Nobuaki Kambe

Cross-Coupling Reaction of Alkyl Halides with Grignard Reagents Catalyzed by Ni, Pd, or Cu Complexes with π-Carbon Ligand(s)

Transition metal-catalyzed cross-coupling reactions of organic halides and pseudo-halides containing a C-X bond (X = I, Br, Cl, OTf, OTs, etc.) with organometallic reagents are among the most important transformations for carbon-carbon bond formation between a variety of sp, sp(2), and sp(3)-hybridized carbon atoms. In particular, researchers have widely employed Ni- and Pd-catalyzed cross-coupling to synthesize complex organic structures from readily available components. The catalytic cycle of this process comprises oxidative addition, transmetalation, and reductive elimination steps. In these reactions, various organometallic reagents could bear a variety of R groups (alkyl, vinyl, aryl, or allyl), but the coupling partner has been primarily limited to sp and sp(2) carbon compounds: alkynes, alkenes, and arenes. With alkyl coupling partners, these reactions typically run into two problems within the catalytic cycle. First, oxidative addition of alkyl halides to a metal catalyst is generally less efficient than that of aryl or alkenyl compounds. Second, the alkylmetal intermediates formed tend to undergo intramolecular beta-hydrogen elimination. In this Account, we describe our efforts to overcome these problems for Ni and Pd chemistry. We have developed new catalytic systems that do not involve M(0) species but proceed via an anionic complex as the key intermediate. For example, we developed a unique cross-coupling reaction of alkyl halides with organomagnesium or organozinc reagents catalyzed by using a 1,3-butadiene as the additive. This reaction follows a new catalytic pathway: the Ni or Pd catalyst reacts first with R-MgX to form an anionic complex, which then reacts with alkyl halides. Bis-dienes were also effective additives for the Ni-catalyzed cross-coupling reaction of organozinc reagents with alkyl halides. This catalytic system tolerates a wide variety of functional groups, including nitriles, ketones, amides, and esters. In addition, we have extended the utility of Cu-catalyzed cross-coupling reactions. With 1-phenylpropyne as an additive, Cu-catalyzed reactions of alkyl chlorides, fluorides, and mesylates with Grignard reagents proceed efficiently. These new catalytic reactions use pi-carbon ligands such as pi-allyl units or alkynes instead of heteroatom ligands such as phosphines or amines. Overall, these reactions provide new methodology for introducing alkyl moieties into organic molecules.

Synthesis of Organic-Soluble Conjugated Polyrotaxanes by Polymerization of Linked Rotaxanes

Extensive research on the use of cyclodextrin for insulating pi-conjugated polymer chains has been carried out. However, the resulting polyrotaxanes do not exhibit high and constant covering ratios and are generally insoluble in organic solvents. Here we demonstrate a new method of synthesizing permethylated cyclodextrin-based polyrotaxanes involving the polymerization of linked rotaxane monomers. The insulated molecular wires obtained by this method are highly soluble in organic solvents and have a high covering ratio, rigidity, and photoluminescence efficiency. A cholesteric liquid-crystal phase was observed for these highly rigid polyrotaxanes, in which threading of a pi-conjugated polymer chain through chiral macrocycles occurs.

Insulated Molecular Wire with Highly Conductive π-Conjugated Polymer Core

We have recently developed a new method for synthesizing polyrotaxanes with a high covering ratio, rigidity, photoluminescence efficiency, and solubility in a variety of organic solvents through the polymerization of structurally defined rotaxane monomers. The rigid rodlike structure of the pi-conjugated core polymers in these polyrotaxanes is thought to facilitate the effective transport of charge carriers. Here we applied this method to the synthesis of a polyrotaxane having a poly(phenylene ethynylene) backbone by the Sonogashira copolymerization of a structurally defined rotaxane with a linker molecule. According to time-resolved microwave conductivity and transient absorption spectroscopy measurements, the hole mobility along the pi-conjugated polymer chain of the polyrotaxane thus formed was extremely high and comparable to that in amorphous silicon.

Selenium, carbon monoxide and water as a new reduction system: Reductive cleavage of disulfides and diselenides to thiols and selenols

Abstract Disulfides and diselenides were effectively reduced to the corresponding thiols and selenols with carbon monoxide and water using selenium. Disulfides and diselenides were effectively reduced to the corresponding thiols and selenols with carbon monoxide and water using selenium.

Rhodium-catalyzed intermolecular oxidative cross-coupling of (hetero)arenes with chalcogenophenes.

A straightforward and efficient method for the rhodium-catalyzed intermolecular oxidative cross-coupling of arenes and heteroarenes with thio- and selenophene derivatives (chalcogenophenes) via double C-H bond cleavage has been developed by using Cu(OAc)2/AgSbF6 as an oxidant. The reaction is applicable to a wide range of (hetero)arenes carrying a directing group and chalcogenophenes to yield substituted biaryl heterocyclic derivatives and oligothiophene derivatives in moderate to high yields.

Conversion of a (sp3)C–F bond of alkyl fluorides to (sp3)C–X (X = Cl, C, H, O, S, Se, Te, N) bonds using organoaluminium reagents

A simple method for the conversion of (sp(3))C-F bonds of alkyl fluorides to (sp(3))C-X (X = Cl, C, H, O, S, Se, Te, N) bonds has been achieved by the use of a hexane solution of organoaluminum reagents having Al-X bonds.

Photo-Induced Ditelluration of Acetylenes with Diphenyl Ditelluride

Abstract Diphenyl ditelluride (phTeTePh) adds to a variety of acetylenes upon irradiation with visible light in the absence of solvent to provide vic-bis(phenyltelluro)alkenes in good yields. The reaction may proceed by a radical-chain mechanism that includes the addition to acetylenes of phenyltelluro radical (PhTe e ) generated in situ by photolysis of diphenyl ditelluride, followed by the S H 2 reaction between thus formed β-(phenyltelluro)alkenyl radicals and diphenyl ditelluride. In the cases of unactivated acetylenes such as 1-octyne, the addition proceeds stereoselectively to provide only (E)-vic-bis(phenyltelluro)alkenes. Contrary to this, activated acetylenes like phenylacetylene give rise to a mixture of E- and Z-isomers of vic-bis(phenyltelluro)alkenes. Since the obtained vic-bis(phenyltelluro)alkenes indicate absorption in the near-UV, irradiation with near-UV light in solvent causes a novel reverse reaction of the adducts to the starting acetylenes and diphenyl ditelluride. Accordingly, irradiation with visible light (>400 nm) under high concentrations of the substrates induces the addition of (PhTe) 2 to acetylenes, whereas irradiation with near-ultraviolet (>300 nm) under dilution condition causes the reverse reaction.

The Palladium-Catalyzed Intermolecular C–H Chalcogenation of Arenes

Palladium catalyzes the intermolecular chalcogenation of carbazole, 2-phenylpyridine, benzo[h]quinolone, and indole derivatives with disulfides and diselenides via selective C-H bond cleavage, providing a convenient route to thio and selenoethers.

Co-catalyzed cross-coupling of alkyl halides with tertiary alkyl Grignard reagents using a 1,3-butadiene additive.

The cobalt-catalyzed cross-coupling of alkyl (pseudo)halides with alkyl Grignard reagents in the presence of 1,3-butadiene as a ligand precursor and LiI is described. Sterically congested quaternary carbon centers could be constructed by using tertiary alkyl Grignard reagents. This reaction proceeds via an ionic mechanism with inversion of stereochemistry at the reacting site of the alkyl halide and is compatible with various functional groups. The use of both 1,3-butadiene and LiI was essential for achieving high yields and high selectivities.

Novel selenium catalyzed synthesis of isothiocyanates from isocyanides and elemental sulfur

Abstract A variety of aliphatic and aromatic isothiocyanates were synthesized in good to excellent yields from corresponding isocyanides and elemental sulfur under mild conditions by use of catalytic amounts of elemental selenium.