Oxidative dehydrogenation of C-C and C-N bonds: A convenient approach to access diverse (dihydro)heteroaromatic compounds

Abstract

Nitrogen heteroarenes form an important class of compounds which can be found in natural products, synthetic drugs, building blocks etc. Among the diverse strategies that were developed for the synthesis of nitrogen heterocycles, oxidative dehydrogenation is extremely effective. This review discusses various oxidative dehydrogenation strategies of C-C and C-N bonds to generate nitrogen heteroarenes from their corresponding heterocyclic substrates. The strategies are categorized under stoichiometric and catalytic usage of reagents that facilitate such transformations. The application of these strategies in the synthesis of nitrogen heteroarene natural products and synthetic drug intermediates are also discussed. We hope this review will arouse sufficient interest among the scientific community to further advance the application of oxidative dehydrogenation in the synthesis of nitrogen heteroarenes.

Keywords: aerobic oxidation; bioinspired Flavin mimics; nitrogen heteroarenes; organo catalytic; oxidative dehydrogenation.

Figure 1

Representative bioactive heterocycles.

Scheme 1

The concept of oxidative dehydrogenation.

Scheme 2

IBX-mediated oxidative dehydrogenation of various heterocycles [–34].

Scheme 3

Potential mechanism of IBX-mediated oxidative dehydrogenation of N-heterocycles [–34].

Scheme 4

IBX-mediated room temperature one-pot condensation–oxidative dehydrogenation of o-aminobenzylamines.

Scheme 5

Anhydrous cerium chloride-catalyzed, IBX-mediated oxidative dehydrogenation of various heterocycles at room temperature.

Scheme 6

Oxidative dehydrogenation of quinazolinones with I₂ and DDQ [–40].

Scheme 7

DDQ-mediated oxidative dehydrogenation of thiazolidines and oxazolidines.

Scheme 8

Oxone-mediated oxidative dehydrogenation of intermediates from o-phenylenediamine and o-aminobenzylamine [–43].

Scheme 9

Transition metal-free oxidative cross-dehydrogenative coupling.

Scheme 10

NaOCl-mediated oxidative dehydrogenation.

Scheme 11

NBS-mediated oxidative dehydrogenation of tetrahydro-β-carbolines.

Scheme 12

One-pot synthesis of various methyl(hetero)arenes from o-aminobenzamide in presence of di-tert-butyl peroxide (DTBP).

Scheme 13

Oxidative dehydrogenation of 1, 4-DHPs.

Scheme 14

Synthesis of quinazolines in the presence of MnO₂.

Scheme 15

Selenium dioxide and potassium dichromate-mediated oxidative dehydrogenation of tetrahydro-β-carbolines [–66].

Scheme 16

Synthesis of substituted benzazoles in the presence of barium permanganate.

Scheme 17

Oxidative dehydrogenation with phenanthroline-based catalysts. PPTS = pyridinium p-toluenesulfonic acid, phd = 1,10-phenanthroline-5,6-dione.

Scheme 18

Oxidative dehydrogenation with Flavin mimics.

Scheme 19

o-Quinone based bioinspired catalysts for the synthesis of dihydroisoquinolines.

Scheme 20

Cobalt-catalyzed aerobic dehydrogenation of Hantzch 1,4-DHPs and pyrazolines.

Scheme 21

Mechanism of cobalt-catalyzed aerobic dehydrogenation of Hantzch 1,4-DHPs.

Scheme 22

DABCO and TEMPO-catalyzed aerobic oxidative dehydrogenation of quinazolines and 4H-3,1-benzoxazines.

Scheme 23

Putative mechanism for Cu(I)–DABCO–TEMPO catalyzed aerobic oxidative dehydrogenation of tetrahydroquinazolines.

Scheme 24

Potassium triphosphate modified Pd/C catalysts for the oxidative dehydrogenation of tetrahydroisoquinolines.

Scheme 25

Ruthenium-catalyzed polycyclic heteroarenes.

Scheme 26

Plausible mechanism of the ruthenium-catalyzed dehydrogenation.

Scheme 27

Bi-metallic platinum/iridium alloyed nanoclusters and 5,5’,6,6’-tetrahydroxy-3,3,3’,3’-tetramethyl-1,1’-spiro-bisindane (TTSBI) for the synthesis of quinazolines.

Scheme 28

Magnesium iodide-catalyzed synthesis of quinazolines.

Scheme 29

Ferrous chloride-catalyzed aerobic dehydrogenation of 1,2,3,4-tetrahydroquinolines.

Scheme 30

Cu(I)-catalyzed oxidative aromatization of indoles.

Scheme 31

Putative mechanism of the transformation.

Scheme 32

Oxidative dehydrogenation of pyrimidinones and pyrimidines.

Scheme 33

Putative mechanisms (radical and metal-catalyzed) of the transformation.

Scheme 34

Ferric chloride-catalyzed, TBHP-oxidized synthesis of substituted quinazolinones and arylquinazolines.

Scheme 35

Iridium-catalyzed oxidative dehydrogenation of quinolines.

Scheme 36

Microwave-assisted synthesis of β-carboline with a catalytic amount of Pd/C in lithium carbonate at high temperature.

Scheme 37

4-Methoxy-TEMPO-catalyzed aerobic oxidative synthesis of 2-substituted benzazoles.

Scheme 38

Plausible mechanism of the 4-methoxy-TEMPO-catalyzed transformation.

Scheme 39

One-pot synthesis of 2-arylquinazolines, catalyzed by 4-hydroxy-TEMPO.

Scheme 40

Oxidative dehydrogenation – a key step in the synthesis of AZD8926.

Scheme 41

Catalytic oxidative dehydrogenation of tetrahydroquinolines to afford bioactive molecules.

Scheme 42

Iodobenzene diacetate-mediated synthesis of β-carboline natural products.