Recent Advances in the Synthesis of Selenophenes and Their Derivatives

Abstract

The selenophene derivatives are an important class of selenium-based heterocyclics. These compounds play an important role in prospecting new drugs, as well as in the development of new light-emitting materials. During the last years, several methods have been emerging to access the selenophene scaffold, employing a diversity of cyclization-based synthetic strategies, involving specific reaction partners and particularities. This review presents a comprehensive discussion on the recent advances in the synthesis of selenophene-based compounds, starting from different precursors, highlighting the main differences, the advantages, and limitations among them.

Keywords: benzoselenophene; cyclization; organochalcogen; organoselenium; selenophene.

Figure 1

Selected examples of biologically active and technologically interesting selenophenes.

Scheme 1

Two common protocols to the synthesis of selenophenes.

Scheme 2

Common protocols used to prepare benzoselenophenes.

Scheme 3

Scope of Cu-catalyzed one-pot synthesis of selenophenes 2 via nucleophilic cyclization.

Scheme 4

Scope of Cu-catalyzed one-pot synthesis of selanyl selenophenes 4 via nucleophilic cyclization.

Scheme 5

Synthesis of selenophenes via cyclization of diynols using Bu₂Se₂ and a halogen source.

Scheme 6

Proposed mechanism of the synthesis of 3-iodoselenophene 6.

Scheme 7

Key intermediates in the synthesis of 4-iodoselenophenes 6 and 4-butylselanylselenophenes 7.

Scheme 8

Proposed mechanism of the synthesis of 4-butylselanylselenophenes 7.

Scheme 9

Cross-coupling reactions of 3-iodoselenophene 6a.

Scheme 10

Reaction scope of the synthesis of 3,4-bis(butylselanyl)selenophenes 12.

Scheme 11

Key intermediates in the cyclization of unsymmetrical 1,3-diynes.

Scheme 12

Scope of the iodine-catalyzed reaction of 1,3-dienyl bromides with KSeCN.

Scheme 13

Proposed reaction pathway to prepare the selenophene 14.

Scheme 14

Scope of the synthesis of selenophenes from CF₃-containing 1,3-enynes.

Scheme 15

Cu-promoted cyclization of chalcogenoenynes to form 3-halo-chalcogenophenes.

Scheme 16

Mechanism of the Cu(II)-mediated intramolecular cyclization of (Z)-selenoenynes.

Scheme 17

Synthesis of 2,3,5-triarylselenophenes by Pd-catalyzed Suzuki cross-coupling reaction.

Scheme 18

Synthesis of 3-benzyl-2,5-diarylselenophenes 21 via carbocyclization of (Z)-benzylselenoenynes 20.

Scheme 19

Palladium-catalyzed Suzuki cross-coupling reaction of selenophene 22.

Scheme 20

Mechanism of the carbocyclization of the (Z)-benzylselenoenynes 20.

Scheme 21

Scope of the synthesis of 3-organochalcogen selenophenes.

Scheme 22

Reactions of 3-lithio-selenophene with aldehydes.

Scheme 23

Scope of the Cu(II)/halide-mediated cyclization of homopropargyl selenides.

Scheme 24

Mechanism of the Cu(II) halide-mediated cyclization of homopropargyl selenides 27.

Scheme 25

Reaction scope of the synthesis of halogenated selenophenes 32 and benzo[b]selenophenes 34.

Scheme 26

Proposed mechanism of the synthesis of chloroselenophene 32a.

Scheme 27

Scope and limitations of the synthesis of 3-iodoselenophenes 36.

Scheme 28

Scope of synthesis of 3-organoselanyl-selenophenes 37.

Scheme 29

Proposed mechanism of the synthesis of 3-iodoselenophenes 36 from 35.

Scheme 30

Scope of the synthesis of 3-iodoselenophenes 39.

Scheme 31

Scope of the synthesis of 3-bromo-selenophenes 40.

Scheme 32

Scope of the synthesis of 3-(phenylselanyl)selenophenes 41.

Scheme 33

Mechanism of the synthesis of 3-iodoselenophenes 39.

Scheme 34

Cross-coupling reactions using 3-iodoselenophene 39a.

Scheme 35

Scope and limitations of the synthesis of 3-selanylselenophenes 46.

Scheme 36

Proposed mechanism for the synthesis of 3-selanylselenophenes 46.

Scheme 37

Electrophilic (a) and radical (b) cyclization processes starting from type C precursors.

Scheme 38

Larock’s (a) and Nakamura’s (b) protocols to prepare benzoselenophenes.

Scheme 39

Use of type C precursor in the synthesis of viniferifuran and (±)-dehydroampelopsin B Se-analogues.

Scheme 40

Scope of the synthesis of 2-acylbenzo[b]selenophenes 58.

Scheme 41

Proposed mechanism for the synthesis of 2-acylbenzo[b]selenophenes 58.

Scheme 42

1,1-Dibromoalkenes as precursors of benzo[b]selenophenes.

Scheme 43

Protocols for obtaining type C precursors and benzo[b]selenophenes 67.

Scheme 44

Synthesis of 2-substituted benzo[b]selenophenes.

Scheme 45

Proposed mechanism of the synthesis of 2-substituted benzo[b]selenophenes 68 and 69.

Scheme 46

Synthesis of 2-arylselanyl-benzo[b]selenophenes 70.

Scheme 47

Mechanism of the synthesis of 2-arylselanyl-benzo[b]selenophenes 70.

Scheme 48

Scope of the synthesis of 2,3-bis-organoselanyl-benzo[b]selenophenes 71 using Oxone^®.

Scheme 49

The reaction mechanism of the synthesis of 71.

Scheme 50

Scope of the formation of 3-(arylsulfonyl)benzoselenophenes 74 using sulfinic acid.

Scheme 51

Proposed Mechanism of the formation of 74 using TBHP.

Scheme 52

Scope of the synthesis of benzoselenophenes 74 using sulfuryl chloride.

Scheme 53

The reaction mechanism of the photocatalyzed synthesis of 74.

Scheme 54

Gold-photoredox catalysis in the synthesis of 2,3-diarylbenzo[b]selenophenes.

Scheme 55

Gold-photoredox catalysis mechanism in the synthesis of selenophene 79.

Scheme 56

Scope of the synthesis of 3-phosphinoylbenzo[b]selenophenes 81.

Scheme 57

Scope of the synthesis of 3-nitrobenzo[b]selenophenes 82.

Scheme 58

Synthesis of 2-substituted benzo[b]selenophenes and AT₁ receptors.

Scheme 59

Proposed mechanism of the radical cascade reaction to prepare 85.

Scheme 60

General protocol for cyclization of type D precursors using NaBH₄.

Scheme 61

Synthesis of mono- and diselena[5]helicenes 89 and 91.

Scheme 62

Synthesis of 3-methylidenebenzo[c]selenophenes 94.

Scheme 63

Proposed mechanism of the synthesis of benzo[c]selenophenes 94.

Scheme 64

General protocol to obtaining selenoketenes 96 from 95.

Scheme 65

Synthesis of benzo[b]selenophenes 97.

Scheme 66

Control in the formation of 97 and 98 (a) and possible pathways of the cyclization of selenoketene 96 (b).

Scheme 67

Regioselective synthesis of benzo[b]selenophenes 97 and 98.

Scheme 68

Formation of σ^H- and σ^Cl-adducts from selenoketene 96.

Scheme 69

Synthesis of 3-bromo-benzo[b]selenophenes 103.

Scheme 70

Synthesis of 3-substituted-benzo[b]selenophenes 105.

Scheme 71

Synthesis of 2-aryl-3-bromo-benzo[b]selenophenes 107.

Scheme 72

Reaction pathways to prepare benzoselenophenes 107.

Scheme 73

Retrosynthetic strategy for the preparation of 2-aryl 109 and 3-aryl-benzo[b]selenophenes 110.

Scheme 74

Scope of the synthesis of benzo[b]selenophenes through copper-catalyzed C-Se coupling/cyclization.

Scheme 75

Scope of the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines 116.

Scheme 76

Mechanism of the synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines 116.

Scheme 77

Scope of the synthesis of benzo[b]selenophenes fused to imidazo[1,2-a]-pyridines 118.

Scheme 78

Mechanism of the synthesis of the fused benzo[b]selenophene 118.

Scheme 79

Cobalt-catalyzed synthesis of benzo[b]selenophene-fused imidazo[1,2-a]pyridines 118.

Scheme 80

Proposed mechanism of the cobalt-catalyzed synthesis of fused benzo[b]selenophene 118.

Scheme 81

Scope of the synthesis of the benzoselenopheno[3,2-b]indoles 120.

Scheme 82

Synthesis of the benzoselenophenes from Resveratrol.

Scheme 83

Scope of the synthesis of diaryl[b,d]selenophenes 123.

Scheme 84

Scope of the synthesis of benzo[b]selenophenes 125 from styryl bromides.

Scheme 85

Proposed mechanism of the iodine-catalyzed synthesis of benzo[b]selenophene 125.

Scheme 86

One-pot formation of fused dibenzoselenophenes 128.

Scheme 87

Plausible mechanism of the HDDA annulation to prepare dibenzoselenophenes 128.

Scheme 88

Synthesis of 3-benzo[b]selenophenes-2-aryl-1H-indoles 131.

Scheme 89

The reaction mechanism of the synthesis of selenophene 131a.

Scheme 90

Scope of the synthesis of selenophene[3,2-c]chromene 3-substituted 134.

Scheme 91

Reactivity of 3-iodo-selenophene[3,2-c]chromene 134a toward Sonogashira and Suzuki cross-couplings.

Scheme 92

Scope of the synthesis of 3-organochalcogen-selenophen[2,3-b]thiophenes 138.

Scheme 93

Suzuki and Li-Se exchange reactions of fused selenophenes 138f and 138j.

Scheme 94

Scope and mechanism of the synthesis of benzoselenophene-based palladacycles 142.

Scheme 95

Synthesis of benzoselenophene[2,3-c]pyridinones 144.

Scheme 96

Mechanism of the synthesis of benzoselenophene[2,3-c]pyridinone 144.

Scheme 97

Scope of the synthesis of selenopheno[2,3-b]quinolines 146.

Scheme 98

Proposed mechanism for the synthesis of selenopheno[2,3-b]quinoline 146.

Scheme 99

Scope of the synthesis of 3-iodo-4H-selenopheno[3,2-b]indoles 148.

Scheme 100

Mechanism of the synthesis of 3-iodo-4H-selenopheno[3,2-b]indoles 148.

Scheme 101

Scope of the synthesis of 3-(alkylselanyl)-4H-selenopheno[3,2-b]indoles 149.

Scheme 102

Scope of the synthesis of selenophenes fused to pyridines.

Scheme 103

Proposed mechanism of the synthesis of 151.

Scheme 104

Scope of the synthesis of 2-organylselenopheno[2,3-b]pyridines 151.

Scheme 105

Mechanism of the synthesis of 2-organylselenopheno[2,3-b]pyridines 151.

Scheme 106

Synthetic applications for compound 151a.

Scheme 107

Scope of the synthesis of selenopheno[3,2-c]- and selenopheno[2,3-c]quinolones.

Scheme 108

Proposed mechanism of the synthesis of selenopheno[3,2-c]quinolones.

Scheme 109

Scope of the synthesis of selenopheno[3,2-b]- and selenopheno[2,3-b]thiophenes 162.

Scheme 110

Scope of the synthesis of the selenophenothiophenes 164.

Scheme 111

Scope of the synthesis of polysubstituted selenophenes 166.

Scheme 112

Proposed mechanism of the synthesis of polysubstituted selenophenes 166.

Scheme 113

Scope and mechanism of the synthesis of 2,3-diaryl-benzo[b]selenopheno[3,2-d]selenophenes 168.

Scheme 114

Other common strategies to access fused selenophenes.

Scheme 115

Scope of the synthesis of benzo[b]selenopheno[2,3-d]furans/thiophene/selenophenes 172.

Scheme 116

Competition between selenium, sulfur and oxygen as nucleophiles in the cyclization reaction.

Scheme 117

Proposed mechanism of the synthesis of 172.

Scheme 118

Scope of the synthesis of chalcogenochromene-fused selenophenes 174.

Scheme 119

Mechanism of the synthesis of 3-(butylselanyl)-5H-selenopheno[3,2-c]isoselenochromene 174.

Scheme 120

Scope of the synthesis of 1-(butylselanyl)-selenophene-fused chromenes 176.

Scheme 121

Proposed mechanism of the synthesis of 4H-selenopheno[2,3-c]chromene 176.

Scheme 122

Scope of the synthesis of selenophene-fused quinolines 178.

Scheme 123

Suzuki cross-coupling reactions of 176a and 178a.

Scheme 124

Scope of the synthesis of isochromenones fused to selenophenes 181.

Scheme 125

Seleno- and oxo-cyclization competing reactions.

Scheme 126

Mechanism of the synthesis of isochromenones fused to selenophene 181a.

Scheme 127

Scope of the synthesis of selenophene and diselenophene-fused compounds.

Scheme 128

Mechanism of the synthesis of diselenophene-fused thieno[2,3-c]acridine 190.

Scheme 129

Scope for the synthesis of 3-(arylselanyl/sulfanyl)-2-arylselenopheno[2,3-b]quinoxaline 193 and 6-aryl-7-(phenylselanyl)selenopheno[2,3-b]pyrazine derivatives 194.

Scheme 130

Scope of the synthesis of 2-arylselenopheno[2,3-b]quinoxaline derivatives 196.

Scheme 131

Scope for the synthesis of polyselenophenes fused to benzothiophenes 198.

Scheme 132

Proposed mechanism for the synthesis of selenophene-fused benzothiophene.

Scheme 133

Synthesis of fused selenophenes 200 and 202 by biPEC.

Scheme 134

Proposed mechanism for the synthesis of dibenzo[b]selenopheno[2,3-d]thiophene 202.