Browse
Submit Data
Databases
API
Help

Dataset Information

27 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Direct Vicinal Difunctionalization of Thiophenes Enabled by the Palladium/Norbornene Cooperative Catalysis.

ABSTRACT: Herein we report a direct vicinal difunctionalization of thiophenes via the palladium/norbornene (Pd/NBE) cooperative catalysis. A series of mono- and disubstituted thiophenes can be difunctionalized site-selectively and regioselectively at the C4 and C5 positions in good yields, enabled by an arsine ligand and a unique amide-based NBE. The synthetic utility has been shown in derivatizations of complex bioactive compounds and an open-flask gram-scale preparation. Preliminary results have been obtained in the difunctionalization of furans and a direct C4-selective arylation of 2-substituted thiophenes.

SUBMITTER: Li R

PROVIDER: S-EPMC7075341 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Direct Vicinal Difunctionalization of Thiophenes Enabled by the Palladium/Norbornene Cooperative Catalysis.

Li Renhe R Zhou Yun Y Xu Xiaolong X Dong Guangbin G

Journal of the American Chemical Society 20191122 48

Herein we report a direct vicinal difunctionalization of thiophenes via the palladium/norbornene (Pd/NBE) cooperative catalysis. A series of mono- and disubstituted thiophenes can be difunctionalized site-selectively and regioselectively at the C4 and C5 positions in good yields, enabled by an arsine ligand and a unique amide-based NBE. The synthetic utility has been shown in derivatizations of complex bioactive compounds and an open-flask gram-scale preparation. Preliminary results have been ob ...[more]

PMID: 31744291

Similar Datasets

Modular ipso/ ortho Difunctionalization of Aryl Bromides via Palladium/Norbornene Cooperative Catalysis.

Project description:Palladium/norbornene (Pd/NBE) cooperative catalysis has emerged as a useful tool for preparing poly substituted arenes; however, its substrate scope has been largely restricted to aryl iodides. While aryl bromides are considered as standard substrates for Pd-catalyzed cross coupling reactions, their use in Pd/NBE catalysis remains elusive. Here we describe the development of general approaches for aryl bromide-mediated Pd/NBE cooperative catalysis. Through careful tuning the phosphine ligands and quenching nucleophiles, ortho amination, acylation and alkylation of aryl bromides have been realized in good efficiency. Importantly, various heteroarene substrates also work well and a wide range of functional groups are tolerated. In addition, the utility of these methods has been demonstrated in sequential cross coupling/ ortho functionalization reactions, consecutive Pd/NBE-catalyzed difunctionalization to construct penta-substituted aromatics and two-step meta functionalization reactions. Moreover, the origin of the ligand effect in ortho amination reactions has been explored through DFT studies. It is expected that this effort would significantly expand the reaction scope and enhance the synthetic potential for Pd/NBE catalysis in preparing complex aromatic compounds.

| S-EPMC6430613 | biostudies-literature

Sulfenamide-enabled ortho thiolation of aryl iodides via palladium/norbornene cooperative catalysis.

Project description:Poly-substituted aromatic sulfur compounds are widely found in pharmaceuticals, agrochemicals and organic materials. However, the position that a sulfur moiety can be introduced to is largely restricted to a pre-functionalized site; otherwise, use of electronically biased substrates or auxiliary groups that direct catalysis is required. Here we report a general ortho thiolation of common aryl and heteroaryl iodides via palladium-norbornene cooperative catalysis. Using this approach, an aryl or alky sulfur moiety can be site-selectively introduced at the arene ortho position without using sterically or electronically biased substrates. The arene ipso functionalization is simultaneously achieved through Heck, Suzuki or Sonogashira termination. The reaction is enabled by a unique class of electrophiles in palladium-norbornene cooperative catalysis, which are sulfenamides derived from seven-membered lactams. The broad substrates scope and high chemoselectivity could make this method attractive for synthesis of complex sulfur-containing aromatic compounds.

| S-EPMC6685968 | biostudies-literature

Modular Entry to Functionalized Tetrahydrobenzo[<i>b</i>]azepines via the Palladium/Norbornene Cooperative Catalysis Enabled by a C7-Modified Norbornene.

Project description:Tetrahydrobenzo[b]azepines (THBAs) are commonly found in many bioactive compounds; however, the modular preparation of functionalized THBAs remains challenging to date. Here, we report a straightforward method to synthesize THBAs directly from simple aryl iodides via palladium/norbornene (Pd/NBE) cooperative catalysis. Capitalizing on an olefin-tethered electrophilic amine reagent, an ortho amination followed by 7-exo-trig Heck cyclization furnishes the seven-membered heterocycle. To overcome the difficulty with ortho-unsubstituted aryl iodide substrates, we discovered a unique C7-bromo-substituted NBE (N1) to offer the desired reactivity and selectivity. In addition to THBAs, synthesis of other benzo-seven-membered ring compounds can also be promoted by N1. Combined experimental and computational studies show that the C7-bromo group in N1 plays an important and versatile role in this catalysis, including promoting β-carbon elimination, suppressing benzocyclobutene formation, and stabilizing reaction intermediates. The mechanistic insights gained could guide future catalyst design. The synthetic utility has been demonstrated in a streamlined synthesis of tolvaptan and forming diverse pharmaceutically relevant THBA derivatives. Finally, a complementary and general catalytic condition to access C6-substituted THBAs from ortho-substituted aryl iodides has also been developed.

| S-EPMC9142336 | biostudies-literature

Palladium/Norbornene-Catalyzed Decarbonylative Difunctionalization of Thioesters.

Project description:The transition-metal-catalyzed decarboxylation of aryl carboxylic acids has drawn significant attention as an efficient and practical tool for the synthesis of substituted arenes. However, the decarboxylative construction of polysubstituted arenes with different contiguous substituents has not been widely reported. Herein, we describe a novel decarbonylative Catellani reaction via palladium-catalyzed, norbornene (NBE)-mediated polyfunctionalization of aromatic thioesters, which serve as readily available carboxylic acid derivatives. A variety of alkenyl, alkyl, aryl, and sulfur moieties could be conveniently introduced into the ipso-positions of the aromatic thioesters. By combining carboxyl-directed C-H functionalization and the classical Catellani reaction, our protocol allows for the construction of 1,2,3-trisubstituted and 1,2,3,4-tetrasubstituted arenes from simple aromatic acids. Furthermore, the late-stage functionalization of a series of drug molecules highlights the potential utility of the reaction.

| S-EPMC8611674 | biostudies-literature

Distal Alkenyl C-H Functionalization via the Palladium/Norbornene Cooperative Catalysis.

Project description:A distal-selective alkenyl C-H arylation method is reported through a directed palladium/norbornene (Pd/NBE) cooperative catalysis. The key is to use an appropriate combination of the directing group and the NBE cocatalyst. A range of acyclic and cyclic cis-olefins are suitable substrates, and the reaction is operated under air with excellent site-selectivity. Preliminary mechanistic studies are consistent with the proposed Pd/NBE-catalyzed C-H activation instead of the Heck pathway. Initial success on distal alkylation has also been achieved using MeI and methyl bromoacetate as electrophiles.

| S-EPMC7075342 | biostudies-literature

Redox-Neutral <i>ortho</i> Functionalization of Aryl Boroxines via Palladium/Norbornene Cooperative Catalysis.

Project description:Palladium/norbornene (Pd/NBE) cooperative catalysis, also known as the Catellani reaction, has become an increasingly useful method for site-selective arene functionalization; however, certain constraints still exist due to its intrinsic mechanistic pathway. Herein we report a redox-neutral ortho functionalization of aryl boroxines via Pd/NBE catalysis. An electrophile, such as carboxylic acid anhydrides or O-benzoyl hydroxylamines, is coupled at the boroxine ortho position, and a proton as the second electrophile is introduced at the ipso position. This reaction does not require extra oxidants or reductants, and avoids stoichiometric bases or acids, thereby tolerating a wide range of functional groups. In particular, orthogonal chemoselectivity between aryl iodide and boroxine moieties is demonstrated, which could be used to control reaction sequences. Finally, a deuterium labelling study supports the ipso-protonation pathway. This unique mechanistic feature could inspire the development of a new class of Pd/NBE-catalyzed transformations.

| S-EPMC6879102 | biostudies-literature

Allyl-Palladium-Catalyzed Ketone Dehydrogenation Enables Telescoping with Enone ?,?-Vicinal Difunctionalization.

Project description:The telescoping of allyl-palladium catalyzed ketone dehydrogenation with organocuprate conjugate addition chemistry allows for the introduction of aryl, heteroaryl, vinyl, acyl, methyl, and other functionalized alkyl groups chemoselectively to a wide variety of unactivated ketone compounds via their enone counterparts. The compatibility of the dehydrogenation conditions additionally allows for efficient trapping of the intermediate enolate with various electrophiles. The utility of this approach is demonstrated by comparison to several previously reported multistep sequences.

| S-EPMC5884112 | biostudies-literature

A Cooperative N-Heterocyclic Carbene/Palladium Catalysis System.

Project description:N-heterocyclic carbenes (NHC) have been extensively studied as organocatalysts and ligands for transition metals, but the successful integration of NHCs and late transition metals in cooperative catalysis remains an underexplored area. We have developed a cooperative palladium-catalyzed allylation of NHC-activated aldehydes to access a variety of 3-allyl dihydrocoumarin derivatives. Kinetic experiments support a cooperative pathway for this transformation.

| S-EPMC4212655 | biostudies-literature

Electrochemical Vicinal C-H Difunctionalization of Saturated Azaheterocycles.

Project description:A method to functionalize two vicinal C-H bonds of saturated azaheterocycles is described. The procedure involves subjecting the substrate to a mixture of hydrochloric acid, acetic acid, and acetic anhydride in an undivided electrochemical cell at a constant current, resulting in stereoselective conversion to the corresponding α-acetoxy-β-chloro derivative. The α-position can be readily substituted with a range of other groups, including alkyl, aryl, allyl, alkynyl, alkoxy, or azido functionalities. Furthermore, we demonstrate that the β-chloro position can be engaged in Suzuki cross-coupling. This protocol thus enables the rapid diversification of simple five-, six-, and seven-membered saturated azaheterocycles at two adjacent positions.

| S-EPMC10947584 | biostudies-literature

Mechanistic studies on direct arylation of pyridine N-oxide: evidence for cooperative catalysis between two distinct palladium centers.

Project description:Direct arylations of pyridine N-oxide (PyO), a convenient method to prepare 2-arylpyridines, catalyzed by Pd(OAc)(2) and PtBu(3) have been proposed to occur by the generation of a PtBu(3)-ligated arylpalladium acetate complex, (PtBu(3))Pd(Ar)(OAc) (1), and the reaction of this complex with PyO. We provide strong evidence that 1 does not react directly with PyO. Instead, our data imply that the cyclometalated complex [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2), which is generated from the decomposition of 1, reacts with PyO and serves as a catalyst for the reaction of PyO with 1. The reaction of PyO with 1 occurs with an induction period, and the reaction of 1 with excess PyO in the presence of [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) is zeroth-order in 1. Moreover, the rates of reactions of PyO with bromobenzene catalyzed by [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) and [Pd(PtBu(3))(2)] depend on the concentration of [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) but not on the concentration of [Pd(PtBu(3))(2)]. Finally, the reaction of 1 with a model heteroarylpalladium complex containing a cyclometalated phosphine, [(PEt(3))Pd(2-benzothienyl)(tBu(2)PCMe(2)CH(2))], rapidly formed the arylated heterocycle. Together, these data imply that the rate-determining C-H bond cleavage occurs between PyO and the cyclometalated [Pd(OAc)(tBu(2)PCMe(2)CH(2))](2) rather than between PyO and 1. In this case, the resulting heteroarylpalladium complex transfers the heteroaryl group to 1, and C-C bond-formation occurs from (PtBu(3))Pd(Ar)(2-pyridyl oxide). This mechanism proposed for the direct arylation of PyO constitutes an example of C-H bond functionalization in which C-H activation occurs at one metal center and the activated moiety undergoes functionalization after transfer to a second metal center.

| S-EPMC3320665 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data