ABSTRACT
The first general ß-selective C-H arylation of pyrroles has been developed by using a rhodium catalyst. This C-H arylation reaction, which is retrosynthetically straightforward but results in unusual regioselectivity, could result in de novo syntheses of pyrrole-derived natural products and pharmaceuticals. As such, we have successfully synthesized polycyclic marine pyrrole alkaloids, lamellarins C and I, by using this ß-selective arylation of pyrroles with aryl iodides (C-H/C-I coupling) and a new double C-H/C-H coupling as key steps.
Subject(s)
Alkaloids/chemical synthesis , Biological Products/chemical synthesis , Pyrroles/chemistry , Alkaloids/chemistry , Biological Products/chemistry , Catalysis , Iodides/chemical synthesis , Iodides/chemistry , Pyrroles/chemical synthesis , Rhodium/chemistryABSTRACT
Direct C-H phenylation of 2-ethylthiophene and 2-chlorothiophene with PhPdI(bipy) complex to form either the corresponding 4-phenyl or 5-phenylthiophene derivative is studied under stoichiometric conditions using various Lewis acids as additives. It is shown that reactions occur via the corresponding cationic Pd complex (PhPdbipy(+)) and that the counteranion determines the regioselectivity. High-level DFT calculations reveal that C-C bond formation occurs via a carbopalladation pathway and not via electrophilic palladation. These calculations give some indications regarding the regioselectivity of the thiophene arylation.
Subject(s)
Boronic Acids/chemistry , Palladium/chemistry , Thiazoles/chemistry , Thiophenes/chemistry , Alzheimer Disease/drug therapy , Amyloid Precursor Protein Secretases/antagonists & inhibitors , Amyloid Precursor Protein Secretases/metabolism , Boronic Acids/therapeutic use , Carbon/chemistry , Catalysis , Cyclic N-Oxides/chemistry , Humans , Hydrogen/chemistry , Oxidation-Reduction , Protease Inhibitors/chemical synthesis , Protease Inhibitors/chemistry , Protease Inhibitors/therapeutic use , StereoisomerismABSTRACT
A general protocol for the programmed synthesis of tetraarylthiophenes has been established. The utilization of three catalysts, RhCl(CO){P[OCH(CF(3))(2)](3)}(2), PdCl(2)/P[OCH(CF(3))(2)](3), and PdCl(2)/bipy, enables regioselective sequential arylations at the three C-H bonds of 3-methoxythiophene with iodoarenes. Interesting metal- and ligand-controlled regiodivergent C-H arylations have been uncovered during this study. The installation of fourth aryl groups to the thus-generated 2,4,5-triaryl-3-methoxythiophenes has been accomplished through a sequence of demethylation, triflation, and Suzuki-Miyaura coupling.
Subject(s)
Carbon/chemistry , Hydrogen/chemistry , Thiophenes/chemistry , Thiophenes/chemical synthesis , Oxygen/chemistry , Stereoisomerism , Substrate SpecificityABSTRACT
The biaryl coupling of electron-deficient nitrogen heterocycles and haloarenes can be promoted by potassium t-butoxide alone, without the addition of any exogenous transition metal species. Electron-deficient nitrogen heterocycles such as pyridine, pyridazine, pyrimidine, pyrazine, and quinoxaline are arylated with haloarenes. Control experiments support a radical-based mechanism. Taking these findings into account, radical processes may be partially involved in the reported transition-metal-catalyzed arylation reactions employing t-butoxide bases and haloarenes under elevated temperatures or under microwave irradiation.
