Mechanistic insights into the role of cyclodextrin in the regioselective radical CH trifluoromethylation of aromatic compounds.

The regioselective radical CH trifluoromethylation of aromatic compounds have been shown to proceed in good yield and high regioselectivity when cyclodextrin (CD) is present. Yet, the reaction mechanism and the role of CD during the reaction have remained obscure. To this end, here we performed density functional theory (DFT) calculations to the conformations obtained by semiempirical quantum mechanical molecular dynamics calculations to reveal the reaction mechanism and the role of CD in controlling regioselectivity. The results show that metal salt increases the yield but do not affect the regioselectivity, which we further confirmed by an experiment. In contrast, multiple CD-substrate complex conformations and reaction pathways were obtained, and CD was shown to contribute to improving the regioselectivity by stabilizing the intermediate state via encapsulation. The present study indicates that CDs can increase the regioselectivity by stabilizing the intermediate and product states while only marginally affecting the transition state.

Gold-Catalyzed Synthesis of 5H-Benzo[b]indeno[2,1-d]silines by Insertion of Vinyl Carbocations into the Si-H Bond.

We have developed a gold-catalyzed cascade reaction of aryldiynes bearing a hydrosilyl group to afford a variety of unexplored 5H-benzo[b]indeno[2,1-d]silines. The reaction system is applicable to the synthesis of bidirectionally π-extended silacycles from tetra(alkynyl)aryl compounds. Computational studies suggest that 5H-benzo[b]indeno[2,1-d]silines are formed via the insertion of a vinyl carbocation intermediate into the Si-H bond.

Iridium(III)-Catalyzed Asymmetric Site-Selective Carbene C-H Insertion during Late-Stage Transformation.

C-H functionalization has recently received considerable attention because C-H functionalization during the late-stage transformation is a strong and useful tool for the modification of the bioactive compounds and the creation of new active molecules. Although a carbene transfer reaction can directly convert a C-H bond to the desired C-C bond in a stereoselective manner, its application in late-stage material transformation is limited. Here, we observed that the iridium-salen complex 6 exhibited efficient catalysis in asymmetric carbene C-H insertion reactions. Under optimized conditions, benzylic, allylic, and propargylic C-H bonds were converted to desired C-C bonds in an excellent stereoselective manner. Excellent regioselectivity was demonstrated in the reaction using not only simple substrate but also natural products, bearing multiple reaction sites. Moreover, based on the mechanistic studies, the iridium-catalyzed unique C-H insertion reaction involved rate-determining asynchronous concerted processes.

Highly Modified Lanostane Triterpenes from the Wood-Rot Basidiomycete Ganoderma colossus: Comparative Chemical Investigations of Natural and Artificially Cultivated Fruiting Bodies and Mycelial Cultures.

The wood-rot basidiomycete Ganoderma colossus has been chemically investigated. Comparative analyses of the natural fruiting body, artificially cultivated fruiting bodies, and mycelial cultures resulted in the isolation, in total, of 13 new highly modified lanostanes, ganocolossusins A-H (1-8) and ganodermalactones T-X (9-13), together with 23 known compounds (14-36). There were significant overlaps of the same compounds among the three different states of the fungal materials. Ganocolossusin D (4) displayed the most potent antimalarial activity against Plasmodium falciparum K1 (multi-drug-resistant strain) with an IC50 value of 2.4 µM, while it was noncytotoxic to Vero cells at 50 µg/mL.

Theoretical investigations of Rh-catalyzed asymmetric 1,4-addition to enones using planar-chiral phosphine-olefin ligands.

Recently, planar-chiral phosphine-olefin ligands based on (η6 -arene)chromium(0) and (η5 -cyclopentadienyl)manganese(I), which are known as first- and second-generation, respectively, have been developed. These ligands were employed for Rh-catalyzed asymmetric 1,4-addition to enones. First-generation ligands involve high enantioselectivity for cyclic enones (>98% ee). Second-generation ligands involve high enantioselectivity for not only cyclic enones but also for acyclic enones (>98% ee). In this study, we have performed DFT calculations to investigate the origin of enantioselectivity. The theoretical values of enantioselectivities were found to be in good agreement with the experimental values obtained for a cyclic enone, 2-cyclopenten-1-one, using both the first- and second-generation ligands. Regarding an acyclic enone, 3-penten-2-one, it was found that the s-cis type decreases the enantioselectivity because the transition states in the s-cis type have a large steric repulsion. Energy decomposition analysis (EDA) and natural bond orbital (NBO) analysis indicate that it is important to study the orbital interactions in the transition states of the insertion step for the acyclic enone attacked from si-face with the second-generation ligand. © 2018 Wiley Periodicals, Inc.

π-π Stacking Interaction in an Oxidized CuII -Salen Complex with a Side-Chain Indole Ring: An Approach to the Function of the Tryptophan in the Active Site of Galactose Oxidase.

In order to gain new insights into the effect of the π-π stacking interaction of the indole ring with the CuII -phenoxyl radical as seen in the active form of galactose oxidase, we have prepared a CuII complex of a methoxy-substituted salen-type ligand, containing a pendent indole ring on the dinitrogen chelate backbone, and characterized its one-electron-oxidized forms. The X-ray crystal structures of the oxidized CuII complex exhibited the π-π stacking interaction of the indole ring mainly with one of the two phenolate moieties. The phenolate moiety in close contact with the indole moiety showed the characteristic phenoxyl radical structural features, indicating that the indole ring favors the π-π stacking interaction with the phenoxyl radical. The UV/Vis/NIR spectra of the oxidized CuII complex with the pendent indole ring was significantly different from those of the complex without the side-chain indole ring, and the absorption and CD spectra exhibited a solvent dependence, which is in line with the phenoxyl radical-indole stacking interaction in solution. The other physicochemical results and theoretical calculations strongly support that the indole ring, as an electron donor, stabilizes the phenoxyl radical by the π-π stacking interaction.

Bifunctional 1-Hydroxypyrene Photocatalyst for Hydrodesulfurization via Reductive C(Aryl)-S Bond Cleavage.

We developed the visible-light-induced hydrodesulfurization of alkyl aryl thioethers via the reductive cleavage of the C(aryl)-S bond using 1-hydroxypyrene as a Brønsted acid-reductant bifunctional photocatalyst. The hydrodesulfurization reaction proceeded under simple reaction conditions (1-hydroxypyrene and Et3N in THF under purple LED illumination); this reaction did not require chemicals commonly used for hydrodesulfurization, such as hydrosilanes, transition metal catalysts, and/or stoichiometric amounts of metal reagents. Detailed mechanistic studies based on control experiments, spectroscopic measurements, and computational studies revealed that the cleavage of the C(aryl)-S bond and the formation of the C(aryl)-H bond proceeded via the formation of the ion pair between the radical anion of alkyl aryl thioether and Et3N+H, resulting in the generation of a sulfur radical. In addition, the 1-hydroxypyrene catalyst was regenerated via hydrogen atom transfer (HAT) from Et3N.

Photoinduced Divergent Deaminative Borylation and Hydrodeamination of Primary Aromatic Amines.

We have developed the divergent deaminative borylation and hydrodeamination of primary aromatic amines using bis(pinacolato)diboron. These transformations can be switched by the reaction conditions. Mechanistic and computational studies have suggested that the cleavage of the C-N bond and the formation of C-B bond are unlikely to involve free aryl radical intermediates. However, hydrodeamination is shown to proceed via hydrogen atom transfer between the corresponding aryl radical and an ethereal solvent.

Combined Computational and Experimental Studies on the Asymmetric Michael Addition of α-Aminomaleimides to ß-Nitrostyrenes Using an Organocatalyst Derived from Cinchona Alkaloid.

Maleimides are often used as electrophiles in conventional reactions; however, their application as nucleophiles is limited to only a few reactions, and reactions utilizing α-aminomaleimides as asymmetric Michael donors have not been reported to date. Thus, in this work, asymmetric Michael addition of α-aminomaleimides as Michael donors to ß-nitrostyrenes was conducted for the first time using an organocatalyst derived from a Cinchona alkaloid. Density functional theory investigations were crucial to improve the enantioselectivity of the adduct.

The effect of π-π stacking interaction of the indole ring with the coordinated phenoxyl radical in a nickel(ii)-salen type complex. Comparison with the corresponding Cu(ii) complex.

In order to gain new insights into the effect of the π-π stacking interaction of the indole ring with the phenoxyl radical moiety as seen in the active form of galactose oxidase, we have prepared Ni(ii) complexes of a methoxy substituted salen-type ligand containing a pendent indole ring on the dinitrogen chelate backbone and characterized their one-electron oxidized forms. The X-ray crystal structure analysis and the other physicochemical experiments of the Ni(ii) complex revealed no significant intramolecular interaction of the indole ring with the coordination plane. On the other hand, the X-ray crystal structures of the oxidized Ni(ii) complex exhibited the π-π stacking interaction of the indole ring mainly with one of the two phenolate moieties. While the phenoxyl radical electron was delocalized on the two phenolate moieties in the Ni(ii)-salen coordination plane, the phenolate moiety in close contact with the indole moiety was considered to be the initial oxidation locus, indicating that the indole ring interacted with the phenoxyl radical by π-π stacking. The UV-vis-NIR spectrum of the oxidized Ni(ii) complex with the pendent indole ring was different from that of the complex without the side chain indole ring, but the differences were rather small in comparison with the oxidized Cu(ii)-salen complexes with the π-π stacking interaction of the indole ring. Such differences are due to the electronic structure difference, the localized radical electron on one of the phenolate moieties in the oxidized Cu(ii) complexes being more favorable for the π-π stacking interaction.