Browse
Submit Data
Databases
API
Help

Dataset Information

19 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Selective Functionalization of Arene C(sp²)-H Bonds by Gold Catalysis: The Role of Carbene Substituents.

ABSTRACT: The complete regioselective incorporation of carbene units to nonactivated arene rings has been achieved employing gold(I) catalysts bearing alkoxydiaminophosphine ligands, with readily available, nonelaborated ethyl 2-phenyldiazoacetate as the carbene source. These results are in contrast with the scarce precedents which required highly elaborated diazo substrates. Density functional theory (DFT) calculations have revealed the important role of the R group in the C(R)CO₂Et fragment, which dramatically affects the energy profile of this transformation.

SUBMITTER: Pizarro JD

PROVIDER: S-EPMC9210454 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Site Selective Chlorination of C(sp3 )-H Bonds Suitable for Late-Stage Functionalization.

Project description:C(sp3 )-Cl bonds are present in numerous biologically active small molecules, and an ideal route for their preparation is by the chlorination of a C(sp3 )-H bond. However, most current methods for the chlorination of C(sp3 )-H bonds are insufficiently site selective and tolerant of functional groups to be applicable to the late-stage functionalization of complex molecules. We report a method for the highly selective chlorination of tertiary and benzylic C(sp3 )-H bonds to produce the corresponding chlorides, generally in high yields. The reaction occurs with a mixture of an azidoiodinane, which generates a selective H-atom abstractor under mild conditions, and a readily-accessible and inexpensive copper(II) chloride complex, which efficiently transfers a chlorine atom. The reaction's exceptional functional group tolerance is demonstrated by the chlorination of >30 diversely functionalized substrates and the late-stage chlorination of a dozen derivatives of natural products and active pharmaceutical ingredients.

| S-EPMC8594412 | biostudies-literature

Selective Quadruple C(sp3)-F Functionalization of Polyfluoroalkyl Ketones.

Project description:The significance of organofluorine compounds has inspired the establishment of numerous methods for the functionalization of rather inert C-F bonds. Despite advances achieved in the manipulation of C(sp2)-F bonds by employing transition-metal catalysts, such as Pd, Rh, Cu, Ni, Ru, and Ir, strategies that address the paucity of effective pathways for selective activation of multiple C(sp3)-F bonds remained challenging. In this context, we present an unprecedented coupling-aromatization-cyclization reaction of polyfluorinated ketones with diverse N- and S-nucleophiles that forms regiodefined perfluoroalkylated naphtho[1,2-b]furan/benzofuran derivatives by harnessing Co-promoted distinctive quadruple C(sp3)-F bonds cleavage relay. This chemistry involving controlled and successive selective defluorination at heteronuclear centers would greatly contribute to the preparation of drug-like heterocycles as well as the late-stage elaboration of biorelevant compounds. Controlled experiments and DFT theoretical studies revealed that the combination of cheap cobalt salt with Cs2CO3 enable expeditious C-F functionalization.

| S-EPMC7327834 | biostudies-literature

Enzymatic assembly of carbon-carbon bonds via iron-catalysed sp3 C-H functionalization.

Project description:Although abundant in organic molecules, carbon-hydrogen (C-H) bonds are typically considered unreactive and unavailable for chemical manipulation. Recent advances in C-H functionalization technology have begun to transform this logic, while emphasizing the importance of and challenges associated with selective alkylation at a sp3 carbon1,2. Here we describe iron-based catalysts for the enantio-, regio- and chemoselective intermolecular alkylation of sp3 C-H bonds through carbene C-H insertion. The catalysts, derived from a cytochrome P450 enzyme in which the native cysteine axial ligand has been substituted for serine (cytochrome P411), are fully genetically encoded and produced in bacteria, where they can be tuned by directed evolution for activity and selectivity. That these proteins activate iron, the most abundant transition metal, to perform this chemistry provides a desirable alternative to noble-metal catalysts, which have dominated the field of C-H functionalization1,2. The laboratory-evolved enzymes functionalize diverse substrates containing benzylic, allylic or α-amino C-H bonds with high turnover and excellent selectivity. Furthermore, they have enabled the development of concise routes to several natural products. The use of the native iron-haem cofactor of these enzymes to mediate sp3 C-H alkylation suggests that diverse haem proteins could serve as potential catalysts for this abiological transformation, and will facilitate the development of new enzymatic C-H functionalization reactions for applications in chemistry and synthetic biology.

| S-EPMC6440214 | biostudies-literature

Gold(iii)-arene complexes by insertion of olefins into gold-aryl bonds.

Project description:The synthesis and characterization of the first gold(iii)-arene complexes are described. Well-defined (P,C)-cyclometalated gold(iii)-aryl complexes were prepared and characterized by NMR spectroscopy. These complexes swiftly and cleanly reacted with norbornene and ethylene to provide cationic gold(iii)-alkyl complexes, in which the remote phenyl ring was ?2-coordinated to gold. The interaction between the aromatic ring and the gold(iii) center was thoroughly analyzed by NMR spectroscopy, X-ray diffraction, and DFT calculations. The ?-arene coordination was found to significantly influence the stability and reactivity of low coordinated gold(iii) alkyl species.

| S-EPMC5472032 | biostudies-literature

Functionalization of α-C(sp3 )-H Bonds in Amides Using Radical Translocating Arylating Groups.

Project description:α-C-H arylation of N-alkylamides using 2-iodoarylsulfonyl radical translocating arylating (RTA) groups is reported. The method allows the construction of α-quaternary carbon centers in amides. Various mono- and disubstituted RTA-groups are applied to the arylation of primary, secondary, and tertiary α-C(sp3 )-H-bonds. These radical transformations proceed in good to excellent yields and the cascades comprise a 1,6-hydrogen atom transfer, followed by a 1,4-aryl migration with subsequent SO2 extrusion.

| S-EPMC7898318 | biostudies-literature

Copper-promoted site-selective carbonylation of sp3 and sp2 C-H bonds with nitromethane.

Project description:Copper-promoted direct carbonylation of unactivated sp3 C-H and aromatic sp2 C-H bonds of amides was developed using nitromethane as a novel carbonyl source. The sp3 C-H functionalization showed high site-selectivity by favoring the C-H bonds of ?-methyl groups. The sp2 C-H carbonylation featured high regioselectivity and good functional group compatibility. Kinetic isotope effect studies indicated that the sp3 C-H bond breaking step is reversible, whereas the sp2 C-H bond cleavage is an irreversible but not the rate-determining step. Control experiments showed that a nitromethyl intermediate should be involved in the present reaction.

| S-EPMC6020547 | biostudies-literature

"Sandwich" Diimine-Copper Catalyzed Trifluoroethylation and Pentafluoropropylation of Unactivated C(sp3 )-H Bonds by Carbene Insertion.

Project description:We report here "sandwich"-diimine copper complex-catalyzed trifluoroethylation and pentafluoropropylation of unactivated C(sp3 )-H bonds in alkyl esters, halides, and protected amines by employing CF3 CHN2 and CF3 CF2 CHN2 reagents. Reactions proceed in dichloromethane solvent at room temperature. Identical C-H functionalization conditions and stoichiometries are employed for generality and convenience. Selectivities for C-H insertions are higher for compounds possessing stronger electron-withdrawing substituents. Preliminary mechanistic studies point to a mechanism involving a pre-equilibrium forming a "sandwich"-diimine copper-CF3 CHN2 complex followed by rate-determining loss of nitrogen affording the reactive copper carbene. It reacts with trifluoromethyldiazomethane about 6.5 times faster than with 1-fluoroadamantane explaining the need for slow addition of the diazo compound.

| S-EPMC10642771 | biostudies-literature

Conformational Flexibility as a Tool for Enabling Site-Selective Functionalization of Unactivated sp3 C-O Bonds in Cyclic Acetals.

Project description:A dual catalytic manifold that enables site-selective functionalization of unactivated sp3 C-O bonds in cyclic acetals with aryl and alkyl halides is reported. The reaction is triggered by an appropriate σ*-p orbital overlap prior to sp3 C-O cleavage, thus highlighting the importance of conformational flexibility in both reactivity and site selectivity. The protocol is characterized by its excellent chemoselectivity profile, thus offering new vistas for activating strong σ sp3 C-O linkages.

| S-EPMC9264358 | biostudies-literature

Temperature-modulated selective C(sp3)-H or C(sp2)-H arylation through palladium catalysis.

Project description:Transition metal-catalysed C-H bond functionalisations have been extensively developed in organic and medicinal chemistry. Among these catalytic approaches, the selective activation of C(sp3)-H and C(sp2)-H bonds is particularly appealing for its remarkable synthetic versatility, yet it remains highly challenging. Herein, we demonstrate the first example of temperature-dependent selective C-H functionalisation of unactivated C(sp3)-H or C(sp2)-H bonds at remote positions through palladium catalysis using 7-pyridyl-pyrazolo[1,5-a]pyrimidine as a new directing group. At 120 °C, C(sp3)-H arylation was triggered by the chelation of a rare [6,5]-fused palladacycle, whereas at 140 °C, C(sp2)-H arylation proceeded instead through the formation of a 16-membered tetramer containing four 7-pyridyl-pyrazolo[1,5-a]pyrimidine-palladium chelation units. The subsequent mechanistic study revealed that both C-H activations shared a common 6-membered palladacycle intermediate, which was then directly transformed to either the [6,5]-fused palladacycle for C(sp3)-H activation at 120 °C or the tetramer for C(sp2)-H arylation at 140 °C with catalytic amounts of Pd(OAc)2 and AcOH. Raising the temperature from 120 °C to 140 °C can also convert the [6,5]-fused palladacycle to the tetramer with the above-mentioned catalysts, hence completing the C(sp2)-H arylation ultimately.

| S-EPMC8162910 | biostudies-literature

Intermolecular dialkylation of alkenes with two distinct C(sp3)─H bonds enabled by synergistic photoredox catalysis and iron catalysis.

Project description:The functionalization of unactivated C(sp3)─H bonds represents one of the most powerful and most atom-economical tools for the formation of new carbon-based chemical bonds in synthesis. Although cross-dehydrogenative coupling reactions of two distinct C─H bonds for the formation of carbon-carbon bonds have been well investigated, controlled functionalizations of two or more different C(sp3)─H bonds across a functional group or a molecule (e.g., an alkene or alkyne) in a single reaction remain challenging. Here, we present a three-component dialkylation of alkenes with common alkanes and 1,3-dicarbonyl compounds via synergistic photoredox catalysis and iron catalysis for the synthesis of two functionalized 1,3-dicarbonyl compounds. Mechanistic studies suggest that the photoredox catalysis serves as a promotion system to allow the dialkylation to proceed under mild conditions by reducing the oxidation and reduction potentials of the iron intermediates and the reaction partners.

| S-EPMC6440757 | biostudies-literature