Synthesis of 5H-Dibenzo[c,g]chromen-5-ones via FeCl3-Mediated

Letter Cite This: Org. Lett. XXXX, XXX, XXX−XXX

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Synthesis of 5H‑Dibenzo[c,g]chromen-5-ones via FeCl3‑Mediated Tandem C−O Bond Cleavage/6π Electrocyclization/Oxidative Aromatization Maozhong Miao,* Mengchao Jin, Huaping Xu, Panpan Chen, Shouzhi Zhang, and Hongjun Ren* Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou, Zhejiang 310018, P. R. China

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S Supporting Information *

ABSTRACT: A novel and expedient method for transformation of readily available 1-isochromanones bearing a diaryl allenic moiety at the C4-position to functionalized 5H-dibenzo[c,g]chromen-5-ones under mild conditions is developed. This strategy is based on the dual abilities of iron(III) chloride to promote selective C−O bond cleavage/6π electrocyclization and an oxidative aromatization sequence.

O

streamlined synthetic methods from the available reactants is highly desirable. On the other hand, iron catalysis6 has emerged as a powerful tool in selective activation of inert carbon (C)−oxygen (O) bond to construct carbon−carbon or carbon−hetero bonds due to its low cost, environmental friendliness, and availability. However, the application of iron catalysis on the unstrained and inactivated sp3 C−O bond cleavage7 and subsequent functionalization remains a challenge. Recently, direct ringopening (sp3 C−O bond scission) of unstrained O-heterocycles involving iron catalysts has been investigated as an efficient and selective methodology for building valuable organic backbones. For instance, Li8 has reported an ironcatalyzed tandem C−H bond oxidation and C−O bond cleavage of cyclic ethers with indoles for the synthesis of symmetrical and unsymmetrical 1,1-bis-indolylmethane derivatives. Notably, Sajiki9 and co-workers have presented a novel FeCl3-catalyzed azidation and allylation of O-heterocycles in the presence of TMSN3 or allylsilanes via cleavage of the unreactive C−O bond. In particular, less active lactones could be employed as substrates to gain saturated carboxylic acids in high yields. Based on these facts, we envisioned that a cascade reaction of 1-isochromanones with a diaryl allenic group10 attached at the C4-position under iron catalysis would provide ring-opening intermediates A (Scheme 1). Sequential rearrangement and 6π-ring closure11 might give intermediates C. Finally, oxidative aromatization might furnish desired products 2. Herein, we report a general and mild Fe(III)-mediated tandem C−O bond cleavage/6π electrocyclization and oxidative aromatization for efficient construction of 5Hdibenzo[c,g]chromen-5-one skeletons from diaryl allenic moiety tethered 1-isochromanones. Our initial work began with 4-(2,2-diphenylvinylidene)-3phenylisochroman-1-one 1a, which could be easily prepared via a lithiation of methyl 2-(3,3-diphenylprop-1-yn-1-yl)-

xygen analogues of polycyclic aromatic hydrocarbons (PAHs)1 represent an important class of molecules because the incorporation of oxygen atoms into a PAH system can modulate its pharmacological activity as well as electrical or optical properties.2 In particular, 5H-dibenzo[c,g]chromen5-ones, a new kind of anthracene derivative which are subunits embedded in many natural products3 and organic materials4 (Figure 1), have attracted considerable attention. For example,

Figure 1. Importance of 5H-dibenzo[c,g]chromen-5-ones.

natural products juglanthracenoside A3b (I), WS-5995A3c,e (II), and quinaphthin3f (III) were isolated from the stem bark of Juglans mandshurica Maxim., Streptomyces auranticolor strain, and aero-aquatic fungus Helicoon richonis (Boudier) Linder, respectively. They were found to possess a wide range of biological activities such as antioxidant activity, cytotoxicity, anti-Gram-positive bacteria, etc. With respect to the material field, Liu4b reported a chiral and fluorescent columnar mesogen (IV) bearing a 5H-dibenzo[c,g]chromen-5-one skeleton which emitted fluorescent blue light. The liquid crystal comprises a C2-symmetric chiral core with two staggered aromatic planes. Despite the importance of 5Hdibenzo[c,g]chromen-5-one substances, the general methods to access substituted 5H-dibenzo[c,g]chromen-5-ones are less encountered.5 Thus, the development of convenient and © XXXX American Chemical Society

Received: July 31, 2018

A

DOI: 10.1021/acs.orglett.8b02434 Org. Lett. XXXX, XXX, XXX−XXX

Letter

Organic Letters Table 1. Examinations on Reaction Conditionsa

Scheme 1. Previous Work and Our Design

entry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

benzoate with LDA at −40 °C followed by quenching with benzaldehyde (Scheme 2), under the catalysis of Fe(III) in the Scheme 2. Synthesis of Starting Materials 1a

metal catalyst (equiv) FeCl3 FeCl3 FeCl3 FeCl3

(0.05) (0.05) (0.05) (0.05)

FeCl3 (0.05) FeCl3 (5) FeCl3 (4) FeCl3 (2) FeBr3 (5) Fe(acac)3 (5) Co(acac)3 (5) Mn(OAc)3·2H2O (5) FeCl3 (5) FeCl3 (5) FeCl3 (5) FeCl3 (5) FeCl3 (5) FeCl3 (5) FeCl3 (5)

additive (equiv) TBPB (5) DTBP (5) TBHP (5) BPO (5) TBPB (5)

TEMPO (5) BHT (5)

solvent DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCE DCM toluene THF MeCN DMF DCE DCE

yieldb of 2a (%) 69 49c NR NR NR trace 92 (84d) 72 55 79 NR NR NR 82 48 NR NR NR NR 74

a

Reaction conditions: 1a (0.1 mmol), catalyst or additives (5 equiv), in 2 mL of solvent at rt in open air for 20 min. bIsolated yield. c27% of 1a was recovered. dReaction was carried out on a 1.0 g scale.

presence of oxidants. As a first attempt, we were happy to notice that the reaction of 1a (1 equiv), FeCl3 (5 mol %), and tert-butyl peroxybenzoate (TBPB) (5 equiv) in DCE with stirring at room temperature for 20 min afforded the cyclized product 2a in 69% yield (Table 1, entry 1). The use of di-tertbutyl peroxide (DTBP), tert-butyl hydroperoxide (TBHP), and dibenzoyl peroxide (BPO) as oxidants led to low or no reaction efficiencies (entries 2−4). No reaction occurred without Fe(III) catalysis (entry 5), and only a trace amount of 2a was obtained in the absence of TBPB (entry 6). Gratifyingly, by increasing the load of FeCl3 to 5 equiv, 2a was obtained in 92% yield, which might be due to FeCl3 acting as a catalyst as well as an oxidant to promote the C−O bond cleavage/oxidative cyclization (entry 7). Decreasing the amount of FeCl3 to 4 and 2 equiv resulted in lower yields (entries 8 and 9). Subsequently, several representative metal catalysts, such as FeBr3, Fe(acac)3, Co(acac)3, and Mn(OAc)3· 2H2O, were screened, but no superior results were obtained (entries 10−13). Finally, the solvents were optimized. The results illustrated that DCM and toluene offered the desired product in 82 and 48% yield, respectively, while other solvents such as THF, MeCN, and DMF were completely ineffective in this transformation (entries 16−18). Furthermore, the reaction pathway for producing 2a was briefly investigated. The addition of nitroxyl radical 2,2,6,6-tetramethyl-1-piperidinyloxy (TEMPO) led to no reaction (entry 19) because FeCl3 could react with TEMPO to form FeCl3(η1-TEMPO)12 complex, which could not promote the C−O bond cleavage reaction, while the employment of radical scavenger 2,6-di-tert-butyl-4methylphenol (BHT) did not significantly affect the reaction

for production of 2a (entry 20), indicating that a cation process might be involved. With the optimal conditions in hand, we examined the substrate scope of this reaction as shown in Scheme 3. Diaryl allenic moiety tethered 1-isochromanone derivatives 1 having different substituents at the C3-position were first investigated under the standard conditions (2b−l). Electron-donating groups such as 4-OMe and 2,5-diMeO on the aromatic ring were well tolerated, affording the desired compounds 2b and 2c in excellent yields. Moreover, the FeCl3-mediated “one-pot” cyclization and deprotection was achieved to give 2d in good yield (80%) when substrate 1d bearing tert-butyldimethylsilyl (TBS) protected hydroxyl was employed. Substrates with electron-withdrawing groups including p-Cl (2e), p-Br (2f), oBr (2g), and p-CF3 (2h) on the phenyl ring could be successfully converted to targeted products in moderate to good yields (48−76%). The 2-naphthyl (2i), aromatic heterocycles (2j, 2k), and 2-methylpropenyl (2l) substituents were proven to be compatible in the present reaction to generate the corresponding products in 25−74% yields. A low yield (25%) was observed in the case of the N-Me-carbazolesubstituted substrate 2k probably due to decomposition of starting material under strong Lewis acid conditions. The substituent effect of symmetric diaryl groups attaching to the end of the allenic moiety was next checked. As can be seen, substituents such as p-Me-C6H4, p-Cl-C6H4, and 2-naphthyl were suitable for this reaction to furnish the corresponding products 2m, 2n, and 2o in 87%, 70%, and 64% yields, respectively. Notably, this protocol proved useful for the B

DOI: 10.1021/acs.orglett.8b02434 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Scheme 3. Substrate Scopea,b

Scheme 4. Highly Selective Cyclization of Unsymmetric Substrates 1u and 1u′

with decomposition of starting material under excess FeCl3 conditions when the diastereoisomer 1u′ was utilized. To explain the well-defined regioselectivity of current transformation, a plausible mechanism involving 1u as the model substrate was outlined in Scheme 5. In the presence of Scheme 5. Proposed Mechanism

Fe(III) catalyst, the C−O bond cleavage reaction of 1u occurs to provide iron complex Int-A. Then the unlocked benzene ring attaching to the allenic moiety may rotate to the back side to form Int-A′ probably due to steric interaction between the phenyl and carboxylate anion-coordinated FeCl3 groups. The nucleophilic attack of oxygen at allylic carbocation takes place to give Int-B with high geometric selectivity. It should be mentioned that diastereoisomer 1u′ provides the opposite regioselectivity at this step. The subsequent 6π electrocyclization of Int-B affords Int-C, which can be further oxidized to produce 2u with excellent regioselectivity. To further probe the utility of this FeCl3-promoted C−O bond cleavage/oxidative cyclization protocol in preparative organic synthesis, several useful transformations were conducted (Scheme 6). Treatment of 2a with a BF3·Et2O−NaBH4 reductive system or with access to RLi and then catalyzed cyclization by trifluoroacetic acid (TFA) gave the corresponding 5H-dibenzo[c,g]chromene derivatives 4a−c in 79−94% yields. Moreover, in the presence of 1.05 equiv of DIBAL-H, 2a could be transferred to 5H-dibenzo[c,g]chromen-5-ol 4d in 81% yield. The TFA-catalyzed C−C bond-forming strategy was also realized by treatment of 4d with carbon nucleophiles such as indole, 4-hydroxycoumarin and allyltrimethylsilane to afford 5a−c in high yields. 5H-Dibenzo[c,g]chromen-5-one derivatives, oxygen analogues of polycyclic aromatic hydrocarbons (PAHs), are new fluorophores that might show potential application in optoelectronic devices, luminescent sensors, and biomedical imaging. Next, we assessed the fluorescent spectroscopic properties of the selected compounds 2a, 2c, 2p, and 2r in dilute DCM solution (10−5 M) and in the solid state (powder) (Figure 2). All of the tested compounds displayed fluorescent

a

Reaction conditions: 1a (0.2 mmol), FeCl3 (5 equiv), in 2 mL of DCE at room temperature in open air for 20 min. bIsolated yield. c TBS protected substrate 1d was used. d80 °C, 50 min. eThe allenic 1,3-hydrogen shift of 1s to afford product 3a in 33% yield.

construction of 5H-dibenzo[c,g]chromen-5-one-containing polycycles 2p in excellent yield. Unfortunately, substrate 1s with a strongly electron-donating group (p-MeO) failed to give the desired product; instead, the allenic 1,3-hydrogen shift product 3a was isolated in 33% yield. The different reactivity might be attributed to the fact that the electron density of allenic double bonds increased with the presence of p-MeO in the phenyl rings, and FeCl3 might act as a π-Lewis acid to promote the allenic 1,3-hydrogen shift instead of the ability to mediate C−O bond cleavage. Additionally, the reaction proceeded smoothly to give 2q and 2r in high yields when substituents such as Br and phenyl were introduced to C7position of 1-isochromanones 1. Furthermore, switching the oxygen atom to nitrogen (1t) led to a complex mixture at rt or 80 °C. Interestingly, when the diastereoisomers 1u and 1u′ with two differently substituted aryl rings attaching at the allenic moiety were employed in this reaction, excellent regioselectivity was observed (Scheme 4). The reaction of substrate 1u gave 2u in 43% yield as the sole product. Conversely, the regioisomer 2u′ was obtained in 7% yield without detecting 2u C

DOI: 10.1021/acs.orglett.8b02434 Org. Lett. XXXX, XXX, XXX−XXX

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Organic Letters Accession Codes

Scheme 6. Diverse Transformations of 2a

CCDC 1855936−1855938 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Maozhong Miao: 0000-0001-6777-7189 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We are grateful to the National Natural Science Foundation of China (21302169), the Program for Innovative Research Team of Zhejiang Sci-Tech University (Grant Nos. 13060052-Y), and the Zhejiang Provincial Top Key Academic Discipline of Chemical Engineering and Technology of Zhejiang Sci-Tech University for financial support.

Figure 2. (A) Emission spectra of 2a, 2c, 2p, and 2r in DCM (c = 10−5 mol/L). (B) Solid emission spectra of 2a, 2c, 2p, and 2r.

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emission bands around 450 nm (2a, 435 nm; 2c, 480 nm; 2p, 450 nm; 2r, 434 nm) in its DCM solution. As expected, the fluorescent intensity of 2p is higher than that of 2a due to the rotation restriction of the phenyl ring in the C7-position by alkyl group.13 Compared to 2a, the fluorescent emission band of 2c showed a remarkable bathochromic shift (about 45 nm) which may be due to the dimethoxyphenyl group (strong electron-donating ability) at the C12 position. Moreover, to our delight, all of the tested compounds also showed strong fluorescent emission in its solid state. Furthermore, the fluorescent quantum yield of 2c was found to be 63.98%, referring to the standard of quinine sulfate (Φ = 0.55 in 0.1 M H2SO4). In conclusion, we have developed an efficient strategy for the synthesis of substituted 5H-dibenzo[c,g]chromen-5-ones 2 in moderate to excellent yields via a sequence of FeCl3-promoted C−O bond cleavage, 6π electrocyclization, oxidative aromatization of allene-tethered 1-isochromanones 1. Transformations of compounds 2 were also achieved to afford several types of 5H-dibenzo[c,g]chromene derivatives in high yields. Moreover, the new fluorophore of compounds 2 and its photophysical properties were investigated. Further studies on the synthetic application and physical properties examination are currently ongoing.

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b02434. Experimental procedures and copies of 1H and 13C NMR spectra for all new compounds; X-ray data for compounds 1u, 2a, and 2f (PDF) D

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DOI: 10.1021/acs.orglett.8b02434 Org. Lett. XXXX, XXX, XXX−XXX