Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

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

ABSTRACT: 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.

SUBMITTER: Jia J

PROVIDER: S-EPMC8159244 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

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

Jia Jiaqi J Kancherla Rajesh R Rueping Magnus M Huang Long L

Chemical science 20200430 19

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 ad ...[more]

PMID: 34122952

Similar Datasets

Influence of Achiral Phosphine Ligands on a Synergistic Organo- and Palladium-Catalyzed Asymmetric Allylic Alkylation.

Project description:An unusual diastereodivergent stereoselective allylation reaction is presented. It consists of a palladium-catalyzed allylation reaction of an organocatalytically generated amino isobenzofulvene, where the diastereoselectivity is controlled by the electronic properties of a monodentate, achiral ligand on palladium. One major diastereoisomer is formed using triarylphosphines substituted with neutral or electron-donating substituents of the aryl group, while those with electron-withdrawing substituents favor the other diastereoisomer. The diastereoselectivity correlates with the Taft inductive parameter of substituents on the triarylphosphine ligand on palladium. The synergistic reaction involves both a catalytic secondary amine catalyst for the indene-aldehyde activation and the monodentate phosphine ligands on palladium, affording a highly enantioselective reaction with up to 98 % enantiomeric excess. Based on computational investigations, the role of the monodentate phosphine ligand on the diastereoselectivity is discussed.

| S-EPMC10091967 | biostudies-literature

Metal-free direct alkylation of unfunctionalized allylic/benzylic sp3 C-H bonds via photoredox induced radical cation deprotonation.

Project description:Despite notable recent efforts, a catalytic and convenient strategy for the direct alkylation of unactivated allylic or benzylic sp3 C-H bonds remains a formidable challenge facing the synthesis community. We herein report an unprecedented allylic/benzylic alkylation using only an organo-photoredox catalyst, which enables coupling of a broad scope of alkenes/arenes and electron-deficient alkenes in an atom- and redox-economic manner. A photoredox induced alkene/arene radical cation deprotonation is proposed to smoothly generate the key allylic and benzylic radical intermediates. It represents the first C-C bond formation via radical cation deprotonation under visible light conditions. The resulting products can be easily scaled up and directly converted to γ,δ-unsaturated or α,β-diaryl-acids, -esters, -amides, -pyrazoles, -isoxazoles, as well as lactones, which enables this mild and selective sp3 C-H alkylation to rapidly access complex bioactive molecules.

| S-EPMC5618257 | 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

New Bicyclic Azalide Macrolides Obtained by Tandem Palladium Catalyzed Allylic Alkylation/Conjugated Addition Reaction.

Project description:Unprecedented tandem allylic alkylation/intermolecular Michael addition was used in the preparation of novel bicyclic azalides. NMR spectroscopy was used not only to unambiguously determine and characterize the structures of these unexpected products of chemical reaction but also to investigate the effect the rigid bicyclic modification has on the conformation of the whole molecule. Thus, some of the macrolides prepared showed antibacterial activity in the range of well-known antibiotic drug azithromycin.

| S-EPMC8781410 | biostudies-literature

Photoredox-Catalyzed Cyclobutane Synthesis by a Deboronative Radical Addition-Polar Cyclization Cascade.

Project description:Photoredox-catalyzed methylcyclobutanations of alkylboronic esters are described. The reactions proceed through single-electron transfer induced deboronative radical addition to an electron-deficient alkene followed by single-electron reduction and polar 4-exo-tet cyclization with a pendant alkyl halide. Key to the success of the methodology was the use of easily oxidizable arylboronate complexes. Structurally diverse cyclobutanes are shown to be conveniently prepared from readily available alkylboronic esters and a range of haloalkyl alkenes. The mild reactions display excellent functional group tolerance, and the radical addition-polar cyclization cascade also enables the synthesis of 3-, 5-, 6-, and 7-membered rings.

| S-EPMC6492184 | biostudies-literature

The Pd-catalysed asymmetric allylic alkylation reactions of sulfamidate imines.

Project description:The Pd-catalysed asymmetric allylic alkylation (Pd-AAA) of prochiral enamide anions derived from 5H-oxathiazole 2,2-dioxides has been developed. Various 4,5-disubstituted and 4-substituted cyclic sulfamidate imines have participated in the transformation with a range of allyl carbonates-as well as 2-vinyl oxirane, 2-vinyl-N-tosylaziridine, and 2-vinyl-1,1-cyclopropane dicarboxylate-to furnish the desired C-allylated products in moderate to high yields, with high regioselectivites and generally high enantioselectivities. Conversion between N- and C-allyl products was observed, with the N-allylated products converting to the C-allylated products over time. The resulting high-value allylated heterocyclic products all bear a tetrasubstituted stereogenic centre and can be reduced to an allylated chiral sulfamidate or an amino alcohol.

| S-EPMC8494038 | biostudies-literature

Nickel-Catalyzed Reductive Alkylation of Heteroaryl Imines.

Project description:The preparation of heterobenzylic amines by a Ni-catalyzed reductive cross-coupling between heteroaryl imines and C(sp3 ) electrophiles is reported. This umpolung-type alkylation proceeds under mild conditions, avoids the pre-generation of organometallic reagents, and exhibits good functional group tolerance. Mechanistic studies are consistent with the imine substrate acting as a redox-active ligand upon coordination to a low-valent Ni center. The resulting bis(2-imino)heterocycle⋅Ni complexes can engage in alkylation reactions with a variety of C(sp3 ) electrophiles, giving heterobenzylic amine products in good yields.

| S-EPMC9474666 | 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

Palladium-Catalyzed Enantioselective Decarboxylative Allylic Alkylation of Cyclopentanones.

Project description:The first general method for the enantioselective construction of all-carbon quaternary centers on cyclopentanones by enantioselective palladium-catalyzed decarboxylative allylic alkylation is described. Employing the electronically modified (S)-(p-CF3)3-t-BuPHOX ligand, α-quaternary cyclopentanones were isolated in yields up to >99% with ee's up to 94%. Additionally, in order to facilitate large-scale application of this method, a low catalyst loading protocol was employed, using as little as 0.15 mol % Pd, furnishing the product without any loss in ee.

| S-EPMC4640231 | biostudies-literature

Asymmetric α-C(sp3)-H allylic alkylation of primary alkylamines by synergistic Ir/ketone catalysis.

Project description:Primary alkyl amines are highly reactive in N-nucleophilic reactions with electrophiles. However, their α-C-H bonds are unreactive towards electrophiles due to their extremely low acidity (pKa ~57). Nonetheless, 1,8-diazafluoren-9-one (DFO) can activate primary alkyl amines by increasing the acidity of the α-amino C-H bonds by up to 1044 times. This makes the α-amino C-H bonds acidic enough to be deprotonated under mild conditions. By combining DFO with an iridium catalyst, direct asymmetric α-C-H alkylation of NH2-unprotected primary alkyl amines with allylic carbonates has been achieved. This reaction produces a wide range of chiral homoallylic amines with high enantiopurities. The approach has successfully switched the reactivity between primary alkyl amines and allylic carbonates from intrinsic allylic amination to the α-C-H alkylation, enabling the construction of pharmaceutically significant chiral homoallylic amines from readily available primary alkyl amines in a single step.

| S-EPMC10830461 | biostudies-literature