Synthetic Routes to Coumarin(Benzopyrone)-Fused Five-Membered Aromatic Heterocycles Built on the α-Pyrone Moiety. Part 1: Five-Membered Aromatic Rings with One Heteroatom

This review gives an up-to-date overview of the different ways (routes) to the synthesis of coumarin(benzopyrone)-fused, five-membered aromatic heterocycles with one heteroatom, built on the pyrone moiety. Covering 1966 to 2020.

Molecules 2021, 26, x FOR PEER REVIEW In order to enrich the limited versatility of the structures found in nature, syn of coumarin (benzopyrane)-fused, membered aromatic heterocycles has receive siderable attention, including numerous reported routes.
This review gives an up-to-date overview of the different ways (routes) synthesis of benzopyrone-fused, five-membered aromatic heterocycles with In order to enrich the limited versatility of the structures found in nature, synthesis of coumarin (benzopyrane)-fused, membered aromatic heterocycles has received considerable attention, including numerous reported routes.
This review gives an up-to-date overview of the different ways (routes) to the synthesis of benzopyrone-fused, five-membered aromatic heterocycles with one heteroatom, built on the pyrone moiety, from 1966 to 2020. Our main interest in this current work is to describe the components that have one heteroatom in an alicyclic-fused ring with the pyrone part of coumarin. The synthetic pathway of the investigated scaffold has provided systems containing oxygen, nitrogen, sulfur, and selenium in their core structure. The last heteroatom is less described in the output of the synthetic efforts. The fused heterocycles that contain more than one heteroatom will be detailed in the next part, which we intend to publish in the future.

Synthesis of Benzopyrone-Fused, Five-Membered
In order to enrich the limited versatility of the structures found in nature, synthesis of coumarin (benzopyrane)-fused, membered aromatic heterocycles has received considerable attention, including numerous reported routes.
This review gives an up-to-date overview of the different ways (routes) to the synthesis of benzopyrone-fused, five-membered aromatic heterocycles with one heteroatom, built on the pyrone moiety, from 1966 to 2020. Our main interest in this current work is to describe the components that have one heteroatom in an alicyclic-fused ring with the pyrone part of coumarin. The synthetic pathway of the investigated scaffold has provided systems containing oxygen, nitrogen, sulfur, and selenium in their core structure. The last heteroatom is less described in the output of the synthetic efforts. The fused heterocycles that contain more than one heteroatom will be detailed in the next part, which we intend to publish in the future.
Many strategies have been developed for the synthesis of the fused, five-membered aromatic heterocycle-benzopyran-4-ones. There are two main approaches to constructing these skeletons: five-membered, aromatic heterocycle construction, and pyrone-ring construction.
To date, different transition metal (Au, Pt, and Cu) catalyzed/mediated methodologies for benzopyrane synthesis have been reported [27,42,45,46]. Cheng and Hu described a one-pot cascade of an addition/cyclization/oxidation sequence using CuCl2 as the oxidant and CH3SO3H as the acid for regioselective synthesis of 2-substituted-4H-furo[3,2-c]benzopyran-4-ones 22 from the substituted 3-alkynyl-4H-benzopyran-4-one 20 (Scheme 7) [47]. This strategy included the CH3SO3H-acid-catalyzed construction of the furan ring, followed by oxidation of 21 with CuCl2 (Scheme 7) [47]. When the reaction was carried out in the presence of a catalytic Recently, different catalytic methodologies have been developed for the synthesis of 2H-chromenes, and they are based on three main approaches: catalysis with (transition) metals, metal-free Brønsted catalysis, and Lewis acid/base catalysis, which includes examples of nonenantioselective organocatalysis and enantioselective organocatalysis [42][43][44]. Alkynes have been widely employed as building blocks for this reaction in most cases.
Extensive work has been done to investigate the utility of an aryl alkynyl ether as a furan substrate, instead of arylalkynol, in the synthesis of 4H-furo [3,2-c]benzopyran-4-one [29,35]. The treatment of 3-iodo-4-methoxycoumarin (28) with phenylacetylene by means of sequential Sonogashira C-C coupling conditions resulted in a high-yield formation of the 4H-furo[3,2-c]benzopyran-4-one (30) (Scheme 10) [53]. In this reaction, the triethylamine was used as a base to induce the SN2-type demethylation of the Sonogashira coupling product, followed by an intramolecular attack of the enolate onto the cuprohalide π-complex of the triple bond (Scheme 10). As a follow-up to this type of reaction, a novel and rapid assembly of an interesting class of 4H-furo[3,2-c]benzopyran-4-ones, 33, was successfully achieved using a one-pot sequential coupling/cyclization strategy with 3-bromo-4-acetoxycoumarins 31 and dialkynlzincs 32 prepared in situ as reactive acetylides in transition-metal-catalyzed crosscoupling. The cascade transformation relies on palladium/copper-catalyzed alkynylation and intramolecular hydroalkoxylation (Scheme 11) [54]. A transition-metal-free approach was developed to achieve 4-H-furo[3,2-c]benzopyran-4-ones via an iodine-promoted one-pot cyclization between 4-hydroxycoumarins 34 and acetophenones 35. The transformation spontaneously proceeded to produce (36) in the presence of NH4OAc. The possible reaction mechanism suggested for the iodine-promoted one-pot cyclization is depicted (Scheme 12) [55]. As a follow-up to this type of reaction, a novel and rapid assembly of an interesting class of 4H-furo[3,2-c]benzopyran-4-ones, 33, was successfully achieved using a one-pot sequential coupling/cyclization strategy with 3-bromo-4-acetoxycoumarins 31 and dialkynlzincs 32 prepared in situ as reactive acetylides in transition-metal-catalyzed crosscoupling. The cascade transformation relies on palladium/copper-catalyzed alkynylation and intramolecular hydroalkoxylation (Scheme 11) [54].
Extensive work has been done to investigate the utility of an aryl alkynyl ether as a furan substrate, instead of arylalkynol, in the synthesis of 4H-furo [3,2-c]benzopyran-4-one [29,35]. The treatment of 3-iodo-4-methoxycoumarin (28) with phenylacetylene by means of sequential Sonogashira C-C coupling conditions resulted in a high-yield formation of the 4H-furo[3,2-c]benzopyran-4-one (30) (Scheme 10) [53]. In this reaction, the triethylamine was used as a base to induce the SN2-type demethylation of the Sonogashira coupling product, followed by an intramolecular attack of the enolate onto the cuprohalide π-complex of the triple bond (Scheme 10). As a follow-up to this type of reaction, a novel and rapid assembly of an interesting class of 4H-furo[3,2-c]benzopyran-4-ones, 33, was successfully achieved using a one-pot sequential coupling/cyclization strategy with 3-bromo-4-acetoxycoumarins 31 and dialkynlzincs 32 prepared in situ as reactive acetylides in transition-metal-catalyzed crosscoupling. The cascade transformation relies on palladium/copper-catalyzed alkynylation and intramolecular hydroalkoxylation (Scheme 11) [54]. A transition-metal-free approach was developed to achieve 4-H-furo[3,2-c]benzopyran-4-ones via an iodine-promoted one-pot cyclization between 4-hydroxycoumarins 34 and acetophenones 35. The transformation spontaneously proceeded to produce (36) in the presence of NH4OAc. The possible reaction mechanism suggested for the iodine-promoted one-pot cyclization is depicted (Scheme 12) [55]. A transition-metal-free approach was developed to achieve 4-H-furo[3,2-c]benzopyran-4-ones via an iodine-promoted one-pot cyclization between 4-hydroxycoumarins 34 and acetophenones 35. The transformation spontaneously proceeded to produce (36) in the presence of NH 4 OAc. The possible reaction mechanism suggested for the iodine-promoted one-pot cyclization is depicted (Scheme 12) [55].
In conclusion, since coumarins have versatile applications, the synthesis of different structures of the coumarin-based scaffold was attempted. Among all the heterocycles built on the α-pyrone moiety of coumarin, the furan ring is the only available structure in nature. Thus, it has inspired a lot of researchers to replace the oxygen atom with other heteroatoms. Wide varieties of heterocycles were constructed by a synthetic pathway to introduce furans, pyrroles, thiophenes, and selenophenes as a fused ring that is characterized by a single heteroatom to the α-pyrone moiety of coumarin. The fused heterocycles that contain more than one heteroatom will be described in the next part, which we intend to publish in the future.