Hideki Yorimitsu

Nickel-Catalyzed Carboxylation of Organozinc Reagents with CO2

An efficient nickel catalyst system for the carboxylation of organozinc reagents with CO(2) under very mild conditions has been developed. The catalyst system complements the conventional methods and enables the direct synthesis of various saturated carboxylic acid derivatives from the corresponding alkylzinc reagents and CO(2).

New synthetic reactions catalyzed by cobalt complexes

Without suffering from β-elimination, cobalt complexes allow cross-coupling reactions of alkyl halides with Grignard reagents. A combination of a cobalt complex and trimethylsilylmethyl Grignard reagent effects Mizoroki-Heck-type reaction of alkyl halide with styrene, which conventional palladium catalysts have never made possible. Cobalt exhibits intriguing catalytic activities on hydrophosphination and allylzincation of alkynes. Silylmethylcobalt reagent is a powerful tool for the synthesis of highly silylated ethenes.

Synthesis of 3-Trifluoromethylbenzo[b]furans from Phenols via Direct Ortho Functionalization by Extended Pummerer Reaction

A concise and diversity-oriented route to trifluoromethylbenzo[b]furans has been devised. A variety of phenols are directly converted to the corresponding 2-methylthio-3-trifluoromethylbenzo[b]furans by new triflic-anhydride-mediated extended Pummerer annulation reactions with trifluoromethylketene dithioacetal monoxide. The methylthio group of the products undergoes further transformations, which increase the diversity of available trifluoromethylbenzo[b]furans.

Palladium‐Catalyzed Amination of Aryl Sulfides with Anilines

A combination of a palladium-NHC catalyst and potassium hexamethyldisilazide enables the amination of aryl sulfides with anilines to afford a wide variety of diarylamines. The reaction conditions are versatile enough for the reaction of even bulky ortho-substituted aryl sulfides. This amination can be applied to the modular synthesis of N-aryl carbazoles from the corresponding ortho-bromothioanisoles. As aryl sulfoxides undergo extended Pummerer reactions to afford ortho-substituted aryl sulfides, the Pummerer products are thus useful substrates for the amination to culminate in efficient syntheses of a 2-anilinobenzothiophene and an indole as proof-of-principle of the utility of the extended Pummerer reaction/amination cascade.

Synthesis of Aziridines by Palladium‐Catalyzed Reactions of Allylamines with Aryl and Alkenyl Halides: Evidence of a syn‐Carboamination Pathway

Palladium-catalyzed intramolecular carboetherification or carboamination reactions of alkenes with organic halides emerged as an attractive method to construct heterocycles, forming both carbon–heteroatom and carbon–carbon bonds in a single operation. A number of five-membered heterocycles have been synthesized by this methodology, 3] however, the preparation of strained three-membered heterocycles has remained a challenge. We have previously reported palladium-catalyzed carboetherification reactions of tertiary allyl alcohols with aryl or alkenyl halides, which provide multisubstituted epoxides. We expected that the reaction could be extended to carboamination for the synthesis of aziridines starting from allylamines. Herein we present our preliminary results of the carboamination along with evidence for a plausible reaction mechanism. Our investigation began with a reaction of N-phenylallylamine 1a bearing two phenyl groups at the allylic position (Table 1). Treatment of 1a with bromobenzene in the presence of sodium tert-butoxide under palladium catalysis led to aziridination and C C bond formation, providing the corresponding arylated aziridine 2a in 98% yield (Table 1, entry 1). In contrast to our previous epoxidation reactions, the aziridination reaction did not suffer from a competitive Mizoroki–Heck reaction. A wide range of aryl bromides and chlorides were incorporated into the corresponding aziridines 2a–2h in excellent yields (Table 1, entries 2–9). Alkenyl chlorides also proved to be suitable substrates for the aziridination reactions (Table 1, entries 10 and 11). The reactions of several N-arylallylamines with bromobenzene were then examined (Table 2). The electronic nature of aryl substituents on the nitrogen atom did not affect the efficiency of the reaction (Table 2, entries 1 and 2). Gratifyingly, alkyl-substituted allylamines 1d and 1 e also underwent the reaction in satisfactory yields (Table 2, entries 3 and 4).

2-(2,2,2-Trifluoroethylidene)-1,3-dithiane Monoxide as a Trifluoromethylketene Equivalent

A method to prepare 2-(2,2,2-trifluoroethylidene)-1,3-dithiane monoxide has been developed, and its interesting reactivity under Pummerer-like conditions is disclosed. The products are useful synthetic intermediates for the synthesis of alpha-trifluoromethyl ketones.

Practical, Modular, and General Synthesis of Benzofurans through Extended Pummerer Annulation/Cross‐Coupling Strategy

Operationally simple, efficient, and widely applicable Pummerer annulations of simple phenols with ketene dithioacetal monoxides, with the aid of trifluoroacetic anhydride, have been shown to provide a variety of benzofurans having a methylthio group at the 2-position. Subsequent and newly developed nickel-catalyzed arylation at the methylthio group culminates in diversity-oriented synthesis of multisubstituted benzofurans. Our extended Pummerer annulation/cross-coupling sequence is powerful enough to synthesize biologically active natural products as well as highly fluorescent benzofuran derivatives.

Regiocontrolled Palladium-Catalyzed Arylative Cyclizations of Alkynols

Tuning the reactivity of arylpalladium intermediates enables control of catalytic arylative 5-exo and 6-endo cyclizations of alkynols. The two modes of cyclizations represent a rare example of controllable, regioselective difunctionalization of alkynes. The cyclizations are useful in offering a divergent synthesis of oxygen-containing heterocycles, which is of synthetic use for further derivatization. Formal synthesis of an hNK-1 receptor antagonist also showcases the utility of our arylative cyclization.

Oxidative Fusion Reactions of meso‐(Diarylamino)porphyrins

In recent years, meso-aminoporphyrins have received increasing attention owing to their potential for vastly improving the economic and environmental validity of dye-sensitized solar cells (DSSC). As a prime example, Gr tzel and co-workers have recently reported a co-sensitized DSSC device incorporating a meso-aminoporphyrin dye that is capable of a power conversion efficiency of 12.3% under simulated air mass 1.5 global sunlight conditions. Beside this, meso-aminoporphyrins have been explored as scaffolds for realizing novel nitrogen-connected dimers, mixed-valent cation radicals, inter-valence charge-transfer absorption, photo-induced reductive meso–meso dimerization, and light-harvesting supramolecular aggregates. Although the amino groups of meso-(diarylamino)porphyrins raise the porphyrin HOMO level, electronic perturbation is only moderate because the diarylamino groups twist out of the bulky porphyrin plane, minimizing conjugation. 7] Our continued interest in conjugated porphyrinoids led us to envision the fusion of a meso-diarylamino group onto the periphery of porphyrins as the expected fused porphyrin products would be interesting in their own right, because they would be structurally similar to azagraphene-type porphyrinoids. To the best of our knowledge, there are no reports of oxidative fusion of meso-aminoporphyrins, which would enable effective pexpansion by coplanarization of the peripheral nitrogen atom lone pair and porphyrin p-electronic system. meso-Phenoxazinoporphyrin 2a (Scheme 1)was prepared in 93 % yield using a Buchwald–Hartwig amination 11] of meso-bromo Ni-porphyrin 1Ni with phenoxazine using PdPEPPSI-IPent as the catalyst. By following previously reported procedures, 13] oxidative fusion of 2 a was attempted by subjecting 2a to 20 equivalents of FeCl3 and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) for 1.5 hours in CH2Cl2/MeNO2 at room temperature. This reaction afforded an unexpected fused porphyrin 3 a as a sole product in 48 % yield, in which the two 3,5-di-tertbutylphenyl groups had fused to the porphyrin periphery and not the meso-phenoxazine moiety. Although we examined numerous fusion reactions of 2a by changing the oxidants, solvents, and temperature, we could not find reaction conditions that gave us the desired phenoxazine-fused porphyrins. The ESI mass spectrum of 3a showed a parent ion peak at m/z 1107.5374 (calcd for C74H75N5NiO, m/z 1107.5320 [M]), supporting that four protons were removed as a result of oxidation. The H NMR spectrum of 3a in CDCl3 shows a singlet signal owing to the b-protons adjacent to the fused positions at 7.78 ppm. The signals related to the phenoxazine moiety do not show particularly pronounced changes. X-ray crystallographic analysis unambiguously determined the structure of 3a (Figure 1). Interestingly, the fusion reaction took place regioselectively at the bpositions, apart from the phenoxazine moiety. The UV/Vis absorption spectrum of 3a displays broad, red-shifted bands reaching out to around 880 nm, which is similar to that of closely related fused porphyrins that are not functionalized with diarylamino moieties (Figure 2). 14] The electrochemical properties of 2a and 3 a have been studied by cyclic voltammetry (see Supporting Information, Figures S40,S42). The fused porphyrin 3a displays characteristic negative shifts of Eox2 and positive shifts of Ered1, while Eox1 is only slightly affected. As a result, the electrochemical HOMO–LUMO gap of 3a (1.80 eV) is smaller than that of 2a (2.14 eV). Scheme 1. Formulas of porphyrins 1–6. Ar = 3,5-di-tert-butylphenyl.

Synthesis of a Library of Fluorescent 2‐Aryl‐3‐trifluoromethylnaphthofurans from Naphthols by Using a Sequential Pummerer‐Annulation/Cross‐Coupling Strategy and their Photophysical Properties

A library of 2-aryl-3-trifluoromethylnaphthofurans was synthesized with high efficiency from simple naphthols. In this synthesis, the Pummerer-type annulation of naphthols with 3-(2,2,2-trifluoroethylidene)-2,4-dithiapentane 2-oxide was followed by a cross-coupling of the resulting 2-methylthio-3-trifluoromethylnaphthofurans with a variety of arylzinc reagents. A palladium complex, Pd-PEPPSI-IPr, was the most efficient catalyst for the arylation step, which represents the first cross-coupling of aryl sulfides by using an N-heterocyclic-carbene-ligated palladium complex. This library consists of new π-expanded molecules, all of which are fluorescent in the solid state as well as in solution. Their photophysical properties, such as absorption and emission, fluorescence quantum yields, and fluorescence lifetimes, were thoroughly investigated. This library was also useful to identify acidochromic molecules.