ABSTRACT
An efficient and mild protocol for the visible light-induced radical cascade difluoromethylation/cyclization of imidazoles with unactivated alkenes using easily accessible and bench-stable difluoromethyltriphenylphosphonium bromide as the precursor of the -CF2H group has been developed to afford CF2H-substituted polycyclic imidazoles in moderate to good yields. This strategy, along with the construction of Csp3-CF2H/C-C bonds, is distinguished by mild conditions, no requirement of additives, simple operation, and wide substrate scope. In addition, the mechanistic experiments have indicated that the difluoromethyl radical pathway is essential for the methodology.
ABSTRACT
An efficient and facile visible-light-mediated tandem difluoromethylation/cyclization of alkenyl aldehydes, with easily accessible and air-stable [Ph3PCF2H]+Br- as the difluoromethylation reagent, has been established. A range of CF2H-substituted chroman-4-one skeletons and their derivatives, such as 2,3-dihydroquinolin-4(1H)-ones, chroman, 3,4-dihydronaphthalen-1(2H)-one, 2,3-dihydrobenzofuran, and 2,3-dihydro-1H-inden-1-one, are efficiently produced in moderate to good yields with excellent chemoselectivity under mild reaction conditions.
ABSTRACT
The aluminum(III) triflate catalyzed three-component coupling reaction of alkynes, amines and phosphorylated aryl aldehydes to access phosphoryl quinoline derivatives has been developed. The reaction proceeds in a simple system without the use of transition metals, ligands or additives, thus making it attractive for the fast preparation of a variety of new potential N-P bidentate ligands.
ABSTRACT
The visible-light-mediated tandem phosphorylation/cyclization of N-arylacrylamides with H-phosphine oxides has been developed for the synthesis of phosphorylated oxindoles. This efficient and facile process was useful for the construction of a C-P bond and triggered the formation of a C-C bond with good compatibility with functional groups undermild reaction conditions.
ABSTRACT
A Rh/Ni-catalyzed cascade sequence of allylamine isomerization and hydrophosphonylation to synthesize α-aminophosphonates has been disclosed. The reaction, which not only allows the generation of widespread valuable α-aminophosphonates under simple systems and mild conditions, but also enriches the process of olefin isomerization-addition both in catalytic systems and various reaction types.
ABSTRACT
In the cytoplasm of virtually all clear-cell renal cell carcinoma (ccRCC), speckle-type POZ protein (SPOP) is overexpressed and misallocated, which may induce proliferation and promote kidney tumorigenesis. In normal cells, however, SPOP is located in the nucleus and induces apoptosis. Here we show that a structure-based design and subsequent hit optimization yield small molecules that can inhibit the SPOP-substrate protein interaction and can suppress oncogenic SPOP-signaling pathways. These inhibitors kill human ccRCC cells that are dependent on oncogenic cytoplasmic SPOP. Notably, these inhibitors minimally affect the viability of other cells in which SPOP is not accumulated in the cytoplasm. Our findings validate the SPOP-substrate protein interaction as an attractive target specific to ccRCC that may yield novel drug discovery efforts.
Subject(s)
Carcinoma, Renal Cell/drug therapy , Kidney Neoplasms/drug therapy , Nuclear Proteins/antagonists & inhibitors , Repressor Proteins/antagonists & inhibitors , Small Molecule Libraries/pharmacology , Animals , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Female , Humans , Kidney Neoplasms/genetics , Kidney Neoplasms/metabolism , Male , Mice, Inbred BALB C , Mice, Inbred ICR , Molecular Targeted Therapy , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , Repressor Proteins/genetics , Repressor Proteins/metabolism , Signal Transduction , Ubiquitin-Protein Ligases/metabolism , Xenograft Model Antitumor AssaysABSTRACT
A novel and convenient approach to the synthesis of various phosphorated indolines via a copper-catalyzed radical cascade cyclization reaction has been developed. The reaction employs cheap copper as the catalyst and K2S2O8 as the oxidant under mild conditions. Various alkenes and P-radical precursors are compatible with this transformation. Preliminary mechanistic studies reveal that the addition of the P-radical may initiate the reaction, and then oxidative cyclization may be achieved to afford the desired product.
Subject(s)
Copper/chemistry , Indoles/chemistry , Indoles/chemical synthesis , Catalysis , Chemistry Techniques, Synthetic , Cyclization , Free Radicals/chemistry , Oxidation-Reduction , PhosphorylationABSTRACT
An efficient method for the synthesis of phosphoric fluoride via oxidative coupling between hydrophosphine oxide and NaF is reported. DDQ serves as the oxidizing reagent as well as the hydrogen acceptor. The process involves a Cu(II) catalysis and exhibits great functional group tolerance under mild reaction conditions.
Subject(s)
Copper/chemistry , Phosphines/chemistry , Benzoquinones/chemistry , Catalysis , Halogenation , Oxidation-Reduction , Sodium Fluoride/chemistryABSTRACT
A novel oxyfluorination of olefin reactions has been developed. The reactions involve a metal-free and green catalytic system for the synthesis of α-fluoroketones which is an important building block for organic synthesis. Moreover, this reaction system exhibits great functional group tolerance.
Subject(s)
Alkenes/chemistry , Hydrocarbons, Fluorinated/chemical synthesis , Ketones/chemical synthesis , Catalysis , Hydrocarbons, Fluorinated/chemistry , Ketones/chemistry , Molecular Structure , StereoisomerismABSTRACT
The first Cu(i)-catalyzed cross-coupling reaction by hydrogen (H2) removal for the stereoselective synthesis of 3-phosphoindoles is reported. Going beyond the oxidative dehydrogenative coupling reactions reported recently, this reaction completely omits the oxidant and base, producing hydrogen (H2) as the only byproduct.