Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Base-Induced Dehydrogenative and Dearomative Transformation of 1-Naphthylmethylamines to 1,4-Dihydronaphthalene-1-carbonitriles.

ABSTRACT: Solvothermal treatment of 1-naphthylmethylamine with potassium hydride (KH) or n-butyllithium (n-BuLi)-potassium t-butoxide (t-BuOK) in THF induces unusual two consecutive β-hydride eliminations to form 1-naphthonitrile and KH. The freshly generated KH is hydridic enough to undergo dearomative hydride addition to the resultant 1-naphthonitrile regioselectively at the C4 position to afford α-cyano benzylic carbanion, which could be functionalized by a series of electrophiles, liberating the corresponding 1,4-dihydronaphthalene-1-carbonitriles having a quaternary carbon center.

SUBMITTER: Sekiguchi Y

PROVIDER: S-EPMC9795570 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Base-Induced Dehydrogenative and Dearomative Transformation of 1-Naphthylmethylamines to 1,4-Dihydronaphthalene-1-carbonitriles.

Sekiguchi Yoshiya Y Pang Jia Hao JH Ng Jia Sheng JS Chen Jiahua J Watanabe Kohei K Takita Ryo R Chiba Shunsuke S

JACS Au 20221130 12

Solvothermal treatment of 1-naphthylmethylamine with potassium hydride (KH) or n-butyllithium (n-BuLi)-potassium t-butoxide (t-BuOK) in THF induces unusual two consecutive β-hydride eliminations to form 1-naphthonitrile and KH. The freshly generated KH is hydridic enough to undergo dearomative hydride addition to the resultant 1-naphthonitrile regioselectively at the C4 position to afford α-cyano benzylic carbanion, which could be functionalized by a series of electro ...[more]

PMID: 36590271

Similar Datasets

Palladium-Catalyzed Dearomative syn-1,4-Diamination.

Project description:Herein we report a dearomative syn-1,4-diamination protocol using simple nonactivated arenes and amines. This one-pot method utilizes arene-arenophile para-cycloadducts, formed via visible-light-mediated [4+2]-photocycloaddition that undergoes formal allylic substitution with amine nucleophiles under Pd-catalysis. The products are obtained with exclusive syn-1,4-selectivity; the method permits enantioselective desymmetrization of naphthalene, as well as elaborations of amine-containing drug molecules. Furthermore, the resulting unsaturated products are amenable to numerous options for diversification. Overall, this novel dearomative functionalization strategy offers rapid and straightforward access to complex building blocks, which are difficult to prepare otherwise, from simple arenes.

| S-EPMC6488036 | biostudies-literature

Palladium-Catalyzed Dearomative syn-1,4-Oxyamination.

Project description:A palladium-catalyzed dearomative syn-1,4-oxyamination protocol using non-activated arenes has been developed. This one-pot procedure utilizes arenophile chemistry, and the corresponding para-cycloadducts are treated with oxygen nucleophiles via formal allylic substitution, providing direct access to syn-1,4-oxyaminated products. The reaction conditions permit a range of arenes, as well as different O-nucleophiles, such as oximes and benzyl alcohols. Moreover, this process was established in an asymmetric fashion, delivering products with high enantioselectivity. The dearomatized products are amenable to a multitude of further derivatizations ranging from olefin chemistry to C-H activation, giving rise to a diverse set of new functionalities. Overall, this dearomative functionalization offers rapid and controlled formation of molecular complexity, enabling straightforward access to functionalized small molecules from simple and readily available arenes.

| S-EPMC6803049 | biostudies-literature

Palladium-Catalyzed Dearomative syn-1,4-Carboamination.

Project description:A dearomative 1,4-carboamination of arenes has been achieved using arenophile cycloaddition and subsequent palladium-catalyzed substitution with nonstabilized lithium enolates. This protocol delivers products with exclusive syn-1,4-selectivity and can be also conducted in an asymmetric fashion. The method allows rapid dearomative difunctionalization of simple aromatic compounds into functional small molecules amenable to further diversification.

| S-EPMC5971112 | biostudies-literature

Palladium-catalyzed dearomative 1,4-difunctionalization of naphthalenes.

Project description:A highly diastereoselective dearomatization of naphthalenes via a Pd-catalyzed 1,4-difunctionalization reaction is described. In the presence of a commercially available palladium precursor and ligand, intramolecular dearomative Heck-type insertion provides π-allylpalladium intermediates which are readily captured by a series of nucleophiles in excellent yields (up to 99%). This reaction features mild conditions, broad substrate scope, and useful transformations of the products.

| S-EPMC7504896 | biostudies-literature

METABOLISM OF POLYCYCLIC COMPOUNDS. THE METABOLISM OF 1,4-EPOXY-1,4-DIHYDRONAPHTHALENE IN RATS.

Project description:1. 1,4-Epoxy-1,4-dihydronaphthalene is converted by rats into 1,4:2,3-diepoxy-1,2,3,4-tetrahydronaphthalene, which was isolated from the urine. The synthesis of the diepoxide is described. 2. The monoepoxide also yielded a compound that is believed to be 1,4-dihydro-1,4-dihydroxynaphthalene, but no corresponding mercapturic acid was detected. A number of unidentified metabolites of the monoepoxide were detected that appear to arise by the hydroxylation of the diepoxide. 3. The monoepoxide is converted into the diepoxide by a rat-liver microsomal system. 4. 1,4-Epoxy-1,4-dihydronaphthalene does not appear to be an intermediate in naphthalene metabolism.

| S-EPMC1206784 | biostudies-other

Palladium-Catalyzed Dearomative syn-1,4-Carboamination with Grignard Reagents.

Project description:A protocol for palladium-catalyzed dearomative functionalization of simple, nonactivated arenes with Grignard reagents has been established. This one-pot method features a visible-light-mediated [4+2] cycloaddition between an arene and an arenophile, and subsequent palladium-catalyzed allylic substitution of the resulting cycloadduct with a Grignard reagent. A variety of arenes and Grignard reagents can participate in this process, forming carboaminated products with exclusive syn-1,4-selectivity. Moreover, the dearomatized products are amenable to further elaborations, providing functionalized alicyclic motifs and pharmacophores. For example, naphthalene was converted into sertraline, one of the most prescribed antidepressants, in only four operations. Finally, this process could also be conducted in an enantioselective fashion, as demonstrated with the desymmetrization of naphthalene.

| S-EPMC6640109 | biostudies-literature

Dearomative 1,4-difunctionalization of naphthalenes via palladium-catalyzed tandem Heck/Suzuki coupling reaction.

Project description:Dearomative functionalization reactions represent an important strategy for the synthesis of valuable three-dimensional molecules from simple planar aromatics. Naphthalene is a challenging arene towards transition-metal-catalyzed dearomative difunctionalization reactions. Reported herein is an application of naphthalene as a masked conjugated diene in a palladium-catalyzed dearomative 1,4-diarylation or 1,4-vinylarylation reaction via tandem Heck/Suzuki sequence. Three types of 1,4-dihydronaphthalene-based spirocyclic compounds are achieved in excellent regio- and diastereoselectivities. Key to this transformation is the inhibition of a few competitive side reactions, including intramolecular naphthalenyl C-H arylation, intermolecular Suzuki cross-coupling, dearomative 1,2-difunctionalization, and dearomative reductive-Heck reaction. Density functional theory (DFT) calculations imply that the facile exergonic dearomative insertion of a naphthalene double bond disrupts the sequence of direct Suzuki coupling, leading to the tandem Heck/Suzuki coupling reaction. The observed regioselectivity towards 1,4-difunctionalization is due to the steric repulsions between the introduced aryl group and the spiro-scaffold in 1,2-difunctionalization.

| S-EPMC7463262 | biostudies-literature

Crystallization-Induced Diastereoisomer Transformation of Dihydroartemisinic Aldehyde with the Betti Base.

Project description:Artemisinin is an important drug to fight malaria. It is produced either by extraction or via a semisynthetic route involving enzyme engineering. A key intermediate to produce artemisinin by the enzymatic route is dihydroartemisinic aldehyde (DHAAl). However, control of the absolute configuration of the stereocenter α to the aldehyde is highly challenging. Herein we report a protocol that allows the diastereomeric enrichment of a mixture of (11R)/(11S)-DHAAl to the desired (11R)-DHAAl by utilizing a crystallization-induced diastereomer transformation induced by the Betti base. In addition, the Betti base can be quantitatively recovered and reused after the reaction.

| S-EPMC7237042 | biostudies-literature

Oxidative Dearomative Cross-Dehydrogenative Coupling of Indoles with Diverse C-H Nucleophiles: Efficient Approach to 2,2-Disubstituted Indolin-3-ones.

Project description:The oxidative, dearomative cross-dehydrogenative coupling of indoles with various C-H nucleophiles is developed. This process features a broad substrate scope with respect to both indoles and nucleophiles, affording structurally diverse 2,2-disubstituted indolin-3-ones in high yields (up to 99%). The oxidative dimerization and trimerization of indoles has also been demonstrated under the same conditions.

| S-EPMC7024378 | biostudies-literature

The Synthesis and Base-Induced Breakdown of Triaryl 1,4-Oxathiins—An Experimental and DFT Study

Project description: Not available

| S-EPMC10489040 | biostudies-literature