ortho-C(sp³)–H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a L,L-type transient directing group

Organic & Biomolecular Chemistry, Journal Year: 2023, Volume and Issue: 21(9), P. 1878 - 1882

Published: Jan. 1, 2023

Pd-catalyzed ortho-C(sp3)-H arylation of aromatic aldehydes using 2-amino-N-methyl-acetamide as a simple, efficient and commercially available L,L-type transient directing group (TDG) is reported. The reaction exhibited excellent substrate compatibility generated the desired products in moderate-to-high yields up to 78%. Further acid-catalyzed cyclization dehydrative aromatization were also tested, furnished some polycyclic hydrocarbons with 96%. X-ray crystal structure 2-methylbenzaldehyde palladation intermediate was obtained. Then, plausible mechanism involving formation [5,6]-fused palladacycle proposed. This approach offers valuable insights for exploiting novel TDGs.

Language: Английский

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A redox-neutral weak carbonyl chelation assisted C4–H allylation of indoles with vinylcyclopropanes

Chemical Communications, Journal Year: 2023, Volume and Issue: 59(77), P. 11568 - 11571

Published: Jan. 1, 2023

Removable chelating group-assisted Ru-catalyzed distal C4–H allylation of indoles has been accomplished using vinylcyclopropanes as the allylating agent with broad substrate scope.

Language: Английский

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Site-Selective Synthesis of Antitumor C5-Aminated Indoles via Neighboring Aldehyde Group Assisted Catellani Reaction

Organic Letters, Journal Year: 2023, Volume and Issue: 25(51), P. 9231 - 9236

Published: Dec. 18, 2023

A palladium/norbornene (NBE) cooperative catalytic system was developed to access C5-aminated indoles, starting from readily available C4-idonated indoles. Good yields and exclusive site selectivity were achieved for a broad substrate scope, including drug molecule core architectures. Control experiments found that both aldehyde on the C3 position sulfonyl protecting group N1 vital transformation. Preliminary bioactivity evaluation identified promising leading compound 3af with potent antitumor proliferative activity against several cancer cells.

Language: Английский

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Synthesis, biological evaluation and mechanism study of a novel indole-pyridine chalcone derivative as antiproliferative agent against tumor cells through dual targeting tubulin and HK2

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 282, P. 117058 - 117058

Published: Nov. 16, 2024

Language: Английский

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Role of Brønsted Acids in Promoting Pd(OAc)₂-Catalyzed Chlorination of Phenol Carbamates Using N-Chlorosuccinimide

ACS Catalysis, Journal Year: 2022, Volume and Issue: 12(4), P. 2681 - 2693

Published: Feb. 9, 2022

Numerous studies have demonstrated that Brønsted acids (HAs), such as HOTf and HOTs, can promote Pd(OAc)2-catalyzed functionalization of C–H bonds. However, the rationale for using these a promoter is not yet completely obvious. The purpose this work to provide detailed explanation observation with aid density functional theory calculations. This accomplished by investigating chlorination mechanism phenol carbamates (DG∼C–H) N-chlorosuccinimide (NCS) Pd(OAc)2 catalyst. Typically, in order activate bond, it believed trinuclear precatalyst Pd3(OAc)6 reacts substrate DG∼C–H generate chelated complex [Pd(OAc)2(DG∼C–H)], from which activation occurs via concerted metalation–deprotonation mechanism. Because binds relatively weak palladium, corresponding lies much higher energy than reference structure Pd3(OAc)6, resulting very high barrier activation. acid HA capable undergoing ligand-exchange reactions both [Pd(OAc)2(DG∼C–H)] form Pd3(OAc)6–x(A)x [Pd(OAc)(A)(DG∼C–H)], respectively. Our calculations demonstrate while formation [Pd(OAc)(A)(DG∼C–H)] highly exergonic, either nearly thermoneutral or endergonic. feature significantly reduces difference between complex, significant decreased We also found acidity employed influences [Pd(OAc)(A)(DG∼C–H)]; more acidic HA, smaller difference, lower In addition, our show presence only lowers overall but accelerates step protonating one oxygen atoms NCS rather N atom.

Language: Английский

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Pd-Catalyzed Regioselective Deuteration of Indole’s C4-Position with Transient Directing Groups

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(24), P. 17164 - 17171

Published: Nov. 22, 2023

As a representative scaffold of alkaloids, indoles have been extensively subjected to deuteration, but the regioselective C4 labeling has not achieved due its low reactivity. In this work, Pd-catalyzed deuterium at indole's position developed under strategy transient directing, using D2O as source. The substituent effect is found be crucial in facilitating H/D exchange process, where reversing C-D bond formation favors an electron-enriched ligation contrary C-H halogenation counterpart.

Language: Английский

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A Metal-Free Path to 2-Iodo-3-alkyl-1-arylbut-2-en-1-ones and Their Application to the Domino Synthesis of Functionalized 2H-Pyran-2-ones

The Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 87(5), P. 2222 - 2240

Published: Feb. 17, 2022

We report a metal-free selective synthesis of 2-iodo-3-alkyl-1-arylbut-2-en-1-ones from propargylic alcohols that is enabled by N-iodosuccinimide. A variety substituted are amenable to delivering the 2-iodoenone products in very good yields. The utility α-iodoenone derivatives further extended developing an efficient, novel, and new synthetic methodology for 3,5,6-trisubstituted 2H-pyran-2-ones. To best our knowledge, this protocol first its kind accomplish 2H-pyran-2-ones through unprecedented domino (formation two C-C bonds one C-O bond) one-pot process via intermolecular Heck coupling, base-driven Michael addition, base-mediated double bond isomerization followed cyclo-condensation. This showed compatibility with wide range iodoenones (18 examples) (42 examples). Mechanistic studies indicate palladium only involved coupling; base solely drives rest steps.

Language: Английский

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Different Performances of BF₃, BCl₃, and BBr₃ in Hypervalent Iodine-Catalyzed Halogenations

The Journal of Organic Chemistry, Journal Year: 2023, Volume and Issue: 88(7), P. 4359 - 4371

Published: March 20, 2023

Herein, hypervalent iodine-catalyzed halogenation of aryl-activated alkenes using BX3 (X = Cl, Br) as the halogen source and activating reagents was reported. Various halogenated 1,3-oxazine/2-oxazoline derivatives were obtained in good-to-high yields. Using BF3 resulted different substitute sites from BBr3 BCl3 products, indicating reactive intermediates reaction pathways. The underwent a "ligand coupling/oxidative addition/intermolecular nucleophilic attack/1,2-aryl migration/reductive elimination/intramolecular attack" cascade when applied source, while 1,2-aryl migration has "disappeared" or BCl3. Possible catalytic cycles proposed, DFT calculations conducted to demonstrate differences among F, halogenations.

Language: Английский

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Trifluoromethylated Indolopyranones through Regioselective Annulation of Indole Carboxylic Acids with Unsymmetric Internal Trifluoromethylated Alkynes

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(32)

Published: July 27, 2022

Abstract A rhodium‐catalyzed oxidative cross coupling/annulation of indole carboxylic acids with unsymmetric internal trifluoromethylated alkynes was accomplished, which enabled direct access to diverse indolopyranones, by combining indole, pyranone and trifluoromethyl, three valid pharmacophores, into one molecule. Diverse indole‐3‐carboxylic indole‐2‐carboxylic were proved be suitable reaction partners. Excellent regioselectivity dominated electron difference alkynes. Moderate good yields, high efficiency atom economy achieved for a broad substrate scope functional group tolerance.

Language: Английский

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Rhodium‐Catalyzed Vinyl Sulfonylation of 3‐Carbonyl‐Substituted Indoles with Ethenesulfonyl Fluoride by Cross‐Dehydrogenative Coupling: An Application in (3+2) Cycloaddition

European Journal of Organic Chemistry, Journal Year: 2022, Volume and Issue: 2022(43)

Published: Nov. 14, 2022

Abstract A Rh(III)‐catalyzed site‐selective vinyl sulfonylation of indoles with ethenesulfonyl fluoride (ESF) by a carbonyl oxygen‐directed method is reported. This chemoselective strategy delivers the corresponding cross‐dehydrogenative coupled products exclusively as E ‐isomers in high yields under mild conditions and has shown efficiency good functional group tolerance. The synthetic potential developed route demonstrated utilizing cross‐coupled adducts click chemistry to access triazoles through thermal (3+2) cycloaddition excellent regioselectivity absence metal catalyst.

Language: Английский

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