RESUMEN
We synthesized a cyclic molecule from diarylalkynes and Meldrum's acid derivatives as the methylenation reagent via double Friedel-Crafts reaction. Single-crystal X-ray structure analysis confirmed the twisted structure of the molecule. We also investigated their physical properties and homoconjugation by UV-Vis, photoluminescence, DFT and TD-DFT calculations.
RESUMEN
We synthesized cyclic π-conjugated molecules by double Friedel-Crafts reaction of amino group-substituted 1,2-bis(2-phenylethynyl)benzene with Meldrum's acid derivative. The structures of the cyclic π-conjugated molecules were determined by single-crystal X-ray structure analysis. The oxidation of the dimethylamino group-substituted π-conjugated molecule with NOBF4 gave a closed-shell dication that is stable at >210 °C. The monoradical cation of the di(4-methoxyphenyl)amino group-substituted π-conjugated molecule is stable in dichloromethane solution (half-life of nearly 15 days) and shows near-infrared absorption.
RESUMEN
Boronic acid synthesis primarily involves the introduction of boronyl groups. However, an alternative route that involves the functionalization of boronic acids has not received much attention. This study describes the catalytic C(sp3)-H alkylation of ortho-tolylboronic acids utilizing the interaction between a free boronyl group [-B(OH)2] and a decatungstate photocatalyst [W10O32]4-. The boronyl groups of the alkylated products could be converted without isolation of the alkylated product.
RESUMEN
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.
RESUMEN
Site-selective C-H transformations are important to obtain desired compounds as single products in a highly efficient manner. However, it is generally difficult to achieve such transformations because organic substrates contain many C-H bonds with similar reactivities. Therefore, the development of practical and efficient methods for controlling site selectivity is highly desirable. The most frequently used strategy is "directing group method". Although this method is highly effective and promotes site-selective reactions, it has several limitations. Our group recently reported other methods to achieve site-selective C-H transformations using non-covalent interactions between a substrate and a reagent or a catalyst and a substrate (non-covalent method). In this personal account, the background of site-selective C-H transformations, our reaction design to achieve site-selective C-H transformations, and recently reported reactions are explained.
RESUMEN
The decatungstate photocatalyst [W10O32]4- efficiently promoted the C(sp3)-H alkylation of the trifluoroacetic acid salt of valine methyl ester (H-Val-OMe·TFA) with electron-deficient alkenes under UV irradiation. The electrostatic interaction between the cationic ammonium group (+NH3) of the main chain and anionic [W10O32]4- played an important role in this reaction. The influence of various protected amino acids in the C(sp3)-H alkylation was investigated as the model reaction for the alkylation of Val-containing peptides. The introduction of an alkyne moiety into Val through this alkylation was successful, and successive copper-catalyzed azide-alkyne cycloaddition (CuAAC) was demonstrated. The C(sp3)-H bond of a Val residue located at the second from the N-terminus was also successfully converted. C(sp3)-H alkylation of oligopeptides containing two Val residues selectively proceeded proximally to the N-terminus.
RESUMEN
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.
RESUMEN
Fluorinated functional groups, including trifluoromethyl group, play important roles in the development of drugs, agrochemicals, and organic functional materials. Therefore, the development of highly effective and practical reactions to introduce fluorinated functional groups into (hetero)aromatic compounds is highly desirable. We have achieved several regioselective C-H trifluoromethylation and related reactions by electrophilic and nucleophilic activation of six-membered heteroaromatic compounds and steric protection of aromatic compounds. These reactions proceed in good to excellent yields, even on a gram scale, with high functional group tolerance, and are applicable to the regioselective trifluoromethylation of drug molecules. In this personal account, the background of the introduction reactions of fluorinated functional groups, our reaction designs to achieve regioselective C-H trifluoromethylation and the related reactions of (hetero)aromatic compounds are explained.
RESUMEN
The first example of the 3-position-selective C(sp2)-H trifluoromethylation of pyridine rings was established. 3-Position-selective trifluoromethylation was achieved by the nucleophilic activation of pyridine and quinoline derivatives through hydrosilylation and successive electrophilic trifluoromethylation of the enamine intermediate. This reaction was applicable to perfluoroalkylation at the 3 position of the pyridine rings and late-stage trifluoromethylation of a bioactive molecule. Mechanistic studies indicated that the reaction proceeds via the formation of N-silyl enamine and trifluoromethylated enamine intermediates.
RESUMEN
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.
RESUMEN
New ligands for the iridium-catalyzed C(sp3 )-H borylation of aliphatic compounds were established. In sharp contrast to 6-methyl-2,2'-bipyridine and 6-isobutyl-2,2'-bipyridine, 2,2'-bipyridine and 1,10-phenanthroline derivatives bearing a hydrosilylmethyl group (which would give a thermally stable NNSi pincer complex) served as suitable ligands for the reaction. Among them, a phenanthroline-based NNSi pincer ligand was shown to be an excellent ligand, and various aliphatic compounds were efficiently converted to the corresponding borylated products using the Ir/NNSi pincer catalyst system. The NNSi pincer ligand showed unique selectivity and enabled the iridium-catalyzed C(sp3 )-H borylation using pinacolborane [H-B(pin)] instead of B2 (pin)2 . The formation of an iridium complex bearing a quinoline-based NNSi pincer ligand from [IrCl(cod)]2 was observed, and the catalytic activity of the complex was demonstrated.
RESUMEN
A palladium(II)-catalyzed enantioselective arylation of unbiased secondary C(sp3)-H bonds was developed. The enantioselectivity was controlled by the combination of a pyridyl or isoquinolinyl directing group and an amino acid, N-Boc-2-pentyl proline. A variety of 2-propyl azaaryls and biaryl iodides were employed to provide arylated products in moderate to good yields (up to 82%) with high enantioselectivities (up to 93:7 er). This reaction is a rare example of an amino-acid-enabled enantioselective acyclic methylene C(sp3)-H arylation. Furthermore, the reaction proceeded with high enantioselectivity even on a gram scale, and the product was transformed to a 5,6,7,8-tetrahydroisoquinoline bioactive molecule. Kinetic isotope effect (KIE) experiments indicated that C-H activation is the rate-determining step for the enantioselective C(sp3)-H arylation.
RESUMEN
A new synthetic method for preparing fluorenes from amino group-containing biaryls and Meldrum's acid derivatives was developed. The reaction proceeded without a catalyst and loss of functional groups. The corresponding six- and seven-membered cyclic products were obtained using biaryl ether and ortho-terphenyl as substrates, respectively.
RESUMEN
Tribenzosilepins were synthesized from terphenyls and dihydrosilanes via a facile approach using a double sila-Friedel-Crafts reaction. Several silepin derivatives were obtained in moderate to high yield. The reaction system was found to be suitable for synthesizing a bidirectional silepin. Furthermore, the transformation of the amino groups of tribenzosilepin derivatives to aryl groups and the extension of the backbone π-system in tribenzosilepin were demonstrated.
RESUMEN
Herein, direct unreactive C-N borylation of aromatic amines by a photocatalyst was achieved. The C-N borylation of aromatic amines with bis(pinacolato)diboron (B2pin2) proceeded using a pyrene catalyst under light irradiation to afford desired borylated products and aminoborane as a byproduct. The yield of the borylated product improved under a CO2 atmosphere which probably reduced the inhibitory effect of aminoborane. Mechanistic studies suggested that the C-N bond cleavage and C-B bond formation proceeded via a concerted pathway.
RESUMEN
A Mn(II)/bipyridine-catalyzed bromination reaction of unactivated aliphatic C(sp3)-H bonds has been developed using N-bromosuccinimide (NBS) as the brominating reagent. The reaction proceeded in moderate-to-good yield, even on a gram scale. The introduced bromine atom can be converted into fluorine and allyl groups.
RESUMEN
A regioselective radical C-H trifluoromethylation of aromatic compounds was developed using cyclodextrins (CDs) as additives. The C-H trifluoromethylation proceeded with high regioselectivity to afford the product in good yield, even on the gram scale. In the presence of CDs, some substrates underwent a single trifluoromethylation selectively, whereas mixtures of single- and double-trifluoromethylated products were formed in the absence of the CD. 1H NMR experiments indicated that the regioselectivity was controlled by the inclusion of a substrate inside the CD cavity.
RESUMEN
Regioselective C(sp3)-H alkylation of a fructopyranose derivative using electron-deficient alkenes as alkylation reagents was achieved. The reaction proceeded via 1,6-hydrogen atom transfer under photoredox iridium catalysis. Several functional groups were introduced into the fructopyranose derivative.
RESUMEN
Mechanistic studies on Cu-catalyzed/mediated sp3 C-H amidation and acetoxylation are investigated from experimental and computational aspects. The concerted metalation-deprotonation (CMD) mechanism rather than a radical-involved pathway is proved to occur in amidation and acetoxylation reactions, and this is the rare example of the CMD mechanism involved in the more challenging sp3 C-H activations. Theoretical calculations demonstrated that CMD is the rate-determining step either for methylic or benzylic positions in amidation and acetoxylation reactions, and intermolecular nucleophilic addition of acetate anions is more favorable than the ring opening of ß-lactams and intramolecular acetoxylation. These mechanistic studies on the divergent and condition-dependent product formation are critical for developing Cu-promoted C-H functionalization via the CMD mechanism.
RESUMEN
Transition metal-catalysed C-H transformations are powerful methods to obtain functionalised organic molecules from simple starting materials. Controlling regioselectivity is one of the most important issues in C-H transformations. Since the remarkable work by Murai and co-workers in 1993, many groups have reported ortho-selective C(sp2)-H transformations using directing group methods, in which interactions exist between substrates and catalytically active metal centres. In this review, new methodologies to achieve regioselective C-H transformations are described. In these methhodologies, noncovalent interactions between substrates and reagents or ligands of catalysts play important roles. In these cases, selective functionalization of remote C-H bonds, such as meta- and para-C-H bonds, can also be realized.
