Recent Advances in Transition-Metal-Free Late-Stage C-H and N-H Arylation of Heteroarenes Using Diaryliodonium Salts

Abstract

Transition-metal-free direct arylation of C-H or N-H bonds is one of the key emerging methodologies that is currently attracting tremendous attention. Diaryliodonium salts serve as a stepping stone on the way to alternative environmentally friendly and straightforward pathways for the construction of C-C and C-heteroatom bonds. In this review, we emphasize the recent synthetic advances of late-stage C(sp2)-N and C(sp2)-C(sp2) bond-forming reactions under metal-free conditions using diaryliodonium salts as arylating reagent and its applications to the synthesis of new arylated bioactive heterocyclic compounds.

Keywords: C-H arylation; N-arylation; diaryliodonium salts; eco-friendly; heteroarenes; late-stage functionalization; metal-free.

Scheme 1

Metal-free C2-H arylation of five-membered heteroarenes using diaryliodonium salts.

Scheme 2

C2-H arylation of tryptophane amino acids and peptide derivatives with diaryliodonium tosylates.

Scheme 3

C2-H arylation of azaheteroanes using unsymmetrical aryl(TMB)iodonium triflates in the presence of NaOH.

Scheme 4

Late-stage SF₅-pyridinylation of pyrrole derivatives.

Scheme 5

Base-mediated C-H arylation of α-free BODIPYs for the synthesis of α-arylBODIPY dyes.

Scheme 6

Plausible radical mechanism for the regioselective synthesis of α-arylBODIPY.

Scheme 7

Direct late-stage C3-H arylation of various 2-arylimidazolo[1,2-a]pyridines using diphenyliodonium or di(p-tBu)phenyliodonium chlorides.

Scheme 8

Direct late-stage C3-H arylation of various 2-arylbenzo[d]imidazolo[2,1-b]thiazoles using diphenyliodonium chlorides.

Scheme 9

Direct late-stage C3-H arylation of quinoxalin-2(1H)-ones with diaryliodonium tetrafluoroborates.

Scheme 10

Plausible radical pathway for the synthesis of 3-aryl-quinoxalin-2(1H)-ones.

Scheme 11

Visible-light-mediated late-stage C2-H arylation of diverse quinoline N-oxides using eosin Y as a photocatalyst.

Scheme 12

Visible-light-mediated late-stage C2-H phenylation of diverse pyridine N-oxides using eosin Y as a photocatalyst and K₂S₂O₈ as additive.

Scheme 13

Suggested radical mechanism for the metal-free synthesis of 2-aryl quinoline and pyridine N-oxides.

Scheme 14

Direct late-stage N-arylation of substituted pyrazoles with diaryliodonium salts.

Scheme 15

Direct N-heteroarylation of 3,5-diphenylpyrazole with unsymmetrical diaryliodonium triflates.

Scheme 16

Synthesis of N-mesitylpyrrolo[2,3-b]pyridines and -pyrimidine derivatives.

Scheme 17

Synthesis of N-mesitylbenzo[d][1,2,3]triazole and 4-chloro-2-mesitylphthalazin-1(2H)-one.

Scheme 18

Selective iodoarylation of pyrazole derivatives via the generation of the heteroayliodonium salt as key intermediate.

Scheme 19

Selective tBuOK mediated N-arylation of indazole and triazole using diaryliodonium triflates as arylating reagents.

Scheme 20

Microwave-assisted metal-free N-arylation of quinolin-4(1H)one and 4-methylquinolin-2(1H)-one in water.

Scheme 21

Scope of the heteroarenes for the microwave-assisted transition-metal-free N-arylation using diphenyliodonium triflate.

Scheme 22

Synthesis of N-arylated pyridinones as major products under optimized conditions.

Scheme 23

N-arylation of pyridin-2-ones under metal-free conditions.

Scheme 24

Base-free and metal-free N-arylation of pyridazinones with diaryliodonium hexafluorophosphates.