Multicomponent synthesis of chromophores - The one-pot approach to functional π-systems

Abstract

Multicomponent reactions, conducted in a domino, sequential or consecutive fashion, have not only considerably enhanced synthetic efficiency as one-pot methodology, but they have also become an enabling tool for interdisciplinary research. The highly diversity-oriented nature of the synthetic concept allows accessing huge structural and functional space. Already some decades ago this has been recognized for life sciences, in particular, lead finding and exploration in pharma and agricultural chemistry. The quest for novel functional materials has also opened the field for diversity-oriented syntheses of functional π-systems, i.e. dyes for photonic and electronic applications based on their electronic properties. This review summarizes recent developments in MCR syntheses of functional chromophores highlighting syntheses following either the framework forming scaffold approach by establishing connectivity between chromophores or the chromogenic chromophore approach by de novo formation of chromophore of interest. Both approaches warrant rapid access to molecular functional π-systems, i.e. chromophores, fluorophores, and electrophores for various applications.

Keywords: absorption; chromophores; diversity-oriented synthesis; donor-acceptor systems; fluorescence; multicomponent reactions; one-pot synthesis.

SCHEME 1

Conceptual MCR formation of functional chromophores by scaffold and chromophore approaches (Reprinted from Levi and Müller (2016b), Copyright (2016), with permission from The Royal Society of Chemistry).

SCHEME 2

(A) Consecutive one pot four-component synthesis of allylidene indolone chromophores 5 by a Heck condensation sequence and selected examples (Wilbert and Müller, 2022). (B) Consecutive three-component Heck-Knoevenagel synthesis of merocyanine esters 6 (Stephan et al., 2022). (C) Consecutive three-component reaction to synthesize N-benzyl aroyl-S,N-keteneacetal bichromophores 7 and an insight into the compound library sorted by the employed blue emitters (Biesen et al., 2021).

SCHEME 3

(A) Three-component Suzuki–Knoevenagel synthesis of merocyanines 9–13 as well as representative derivatives of the substance libraries. The position of the acceptor group is indicated by Acc (Meyer et al., 2021). (B) One-pot synthesis of a triflate compound, terminal alkyne and various amines to form cyclohexene-embedded merocyanines 14 and 15 as well as cyanines 16 (Papadopoulos et al., 2022).

SCHEME 4

(A) One-pot synthesis of 6-5-bicyclic γ-alkylidene-2-butenolides 17 and 18 from ketone lithium enolates or from imide lithium enolates (Suero et al., 2012). (B) Three-component synthesis of highly functionalized dihydroindeno[1,2-b]pyrrole fluorophores 19 (Mal et al., 2018). (C) Pseudo five-component synthesis of tetraaryl-1,4-dihydropyrrolo-[3,2-b]pyrrole derivatives 20 (Martins et al., 2018).

SCHEME 5

(A) Synthesis of GBB products 21 and 23 via twofold GBBR of 2,4-diaminopyrimidine in a direct (I) and a sequential approach (II) (Ghashghaei et al., 2018). (B) Debus-Radziszwski multicomponent reaction to form imidazole-based fluorophores 25 (Somasundaram et al., 2018).

SCHEME 6

(A) Synthesis of biaryl-substituted isoxazoles 26 and 27 via a coupling-cyclocondensation-coupling (C³) sequence (Deden et al., 2020). (B) Enzyme-catalyzed three-component isoxazol-5(4H)-one 28 synthesis and selected fluorophores (Oliveira et al., 2021).

SCHEME 7

(A) Synthesis of isoxazol-5-one 29 via a two-step one-pot reaction and the three obtained fluorophores (Tasior et al., 2021). (B) One-step synthesis of 5-amino-4-carboxamidothiazoles 30 based on the chromophore approach and the synthesized chromophores (Tong et al., 2017).

SCHEME 8

(A) Three-component synthesis of indolylmalonamides 31 (Jennings et al., 2016). (B) Sequentially catalyzed consecutive three-component Masuda–Suzuki–Sonogashira synthesis of 2-alkynyl-4-(7-azaindol-3-yl) pyrimidines 32 and selected fluorophores (Drießen et al., 2021).

SCHEME 9

(A) Amine-appended spiro[indoline-3,4′-pyridine] ON–OFF chemosensor 33 and selected derivates (Mondal et al., 2018). (B) MCR synthesis of spiro[diindenopyridine-indoline]triones 34 with different catalyst systems (PEG-OSO₃H or [NMP]H₂PO₄) under conventional heating and ultrasonic irradiation (Sindhu et al., 2015).

SCHEME 10

(A) Domino reaction for synthesis of triazolyl spirocyclic oxindoles 35 and 36 in the sense of the chromophore concept and the most potent fluorescent, antibacterial triazolyl spirocyclic oxindole 36a (Singh et al., 2014) (B) Sequential one-pot synthesis of oxindole bearing pyrrolo[2,3-c]pyrazoles 37 (Nazeri et al., 2020).

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(A) Diversity-oriented one-pot process for the synthesis of 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones 40 (Denissen et al., 2017b). (B) Iodine catalyzed, selenium assisted sequential multicomponent synthesis of benzo-oxazino-isoindoles 41 and selected examples (Sedighian et al., 2021).

SCHEME 12

(A) Three-step one-pot synthesis of α-acyloxy carboxamides 44 (Paprocki et al., 2020). (B) Biginelli reaction to synthesize 3,4-dihydropyrimidin-2(1H)-one/thiones 47 in the sense of the scaffold concept (Vitório et al., 2015). (C) MMT K10 clay catalyzed three-component synthesis of diversified HTC derivatives 49 (Godugu et al., 2020). (D) Microwave-induced synthesis of coumarin-3-yl-thiazol-3-yl-1,2,4-triazolin-3-ones 50 (Shaikh et al., 2018).

SCHEME 13

Consecutive three-component Suzuki−Suzuki and Sonogashira−Sonogashira synthesis of 8-donor-5-acceptor-substituted psoralens 59 and 60 in the sense of the scaffold concept and selected derivates (Geenen et al., 2020).

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(A) Domino synthesis of 14-aryl-14H-dibenzo[a,i]xanthene-8,13-diones 61 and selected fluorophores (Khurana et al., 2012). (B) One-pot synthesis of fluoresceins 62 using NbCl₅ as a catalyst (Sacoman Torquato da Silva et al., 2017).

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(A) Groebke-Blackburn-Bienaymé synthesis of fluorescent α,β-substituted imidazo[1,2-a]pyridines 64 via the chromophore approach (Burchak et al., 2011). (B) Solvent-free MCR synthesis of pyrazole[3,4-b]thieno[2,3-e]pyridine derivatives 68 in the sense of the chromophore approach and selected fluorophores (Yao et al., 2014). (C) Pseudo four-component synthesis of functionalized 2-amino pyridine dyes 70 and selected derivates (Khan et al., 2012b).

SCHEME 16

(A) Catalyst-free pseudo four-component synthesis of 3,4,5-substituted 1,4-dihydropyridines 71 and 72 and selected fluorophores (Sueki et al., 2014). (B) Synthesis of photoactiv Hantzsch 1,4-DHPs 74 as well as one selected derivate 74a (Affeldt et al., 2012). (C) Pseudo four-component synthesis of 1,8-dioxodecahydroacridines 78 with the green catalysts HPA1 or HPA2 (Baradaran-Sirjani et al., 2018).

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(A) Five-component reaction of tetrahydropyrimidines 81 and selective dyes with quantum yields above 0.50 (Zhu et al., 2013). (B) Synthesis of disperse dyes with a dihydropyrimidinone scaffold 82 via one-pot multicomponent reaction (Patel et al., 2022). (C) Modified Gewald synthesis of 2-arylthieno[2,3-d]pyrimidin-4-amines 84 and selected examples (Abaee et al., 2017).

SCHEME 18

(A) Silica gel-catalyzed one-pot syntheses of 5-amino-2-aryl-3H-chromeno[4,3,2-de][1,6]naphthyridine-4-carbonitriles 88 and 5-amino-2-aryl-3H-quinolino[4,3,2-de][1,6]naphthyridine-4-carbonitriles 89 (Wu et al., 2010). (B) Synthesis of spirofluorenonaphthoquinolines 91 and 92 through MCR of 9-fluorenones, aryl alkynes, and aminoanthraquinones 1-aminopyrene (Meerakrishna et al., 2016).

SCHEME 19

(A) Green one-pot three-component synthesis of chromeno[4,3-b]quinolin-6-ones 94–98 (Ataee-Kachouei et al., 2019). (B) Three-component synthesis of hexahydroquinolin-5-ones 101 (Oskuie et al., 2020).

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(A) Sequentially Pd-catalyzed arylation-amination consecutive three-component synthesis of 3,10-diaryl 10H-phenothiazines 104 (TRZ = 2,4-diphenyl-1,3,5-triazine) (Mayer et al., 2020; Mayer and Müller, 2021). (B) One-pot sequence to synthesize disubstituted phenothiazine-triazine dyes 105 (Kloeters et al., 2022). (C) Pseudo five-component Sonogashira–Glaser cyclization synthesis of thienyl-bridged oligophenothiazines 106 (Urselmann et al., 2016). (D) One-pot LiForK synthesis of a 3,7-diacceptor substituted phenothiazine 107 (May and Müller, 2020).

SCHEME 21

(A) One-pot Ugi 4CR synthesis of donor-acceptor dyads 112 and selected examples (Ochs et al., 2019). (B) One-pot synthesis of functionalized benzo[b]phosphole derivatives 114 and selected fluorophores (Wu et al., 2014).

SCHEME 22

(A) Hantzsch synthesis of pyrimido[4,5-b]quinolines 116 and the four obtained derivates (Gholami et al., 2020). (B) Meglumine catalyzed one-pot synthesis of fluorescent 2-amino-4-pyrazolyl-6-aryldiazenyl-4H-chromene-3-carbonitriles 117 and selected derivates (Korade et al., 2021).

SCHEME 23

(A) One-pot synthesis of boron Schiff base dyes 118 (Corona-Lopez et al., 2021). (B) Derivatization of an isonitrile functionalized BODIPY dye via various MCR to synthesize compounds 121–124 (Vazquez-Romero et al., 2013).

SCHEME 24

(A) One-pot condensation reaction to synthesized pentacoordinate and chiral organotin compounds 127 and 128 derived from amino acid based Schiff bases (Lara-Ceron et al., 2017). (B) Microwave-assisted pseudo seven-component condensation reaction to synthesize two fluorescent pentacoordinated organotin complexes 129 derived from Schiff bases with three central tin atoms (Canton-Diaz et al., 2021).

SCHEME 25

(A) One-pot catalyst-free Ugi 4CR for the synthesis carboxamide-modified-metallophthalocyanines 131 and 132 (Afshari et al., 2019). (B) One-pot synthesis of fluorophore decorated macrocyclic peptides 133 (Rotstein et al., 2011).