ABSTRACT
A mild protocol for the synthesis of diaryl and heteroaryl sulfides is described. In a one-pot procedure, thiols are converted to sulfenyl chlorides and reacted with arylzinc reagents. This method tolerates functional groups including aryl fluorides and chlorides, ketones, as well as N-heterocycles including pyrimidines, imidazoles, tetrazoles, and oxadiazoles. Two compounds synthesized by this method exhibited selective activity against the MCF-7 breast cancer cell line in the micromolar range.
Subject(s)
Antineoplastic Agents/chemical synthesis , Chlorides/chemistry , Imidazoles/chemistry , Ketones/chemistry , MCF-7 Cells/chemistry , MCF-7 Cells/drug effects , Sulfenic Acids/chemical synthesis , Sulfhydryl Compounds/chemistry , Sulfides/chemical synthesis , Antineoplastic Agents/chemistry , Catalysis , Humans , Molecular Structure , Sulfides/chemistryABSTRACT
Alkyl Grignard reagents that contain ß-hydrogen atoms were used in a stereospecific nickel-catalyzed cross-coupling reaction to form C(sp(3))-C(sp(3)) bonds. Aryl Grignard reagents were also utilized to synthesize 1,1-diarylalkanes. Several compounds synthesized by this method exhibited selective inhibition of proliferation of MCF-7 breast cancer cells.
Subject(s)
Alkanes/chemical synthesis , Alkanes/pharmacology , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Nickel/chemistry , Alkanes/chemistry , Antineoplastic Agents/chemistry , Catalysis , Cell Line, Tumor , Female , Humans , Hydrocarbons, Aromatic/chemical synthesis , Hydrocarbons, Aromatic/chemistry , Hydrocarbons, Aromatic/pharmacology , Indicators and Reagents , StereoisomerismABSTRACT
Stereospecific nickel-catalyzed cross-coupling reactions of benzylic 2-methoxyethyl ethers are reported for the preparation of enantioenriched 1,1-diarylethanes. The 2-methoxyethyl ether serves as a traceless directing group that accelerates cross-coupling. Chelation of magnesium ions is proposed to activate the benzylic C-O bond for oxidative addition.
