Cp*M-Catalyzed Direct Annulation with Terminal Alkynes and Their Surrogates for the Construction of Multi-Ring Systems

Transition-metal-catalyzed C–H activation followed by oxidative cyclization with unsaturated coupling partners has been a valuable synthetic tool for the multi-ring molecular scaffolds. This Perspective introduces the recent progress on the Cp*M-catalyzed (M = Co, Rh, and Ir) oxidative direct annulation of functionalized arenes with terminal alkynes and their equivalents through C–H bond cleavage. The highlighted examples are categorized according to the ten different types of reagents used in the transfor-mations. The representative conditions, selected examples of the reaction scope, and key mechanistic aspects are briefly summarized.Nishii Y., Miura M.. Cp*M-Catalyzed Direct Annulation with Terminal Alkynes and Their Surrogates for the Construction of Multi-Ring Systems. ACS Catalysis. 10(17), 9747-9757, (2020), 4 September 2020; ©2020 American Chemical Society. https://doi.org/10.1021/acscatal.0c02972

Copper-catalyzed site-selective direct arylation of triptycene

A site-selective direct CH arylation protocol for the triptycene skeleton is developed using copper catalyst and diaryliodonium reagents. With the aid of directing groups, C₃-symmetric trisubstituted triptycenes are selectively synthesized, and the structure was determined by X-ray diffraction analysis. Further derivatization of the installed bromo functionalities is also described

Oxidative C-H/C-H Annulation of Imidazopyridines and Indazoles through Rhodium-Catalyzed Vinylene Transfer

Transition-metal-catalyzed C−H activation followed by oxidative annulation with alkynes has been an efficient syn-thetic tool for the assembly of various poly-aromatic scaffolds. Despite the substantial progress in this field, it is still a significant challenge to achieve the synthesis of non-substituted vinylene-fused compounds. In this contribution, we report a Rh-catalyzed C−H/C−H vinylene cyclization adopting vinylene carbonate as a “vinylene transfer” agent. This protocol achieves the direct annula-tive π-extension of imidazole- and pyrazole-fused aromatics.Ghosh K., Nishii Y., Miura M.. Oxidative C-H/C-H Annulation of Imidazopyridines and Indazoles through Rhodium-Catalyzed Vinylene Transfer. Organic Letters. 22(9), 3547-3550, (2020), 1 May 2020; ©2020 American Chemical Society. https://doi.org/10.1021/acs.orglett.0c00975

Synthesis and Optical Properties of Axially Chiral Bibenzo[ b]carbazole Derivatives

Pure organic materials with the circularly polarized luminescence (CPL) property have attracted significant research interest over the past few decades. In this study, a series of axially chiral bibenzo[b]carbazole derivatives were synthesized by adopting palladium- and iridium-catalyzed direct C–H functionalization reactions as the key steps. These compounds exhibited CPL characteristics with considerably large dissymmetry factors up to 2.81 × 10–2 in the solid state, indicating the formation of well-ordered aggregates.Takishima R., Nishii Y., Miura M.. Synthesis and Optical Properties of Axially Chiral Bibenzo[ b]carbazole Derivatives. Organic Letters. 23(4), 1349-1354, (2021); 19 February 2021: ©2021 American Chemical Society. https://doi.org/10.1021/acs.orglett.1c00011

Ligand-Enabled Copper-Catalyzed Regio- and Stereoselective Allylboration of 1-Trifluoromethylalkenes

A copper-catalyzed regio- and stereoselective allylboration of 1-trifluoromethylalkenes with bis(pinacolato)diboron (pinB-Bpin) and allylic chlorides has been developed to form functionalized trifluoromethylated products with high diastereoselectivity. The key to success is the judicious choice of Cs2CO3 base and t-Bu-modified dppe-type ligand, which enables the otherwise challenging high catalyst turnover and suppression of the competing defluorination side reaction from an alkylcopper intermediate. The product derivatization of the resulting Bpin moiety can deliver diverse CF3-containing molecules with high stereochemical fidelity.Kojima Y., Nishii Y., Hirano K.. Ligand-Enabled Copper-Catalyzed Regio- and Stereoselective Allylboration of 1-Trifluoromethylalkenes. Organic Letters. 24(40), 7450-7454, 14 October 2022; https://doi.org/10.1021/acs.orglett.2c03024

Selective Synthesis of C4-Functionalized Benzofurans by Rhodium-Catalyzed Vinylene Transfer: Computational Study on the Cyclopentadienyl Ligand

Benzofuran is a privileged structure in many bioactive compounds; however, the controlled synthesis of C2,C3-non-substituted benzofurans has been scares. In particular, cumbersome multistep processes are inevitable for the most inaccessible C4-substituted isomers. Herein, we report a Rh-catalyzed direct vinylene annulation of readily available m-salicylic acid derivatives with vinylene carbonate to achieve selective construction of C4-substituted benzofurans. The Weinreb amide directing group facilitated the following product derivatization. The reaction mechanism was investigated by DFT calculations.Kitano J., Nishii Y., Miura M.. Selective Synthesis of C4-Functionalized Benzofurans by Rhodium-Catalyzed Vinylene Transfer: Computational Study on the Cyclopentadienyl Ligand. Organic Letters. 24(31), 5679-5683, (2022), 12 August 2022; ©2022 American Chemical Society. https://doi.org/10.1021/acs.orglett.2c02030

Electrophilic substitution of asymmetrically distorted benzenes within triptycene derivatives

Herein we disclose a unique directing effect of 9-substituted triptycenes in electrophilic substitution to achieve the regioselective functionalization of the triptycene core. The Hirshfeld population analysis was adopted to predict the selectivity in electrophilic substitution. TMS and t-Bu groups were found to considerably accelerate the reaction at C2 positions to produce C3-symmetric isomers. Correlation between distortion and charge distribution within benzene rings was systematically examined.Ueno K., Nishii Y., Miura M.. Electrophilic substitution of asymmetrically distorted benzenes within triptycene derivatives. Organic Letters. 23(9), 3552-3556, (2021), 7 May 2021; ©2021 American Chemical Society. https://doi.org/10.1021/acs.orglett.1c00970

Rhodium-Catalyzed Annulative Coupling Using Vinylene Carbonate as an Oxidizing Acetylene Surrogate

Transition-metal-catalyzed C–H activation and subsequent oxidative cyclization with alkynes has been a pow-erful tool for the synthesis of polycyclic aromatic compounds. Despite the substantial progress in this field, it is still a significant challenge to establish synthetic methodologies for the construction of non-substituted vinylene-fused aromatics. We herein report a Rh(III)-catalyzed C–H/N–H annulation with vinylene carbonate as an acetylene surrogate. Vinylene carbonate also acts as an internal oxidant to regenerate the Rh(III) species in situ; thus no external oxidant is required to trigger the oxidative annulation. This protocol is applicable to the direct synthesis of various N-heteroaromatics.Ghosh K., Nishii Y., Miura M.. Rhodium-Catalyzed Annulative Coupling Using Vinylene Carbonate as an Oxidizing Acetylene Surrogate. ACS Catalysis. 9(12), 11455-11460, (2019), 6 December 2019; ©2019 American Chemical Society. https://doi.org/10.1021/acscatal.9b04254

Metal-Free Direct Trifluoromethylthiolation of Aromatic Compounds Using Triptycenyl Sulfide Catalyst

Herein we report an efficient synthetic method for the electrophilic trifluoromethylthiolation of aromatic compounds. The key is to use triptycenyl sulfide (Trip-SMe) and TfOH to enhance the electrophilicity of SCF3 fragment through the formation of sulfonium intermediates. This method enables direct installation of an SCF3 group onto unactivated aromatics at room temperature adopting a commercially available saccharin-based reagent. Preliminary DFT calculation was carried out to investigate the substitu-tion effect on the catalytic activity.Kurose R., Nishii Y., Miura M.. Metal-Free Direct Trifluoromethylthiolation of Aromatic Compounds Using Triptycenyl Sulfide Catalyst. Organic Letters. 23(6), 2380-2385, (2021), 19 March 2021; ©2021 American Chemical Society. https://doi.org/10.1021/acs.orglett.1c00727

Rhodium-Catalyzed Cascade Annulative Coupling of 3,5-Diarylisoxazoles with Alkynes

A rhodium-catalyzed cascade annulative coupling of 3,5-diarylisoxazoles with three equivalents of an alkyne proceeds smoothly in the presence of a Cu(II) oxidant, where the sequential construction of isoquinoline and naphtho[1,8- bc ]pyran frameworks connected by a biaryl linkage is achieved by a single operation. Most of the obtained polycyclic compounds exhibit visible fluorescence in both the solution and the solid state. The hexaphenylated isoquinoline-naphthopyran conjugate (R = Ph) as a representative product shows a green emission which can be turned off by making an isoquinolinium salt with an acid. The emission is also reversibly turned on by treatment with a base.Noguchi T., Nishii Y., Miura M.. Rhodium-Catalyzed Cascade Annulative Coupling of 3,5-Diarylisoxazoles with Alkynes. Synthesis (Germany) 51, 258 (2019); https://doi.org/10.1055/s-0037-1610376