Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Iron-Catalyzed Photoinduced LMCT: a 1° C-H Abstraction Enables Skeletal Rearrangements and C(sp³)-H Alkylation.

ABSTRACT: Herein we disclose an iron-catalyzed method to access skeletal rearrangement reactions akin to the Dowd-Beckwith ring expansion from unactivated C(sp³)-H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates a chlorine radical, which abstracts electron-rich C(sp³)-H bonds. The resulting unstable alkyl radicals can undergo rearrangement in the presence of suitable functionality. Addition to an electron deficient olefin, recombination with a photoreduced iron complex, and subsequent protodemetallation allows for redox-neutral alkylation of the resulting radical. Simple adjustments to the reaction conditions enable the selective synthesis of the directly alkylated or the rearranged-alkylated products. As a radical clock, these rearrangements also enable the measurement of rate constants of addition into various electron deficient olefins in the Giese reaction.

SUBMITTER: Kang YC

PROVIDER: S-EPMC9164223 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Iron-Catalyzed Photoinduced LMCT: a 1° C-H Abstraction Enables Skeletal Rearrangements and C(sp3)-H Alkylation.

Kang Yi Cheng YC Treacy Sean M SM Rovis Tomislav T

ACS catalysis 20210608 12

Herein we disclose an iron-catalyzed method to access skeletal rearrangement reactions akin to the Dowd-Beckwith ring expansion from unactivated C(sp3)-H bonds. Photoinduced ligand-to-metal charge transfer at the iron center generates a chlorine radical, which abstracts electron-rich C(sp3)-H bonds. The resulting unstable alkyl radicals can undergo rearrangement in the presence of suitable functionality. Addition to an electron deficient olefin, recombination with a photore ...[more]

PMID: 35669035

Similar Datasets

Copper Catalyzed C(sp3)-H Bond Alkylation via Photoinduced Ligand-to-Metal Charge Transfer.

Project description:Utilizing catalytic CuCl2 we report the functionalization of numerous feedstock chemicals via the coupling of unactivated C(sp3)-H bonds with electron-deficient olefins. The active cuprate catalyst undergoes Ligand-to-Metal Charge Transfer (LMCT) to enable the generation of a chlorine radical which acts as a powerful hydrogen atom transfer reagent capable of abstracting strong electron-rich C(sp3)-H bonds. Of note is that the chlorocuprate catalyst is an exceedingly mild oxidant (0.5 V vs SCE) and that a proposed protodemetalation mechanism offers a broad scope of electron-deficient olefins, offering high diastereoselectivity in the case of endocyclic alkenes. The coupling of chlorine radical generation with Cu reduction through LMCT enables the generation of a highly active HAT reagent in an operationally simple and atom economical protocol.

| S-EPMC8608032 | biostudies-literature

Iridium-catalyzed enantioselective olefinic C(sp2)-H allylic alkylation.

Project description:The first iridium-catalyzed enantioselective olefinic C(sp2)-H allylic alkylation is developed in cooperation with Lewis base catalysis. This reaction, catalyzed by cinchonidine and an in situ generated cyclometalated Ir(i)/phosphoramidite complex, makes use of the latent enolate character of an α,β-unsaturated carbonyl compound, namely coumalate ester, to introduce an allyl group at its α-position in a branched-selective manner in moderate to good yield with good to excellent enantioselectivities (up to 98 : 2 er).

| S-EPMC8179414 | biostudies-literature

Direct C(sp2)-H alkylation of unactivated arenes enabled by photoinduced Pd catalysis.

Project description:Despite the fundamental importance of efficient and selective synthesis of widely useful alkylarenes, the direct catalytic C(sp2)-H alkylation of unactivated arenes with a readily available alkyl halide remains elusive. Here, we report the catalytic C(sp2)-H alkylation reactions of unactivated arenes with alkyl bromides via visible-light induced Pd catalysis. The reaction proceeds smoothly under mild conditions without any skeletal rearrangement of the alkyl groups. The direct syntheses of structurally diverse linear and branched alkylarenes, including the late-stage phenylation of biologically active molecules and an orthogonal one-pot sequential Pd-catalyzed C-C bond-forming reaction, are achieved with exclusive chemoselectivity and exceptional functional group tolerance. Comprehensive mechanistic investigations through a combination of experimental and computational methods reveal a distinguishable Pd(0)/Pd(I) redox catalytic cycle and the origin of the counter-intuitive reactivity differences among alkyl halides.

| S-EPMC7572399 | biostudies-literature

Iridium(I)-Catalyzed α-C(sp3)-H Alkylation of Saturated Azacycles.

Project description:Saturated azacycles are commonly encountered in bioactive compounds and approved therapeutic agents. The development of methods for functionalization of the α-methylene C-H bonds of these highly privileged building blocks is of great importance, especially in drug discovery. While much effort has been dedicated toward this goal by using a directed C-H activation approach, the development of directing groups that are both general as well as practical remains a significant challenge. Herein, the design and development of novel amidoxime directing groups is described for Ir(I)-catalyzed α-C(sp3)-H alkylation of saturated azacycles using readily available olefins as coupling partners. This protocol extends the scope of saturated azacycles to piperidines, azepane, and tetrahydroisoquinoline that are incompatible with our previously reported directing group. A variety of olefin coupling partners, including previously unreactive disubstituted terminal olefins and internal olefins, are compatible with this transformation. The selectivity for a branched α-C(sp3)-alkylation product is also observed for the first time when acrylate is used as the reaction partner. The development of practical, one-step installation and removal protocols further adds to the utility of amidoxime directing groups.

| S-EPMC7219544 | biostudies-literature

Photoredox-Catalyzed Site-Selective α-C(sp3 )-H Alkylation of Primary Amine Derivatives.

Project description:The synthetic utility of tertiary amines to oxidatively generate α-amino radicals is well established, however, primary amines remain challenging because of competitive side reactions. This report describes the site-selective α-functionalization of primary amine derivatives through the generation of α-amino radical intermediates. Employing visible-light photoredox catalysis, primary sulfonamides are coupled with electron-deficient alkenes to efficiently and mildly construct C-C bonds. Interestingly, a divergence between intermolecular hydrogen-atom transfer (HAT) catalysis and intramolecular [1,5] HAT was observed through precise manipulation of the protecting group. This dichotomy was leveraged to achieve excellent α/δ site-selectivity.

| S-EPMC6442930 | biostudies-literature

Mechanism of Iminium Salt-Catalyzed C(sp3)-H Amination: Factors Controlling Hydride Transfer versus H-Atom Abstraction.

Project description:Carbon-nitrogen bonds are extremely prevalent in pharmaceuticals, natural products, and other biologically relevant molecules such as nucleic acids and proteins. Intermolecular amination of C(sp3)-H bonds by catalytic nitrene transfer is a promising method for forging C-N bonds. An organocatalytic approach to nitrene transfer by way of an iminium salt offers a site-selective method for C(sp3)-H amination. Understanding of this amination mechanism including the nature of the relevant intermediates and the factors controlling the mechanism of the N-H bond formation step would aid in the design of catalysts and C(sp3)-H amination methods. In this work, the mechanism of the iminium salt-catalyzed C(sp3)-H amination via nitrene transfer was elucidated computationally using quantum mechanical methods and molecular dynamics simulations. Dispersion-corrected density functional theory (DFT) calculations provide support for an open singlet biradical species in equilibrium with the lower energy triplet species. Calculations further reveal that while the singlet biradical species undergoes N-H bond formation by a hydride transfer process, the triplet species forms the N-H bond by H-atom abstraction. Molecular dynamics (MD) simulations rule out the possibility of a fast rebound of the carbon substrate following N-H bond formation. A predictive model for mode of activation and site-selectivity that is consistent with experimental observations is presented.

| S-EPMC8188841 | biostudies-literature

Optimization of a Decatungstate-Catalyzed C(sp3)-H Alkylation Using a Continuous Oscillatory Millistructured Photoreactor.

Project description:Tetrabutylammonium decatungstate (TBADT) has emerged as an efficient and versatile photocatalyst for hydrogen atom transfer (HAT) processes that enables the cleavage of both activated and unactivated aliphatic C-H bonds. Using a recently developed oscillatory millistructured continuous-flow photoreactor, investigations of a decatungstate-catalyzed C(sp3)-H alkylation protocol were carried out, and the results are presented here. The performance of the reactor was evaluated in correlation to several chemical and process parameters, including residence time, light intensity, catalyst loading, and substrate/reagent concentration. In comparison with previously reported batch and flow protocols, conditions were found that led to considerably higher productivity, achieving a throughput up to 36.7 mmol/h with a residence time of only 7.5 min.

| S-EPMC7573979 | biostudies-literature

Photoinduced Nickel-Catalyzed Selective N-Demethylation of Trialkylamines Using C(sp2)-Bromides as HAT Reagents.

Project description:N-Demethylation of trialkylamines is a useful transformation, but typically requires harsh reaction conditions and stepwise procedures, as well as judicious protection of labile functional groups. Herein we report a mild, catalytic approach for the demethylation of trialkylamines by utilizing photoinduced nickel catalysis wherein C(sp2)-bromides serve as hydrogen-atom transfer (HAT) reagents. This method achieves direct demethylation of trialkylamines with wide functional group compatibility, making it highly suitable for late-stage derivatization of complex molecules. Mechanistic investigations provide evidence that C(sp2) radicals generated via photoinduced Ni-C(sp2) bond homolysis are involved in hydrogen atom abstraction from trialkylamines. Utilizing steric control of the C(sp2)-bromides, our HAT approach achieves demethylation with excellent site selectivity in the presence of benzyl-substituted amines, which is complementary to the selectivity of classical approaches that afford debenzylation product instead.

| S-EPMC9997100 | biostudies-literature

Allylic C(sp3)-H alkylation via synergistic organo- and photoredox catalyzed radical addition to imines.

Project description:A new catalytic method for the direct alkylation of allylic C(sp3)-H bonds from unactivated alkenes via synergistic organo- and photoredox catalysis is described. The transformation achieves an efficient, redox-neutral synthesis of homoallylamines with broad functional group tolerance, under very mild reaction conditions. Mechanistic investigations indicate that the reaction proceeds through the N-centered radical intermediate which is generated by the allylic radical addition to the imine.

| S-EPMC8159244 | biostudies-literature

Photoredox-Catalyzed Site-Selective Intermolecular C(sp3)-H Alkylation of Tetrahydrofurfuryl Alcohol Derivatives.

Project description:4'-Selective alkylation of nucleosides has been recognized as one of the ideal and straightforward approaches to chemically modified nucleosides, but such a transformation has been scarce and less explored. In this Letter, we combine a visible-light-mediated photoredox catalysis and hydrogen atom transfer (HAT) auxiliary to achieve β-C(sp3)-H alkylation of alcohol on tetrahydrofurfuryl alcohol scaffolds and exploit it for 4'-selective alkylation of nucleosides. The reaction involves an intramolecular 1,5-HAT process and stereocontrolled Giese addition of the resultant radicals.

| S-EPMC11773563 | biostudies-literature