Kou Hiroya

Palladium-Catalyzed Synthesis of 2-Substituted Benzothiazoles via a C−H Functionalization/Intramolecular C−S Bond Formation Process

Catalytic synthesis of 2-substituted benzothiazoles from thiobenzanilides was achieved in the presence of a palladium catalyst through C-H functionalization/C-S bond formation. This method features the use of a novel catalytic system consisting of 10 mol % of Pd(II), 50 mol % of Cu(I), and 2 equiv of Bu4NBr that produced variously substituted benzothiazoles in high yields with good functional group tolerance.

Palladium-Catalyzed Intramolecular Amidation of C(sp2)−H Bonds: Synthesis of 4-Aryl-2-quinolinones

A catalytic synthetic approach for the synthesis of 2-quinolinone compounds through a Pd-catalyzed C(sp(2))-H functionalization/intramolecular amidation sequence is described. The cyclization process efficiently proceeds in the presence of a catalytic amount of PdCl(2) and Cu(OAc)(2) under an O(2) atmosphere, providing practical access to a range of variously substituted 4-aryl-2-quinolinones.

Efficient construction of indole rings from 2-ethynylaniline derivatives catalyzed by copper(II) salts and its application to the tandem cyclization reactions

Abstract The efficient cyclization reactions of the N -methanesulfonyl or N -ethoxycarbonyl derivatives of 2-ethynylanilines, functionalized on the benzene ring and/or the acetylene terminal into indoles catalyzed by either Cu(OTf) 2 or Cu(OAc) 2 are accomplished. The application of this reaction to the tandem cyclization reaction is also described.

Cyclization reactions of 2-alkynylbenzyl alcohol and 2-alkynylbenzylamine derivatives promoted by tetrabutylammonium fluoride

Abstract The regioselectivity of the cyclization reaction of 2-ethynylbenzyl alcohol and 2-ethynylbenzylamine derivatives promoted by TBAF was investigated. Six-membered ring derivatives were obtained from the compounds, which have a butyl group on the triple bond. Whereas five-membered ring products were afforded from the substrates having hydrogen or aromatic substituents on the acetylene moiety. It was also concluded that both the tetrabutylammonium cation and fluoride anion were essential for the cyclization. Thus, the actual mechanism and catalytic cycle were also suggested.

Cobalt-catalyzed hydrofluorination of unactivated olefins: a radical approach of fluorine transfer.

Catalytic hydrofluorination of olefins using a cobalt catalyst was developed. The exclusive Markovnikov selectivity, functional group tolerance, and scalability of this reaction make it an attractive protocol for the hydrofluorination of olefins. A preliminary mechanistic experiment showed the involvement of a radical intermediate.

Hydroalkoxylation of Unactivated Olefins with Carbon Radicals and Carbocation Species as Key Intermediates

A unique Markovnikov hydroalkoxylation of unactivated olefins with a cobalt complex, silane, and N-fluoropyridinium salt is reported. Further optimization of reaction conditions yielded high functional group tolerance and versatility of alcoholic solvent employed, including methanol, i-propanol, and t-butanol. Use of trifluorotoluene as a solvent made the use of alcohol in stoichiometric amount possible. Mechanistic insight into this novel catalytic system is also discussed. Experimental results suggest that catalysis involves both carbon radical and carbocation intermediates.

Catalytic Hydroamination of Unactivated Olefins Using a Co Catalyst for Complex Molecule Synthesis

Functional group tolerance is one of the important requirements for chemical reactions, especially for the synthesis of complex molecules. Herein, we report a mild, general, and functional group tolerant intramolecular hydroamination of unactivated olefins using a Co(salen) complex, an N-fluoropyridinium salt, and a disiloxane reagent. This method, which was carried out at room temperature (or 0 °C), afforded three-, five-, six-, and seven-membered ring nitrogen-containing heterocyclic compounds and was compatible with diverse functional groups.

Synthesis of betulin derivatives and their protective effects against the cytotoxicity of cadmium.

The protecting effect of betulin against cadmium toxicity was investigated using 11 kinds of analogues. It was elucidated by analyzing the analogue activities that both hydroxyl groups on C-3 and C-28 and the isopropenyl group on C-19 played important roles for expressing efficient activities. In addition, the cytotoxicity of betulin was also reduced by being functionalized using the above functional group.

Role of Glu318 and Thr319 in the catalytic function of cytochrome P450d (P4501A2): effects of mutations on the methanol hydroxylation.

Polar amino acids in the (putative) distal site are well conserved in P450s. For example, Glu318 for P450d is well conserved as either Glu or Asp for P450s, and Thr319 for P450d is also conserved for P450s. We have studied how mutations at Glu318 and Thr319 of P450d influence the catalytic activity toward methanol associated with the activation of O2. Catalytic activities of Glu318Asp, Glu318Ala, and Thr319Ala mutants toward methanol were 60, 25, and 38%, respectively, compared with that of the wild type. O2 consumption and NADPH oxidation rates of each mutants varied corresponding to the catalytic activities. However, surprisingly, efficiency (16–40%) of incorporated O to the substrate vs. consumed O2 for the Glu318Ala and Thr319Ala mutants were higher than that (9%) of the wild type. In addition, H2O2, which is produced from uncoupling for the wild‐type P450d, was not observed for reaction of the Glu318Ala and Thr319Ala mutants. It seemed that consumed O2 was partially reduced to 2 mol of H2O by 4‐electron transfer from NADPH for the wild‐type and Thr319Ala mutant. However, for the two Glu318 mutants, it appeared that the consumed O2 was not reduced in the same way. It was thus suggested that the conserved Glu318 and Thr319 of P450d are not essential for the activation of O2 in the methanol oxidation. Role of the water molecule or the methanol molecule in the catalytic function was implied.—Hiroya, K.; Ishigooka, M.; Shimizu, T.; Hatano, M. Role of Gly318 and Thr319 in the catalytic function of cytochrome P450d: effects of mutations on the methanol hydroxylation. FASEB J. 6: 749‐751; 1992.

An efficient and highly regioselective intramolecular Mannich-type reaction: A construction of the AEF ring system of aconitine-type diterpene alkaloids

Abstract An efficient and highly regioselective intramolecular Mannich-type reaction has been developed. The utility of the methodology, combined with a stereoselective intramolecular Diels-Alder reaction, for the construction of the AEF ring system of aconitine-type alkaloids has been exemplified.