In contrast, we herein report on a ruthenium(II)-catalyzed highly regio-, diastereo- and enantioselective C-H alkylation. The key to success was represented by the identification of novel C2-symmetric chiral imidazolidine carboxylic acids (CICAs), which are easily accessible in a one-pot fashion, as highly effective chiral ligands. This ruthenium/CICA system enabled the efficient installation of central and axial chirality, and featured excellent branched to linear ratios with generally >20 : 1â dr and up to 98 : 2â er. Mechanistic studies by experiment and computation were carried out to understand the catalyst mode of action.
ABSTRACT
Thioethers allowed for highly atroposelective C-H olefinations by a palladium/chiral phosphoric acid catalytic system under ambient air. Both N-C and C-C axial chiral (hetero)biaryls were successfully constructed, leading to a broad range of axially chiral N-aryl indoles and biaryls with excellent enantioselectivities up to 99% ee. Experimental and computational studies were conducted to unravel the walking mode for the atroposelective C-H olefination. A plausible chiral induction model for the enantioselectivity-determining step was established by detailed DFT calculations.
ABSTRACT
A highly diastereoselective method for the synthesis of novel spiro-tetrahydroquinoline derivatives is reported here, using a one-pot reaction method. All compounds were characterized by 1H-nuclear magnetic resonance (NMR) and mass spectroscopy, and their stereo configurations were confirmed by X-ray analysis. These activities of these derivatives were then tested in human keratocyte cells. The responses of cells to treatment with selected compounds were studied using scratch analysis, and the compounds were tested in a mouse excision wound model. Three of the derivatives demonstrated significant wound-healing activities.
Subject(s)
Keratinocytes/drug effects , Quinolines/chemistry , Spiro Compounds/pharmacology , Wound Healing/drug effects , Animals , Humans , Keratinocytes/cytology , Male , Mice , Mice, Inbred C57BL , Models, Molecular , Spiro Compounds/chemistry , StereoisomerismABSTRACT
An efficient protocol for the construction of functionalized 3-alkenyl benzofurans is demonstrated under metal-free conditions using catalytic amount of phosphine proceeding an intramolecular Wittig reaction. This one-pot reaction initiated by the phospha-Michael addition of phosphine to O-acylated nitrostyrene, in which phosphine was in-situ-generated from the chemoselective reduction of phosphine oxide with PhSiH3, would provide the phosphorus ylide to result in the aforementioned multifunctionalized benzofuran via O-acylation/nitrous acid elimination/Wittig reaction.
ABSTRACT
We report a phosphine-mediated direct ß-acylation of α,ß-unsaturated 1,3-diketones with acyl chlorides and a base. Functionalized furanones were also prepared by the reaction of cinnamic acid and acyl chloride according to our protocol via ß-acylation. Our studies revealed that α,ß-unsaturated 1,3-diketones with an electron-donating group at the second position favor the formation of ß-acylated products, whereas those with oxygen, such as anhydrides, favor furanones via an unprecedented C-acylation/cyclization sequence.
ABSTRACT
An efficient synthesis of functionalized benzofurans is achieved under mild and metal-free conditions from stable para-quinone methides by treatment with phosphine, acyl chloride, and a base. This one-pot phospha-1,6-addition/O-acylation/Wittig reaction is also demonstrated under catalytic conditions with similar efficacy.
ABSTRACT
An efficient organocatalytic quadruple cascade reaction resulting in spiroxindole scaffolds bearing five quaternary stereocenters is reported. The complex cascade reaction is triggered by the scarcely explored vinylogous Michael addition of 3-alkylidene oxindoles to fully substituted enones and demonstrates the usefulness of the latter as efficient Michael acceptors in generating complex caged products in 26-92% yields, 14-98% ee and up to >25 : 1 d.r. values.
ABSTRACT
A new type of all-carbon 1,3-dipole precursor, 3-homoacylcoumarin, was employed for the stereoselective (3+2) cycloaddition with indandione alkylidenes to generate a series of coumarin/indandione-fused spirocyclopentanes bearing four contiguous stereogenic centers. While two reaction pathways progressed simultaneously, detailed mechanistic investigation revealed that the highly efficient stereoselective concerted route dominated the extremely slow stepwise pathway.