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Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization
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Shanghui Tiana, Tian Luoa, Yanping Zhu*, b, Jie-Ping Wan*, a
Chinese Chemical Letters | 2020, 31(12) : 3073 - 3082
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Chinese Chemical Letters | 2020, 31(12): 3073-3082
• Review •
Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization
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Shanghui Tiana, Tian Luoa, Yanping Zhu*, b, Jie-Ping Wan*, a
Affiliations
  • a College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China
  • b School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
Published: 2020-12-15 doi: 10.1016/j.cclet.2020.07.042
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Chromone and flavone are both central backbones of natural products and clinical medicines. Synthesis of diversely functionalized chromones and flavones constitutes significant research contents of the modern synthetic science because abundant molecular libraries of such types are crucial in providing candidate compounds for the discovery of new pharmaceuticals and functional materials. The direct C-H bond activation or functionalization on these heterocyclic backbones provides highly powerful tools for the rapid accesses to densely functionalized chromone and flavone derivatives. Considering the importance of the functionalized chromone and flavone compounds as well as the notable advances in the synthesis of such products by direct C-H activation or functionalization, we review herein the research advances in the C-H bond activation and functionalization reactions of chromone and flavones, in hope of showing the current states and promise of the research domain.

Chromones  /  Flavones  /  C-H bond  /  Activation  /  Functionalization
Shanghui Tian, Tian Luo, Yanping Zhu, Jie-Ping Wan. Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization[J]. Chinese Chemical Letters, 2020 , 31 (12) : 3073 -3082 . DOI: 10.1016/j.cclet.2020.07.042
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1 Introduction
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The chromone and its derivatives such as flavones are heterocyclic system with strategic importance in a number of research and industrial domains. Chromone has been identified as the central backbone in a number of functional organic compounds, including natural products such as flavones, isoflavones as well as other natural molecules featured with chromone fragment [1-10]. What is more, many chromone-based compounds have also been identified with interesting optical as well as chelating functions, enabling their broad application in the designation of organic materials [11-15]. Moreover, on the basis of those well documented utilizations and activities, much more novel bioactivities and other utilities are yet to explore and discover weith these heterocyclic derivatives because of their intrinsically enriched functions [16-18]. By analyzing the structures of the chromone/flavone-based natural products, drugs and other functional molecules, it can be found that the common feature is that multiple substituents exist in both the heteroaryl ring and the phenyl fragments of the central backbone (Fig. 1). Therefore, the synthesis of chromones and flavones with diversely functionalized substructures has accordingly become attractive topic in the area of organic synthesis [19-21].
Typically, the synthesis of chromones can be accessed by two different tactics: One is the synthesis via reactions involving the hetero-ring construction. The other is the direct bond elaboration on the readily available chromones/flavone substrates. For the former strategy, the substrate sources as well as reaction pathways are considerably more abundant and flexible, thus enables the synthesis of the target product with highly divergent catalytic methods as well as substitution styles [22-29]. The synthetic methods by the direct elaboration on chromones/flavones, on the other hand, features the major advantages of more flexibly tunable site selectivity, and the step economy resulting from the straightforward C—H bond transformation or functionalization [30-40] in constructing both C—C [41-50], and C-heteroatom bonds [51-56]. Considering the importance of the synthetic methods toward these titled molecules as well as the notable advances taking place in the synthetic research area of C—H bond elaboration of chromones and flavones, we present herein the research advances on chromones and flavones synthesis byfocusingon the directC—H activation and functionalization of the readily available chromones/flavones substrates. On the basis of the actual reports, the reactions transforming the C—H bonds both in the heterocycle and phenyl ring fragments in these molecules are covered.
2 C—H elaboration on the heterocyclic fragment of chromones
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The C(sp2)—H bonds in the pyranone ring of chromone or related derivatives are intrinsically more reactive than conventional aryl or alkenyl C—H bonds. Therefore, the direct transformation on the C2— and C3—H bonds in chromones constitutes the reliable and powerful routes to access chromones bearing functional substitution in the C2 and/or C3 site. In 2012, Hong's group [57] reported the Pd(OAc)2/Fe(OTf)3-cocatalyzed synthesis of flavonoids via the C2-arylation of chromones. The reactions of chromones 1 and phenyl boronic acids 2 in the presence of Pd(OAc)2/Fe(OTf)3 catalyst and oxidant additive of DDQ/KNO2 to provide flavones 3 with broad scope in PivOH at 60 ℃ heating. The reactions were proposed to be initiated by the aryl palladation of the C=C bond in chromone with the in situ generated ArPdX species by which the intermediate 1A/1A' was generated via the assistance of Fe(Ⅲ). The subsequent protonolysis led to the formation of chromanone 1B which underwent oxidation to afford products 3 (Scheme 1).
In the same year, Shafiee and Jafapour et al. [58] reported the Pd(OAc)2-catalyzed C—H arylation reactions of coumarins and chromones by oxidative C—H bond transformation. The reactions involving chromone substrates were run under balloon O2 with the assistance of 1, 10-phenanthroline (phen) ligand, which allowed the synthesis of 2-aryl chromones with good to excellent yield (Scheme 2).
On the other hand, Kim and co-workers [59] developed a different method for the synthesis of compounds 3 by employing directly arenes 4 as the aryl sources. Under the catalysis of Pd(OAc)2, a series of products were provided with moderate to good yields in the presence of AgOAc terminal oxidant as well as PivOH and CsOPiv. Because arene component also served the solvent, the application scope of arene was not as broad as the boronic acid-based synthesis (Scheme 3). The Pd-complexes 3A-3C were the key intermediates throughout the reaction process. Notably, by incorporating experimental and computational investigation on the site selectivity of the chromone arylation, Hong, Peng and Paton et al. [60] disclosed that the selective C2-arylation of chromones with palladium catalysis could be ascribed to the favorable C2 carbopalladation via the strong interaction of the neighboring C3 site and the Pd-species.
Alongside the arylation, other carbon functionalization in the chromone C2 site were also realized. Zhou and Ge et al. [61] achieved the synthesis of ether functionalized chromones 6 via the reactions of chromones 1 and ethers 5 via CuO catalysis in the presence of TBHP/DABCO. The reactions took place selectively in the carbon site adjacent to the oxygen in the ether. In terms of mechanism, the reactions were proposed to proceed via a free radical pathway involving the O-centered free radical from TBHP. The free radical 4A was first generated from the coupling of TBHP-derived free radical and ether 5. The addition of 4A to chromone gave rise to free radical intermediate 4B which was transformed into a cation species and gave the product successively via SET by the oxidation of Cu(Ⅱ) (Scheme 4).
As another example of transition metal-catalyzed chromone C2 elaboration, Jin and co-workers [62] reported recently the C2-alkylation reaction of chromones via Fe(Ⅲ)-catalyzed reactions of chromones and diacyl peroxides. While the reactions of coumarins and different peroxides forming diverse 3-alkyl coumarins were defined via the catalytic protocol, the reactions of chromones and lauroyl peroxide (LPO) 7 were conducted to provide 2-alkylated chromones 8 with fair to good yields. The generation of alkyl radical was a key transformation in the reactions, which enabled the formation of intermediate 5A to mediate the product generation and the formation of Fe(Ⅱ) species for the catalytic cycle (Scheme 5).
In addition to these transition metal-catalyzed methodologies, the C2—H functionalization of chromones was also proved to be applicable under transition metal-free conditions. As one representative example of such type, Antonchick et al. [63] developed the PhI(CF3CO2)2/NaN3 mediated C2-alkylation of chromones the thiochromones 9 by employing a series of cycloalkanes and acyclic alkanes 10 as coupling partners. Under the promotion of PhI(CF3CO2)2 and NaN3, divergent 2-alkylated chromones and thiochromones 11 were practically afforded at room temperature. A free radical-based reaction mechanism was proposed for the titled reactions. First, the coupling of PhI(CF3CO2)2 and NaN3 provided intermediate 6A, which generated azide free radical and iodine centered PhICF3CO2 free radical 6B via homo-cleavage of the N—I bond. The reaction of azide free radical and alkane C—H bond led to the production of alkyl free radical 6C which could couple chromone/thiochromone to provide free radical intermediate 6D. The coupling of 6D with 6B then yielded products 11 by releasing PhI and TFA (Scheme 6).
Later on, the same group [64] reported the C2-azolation reactions of chromones via the promotion of molecular iodine and K2CO3. For the reaction of 1, 2, 4-triazole 12a, the reactions took place directly in the presence of I2 and K2CO3 to afford products 13. On the other hand, when other azoles such as pyrazole, (benz) imidazole, pyrrole and substituted 1, 2, 4-triazole were used, the stoichiometric 12a should be additionally employed. The authors hypothesized that the 12a played a key role to promote the reaction by coupling iodine to generate reactive N-iodoazole 7A to mediate the formation of the ionic intermediate 7B/7B'. The subsequent incorporation of 7B with anionic iodine then afforded 7C. Depending on the structure of R', the transformations via intermediates 7D and 7E (R' = H), or 7 F and 7 G (R' = Ar) then gave the target products 13 and 14 (Scheme 7).
Alongside the functionalization reactions of the C2—H bond of chromones, corresponding functionalization reaction in the C3—H bond of chromones also received splendid advances for the synthesis of diverse C3-functionalized chromones. As fundamental intermediates for the synthesis of numerous C3-substituted chromone via C-halogen bond cross coupling, the 3-halogenated chromones constituted one of the major targets in the chromone C—H functionalization reactions. While the synthesis of 3-halochromones by cascade chromone ring formation and C—H halogenated were realized [25, 65, 66], the direct C—H halogenation of chromones made up the other major strategy.
In 1998 and 2002, Joo and co-workers reported successively the C-3 bromination of flavones by employing pyridinium bromide perbromide (PHPB) [67] and 2, 4, 4, 6-tetrabromo-2, 5-cyclohexadienone (TBCO) [68] as the brominating reagent, respectively (Scheme 8). In order to developed synthetic methods using more stable reagents and of broader substrate scope, continuous efforts were made toward 3-halochromone and related flavone synthesis. Rho et al. [69] reported an alternative method to access 3-haloflavones 17 via hypervalent iodine (PhI(OAc)2 promoted reactions of flavones 16 and trimethyl silyl halide (X = Cl or Br). The reactions were run at 0 ℃, and 3-bromo-/chloroflavones could be synthesized, but broad scope of synthesis was not yet defined (Scheme 9).
In their work of synthesizing 3-iodoflavones via the reactions of chalcone precursors, Lokhande et al. [70] disclosed that the reactions of flavones 16 and molecular iodine could also afford 3-iodoflavones 18 by heating at 130 ℃ in DMSO. The formation of iodonium ion 10A and diiodochromanone intermediate 10B were proposed as the main stages during the formation of 18(Scheme 10).
Recently, Wang and Liu et al. [71] developed a new approach for the synthesis of halogenated flavones 17 and 18 (X = Cl, Br, I) by employing potassium halide (KX) as halogen source in the presence of Oxone. The key process was the in situ oxidation of Oxone to KX to provide reactive molecular halogen. The formation of halogenium ion 11A, intermediates 11B and 11C constituted as additional main transformations enabling the generation of the target products (Scheme 11).
The formation of C—S bond in the C3 site of chromones constituted a highly practical tactic in the decoration of chromones for the synthesis of their sulfur derivatives. In 2015, Zhou and Ge et al. [72] reported the synthesis of 3-methylthiolated chromones 19 and 3-sulfenylated chromones 21 by reacting chromone with DMSO and sulfonyl hydrazines 20, respectively. In the reaction conditions consisted of NH4I/MeCN and 135 ℃ heating in DMSO, the methylthiolated products 19 were provided via key intermediates 12A-12D. On the other hand, by the reactions employing sulfonyl hydrazines conducted in DMAC in the presence of NH4I, 21 were synthesized via a plausible process involving intermediates 12E-12J. Notably, when 12H was generated, it might be further transformed into 12I to enable the subsequent transformation (Scheme 12, route a), or directly incorporate chromones to yield the target products (Scheme 12, route b).
Following the work on the successful synthesis of 3-sulfenyl chromones, the group developed later different methods for the synthesis of such functionalized chromones by employing thiophenols 22 (Scheme 13a) [73] and sodium benzenesulfinates 23 (Scheme 13b) [74] as sulfenylation reagents, respectively. The Ar-S-I intermediate 12J (Scheme 12) was also proposed as the key intermediate in these reactions.
In addition, Zhou et al. [75] realized also the synthesis of 3-sulfenyl and 3-alkylthiochromones via the chromone C3—H bond functionalization with different sulfur sources by the catalysis of CuI. The reactions employing chromones, aryl iodide 25 and sulfur powder led to 3-sulfenyl chromones 21 via CuI catalysis by heating at 135 ℃ in DMF. On the other hand, the reactions of chromones, alkyl halides 25 and Na2S2O3 led to 3-alkylthiochromones 26 under identical conditions. The CuI-catalyzed generation of aryl/alkyl disulfide intermediate 14A was proposed as the initial step in the reactions. The formation of sulfur cation 14B via CuI incorporation and its electrophilic addition to chromone generating intermediate 14C enabled the formation of target products via proton elimination. The simultaneously produced RSH could be easily oxidized to regenerate the reactive disulfide species (Scheme 14).
By similar method employing elemental selenium and aryl halide as reaction partners, they also established the synthetic method to 3-arylselenyl chromones 27 via CuCN-catalyzed C—H bond transformation [76]. According to the proposed mechanism, the formation of aryl diselenide 15A was also the initiating step, which mediated the formation of 15B by coupling CuCN. The further addition of 15B to chromone gave 15C, and the successive elimination of proton led to 15D which subsequently yielded 27 by the elimination of CuCN (Scheme 15).
Moreover, Zhou's [77] subsequent work on this area disclosed that the reactions of chromones, aryl halides and KSeCN, by which products 27 could be efficiently accessed with the catalysis of CuI by heating at 140 ℃ in DMF (X = I). Notably, similar reactions using KSCN providing 3-sulfenyl chromones 21 was also practical by using CuCN as the alternative copper catalyst (Scheme 16).
Alternatively, by employing directly disulfides and diselenides 29 as substrates, Guo [78] realized the synthesis of 3-sulfenyl/3-selenyl chromones 30 via NH4I-promoted C—H sulfenylation and selenylation. Besides chromones, the aza-equivalent quinolinones (X = NH in 28) were also applicable substrates for the synthesis of corresponding C3-functionalized quinolinones. The ArY-I (17A) and cationic heterocycle 17B were believed as the key intermediate during the reaction process (Scheme 17).
Unlike the relatively enriched reports in the C3—H sulfenylation/thiolation and selenylation via new C—S/Se bond formation, corresponding reports on the C—O bond formation via the chromone C—H functionalization or activation was rather hardly available. The typical example on the chromone C3—H bond oxygenation was reported by Hong et al. in their work synthesizing chromone fused benzofurans [79]. By employing o-hydroxyphenyl functionalized flavones 31 as starting materials, the co-catalysis of Cu(OAc)2/Zn(OTf)2 and heating at 120 ℃ in mixed toluene and DMSO enabled the intramolecular C—O bond formation to provide products 32. The species of Zn(Cu)-complex 18A and Cu-complex 18B were hypothesized as the major intermediates in the general reaction pathway (Scheme 18).
As another type of typical C-heteroatom bond, the C—N bond had also received sound concerns in the domain of chromone C3—H bond functionalization. However, successful method for such transformation remained yet as a challenge. Besides the examples of two products reported in Hong's intramolecular annulation via substrates of type 31 (Scheme 18), Antonchick et al.[80] reported the synthesis of product 35 as a single example in their work of arene C—H hydrazination by using biaryl 34 as organocatalyst (Scheme 19).
In parallel with the C-heteroatom bond construction via the chromone C3—H bond activation and functionalization, the equivalent C—H bond transformation enabling C—C bond generation has also received extensive concern. Hong and coworkers [81] developed an interesting method for the synthesis of 3-alkenyl chromones 37 via the direct C—H alkenylation of chromones and terminal alkenes 36 via the catalysis of Pd(OAc)2 using Cu(OAc)2 and Ag(Ⅰ) as terminal oxidants. The reactions were proposed to proceed via intermediate 20A by the insertion of Pd(Ⅱ) to C—H bond as well as the formation of intermediate 20B resulting from carbopalladation of alkenes. The elimination of Pd(0) and PivOH from 20B then led to the production of alkenyl chromones 37 (Scheme 20).
On the basis of this C—C bond forming reaction, the same group [82] again reported the reactions of chromones and quinones for the synthesis of quinone functionalized flavones 39 by employing quinones 38 as reaction partners using the catalyst system consisted of Pd(OAc)2 and AgOAc. In addition, this C—H activation protocol could also be expanded to the synthesis of product 41 by employing N-methylmaleimide 40 as alternative reaction partners (Scheme 21).
3 Activation of the phenyl C—H bond
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In parallel with the elaboration on the C—H bond located in the heteroaryl fragment, the activation of the phenyl C—H bond in the chromone constituted the other major route to access chromone derivatives with expanded molecular diversity. In 2012, Antonchick and co-workers [83] reported the C5—H and alkenylation of chromone via oxidative coupling by employing alkenes 42 as reaction partners via Rh(Ⅲ) catalysis. The C5-alkenylated chromones 43 were synthesized with high efficiency under the catalytic conditions consisting of [(Rh(Ⅱ)Cp*Cl2)2], AgSbF6 and Cu(OAc)2 by heating in dioxane. As alkene substrates, naphthoquinone, terminal alkenes and dimethyl but-2-enedioate could be tolerated. The reactions were proposed to start from the RhⅢCp*Sn given by the interaction of [(Rh(Ⅱ)Cp*Cl2)2] and AgSbF6. The assistance of the carbonyl group in 1 then enabled the insertion of Rh(Ⅲ) to the C5—H bond of chromone to generate intermediate 22A, which coupled the alkene and led to the formation of intermediate 22B. The reductive elimination of Rh(Ⅰ) from 22B gave rise to products 43. And the Rh(Ⅲ) could be regenerated by the oxidation of Cu(Ⅱ) to Rh(Ⅰ) (Scheme 22).
Alternatively, Hong et al. [84] developed a synthetic routes to C5-alkenylated chromonesby the Ru-catalyzed C5—H bond addition to symmetrical internal alkynes 44. The [Ru(p-cymene)Cl2]2 catalyst, AgSbF6 as well as Cu(OAc)2 and AcOH were required for the desired C—H addition to alkynes. Interestingly, modifying the loading of AgSbF6 enabled the selective synthesis of Z-isomers 45 and E-isomers 46. The control experiments proved that treating the Z-isomers with additional AgSbF6 in AcOH promoted their transformation to corresponding E-isomers. The Ru-insertion to the C5—H bond forming intermediate 23A and the subsequent alkyne insertion providing 23B were believed to mediate the synthesis of Z-alkenylated products 45. The transformation of this isomer to E-alkenylated products, on the other hand, was proposed to take place by forming cation intermediate 23C in the presence of additional Ag+ (Scheme 23).
On the other hand, the C5—H bond addition of chromones and analogous benzoketone derivative to C=C double bond was realized by Kim et al. [85] With the co-catalysis of [RhCp*Cl2]2 and AgSbF6 in the presence of PivOH, the addition of chromones and analogous cyclic enone substrates 47 to maleimides 48 proceeded practically to deliver diverse maleimide functionalized chromones, 1, 4-naphthoquinones, and xanthones, etc. via the direction of the ketone carbonyl group via weak coordination (Scheme 24).
Moreover, the same group also reported the amination reactions of similar C—H bond in substrates 47. The reactions of sulfonyl azides 50 with 47 provided aminated products 51 [86]. The main transformations were also proposed as the metal insertion to the reactive C—H bond, and the addition of coupling partners forming intermediates 25A and 25B, respectively. In addition, an additional migratory insertion of N atom providing intermediate 25C by releasing nitrogen gas was believed to be involved to mediate the formation of products 51 (Scheme 25).
As a typical example on the aryl C—H oxygen functionalization, Hong and co-workers [87] disclosed the C5—H bond hydroxylation of chromones and flavones via Ru(Ⅱ) catalysis. The Ru-species which was prepared by reacting [Ru(p-cymene)Cl2]2 with trifluoroacetic acid (TFA) was discovered as the efficient catalyst for the reactions of chromones/flavones 1 and PhI(CF3CO2)2 to provide 5-hydroxyl chromones/flavones 52 by heating at 80 ℃ in the presence of TFA/TFAA. According the proposed reaction mechanism, the reactions were initiated by the generation of Ru-species 26A from the dehydration of the Ru cat. The insertion of 26A to the C5—H bond gave 26B which coupled PhI(CF3CO2)2 to generate another Ru-complex 26C. The elimination of Ru-catalyst 26A from 26C led to the production of intermediate 26D. The aqueous workup on 26D yielded the final products 52 via hydrolysis (Scheme 26).
In addition to the systematic investigation in the phenyl C—H activation and functionalization of chromones and its derivatives, as specific example(s) of cyclic enone compounds, chromones were also frequently used in the methodologies of catalytic C—H activation reactions directed by ketone carbonyl. For example, Padala and Jeganmohan [88] reported that 5-alkenyl chromone 53 could be accessed via [Ru(p-cymene)Cl2]2, AgSbF6 and Cu(OAc)2-co-catalyzed C—H alkenylation reactions (Scheme 27). Maji et al.[89] reported the same reaction synthesizing 53 in the catalyst system of Cp*Co(CO)I2, AgSbF6 and Cu(OAc)2 in 2, 2, 2-trifluoromethyl ethanol (Scheme 27). Chang and co-workers [90] reported the synthesis of alkenylated chromones 54 via C5—H alkenylation of chromone with the catalysis of [IrCp*Cl2]2 and AgNTf2(Scheme 27). In addition, Huestis and Ncube [91] realized the synthesis of 5-fluorosulfonylvinyl chromone 55 via corresponding arene C—H 5-fluorosulfonylvinylation of chromones by the catalysis of [Cp*Rh(MeCN)3](SbF6)2 in the presence of Cu(OAc)2·H2O by using ethenesulfonyl fluoride as coupling partner (Scheme 27). Interestingly, in a catalytic nondirected oxidative C—H alkenylation method, Yu et al. [92] disclosed the synthesis C6-alkenyl chromone 56 via the catalysis of Rh2(OAc)4 catalysis, and PCy3 ligand, Cu(TFA)2 as well as V2O5 were also required to performed the reaction under nitrogen atmosphere (Scheme 27).
By means of a phosphine ligand NMe2-TP (4-(bis(2-(diphenylphosphanyl)phenyl)phosphanyl)-N, N-dimethylaniline) assisted Fe(acac)2-catalysis in the presence of 2, 3-dichlorobutane (2, 3-DCB) additive, Nakamura et al. [93] realized the synthesis of 5-methyl flavone 57 by C5—H methylation of flavone (Scheme 27).
In addition to these C—H alkenylation and methylation protocols, the [IrCp*Cl2]2/AgNTf2/Cu(OAc)2-co-catalyzed arene C—H arylation developed by Chang et al. [94] enabled the synthesis of C5-arylated chromone 58 by employing triethoxy (aryl)silane as aryl source (Scheme 28). In addition, Li, Huo and Jiang et al. [95] reported earlier the synthesis of C5-alkynyl chromone 59a and flavone 59b via their [IrCp*Cl2]2/AgNTf2/-cocatalyzed arene C—H alkynylation method with (bromoethynyl) triisopropylsilane as the coupling partner (Scheme 28). Moreover, the synthesis of optically pure cyclic ether functionalized chromone 60 was successfully accessed by the enantioselective hydroarylation reaction to 2H-chromene involving the transformation of stable arene C—H bonds [96]. The product 60 was afforded with good yield and high ee value via the catalysis of [IrCl(cod)]2 and chiral ligand (R)-DM-Binap (Scheme 28). Although the reaction of chromone or flavone was reported as just specific examples, it should reasonable to deduce that most of the above C—H activation reactions in Schemes 27 and 28 would be applicable for other chromone and flavone derivatives bearing similar reactive C–H bond, thus provided potentially applicable routes to access chromones with more diverse substructures.
4 Conclusion and outlook
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In conclusion, as well documented privileged heterocyclic motifs, the structurally diverse chromones and flavones are inarguably the longstanding targets of organic synthesis. The application of the powerful C—H bond activation and functionalization has brought tremendous advances in the synthesis of chromone and flavone derivatives elaborated with various carbonand heteroatom-based functional structure by direct transformation on either the heterocyclic C(sp2)—H bonds or the arene C—H bond in the readily available chromone/flavone substrates. On the other hand, the presently known literatures in this research area deliver also some challenges for future research efforts. One is the flexible control of the selective reaction of the C2—H and C3—H bonds of in heterocyclic fragment. Most known transformations take place either on the C2- or C3-site depending on the property of the coupling reagent. Tunable transformations on the chromone C2- and C3-sites with identical or similar reaction partners are yet rather difficult task. In addition, for the activation reactions in the arene part, the known reactions generally take place in the C5-site for both chromones and flavones because of the inherent direction of the carbonyl group. The C—H activation reaction in other sites of the arene moiety remains rigorously restricted. Therefore, applicable arene C—H activation methods in other sides beyond C5 of chromones and flavones are yet highly desirable. Of course, developing low cost metal-catalysis to enable the arene C—H activation in these scaffolds constitutes also important target for future research.
Declaration of competing interest
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The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgment
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The authors thank National Natural Science Foundation of China (Nos. 21861019 and 21702091) for financial support.
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Year 2020 volume 31 Issue 12
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Article Info
doi: 10.1016/j.cclet.2020.07.042
  • Receive Date：2020-06-17
  • Online Date：2026-01-31
  • Published：2020-12-15
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  • Received：2020-06-17
  • Revised：2020-07-10
  • Accepted：2020-07-24
Affiliations
    a College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang 330022, China
    b School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai 264005, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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