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Review
. 2020 Apr 15;25(8):1806.
doi: 10.3390/molecules25081806.

Iron-Catalyzed C-H Functionalizations under Triazole-Assistance

Matteo Lanzi  1 , Gianpiero Cera  2
Affiliations
Review

Iron-Catalyzed C-H Functionalizations under Triazole-Assistance

Matteo Lanzi et al. Molecules. .

Abstract

3d transition metals-catalyzed C-H bond functionalizations represent nowadays an important tool in organic synthesis, appearing as the most promising alternative to cross-coupling reactions. Among 3d transition metals, iron found widespread application due to its availability and benign nature, and it was established as an efficient catalyst in organic synthesis. In this context, the use of ortho-orientating directing groups (DGs) turned out to be necessary for promoting selective iron-catalyzed C-H functionalization reactions. Very recently, triazoles DGs were demonstrated to be more than an excellent alternative to the commonly employed 8-aminoquinoline (AQ) DG, as a result of their modular synthesis as well as the mild reaction conditions applied for their removal. In addition, their tunable geometry and electronics allowed for new unprecedented reactivities in iron-catalyzed C-H activation methodologies that will be summarized within this review.

Keywords: 1,2,3-triazole; C‒H activation; catalysis; iron.

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Conflict of interest statement

“The authors declare no conflict of interest.”

Figures

Scheme 1
Scheme 1
Examples of 1,2,3-triazoles directing groups (DGs).
Scheme 2
Scheme 2
Triazole-assisted C(sp2)–H arylation; (a) Aryl amides functionalizations; (b) Acrylamide functionalization; (c) Removal of TAM DG.
Scheme 3
Scheme 3
Iron-catalyzed C(sp2)–H arylation of ferrocenes aromatic rings with TAM DG.
Scheme 4
Scheme 4
Iron-catalyzed C(sp3)–H arylation with TAM DG.
Scheme 5
Scheme 5
Iron-catalyzed C(sp2)–H arylations of benzylamides with tri-substituted triazole (TST) DG.
Scheme 6
Scheme 6
Electrochemical iron-catalyzed C(sp2)–H arylation with TAM DG.
Scheme 7
Scheme 7
Proposed mechanism for iron-catalyzed C(sp2)–H bond arylation with TAM DG.
Scheme 8
Scheme 8
Triazole-assisted methylation of C(sp2)–H bond; (a) Selected examples of aryl amides; (b) C(sp2)–H methylation of ferrocene.
Scheme 9
Scheme 9
(a) Triazole-assisted methylation of amides; (b) Mild triazole removal to 2-methyl benzoic acid 5e.
Scheme 10
Scheme 10
Iron-catalyzed triazole-assisted methylation of C(sp2)–H bonds; (a) Methylation of benzylamides 17a-c; (b) Methylation of the enantioenriched amine (S)-10d.
Scheme 11
Scheme 11
Removal and recovery of TST DG under acidic conditions.
Scheme 12
Scheme 12
Iron-catalyzed triazole assisted ethylation of C(sp2)–H bond. (a) Ethylation of TAM amides 1; (b) Ethylation of TST amide 10f; (c) Ethylation of ferrocene amide 6a; (d) Triazole removal protocol.
Scheme 13
Scheme 13
(a) Iron-catalyzed, TAM-assisted alkylation of C(sp2)–H bond; (b) TAM removal.
Scheme 14
Scheme 14
Radical mechanistic finding in iron-catalyzed alkylation of C(sp2)–H bond with (a) 6-bromohex-1-ene 24i, (b) cyclopropylmethyl bromide 24j, (c) cis-1-bromo-4-methylcyclohexane 24k.
Scheme 15
Scheme 15
Iron-catalyzed TAM-assisted allylation of C(sp2)–H bond with allylchloride 27.
Scheme 16
Scheme 16
(a) Iron-catalyzed TAM-assisted allylation of C(sp2)–H bond with allylchlorides 27i-l; (b) Isochromanone synthesis via TAM-deprotection.
Scheme 17
Scheme 17
Iron-catalyzed TAM-assisted alkynylation of C(sp2)–H bonds with bromoalkyne 30.
Scheme 18
Scheme 18
Probing iron-catalyzed C(sp2)–H alkynylation with haloakynes 30.
Scheme 19
Scheme 19
Proposed mechanism of iron-catalyzed TAM-assisted C–H alkynylation of amides.
Scheme 20
Scheme 20
Iron-catalyzed C–H alkynylation/annulation. (a) Isoquinolones synthesis; (b) Isoindolinones synthesis; (c) Removal of TAM DG.
Scheme 21
Scheme 21
Iron-catalyzed C–H annulation of triazolyldihydrogenmethyl (TAH) amides. (a) Symmetric internal alkynes; (b) Methyl-aryl alkynes.
Scheme 22
Scheme 22
Mechanistic experiments for iron-catalyzed C–H annulations with alkynes; (a) Reaction conduced in presence of BHT as radical scavenger; (b) Stoichiometric reaction in absence of oxidant.
Scheme 23
Scheme 23
(a) Iron-catalyzed C–H annulation with propargyl acetate; (b) Electrochemical removal of TAH DG. (c) Oxidative cleavage of aminoquinoline (AQ) DG.
Scheme 24
Scheme 24
Proposed catalytic cycle for TAH-assisted C–H/N–H annulation with propargyl acetates.
Scheme 25
Scheme 25
Iron-catalyzed C–H/N–H bonds activation/annulation with allenes; (a) TAH-assisted isoquinolones synthesis; (b) TAM-assisted dihydroisoquinolones synthesis; (c) One-pot/two-step isoquinolone 48a synthesis.
Scheme 26
Scheme 26
Mechanism investigation with isotopically labelled allene [D2]-45a.
Scheme 27
Scheme 27
TAM-assisted C–H/N–H/C–O/C–H activation/annulation with allenes.
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