Photoenols generated in situ from ortho-methyl-substituted phenylketones such as benzophenones and acetophenones were trifluoromethylated with Togni reagent without any additive or catalyst. This trifluoromethylation reaction proceeded smoothly under photoirradiation conditions (365 nm). Various functional groups were tolerant of the reaction conditions. Interestingly, the trifluoromethyl group was exclusively introduced at the ortho-benzylic position. Mechanistic studies suggested that this reaction proceeds via formation of a photoenol, not via a radical pathway.

Difunctionalization of alkenes with 1-chloro-1,2-benziodoxol-3-(1H)-one (1) was investigated. Various additional nucleophiles were tested, and oxychlorination, dichlorination, azidochlorination, chlorothiocyanation, and iodoesterfication were demonstrated. The oxychlorination product was obtained efficiently when the reaction was operated in water. Dichlorination occurred in the presence of a Lewis basic promoter, such as 4-phenylpyridine N-oxide, as an additive. The reaction with in situ-generated azido anion afforded azidochlorinated compounds with a chlorine atom at the terminal position, while the reaction with trimethylsilyl isothiocyanate produced chlorothiocyanation adducts with a chlorine atom at the benzylic position. On the other hand, when 1 was treated with tetra-n-butylammonium iodide prior to the addition of alkenes, only iodoesterification occurred selectively. These mild reactions enable convenient site-selective difunctionalizations of substrates having two alkene moieties. NMR experiments suggested that the electrophilic reactive species in each reaction varied depending on the nature of the added nucleophile.

We report the first successful example of a highly enantioselective fluorolactonization with an electrophilic fluorinating reagent, Selectfluor®, in the presence of a novel bifunctional organocatalyst. The catalyst design includes a carboxylate anion functioning as a phase-transfer agent and a benzyl alcohol unit to capture the substrate through hydrogen bonding. Fluorinated isobenzofuranones were obtained in good yields with up to 94% ee (97:3 er). On the basis of mechanistic studies, we propose a unique reaction mechanism with potential for further applications.

Phenol derivatives were trifluoromethylated using copper/Togni reagent. In dimethylformamide, the benzylic C–H bond at the para position of the hydroxyl group was selectively substituted with a CF3 group. In contrast, aromatic C–H trifluoromethylation occurred in alcoholic solvents. Practical utility of the reactions was demonstrated by application to the synthesis of a potent enoyl-acyl carrier protein reductase (FabI) inhibitor.

A highly enantioselective bromocyclization of allylic amides with N-bromosuccinimide (NBS) was developed with DTBM-BINAP as a catalyst, affording chiral oxazolines with a tetrasubstituted carbon center in high yield with up to 99% ee. By utilizing the bromo substituent as a handle, the obtained compounds were converted to synthetically useful chiral building blocks.

3,3′-Disubstituted 1,1′-binaphthyl-2,2′-dicarboxylic acids (1) were synthesized in three or four steps from commercially available BINOL via carbon dioxide fixation with organolithium to incorporate the carboxylic acid moieties, followed by either carboxylate-directed ortho-C–H arylation or Suzuki cross-coupling. This method provides easy access to various types of axiially chiral dicarboxylic acids, which should be useful for studies of chiral Brønsted acid-catalyzed asymmetric reactions.

Practical total syntheses of acromelic acids A (1) and B (2), which have potent neuro-excitatory activity, were accomplished in 13 (36% total yield) and 17 steps (6.9% total yield), respectively, from 2,6-dichloropyridine (8). Regioselective transformation of symmetric 8 provided nitroalkenes 15 and 16. The pyrrolidine ring was efficiently constructed by Ni-catalyzed asymmetric conjugate addition followed by intramolecular reductive amination.

The total synthesis of hedyotol A (1), a natural product isolated from Hedyotis lawsoniae (DC.) Wight et Arn. (Rubiaceae), was accomplished in a highly stereocontrolled manner. Key steps include an l-proline-catalyzed cross-aldol reaction and the biomimetic construction of a furofuran lignan skeleton through a quinomethide intermediate.

A practical total synthesis of kainoid MFPA (5) was achieved in only six steps, via a novel Ni-catalyst-mediated asymmetric conjugate addition reaction. Furthermore, a fluorescein-based fluorescent ionotropic glutamate receptor probe 28 was efficiently synthesized from a precursor derived from a synthetic intermediate of 5.

Asymmetric bromolactonization of prochiral cyclohexadiene derivatives with N-bromosuccimide proceeded in the presence of (DHQD)2PHAL as a chiral catalyst to afford the corresponding bromolactones with up to 93% ee. This reaction was also applicable to the kinetic resolution of a racemic cyclic ene-carboxylic acid, where the starting material was recovered with high enantioselectivity.

Phenol derivatives were trifluoromethylated using copper/Togni reagent. In dimethylformamide, the benzylic C–H bond at the para position of the hydroxyl group was selectively substituted with a CF3 group. In contrast, aromatic C–H trifluoromethylation occurred in alcoholic solvents. Practical utility of the reactions was demonstrated by application to the synthesis of a potent enoyl-acyl carrier protein reductase (FabI) inhibitor.