Recently, we have developed visible-light-mediated functionalization of nitrogen-containing organic compounds. These reactions include photoinduced electron transfer as a key step, where the fragmentation of aminium radicals generated from one electron oxidation of amines provides the coresponding α-aminoalkyl radicals and aminobenzyl radicals and they work as reactive intermediates. This methodology provides a new approach for the synthesis of nitrogen-containing organic compounds.
Dicoordinate phosphorus-centered radical (phosphinyl radical) is a fascinating reactive intermediate in phosphorus chemistry because it has a bifunctional phosphorus center owing to an unpaired electron and a lone pair. I report herein synthesis, structure, properties, and various reactions of the first stable dialkylphosphinyl radical, 2,2,5,5-tetrakis(trimethylsilyl)-1-phosphacyclopentane-1-yl (8), which is monomeric both in solution and in the solid state. Palladium complex bearing two phosphinyl radicals as ligands (24) is also synthesized by the ligand exchange reaction of tetrakis(trimethylphosphine)palladium with two equivalents of radical 8. Complex 24 shows unique phosphorus-palladium double bond character. Antimony and bismuth analogues of phosphinyl radicals are elusive species but are thought to be important intermediates. We have succeeded in the observation of antimony- and bismuth-centered radicals (30 and 31) as persistent species in solution by the dissociation of the corresponding dimer.
This article highlights our recent studies on radical chemistry using the domino reactions constructing the carbon-carbon and carbon-heteroatom bonds. Stereocontrol in domino radical addition-cyclization-trapping reactions was achieved by new approach, which contains hydroxamate ester moiety as a chiral Lewis acid-coordinating tether between two radical acceptors. The polarity-mismatched perfluoroalkyl radical addition was next studied. The domino reaction with perfluoroalkyl radicals proceeded via the unfavorable polarity-mismatched addition of electrophilic radicals to electron-deficient acceptors. The photo-induced domino reactions were also studied in aqueous media. The photocatalyst, Ru(bpy)3Cl2·6H2O, has the potential to induce the carbon-carbon bond-forming reactions in aqueous media. In the presence of water, the photo-induced electron transfer (PIET) from the excited singlet state of rhodamine B smoothly proceeded and promoted domino reactions.
The first total synthesis of (±)-neovibsanin B (6), a novel polyfunctionalized diterpenoid, was established based on an intramolecular Diels-Alder reaction accelerated with 1,3-dimethyl-2-imidazolidinone (DMI) and a subsequent oxa-Michael addition-lactonization reaction. Furthermore we revealed that the neurite outgrowth activity of racemic 6 is almost the same as that of natural (+)-6. We have also synthesized structurally-simplified neovibsanin derivatives, such as 32, based on the synthetic method developed for the total synthesis of (±)-6. A fluorescent analog 49 that retains neurite outgrowth activity was synthesized, and its behavior in PC12 cells has been analyzed. We also established the formal synthesis of (+)-6 based on a newly developed asymmetric Michael addition and palladium (0)-catalyzed carbonylative cyclization.
Use of easily handled, liquid or solid carbon monoxide (CO) sources instead of toxic CO gas can contribute to reduce the risk and anxiety of accidents in organic synthesis, thus accelerating the research in carbonylative transformations and increasing the diversity of chemical products. Based on the discovery that phenyl formate could generate CO in the presence of a weak base, we considered utilization of phenyl formate as a CO source to develop “external-CO-free” synthetic methods of high safety and practicality. This concept led us to develop a series of Pd-catalyzed carbonylative transformations with formic acid derivatives as CO sources. In parallel, 2,4,6-trichlorophenyl formate and N-formylsaccharin were developed as highly crystalline but highly reactive CO sources. These novel reactions without use of CO gas efficiently afforded various carbonyl compounds in a one-pot manner in good to excellent yields. We also demonstrated gram-scale synthesis using ordinary glassware, which showed high practicality and feasibility for further scale-up.
Axially chiral biaryl units are key components of natural products and biologically active compounds as well as chiral molecular catalysts, and thus significant efforts have been focused on the efficient synthesis of atropisomerically enriched axially chiral biaryls. Among a variety of strategies, dynamic kinetic resolution is considered as an efficient method in asymmetric synthesis since highly enantio-enriched products could be furnished in quantitative yields from racemic starting materials in the best case. This review highlights recent progress of dynamic kinetic asymmetric transformations of racemic axially chiral biaryls by using transition-metal catalysts.
Looking back on a quarter-century or so, what kinds of discovery have been achieved in terms of asymmetric catalysis by use of optically active nitrogen-based tridentate ligands, 2,6-bis(oxazolinyl)pyridine (Pybox) and 2,6-bis(oxazolinyl)phenyl (Phebox).