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Review
. 2025 Jan 10;30(2):250.
doi: 10.3390/molecules30020250.

Iron-Catalyzed Cross-Dehydrogenative Coupling

Haiyan Diao  1 , Yujia Chen  2 , Feng Liu  1
Affiliations
Review

Iron-Catalyzed Cross-Dehydrogenative Coupling

Haiyan Diao et al. Molecules. .

Abstract

This review highlights significant advances in iron-catalyzed cross-dehydrogenative coupling (CDC), a method pivotal for forming carbon-carbon (C-C) bonds directly from C-H bonds. This technique uses iron-a naturally abundant, inexpensive, and environmentally benign transition metal-as a catalyst to facilitate the coupling of two unfunctionalized C-H bonds. This method stands out for avoiding pre-functionalized substrates, reducing both waste and cost in organic synthesis. The discussion includes a variety of CDC methodologies involving combinations of C(sp3)-H with C(sp3)-H, C(sp3)-H with C(sp2)-H, and C(sp3)-H with C(sp)-H bonds. These methods have been successfully applied in synthesizing complex molecules and pharmaceuticals, highlighting the versatility and efficiency of iron catalysis.

Keywords: C-H bond activation; cross-dehydrogenative coupling; green synthesis; iron catalysis; organic transformations.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Scheme 1
Scheme 1
Cross-dehydrogenative coupling.
Scheme 2
Scheme 2
Selective CDC reaction of benzyl C-H bond catalyzed by FeCl2.
Scheme 3
Scheme 3
Direct alkylation of cycloalkane and activated methylene.
Scheme 4
Scheme 4
Oxygen acts as a terminal oxidant to catalyze the alkylation of benzyl C-H bonds.
Scheme 5
Scheme 5
Iron catalyzes the activation of C-H bonds adjacent to heteroatoms.
Scheme 6
Scheme 6
Iron-catalyzed synthesis of bis 1,3-dicarbonyl compounds.
Scheme 7
Scheme 7
Iron-catalyzed oxidation of tertiary amines to β-1,3-dicarbonyl aldehyde.
Scheme 8
Scheme 8
Iron-catalyzed CDC of simple toluene derivatives with 1,3-dicarbonyl compounds.
Scheme 9
Scheme 9
Fe-catalyzed tandem cross dehydrogenation coupling.
Scheme 10
Scheme 10
Solvent-free CDC of 3-benzylindole and methylene/indole catalyzed by Fe(III).
Scheme 11
Scheme 11
Iron-catalyzed CDC reaction of N-acylglycinate and malonate.
Scheme 12
Scheme 12
The iron-catalyzed CDC reaction of tetrahydroisoquinoline with nitroalkane and activated methylene.
Scheme 13
Scheme 13
CDC catalyzed by iron nanoparticles.
Scheme 14
Scheme 14
Alkylation of propargyl ether catalyzed by FeCl2.
Scheme 15
Scheme 15
Synthesis of α-cyanomethyl-β-dicarbonyl compound by CDC reaction.
Scheme 16
Scheme 16
Chemoselective catalytic activation of 2-acylimidazole.
Scheme 17
Scheme 17
The CDC of indole-2-ones and active methylene group.
Scheme 18
Scheme 18
Efficient synthesis of benzofuran-4(5H)-one derivatives through CDC reaction.
Scheme 19
Scheme 19
Fe-catalyzed CDC reaction generates vinyl aromatic hydrocarbons.
Scheme 20
Scheme 20
iron-catalyzed vinylation of 2-methylquinoline.
Scheme 21
Scheme 21
Iron-catalyzed C(sp3)-H activation to synthesize 2-vinylquinoline.
Scheme 22
Scheme 22
Iron-catalyzed dual-oxidative dehydrogenative (DOD) tandem annulation.
Scheme 23
Scheme 23
Iron-catalyzed C(sp3)-C(sp3) bond formation.
Scheme 24
Scheme 24
Iron catalyzes the CDC between C(sp3)-H and C(sp3)-H bonds through a radical process.
Scheme 25
Scheme 25
Iron catalyzes CDA of aryl C(sp2)-H bonds and aromatic C(sp3)-H bonds.
Scheme 26
Scheme 26
Iron catalyzes the CDC of aryl C(sp2)H bonds and aromatic C(sp3)H bonds.
Scheme 27
Scheme 27
Iron-catalyzed tandem CDC and cyclization to construct polysubstituted benzofurans.
Scheme 28
Scheme 28
Ligand-controlled iron-catalyzed cross-dehydrogenation coupling.
Scheme 29
Scheme 29
CDC based on iron catalysis realizes the synthesis of selective estrogen receptor modulators based on coumarin.
Scheme 30
Scheme 30
Asymmetric cross dehydrogenation coupling reaction catalyzed by iron phosphate.
Scheme 31
Scheme 31
Iron-catalyzed construction of C(sp3)-C(sp2).
Scheme 32
Scheme 32
Iron-catalyzed asymmetric tandem spirocyclization.
Scheme 33
Scheme 33
Fe(II) catalyzed CDC of indoles/pyrrole with acetonitriles.
Scheme 34
Scheme 34
Fe-catalyzed CDC reaction to synthesize lithospermic acid.
Scheme 35
Scheme 35
FeCl2-catalyzed CDC of diarylmethane with benzofuran.
Scheme 36
Scheme 36
Iron-catalyzed oxidative cross-coupling for oxindole functionalization.
Scheme 37
Scheme 37
Iron-catalyzed cross dehydrogenation coupling of heteroarene with methylamine.
Scheme 38
Scheme 38
1,1-bis-indolemethane were synthesized by one-pot method.
Scheme 39
Scheme 39
Iron-catalyzed functionalization of tetrahydroisoquinoline and isochroman.
Scheme 40
Scheme 40
Iron-catalyzed CDC reaction of alkyl amides with aromatic hydrocarbons.
Scheme 41
Scheme 41
A highly efficient α-quaternary-α-amino acid derivative pathway catalyzed by iron.
Scheme 42
Scheme 42
Iron-catalyzed C-H functionalization of N,N-dialkylanilines.
Scheme 43
Scheme 43
FeCl3 catalyzed one-pot synthesis of ring-fused tetrahydroquinoline derivatives.
Scheme 44
Scheme 44
Regioselective cross dehydrogenation coupling of coumarin and flavonoids with ethers.
Scheme 45
Scheme 45
Iron-catalyzed cross dehydrogenation coupling reaction of ether and pyrrole.
Scheme 46
Scheme 46
Iron-catalyzed activation of the C(sp3) bond.
Scheme 47
Scheme 47
6-Aroyl phenanthridines were synthesized by Fe-catalyzed CDC reaction.
Scheme 48
Scheme 48
Iron-catalyzed tandem oxidative coupling and acetal hydrolysis reaction to prepare formylated benzothiazoles and isoquinolines.
Scheme 48
Scheme 48
Iron-catalyzed tandem oxidative coupling and acetal hydrolysis reaction to prepare formylated benzothiazoles and isoquinolines.
Scheme 49
Scheme 49
Direct functionalization of benzyl C-H.
Scheme 50
Scheme 50
CDC reaction of terminal allyl C(sp3)-H with styrene C(sp2)-H.
Scheme 51
Scheme 51
The substituted cyclopentenes were synthesized by tandem CDC and cyclization.
Scheme 52
Scheme 52
Iron-mediated oxidative C–H alkylation of S,S-functionalized internal olefins.
Scheme 53
Scheme 53
Iron-catalyzed cyanoalkylation/free radical dearomatization of N-phenylcinnamamide.
Scheme 54
Scheme 54
72 Cross-dehydrocoupling reaction of C(sp3)-H with C(sp)-H.
Scheme 55
Scheme 55
Iron-catalyzed coupling reaction of aldehydes, terminal alkynes, and amines.
Scheme 56
Scheme 56
SBA-15-supported iron pyridine-catalyzed carbon-carbon bond coupling.
Scheme 57
Scheme 57
CuFe2O4 catlyzed CDC of aryl amines with acetylenes.
Scheme 58
Scheme 58
Iron catalyzes the CDC reaction of glycine derivatives.
Scheme 59
Scheme 59
β-aryl-α-naphthol was synthesized by iron-catalyzed tandem CDC reaction.
Scheme 60
Scheme 60
Iron-catalyzed CDC reaction of terminal alkynes with 1,3-diesters.
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