Hydroamination, Aminoboration, and Carboamination with Electrophilic Amination Reagents: Umpolung-Enabled Regio- and Stereoselective Synthesis of N-Containing Molecules from Alkenes and Alkynes

Nitrogen (N) is ubiquitously found in bioactive molecules, pharmaceutical agents, and organic functional materials. Accordingly, development of new C–N bond-forming catalysis has been one of the long-standing research subjects in synthetic organic chemistry. In this Perspective, recent advances in highly selective amination reactions with electrophilic amination reagents are described: by taking advantage of the concept of nitrogen umpolung, otherwise challenging aminofunctionalizations, such as hydroamination, aminoboration, and carboamination, of readily available feedstock-like alkenes and alkynes are possible, giving densely functionalized complex and often chiral alkylamines with high selectivity. The scope, limitations, and reaction mechanism are briefly summarized.Hirano K., Miura M.. Hydroamination, Aminoboration, and Carboamination with Electrophilic Amination Reagents: Umpolung-Enabled Regio- and Stereoselective Synthesis of N-Containing Molecules from Alkenes and Alkynes. Journal of the American Chemical Society. 144(2), 648-661, (2022), 19 January 2022; © 2022 American Chemical Society. https://doi.org/10.1021/jacs.1c12663

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 Electrophilic Amination of gem-Diborylalkanes with Hydroxylamines Providing α-Aminoboronic Acid Derivatives

A copper-catalyzed electrophilic amination of gem-diborylalkanes with hydroxylamines has been developed. The key to its success is the use of the Me3Si-modified 1,2-bis(diphenylphosphino)benzene ligand. Additionally, the reactivity of neopentylglycol derivatives compared to that of commonly used pinacol-derived ones is found to be higher, particularly in the case of relatively sterically congested substrates. The copper catalysis presented here enables the first successful catalytic carbon-heteroatom bond forming reaction of gem-diborylalkanes to form the corresponding α-aminoboronic acid derivatives, which are of great interest in medicinal and pharmaceutical chemistry.Nishino S., Hirano K., Miura M.. Copper-Catalyzed Electrophilic Amination of gem-Diborylalkanes with Hydroxylamines Providing α-Aminoboronic Acid Derivatives. Organic Letters. 21(12), 4759-4762, (2019), 21 June 2019; © 2019 American Chemical Society. https://doi.org/10.1021/acs.orglett.9b01640

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

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

An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids

A copper-catalysed regio- and stereoselective hydroamination of acrylates with hydrosilanes and hydroxylamines has been developed to afford the corresponding α-amino acids in good yields. The key to regioselectivity control is the use of hydroxylamine as an umpolung, electrophilic amination reagent. Additionally, a judicious choice of conditions involving the CsOPiv base and DTBM-dppbz ligand of remote steric hindrance enables the otherwise challenging C-N bond formation at the α position to the carbonyl. The point chirality at the β-position is successfully controlled by the Xyl-BINAP or DTBM-SEGPHOS chiral ligand with similarly remote steric bulkiness. The combination with the chiral auxiliary, (−)-8-phenylmenthol, also induces stereoselectivity at the α-position to form the optically active unnatural α-amino acids with two adjacent stereocentres.Nishino S., Miura M., Hirano K.. An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids. Chemical Science 12, 11525 (2021); https://doi.org/10.1039/d1sc03692k

Copper-Catalyzed Regio- And Enantioselective Hydroallylation of 1-Trifluoromethylalkenes: Effect of Crown Ether

A Cu-catalyzed regio- and enantioselective hydroallylation of 1-trifluoromethylalkenes with hydrosilanes and allylic chlorides has been developed. Anin situgenerated CuH species undergoes the hydrocupration regio- and enantioselectively to form a chiral α-CF3alkylcopper intermediate, which then leads to the optically active hydroallylated product. The key to success is the use of not only an appropriate chiral bisphosphine ligand but also 18-crown-6 to suppress the otherwise predominant β-F elimination from the α-CF3alkylcopper intermediate. The asymmetric Cu catalysis successfully constructs the nonbenzylic and nonallylic CF3-substituted Csp3chiral center, which is difficult to operate by other means.Kojima Y., Miura M., Hirano K.. Copper-Catalyzed Regio- And Enantioselective Hydroallylation of 1-Trifluoromethylalkenes: Effect of Crown Ether. ACS Catalysis. 11(18), 11663-11670, (2021), 17 September 2021; © 2021 American Chemical Society. https://doi.org/10.1021/acscatal.1c02947

Synthesis of Isothiazoles and Isoselenazoles through Rhodium-Catalyzed Oxidative Annulation with Elemental Sulfur and Selenium

A rhodium-catalyzed oxidative annulation of benzimidates with elemental sulfur for the direct construction of isothi-azole rings is reported. The proposed reaction mechanism involving Rh(I)/Rh(III) redox is supported by a stoichiometric reaction of metallacycle species as well as DFT calculations. This method is also applicable to the selenium cyclization to produce isoselenazole derivatives. The alkoxy substituent at the C3 position can be used for further functionalization of the azole cores.Moon S., Nishii Y., Miura M.. Synthesis of Isothiazoles and Isoselenazoles through Rhodium-Catalyzed Oxidative Annulation with Elemental Sulfur and Selenium. Organic Letters. 23(1), 49-53, (2021), 1 January 2021; ©2021 American Chemical Society. https://doi.org/10.1021/acs.orglett.0c03674

Palladium-Catalyzed Intramolecular Mizoroki-Heck-Type Reaction of Diarylmethyl Carbonates

A palladium-catalyzed intramolecular Mizoroki-Heck-type reaction of diarylmethyl tert-butyl carbonates has been developed. The reaction proceeds under external base-free, neutral conditions to form the corresponding methyleneindanes in good yields only with liberation of CO2 and tBuOH. The resulting exo-methylene moiety is reactive and thus a good synthetic handle for further manipulations. Additionally, the asymmetric synthesis is also possible through a Pd/chiral Mandyphos ligand-mediated kinetic resolution. To the best of our knowledge, this is the first successful example of catalytic enantioselective Mizoroki-Heck-type reaction of secondary benzyl electrophiles. (Figure presented.).This is the accepted version of the following article: Matsude A., Hirano K., Miura M.. Palladium-Catalyzed Intramolecular Mizoroki-Heck-Type Reaction of Diarylmethyl Carbonates. Advanced Synthesis and Catalysis 362, 518 (2020), which has been published in final form at https://doi.org/10.1002/adsc.201901398. This article may be used for non-commercialpurposes in accordance with the Wiley Self-ArchivingPolicy [https://authorservices.wiley.com/author-resources/Journal-Authors/licensing/self-archiving.html