Dihydronaphthofurans: synthetic strategies and applications

Dihydronaphthofurans (DHNs) are an important class of arene ring-fused furans which are widely found in many natural and non-natural products and drug candidates with relevant biological and pharmacological activities. Furthermore, vinylidene-naphthofurans exhibit photochromic properties when exposed to UV or sun light at room temperature. For these reasons, a vast array of synthetic procedures for the preparation of dihydronaphthofurans including annulation of naphthols with various reagents, cycloaddition reactions ([3 + 2], [4 + 1] and Diels–Alder), intramolecular transannulation, Friedel–Crafts, Wittig, Claisen rearrangement, neophyl rearrangement and other reactions under various conditions have been developed over the past decades. This review aims to describe the different strategies developed so far for the synthesis of dihydronaphthofurans and their applications. After a brief introduction to the types of dihydronaphthofurans and their biological activities, the different synthetic approaches such as chemical, photochemical, and electrochemical, methods are described and organized on the basis of the catalysts and the other reagents employed in the syntheses. The subsequent section focuses on biological and pharmacological applications and photochromic properties of the target compounds.


Introduction
Furans are ve-membered aromatic heterocycles containing one oxygen atom that are commonly found in many important compounds such as natural products, pharmaceuticals and polymers. Moreover, furans can be utilized as synthetic intermediates to access other useful compounds. The synthesis of this fundamental structural building block has received signicant attention and a wide variety of approaches are available to the synthetic practitioner. 1 Arene ring-fused furan derivatives such as dihydronaphthofurans (DHNs) have attracted widespread interest in view of their presence in many important natural and non-natural products. Natural products with DHN moieties have been shown to have a wide range of biological and pharmacological properties. 2-4 For example, furaquinocins (A), consisting of highly oxygenated p-quinone rings, are antihypertensive, cytotoxic against HeLa S3 and B16 melanoma cells, and also inhibit platelet aggregation and coagulation. 2 In contrast, (À)-nocardione (B) with an o-quinone moiety is a Cdc25B tyrosine phosphatase inhibitor with moderate antifungal and cytotoxic activity. 3 Also, rubioncolin A (C) and rubioncolin B (D) were isolated from Rubia oncotricha in racemic forms. 4 They are also found in Rubia cordifolia, which is used in traditional Korean medicine to treat coughs, bladder and kidney stones, joint inammation, uterine hemorrhage, and uteritis. 5 Interestingly, the electron rich catechol derivative aegyptinone (E) shows antibacterial and antifungal activity 6 ( Fig. 1).
Furthermore, some of the synthesized dihydronaphthofuran derivatives exhibit a variety of interesting biological and pharmacological properties including 5-lipoxygenase inhibitor, 7 C 17,20 lyase inhibitors, 8 antitubercular activity against Mycobacterium tuberculosis H 37 Rv, 9 anti-tyrosinase, antioxidant, and antibacterial, 10 inhibitors of NFk B activity, 11 a-glucosidase inhibitors, 12 inhibitor of a-chymotrypsin 13 and anti cancer activities (liver tumor growth inhibitors). 14 Moreover, vinylidene-naphthofurans are a new class of polycyclic compounds that exhibit photochromic properties when exposed to the UV or sunlight at room temperature and adsorbed in silica gel or dissolved in acidied alcoholic solutions (Fig. 2). [15][16][17][18][19][20] This wide range of biological activities and properties has stimulated interest in the synthesis of dihydronaphthofuran derivatives. During the past decades, several synthetic approaches to 2,3-dihydronaphtho[2,1-b]furan, 2,3-dihydronaphtho [1,2-b]furan, 2,3-dihydronaphtho[2, 3-b]furan, 1,3dihydronaphtho[2,3-c]furan, 1,3-dihydronaphtho[1,2-c]furan and vinylidene-1,2-dihydronaphtho[2,1-b]furan derivatives (F-K) (Fig. 3) have been reported. The general methods used for the synthesis of these compounds include chemical, photochemical and electrochemical methods have been described and organized on the basis of the catalysts and the other reagents. To the best of our knowledge, there is no review on synthesis of dihydronaphthofuran derivatives. Hence, the main purpose of this review is to show all types of reactions for the synthesis of these heterocyclic compounds, such as annulation of naphthols with various reagents, cycloaddition reactions ( [3 + 2], [4 + 1] and Diels-Alder), intramolecular transannulation, Friedel-Cras, Wittig, Claisen rearrangement,   neophyl rearrangement and the other reactions in various conditions and their biological, pharmacological and photochromic properties.
A one-step synthesis of ethyl 1,2-dihydronaphtho[2,1-b] furan-2-carboxylates 23 from substituted naphthols and ethyl 2,3-dibromopropanoate in the presence of K 2 CO 3 in reuxing acetone for 18 h has been reported by Merour et al. 27 First, ethyl 2,3-dibromopropanoate is easily transformed in situ into ethyl-2-bromoacrylate with potassium carbonate in reuxing acetone. Then, a Michael-type addition of the naphthalenolate to the 2-bromoacrylate generates the C-C bond forming intermediate 21. Aromatization and formation of the 2-naphthalenolate anion gives the intermediate 22. This is followed by an intramolecular nucleophilic substitution on the carbon bearing the bromo atom in 22 affording the gave the corresponding product 23 in 35-83% yields. Following the same methodology, the reaction of 2-naphthol with 2-chloroacrylonitrile and 3,4-dibromobutan-2-one in reuxing acetonitrile for 18 h afforded 24 and 25 in 75 and 60% yields, respectively (Scheme 7). Treatment of 1-naphthol derivatives with ethyl 2,3-dibromopropanoate in the presence of K 2 CO 3 in reuxing acetone for 28 h led to the formation of the expected ethyl 2,3-dihydronaphtho[1,2-b]furan-2-carboxylates 26 in 0-31% yields and unexpected ethyl 4 0 -oxospiro[cyclopropane-1,1 0 (4 0 H)naphthalene]-2-carboxylates in 0-71% yields besides starting materials. Also, the reaction of 1-naphthols with 3,4dibromobutan-2-one by applying the same methodology gave 2,3-dihydronaphtho[1,2-b]furan-2-yl ketones 27 in 0-25% yields and unexpected products in 16-32% yields (Scheme 8). 28 Formation of 26 and 27 took place according to similar reported mechanism in Scheme 7. 27 An efficient procedure for the conjugate addition of methyl acetoacetate to 2-(methoxycarbonyl)-1,4-naphthoquinone using K 2 CO 3 has been developed. The reaction was carried out in CH 2 Cl 2 at room temperature for 12 h yielded 61% of a mixture of cis and trans (20 : 80) 2,3-dihydronaphtho[1,2-b]furan derivatives 28 (Scheme 9). 29 Alla et al. 30 noted that one-pot reaction of 2-amino-4H-pyran derivatives 29 with N-chlorosuccinimide and a base (piperidine or aqueous KOH) in alcohol medium at room temperature for 8-9 h gave dihydronaphthofurans 30 in 68-90% yields. Plausible mechanism for the formation of 30 has been arrived at Scheme 10. Initially aminopyran undergoes oxidative difunctionalization with NCS in the presence of an alcohol solvent. Subsequent addition of base to the aminopyran leads to proton abstraction from the amino group. This leads to a cascade pyran ring opening by the cleavage of the (C 2 -O 1 ) bond, and ring closure of the (O 1 -C 3 ) bond to dihydrofuran via elimination of HCl. The sequential elementary processes lead to formation of the ring contracted dihydrofuran carbimidate ester 30. In a similar manner, highly functionalized pyran derivatives 31 were treated with methanolic KOH (1 N) at room temperature for 36 h to obtain the products 32 in good yields (70-75%) (Scheme 10).

Acid-catalyzed synthesis
In 1971, Martini reported that preparation of dihydronaphthofuran 3 was accomplished by the treatment of 2-naphthol with isobutylaldehyde using HCl in EtOH at 80 C for 0.5 h in 74.6% yield (Scheme 17). 3 In a similar fashion, synthesis of 2,3-dihydro-2,2-dimethylnaphthol[1,2-b] furan (47) in 43.1% yield has been accomplished by the treatment of 1-naphthol with isobutylaldehyde using H 2 SO 4 in toluene at 90-160 C for 3 h (Scheme 18). 33 Similarly, dihydronaphthofuran 47 was obtained via the reaction of isobutyraldehyde with 1-naphthol in the presence of catalytic amount of p-TSA under closed vessel solvent-free microwave irradiation conditions at 180 C for 5 min in 80% yield (Scheme 19). 34 Treatment of 4 with p-toluenesulfonic acid monohydrate in benzene under reux condition for one hour with simultaneous removal of 50 cm 3 of benzene containing the water formed, gave dihydronaphthofuran 6 in 80.6% yield (Scheme 20). 22  It was also shown that dihydronaphthofuran 6 was obtained by the reaction of styrene oxide with 2-naphthol in reuxing benzene for 1 h in 48.8% yield (Scheme 21). This reaction proceed via the acid catalyzed unimolecular ring opening of styrene oxide, followed by nucleophilic attack of naphthol to the resulting adduct 48 and cyclization, then elimination of water afforded the nal product 6. 35 In 1953, Guss et al. 36 have obtained 1,2-diphenyl-1,2-dihydronaphtho[2,1-b]furan (49) in 69.9% yield from the reaction of 2-naphthol and trans-stilbene oxide by using p-toluenesulfonic acid monohydrate as catalyst in 105 C for 15 min under solvent-free condition. Presumably a phenol-alcohol 50 was rst formed and then cyclized under these reaction conditions to the desired product 49 (Scheme 22).
In a similar fashion, synthesis of 2,3-dihydronaphtho[1,2-b] furan derivatives 85 in 11-86% yields has been achieved by the cycloaddition reaction of diazonaphthoquinones 86 with enol ethers in CH 2 Cl 2 at 30 C for 0.5-21.5 h (Scheme 45). 47 Reaction of vinylidene-naphthofuran derivatives 87a-c with boronic acid in the presence of Pd(PPh 3 ) 4 and K 2 CO 3 in reuxing toluene for 4-5 h afforded photochromic vinylidenenaphthofurans 88a-c in 79-85% yields. The reaction of 88c with BBr 3 in dry CH 2 Cl 2 at room temperature for 5 h afforded photochromic vinylidene-naphthofuran 89 in 76% yield (Scheme 46). 20 PtCl 2 -catalyzed cyclization of o-diethynylbenzene derivatives 90 bearing a hydroxyethyl group in toluene under an argon atmosphere at 80 C for 1-40 h afforded dihydronaphthofuran derivatives 93a-c in 11-76% yields. Formation of 93 can be rationalized by initial intramolecular cyclization of the hydroxy group to an activated ethynyl group in 91 to form intermediate 92, followed by attack of the second ethynyl group to give 93 (Scheme 47). 48 Lee and Xia described a novel approach for the synthesis of diverse dihydronaphtho[1,2-b]furans 94 in 11-96% yields from 1,4-naphthoquinones 95 and olens 96 in the presence of ceric ammonium nitrate in CH 3 CN at room temperature for 20-30 min via formal [3 + 2] cycloaddition reaction (Scheme 48). This methodology was also used successfully to synthesize the biologically important natural product furomollugin in only 2  49 Similarly, 2,3-dihydronaphtho[1,2-b]furans 99 were synthesized in 38-96% yields by the reaction of 2-acetylnaphthalene-1,4-dione (95b) with olens in the presence of cerium(IV) ammonium nitrate (CAN, 5.0 mol%) as catalyst in CH 3 CN at room temperature for 20 min (Scheme 50). 10 Also, Lee et al. 50   Subsequent intramolecular benzannulation of 105 via either aldol condensation or 6p-electrocyclization of trienol 106 leads to the 2,3-dihydronaphtho[1,2-b]furan 101. 51 The cascade reaction of alkynols 107 with alkynes 108 under combined Sc(OTf) 3 and rhodium catalyst, Cu(OAc) 2 and HOAc in dichloroethane under nitrogen atmosphere at 80 C for 24 h led to the formation of 2,3-dihydronaphtho[1,2-b]furans 109 in 50-86% yields (Scheme 54). 52 ortho-Carbonylarylacetylenols 110 have been employed for the synthesis of 2,3-dihydronaphtho[2, 3-b]furans 111 in 60-89% yields via AgTFA (2 mol%) catalyzed annulation reaction in DCE at 85 C for 1.5-18 h. In a similar fashion, annulation of ortho-formylarylacetylenol 112 in the presence of AgTFA and PPTS gave 2,3-dihydronaphtho[2, 3-b]furans 113 in 26-79% yields (Scheme 55). 53 The reaction mechanism of this transformation was then proposed as shown in pathway A of Scheme 56. First, alkyne was activated by Ag-catalyst with the assistance of ortho-carbonyl neighboring group to form oxo-carbenium ion intermediate Similarly, an efficient method was developed for the synthesis of dihydronaphthofuran 57 in 80% yield by the treatment of allyl naphthol with molecular iodine in the presence of NaHCO 3 in CH 2 Cl 2 at room temperature for 24 h. The key step involve iodocyclization. In a similar manner, orthoallylnaphthol on reaction with molecular iodine in CH 3 CN under reux condition for 4 h gave dihydronaphthofuran 57 in 62% yield (Scheme 58). This reaction is assisted by the hydroxyl group, involves formation of iodonium ion 119 and proceeds through non radical mechanism pathway. 55 A number of 2-(iodomethyl)-1,2-dihydronaphtho[2,1-b]furan derivatives 120 in 71-85% yields have been synthesized from the corresponding allylhydroxy naphthalene precursors 121 involving N-iodosuccinimide in acetonitrile at 0-5 C and then at room temperature for 2 h or by employing molecular iodine in aqueous micelle using CTAB as surfactant at 0-5 C and then at room temperature for 6 h. At rst the allylhydroxy precursor 121 may generate the iodonium intermediate 122, which undergoes 5-exo-trig cyclization to from the cyclized product 120 (Scheme 59). 56 Recently Deng et al. 57 found that dihydronaphthofurans 123 in 67-93% yields could be prepared from readily available 1-(2nitrovinyl)naphthalen-2-ol 124 and malonate esters 125 in the presence of I 2 (10 mol%), NaHCO 3 and TBHP as oxidant in THF at 30 C for 24 h to 8 days (Scheme 60). A tentative mechanism is proposed in Scheme 61. As depicted in Scheme 61, I 2 could be transformed into hypoiodite [IO] À under basic conditions initially, then, which is further oxidized by TBHP to form the  An efficient method was developed for the synthesis of 2-(iodomethyl)-2,3-dihydronaphtho[1,2-b]furan (127) in 80% yield by the reaction of 2-allyl-1-naphthol 128 with molecular iodine in the presence of NaHCO 3 in CH 2 Cl 2 at room temperature for 24 h (Scheme 62). 58 Regioselective iodocyclization of a series of allylhydroxy naphthalene precursors 129 involving N-iodosuccinimide (method A) and environment friendly green approach associated with surfactant (CTAB)-promoted molecular-iodinemediated (method B) 5-exo-trig cyclization strategies has been explored. Method A: the reaction mixture in CH 3 CN was magnetically stirred for 150 minutes at 0-5 C and then at room temperature for further 30  1,2-Dihydronaphtho[2,l-b]furan (11b) could also be obtained in 50% yield from the Mannich base methiodide of 2-naphthol via the corresponding quinone methide in the presence of dimethyl sulfoxonium methylide in dimethyl sulfoxide (DMSO) and base (B ¼ Na + -CH 2 SOCH 3 ) (Scheme 71). 63 In a similar manner, dihydronaphthofuran 11b was obtained by the reaction of Mannich bases, Mannich base methiodides, and Mannich base N-oxides derived from naphthols with diazomethane in CH 2 Cl 2 at 3 C for 16-96 h or with dimethylsulphoxonium methylide in DMSO at 20-100 C for 2-48 h in 0-28% yields (Scheme 72). 64 Also, 2,3-dihydronaphtho[1,2-b]furan (156) was obtained in 4-53% yields via the reaction of Mannich bases, Mannich base methiodides, and Mannich base N-oxides derived from 1naphthols with diazomethane in CH 2 Cl 2 at 3 C for 24 h or with dimethylsulphoxonium methylide in DMSO at 60-70 C for 2-16 h (Scheme 73). 64 A simple and general route to the synthesis of 1,2-dihydronaphtho[2,1-b]furans 157, substituted in position 2 by an acyl or aroyl group, starting from phenolic Mannich base methiodides and the carbonyl-stablished sulphonium ylide in CH 3 CN has been developed. The reaction proceeds readily at room temperature for 12 h and usually affords desired products 157 in 65-75% yields (Scheme 74). The formation of the products can be rationalised by assuming the known behaviour of stabilised sulphonium ylides towards system bearing an electrophilic centre and a nucleophilic heteroatom. 65 The work of Yan et al. 66 demonstrated that annulation reaction of b-naphthols with (2-bromoethyl)diphenylsulfonium tri-uoromethanesulfonate salt (158) in the presence of K 2 CO 3 in CH 3 CN at 0 C under an argon atmosphere for 16-24 h led to the formation of dihydronaphthofurans 159 in moderate to good yields (54-92%) (Scheme 75). A tentative reaction mechanism is outlined in Scheme 76. The reaction begins with the generation of a vinylsulfonium salt 160 via the elimination of hydrogen bromide from 158. The vinylsulfonium salt 160 reacts with bnaphthols to give sulfonium ylides 161, which then tautomerize to intermediates 162. Aer a proton transfer, the zwitterions 163 are formed. The subsequent intramolecular SN 2 reaction led to the formation of products 159 and eliminates diphenyl sulde.
A mixture of naphtho[b]furans 214-215 and dihydronaphthofuran 216-217 were obtained from allyl halonaphthyl ethers employing photo induced radical cyclization with 100 W highpressure mercury lamp in CH 3 CN under Ar atmosphere for 0.5-3 h (Scheme 99). In addition, observations made in this effort suggest that a plausible mechanism for these photoreactions (Scheme 100) begins with homolytic C-halogen bond cleavage in the triplet states of the substrates to generate radical pairs, which undergo 5-exo type cyclization and halogen atom capture to produce the initially formed 2-halomethyl substituted naphthodihydrofurans 216 similar to atom-transfer radical cyclizations. Subsequently, photoinduced dehydrohalogenation of 216 takes place to generate alkylidene dihydrofuran intermediates 218 that undergo tautomerization to generate the naphthofuran product 214. In the case of R 1 ¼ CH 3 , R 2 ¼ CH 3 , the photochemical dehydrohalogenation leads to the respective formation of 218 and the regioisomeric product 217, which is photochemically tautomerized to 215. 79
Triarylaminium salt was disclosed as an efficient initiator for the novel Friedel-Cras alkylation/annulation cascade reaction between chalcone epoxides 247 and 2-naphthols in CHCl 3 at room temperature for 0.5 h to construct diastereomer poly- An efficient chemoselective tandem Friedel-Cras alkylation/cyclization reaction of glycidic esters with 2-naphthol derivatives in CH 2 Cl 2 at ambient temperature for 0.5 h initiated by stable radical cation triarylaminium salt [tris (4bromophenyl) Wang et al. 87 concluded that tandem reaction between chalcone epoxides and 2-naphthyl ethers in the presence of stable triarylaminium salt (5 mol%) in CHCl 3 at room temperature for 0.5 h afforded dihydronaphthofurans 255 (Scheme 113). And aer subsequent aerobic oxidative aromatization in one pot, a series of polysubstituted naphtho[2, 1-b] furans were delivered. It should be noted that compounds 255 have not isolated. The reaction mechanism similar to the proposed mechanism for the synthesis of 249. Subsequently, the crude acid chlorides in diethyl ether were treated with diazomethane for 3 h and aer that with LiBr in HOAC (80%) at 0-5 C for 10 min (Scheme 115). 13 Admas et al. 7 demonstrated that N-hydroxyurea derivative of dihydronaphthofuran 260 has been prepared in 12% yield from the corresponding ketone in three steps, oximation, reduction, and hydroxyurea formation (Scheme 116).

Other synthetic methods
In a similar fashion, N-hydroxyurea derivative of dihydronaphthofuran 261 could be prepared in 18% yield from the corresponding ketone 262 in three steps, oximation, reduction, and hydroxyurea formation (Scheme 117).

Photochromic properties
Vinylidene-naphthofurans are a new class of photochromic molecules, with a unique structure combining an allene group linked to a dihydrofuran ring. These uncoloured molecules show acidochromism in solution and photochromic properties when adsorbed in silica gel or dissolved in acidied alcoholic solutions but not in common solvents or in the solid state. Mechanism of the photochromic behaviour for those compounds is thermally reversible. For example, vinylidenenaphthofuran 63 exhibit photochromism at room temperature when adsorbed in silica gel. UV or sunlight irradiation leads, in a few seconds, to the formation of intense pink/violet to green colors that bleach completely in a few minutes in the dark (Scheme 124). Also, compound 63 show acidochromic properties: addition of TFA to an uncolored solution of compound 63 leads to the immediate development of an intense violet coloration 283 that bleaches immediately when a weak base (NEt 3 ) is added (Scheme 125). 15 Vinylidene-naphthofurans 63 exhibit acidochromic properties in TFA solutions. They are converted into stable cationic species in strong acidic medium and bleach back to the uncoloured closed form upon neutralisation with Et 3 N. A mechanism for their thermally reversible photochromic behaviour is proposed based on NMR analysis of UV-irradiated CH 3 OD + THF-d 8 acidied solutions: the UV light promotes the addition of methanol to the naphthofuran affording noncoloured photoproduct 284. In the presence of acid, the later is quickly converted into a cationic violet dye 283 that returns thermally to the initial closed naphthofuran in the dark. This photochromic system switches between the uncoloured and violet state aer UV or sunlight exposure (15 s) and returns thermally to the initial uncoloured state in 2-8 min, in the dark, at room temperature (Scheme 126). 16 The introduction of a styryl chain in the structure of the vinylidene-naphthofurans such as 140-142 leads to a new set of uncoloured photochromic compounds that afford grey/brown colourations upon exposure to the UV or sunlight, at room temperature and returning to the uncoloured state, in the dark, in several minutes. The photochromic properties of these smart dyes are very sensitive to the chemical environment, specially their acidity being faster in THF/HCOOH solution than in silica gel. The amount of formic acid inuences the kinetics of the fading reaction as a low concentration leads to a faster system but with a lower colourability. A good compromise was obtained in THF/HCOOH (2/0.5) solutions. The substituents in the styryl group inuences the kinetic of the fading process: electronwithdrawing groups like Br or CF 3 increases the fading rate leading to fast switching compounds but confers an initial yellowish colour to the solution before irradiation (Scheme 127). 17 The photochromic properties of the ormosil materials 68 showed a strong dependence on the nature of the silanes, spacer, acid and curing conditions. The functionalization of the vinylidene-naphthofurans with a reactive siloxane group was essential to avoid their precipitation aer curing. The best results were obtain using a mixture of TEOS, MTES, PTES, 1,2ethanodiol, water, chloroacetic acid and vinylidenenaphthofurans (68: R ¼ OMe) cured at 50 C for 7 days. This uncoloured material is transparent and develops an intense green colouration, characterized by two absorption bands at 460 and 640 nm, aer 2 min under UV light. When the light source is removed a mono-exponential colour decay occurs due to the spontaneously ring closure reaction that afford the initial molecule. These hybrids showed a fast thermal bleaching kinetics, losing almost their total colouration in 20 min in the dark (Fig. 4). 19 A series of photochromic vinylidene-naphthofurans 88 and 89 with extended conjugation, embedded in ormosil matrices affording solid and transparent materials that acquire different colourations (violet, green, bluish), reversibly, when exposed to the UV (sun) light, for 2 min, at room temperature. The presence of an extra phenyl ring in some positions affects both the l max of absorption of the photochromic compounds in the uncoloured closed and open coloured form. Aer removal of the light source the materials lose progressively their colouration returning to the initial uncoloured state in less than 15 min at This journal is © The Royal Society of Chemistry 2020 RSC Adv., 2020, 10, 5794-5826 | 5823 room temperature. Photochromic 1-vinylidene-naphtho[2,1-b] furan derivatives 210 and 211 were successfully anchored onto silica nanoparticles (SiO 2 NPs) through direct adsorption (SiO 2 @211) and covalent post-graing (SiO 2 @210) (Fig. 5).
SiO 2 NPs with different size and surface chemistry (pH pzc in the range of 5-9) were used, offering a wide range of possibilities to fabricate tailor-made photochromic materials. The photochromic behavior of these new nanoparticles indicates that silica surface acidity and the type of vinylidenenaphthofuran immobilization strategy (adsorption vs. covalent graing) were crucial factors for the occurrence of photochromism in the vinylidene-naphthofuran-based SiO 2 NPs. Upon direct UV (l ¼ 365 nm) or sunlight exposure during 1 min, only the SiO 2 @211 nanomaterials prepared by direct vinylidenenaphthofuran adsorption onto SiO 2 NPs with pH pzc z 6.0 showed direct and reversible photochromic properties, developing fast (in seconds) and intense salmon and violet coloration, with high values of total color difference and optical densities; in contrast, all nanomaterials prepared by covalent graing of 210 onto SiO 2 NPs (SiO 2 @210) did not exhibit photochromism. In the case of the photochromic SiO 2 @211 NPs, the decoloration process followed a bi-exponential decay with fast rate constants, which were responsible for the loss of coloration in less than 10 min. Furthermore, they presented very good resistance to fatigue, showing reversibility between the colored/uncolored states without signicant loss of their performance for at least 8 successive UV/dark cycles. Scheme 128 has been represented of the proposed mechanism responsible for the photochromic behavior of 211 onto SiO 2 NPs. 18

Conclusions
In this review, wide range of synthetic strategies of dihydronaphthofurans (DHNs) as an important class of arene ringfused furans has been discussed. We have started with chemical, photochemical and electrochemical methods for the synthesis of DHNs, followed by presenting of their diverse biological, pharmacological activities and photochromic properties. In general, naphthol derivatives play an important role and work well in construction of DHNs. Moreover, different types of reactions such as annulation of naphthols and naphthoquinones, [3 + 2] and [4 + 1] cycloaddition, Friedel-Cras and Diels-Alder reactions, Claisen and neophyl rearrangement, cyclization of allyl naphthols and etc. were demonstrated for synthesis of DHNs. We believed that the reported methods could be of interest in material science, medicinal, photochromic compounds and natural products synthesis and their use has been growing rapidly.

Conflicts of interest
There are no conicts to declare.