Regioselective Synthesis of Bicyclic and Polycyclic Systems by

Dec 8, 2017 - An efficient [3 + 2]/[4 + 2] or double [4 + 2] cycloaddition strategy has been established for the synthesis of heterocyclic systems und...
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Article Cite This: J. Org. Chem. 2018, 83, 75−84

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Regioselective Synthesis of Bicyclic and Polycyclic Systems by Cycloaddition Reactions of Alkenyl p-Benzoquinones Shweta Bisht, Rashmi Rani, and Rama Krishna Peddinti* Department of Chemistry, Indian Institute of Technology, Roorkee 247667, Uttarakhand India S Supporting Information *

ABSTRACT: An efficient [3 + 2]/[4 + 2] or double [4 + 2] cycloaddition strategy has been established for the synthesis of heterocyclic systems under mild conditions. The reaction pathway is governed by the nature of reaction partner. Several dihydrofurocoumarin, furopyranocoumarin, dihydrofuran, dihydrobenzopyran, and dihydrobenzofuran derivatives were obtained as single diastereomers from cyclic or acyclic enol ethers and styrenes. This one-pot transformation constructed C−C and C−O bonds and generated molecular complexity by domino/tandem process to produce the heterocyclic systems in good yields. The ring closure of domino protocol was highly stereoselective and resulted in the formation of cisfused systems.

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INTRODUCTION

Today in organic synthesis, the construction of carbon−carbon and carbon−heteroatom bonds through cycloaddition reactions is one of the most important approaches for the formation of heterocyclic compounds in which domino cycloaddition reactions are recognized as a powerful weapon to construct carbocyclic and heterocyclic compounds with diverse biological activities.1,2 Domino reactions have an unparalleled ability to generate molecular complexity from relatively simple starting materials in a single step. The use of domino approach in organic synthesis is increasing constantly because it allows the synthesis of a wide range of complex molecules including natural products and biologically active compounds such as pharmaceuticals and agrochemicals, in an economically favorable way by using the processes that are reasonably simple.3,4 The construction of tricyclic and tetracyclic heterocyclic systems through one-pot strategy has attracted continuous attention in recent years because of their presence in various natural products.5,6 Furocoumarin, dihydrofurocoumarin, and furopyaranocoumarin derivatives are versatile building blocks in organic synthesis and are widely distributed in nature7 (Figure 1). These compounds are reported to have various biological activities such as anticoagulant, insecticidal, anthelminthic, hypnotic, antifungal, phytoalexin, and HIV protease inhibition.8−10 The unique structures and the highly pronounced biological and pharmacological activity displayed by these polycyclic systems have attracted attention for their synthesis. Recently, several coumarin derivatives have been prepared by transition-metal-catalyzed reactions.11 However, to the best of our knowledge, there are no reports on the synthesis of dihydrofurocoumarins by the cycloaddition reaction of benzoquinones and furans. In general, benzoquinone12 motif has been found in numerous natural products13 and exhibits © 2017 American Chemical Society

Figure 1. Some of the biological active compounds containing furocoumarin, furopyranocoumarin, and dihydrofuran skeletons.

important biological activity such as antimalarial, antitumor, antibacterial, and antifungal actions.14 Importance of these scaffolds coupled with our ongoing efforts in the exploration of the reactivity of benzoquinones15,16 encouraged us to examine the mode of cycloaddition of alkenyl p-benzoquinones, with various olefinic partners. Herein, we report an efficient synthesis of derivatives of furocoumarin, furopyaranocoumarin, and dihydrofuran/dihydropyran and dihydrobenzofuran using alkenyl p-benzoquinones with cyclic/acyclic enol ethers and styrenes in tandem or cascade reaction sequence. Received: September 20, 2017 Published: December 8, 2017 75

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

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The Journal of Organic Chemistry

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RESULTS AND DISCUSSION To test the reactivity of alkenyl p-benzoquinones toward cyclic or acyclic enol ethers, we selected alkenyl p-benzoquinone 1a and dihydrofuran (2a) as model substrates. At first, we performed the reaction of 1a and 2a in DCM at room temperature for 4 days, and no product formation was observed (Table 1, entry 1). A similar result was obtained when the

DHF under the optimized conditions. This reaction, after 9 h, furnished structurally divergent tetracyclic product 3b regioselectively in good yield, whose structure was further confirmed by single crystal X-ray analysis.17 When we performed the reaction of 1a/1b with dihydropyran (2b) under neat condition, it proceeded smoothly at rt to furnish pyranofused furocoumarin derivatives 3c and 3d in good yields (Scheme 1). The stereochemistry of the products 3a−d was

Table 1. Optimization Conditions for the Synthesis of Tetracyclic Compound 3aa

entry

solvent

temp

time

yieldb (%)

1 2 3 4 5 6 7 8 9c

DCM DCM THF THF toluene toluene neat neat neat

rt reflux rt reflux rt reflux rt reflux 0−rt

4d 4d 2d 2d 36 h 24 h 10 h 8h 8h

− − 15 25 30 40 70 45 −

Scheme 1. Reaction of Benzoquinones 1a and 1b with Cyclic Enol Ethers 2a and 2ba

a

a

The reactions in entries 1, 3, and 5 were carried out with 1a (0.3 mmol) and DHF (0.5 mmol) and that of entries 2, 4, and 6 were carried out with 1a (1.0 mmol) and DHF (2.0 mmol). The neat reactions (entries 7−9) were carried out with 1a (1.0 mmol) and DHF (10 mmol). bIsolated yield of 3a. cIn presence of 20 mol % of BF3· OEt2.

Reactions were performed with 1 (1 mmol) and 2 (10 mmol) at rt.

confirmed by 1H NMR analysis through coupling constants. When we treated benzoquinones 1a and 1b with furan under the optimized conditions, no reaction took place. Encouraged by the above results, the scope of this domino protocol was further studied with acyclic enol ethers (Scheme 2). The reaction of 1a/1b with 10 equiv of ethyl vinyl ether at

reaction was carried out with 2-fold excess of 2a at reflux temperature (entry 2). However, the reaction, when carried out in polar solvent THF, proceeded regioselectively to provide fura-fused coumarin 3a, albeit in a low yield (15%) (entry 3). The structure of 3a was characterized by NMR spectroscopy. This fura-fused coumarin 3a was obtained via [3 + 2] cycloaddition of 1a and 2a, followed by ring closure domino process. However, further increase in the temperature of the reaction as well as the amount of both the substrates in THF could not enhance the yield of product significantly (entry 4). We then investigated the reaction in nonpolar solvent such as toluene, and fura-fused coumarin 3a was obtained in moderate yield (entries 5 and 6). To further improve the yield of tetracyclic product, we performed the reaction with 10 equiv of DHF in neat condition, and the reaction was completed in 10 h as indicated by TLC. Then 5 mL of hexane was added in the reaction mixture, and it was kept at 0 °C for 30 min. Gratifyingly, 3a was obtained as a yellow solid after filtration in 70% yield (entry 7). However, when the reaction was carried out at reflux temperature under neat condition, 3a was obtained in moderate yield (entry 8). Next we performed the reaction of 1a and 2a in the presence of BF3·OEt2 to find the reactivity of this reaction in the presence of an acid. Unfortunately, the desired product was not obtained under this condition (entry 9). Thus, solvent-free condition at rt was found to be the optimum condition for the production of fura-fused coumarin. After optimizing the reaction conditions, we turned our attention to the reaction of alkenyl p-benzoquinone 1b with

Scheme 2. Reactions of Benzoquinone 1a and 1b with Ethyl Vinyl Ethera

a

Reactions were performed with 1 (1 mmol) and 2c (10 mmol) at rt.

rt furnished tricyclic products 3e and 3f regioselectively in good yields (Scheme 2). These tetrahydro-benzochromene products were obtained through tandem double inverse electron-demand [4 + 2] cycloaddition. Next we turned our attention toward the use of oxygen containing aromatic heterocycle 2-methylfuran. Interestingly, the reaction of 1a,b with 2-methylfuran under the 76

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

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The Journal of Organic Chemistry standard conditions produced the tricyclic systems 3g and 3h in 78 and 75% yield, respectively, via inverse electron-demand [4 + 2] cycloaddition reaction (Scheme 3). Attempts to oxidize (2,5-dimethoxybenzylidene)malononitrile with CAN to the corresponding alkenyl quinone derivative were not successful.

Table 2. Optimization Conditions for the Synthesis of Dihydrofuran Derivativea

Scheme 3. Reaction of Benzoquinones 1a and 1b with 2Methylfurana

a

Reactions were performed between 1 (1 mmol) and 2d (10 mmol) at rt.

In continuation of our efforts on harnessing the reactivity of alkenyl p-benzoquinone, we next sought to examine whether alkenyl p-benzoquinone could react with styrenes in the same manner. To test our hypothesis, in a preliminary step, we carried out the cycloaddition of alkenyl p-benzoquinone 1a with styrene (4a), but no reaction was observed. We reasoned that 1a is not reactive enough to drive the cycloaddition process with relatively less nucleophilic styrene (Table 2, entry 1). This prompted us to use an acid promoter. Consequently, we performed the reaction of 1a with styrene (4a) in DCM in the presence of Brønsted acids such as TFA, 2,4-dintrobenzoic acid (2,4-DNB) and p-TSA.H2O; however, the reaction did not take place, and starting materials were recovered as such (Table 2, entries 2−4). The reaction using iodine as catalyst could not afford the product (entry 5). The reaction of using silicasulfuric acid (SSA) as a catalyst afforded the 2,3-dihydrobenzofuran 5a in 50% yield (entry 6). The formation of 5a takes place by the attack of β-carbon of styrene regioselectively at sixth position of alkenyl p-benzoquinone followed by ring closure, in a overall [3 + 2] cycloaddition. The 2,3dihydrobenzofuran ring system is an essential motif because of its presence in a number of natural products and pharmaceuticals.18 Consequently, some methods have been reported for their synthesis.19,20 Delightedly, when the reaction was carried out by employing Lewis acids as reagents, dihydrofuran derivative 5a was obtained in good yield. Interestingly, when the reaction of alkenyl p-benzoquinone 1a and 4a was performed with 1 equiv of BF3·OEt2 in DCM, 5a was obtained with 65% yield (entry 7). In this respect, we optimized the reaction with Lewis acids such as ZrCl4, FeCl3, and SnCl4 (entries 8−10). In all the tested Lewis acids, optimum results were obtained with BF3·OEt2. Further, we evaluated the reaction with varying amounts of BF3·OEt2. On increasing the amount of BF3·OEt2 in DCM, the product was obtained in an increased yield of 80% (entry 11), and on changing the solvent from DCM to DCE and CH3CN, 5a was

entry

reagent

solvent

time

yieldb(%)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16c 17d

− TFA (1 equiv) p-TSA·H2O (1 equiv) 2,4-DNB (1 equiv) Iodine (1 equiv) SSA (1 equiv) BF3·OEt2 (1 equiv) ZrCl4 (1 equiv) FeCl3 (1 equiv) SnCl4 (1 equiv) BF3·OEt2 (2 equiv) BF3·OEt2 (2 equiv) BF3·OEt2 (2 equiv) BF3·OEt2 (0.5 equiv) BF3·OEt2 (0.7 equiv) BF3·OEt2 (2 equiv) BF3·OEt2 (2 equiv)

DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCM DCE CH3CN CH3CN CH3CN CH3CN CH3CN

24 h 24 h 24 h 24 h 24 h 1h 30 min 30 min 30 min 30 min 15 min 30 min 10 min 1h 1h 10 min 40 min

nr nr nr nr nr 50 65 55 45 58 80 60 86 44 49 70 83

a The reaction was carried out with 1a (0.5 mmol) and 4a (1 mmol) and 1 equiv of reagent in 2 mL of solvent at rt. bYield of pure and column chromatographically isolated product; nr: no reaction. cTemp.: 50 °C. dTemp.: 0 °C.

obtained in 60 and 86% yield, respectively, at room temperature (entries 12 and 13). The reaction with lower amounts of BF3· OEt2 in CH3CN did not improve the yield of 5a (entries 14 and 15). Additionally, the effect of temperature was also investigated which suggested that rt was the best condition for this transformation. A significant decrease in yield was observed when the reaction was performed at 50 °C (entry 16). The reaction of 1a and 4a at 0 °C furnished the cycloadduct 5a in good yield with slightly longer reaction time (entry 17). Then the optimized conditions (entry 13) were used to explore the generality of the reaction. At first, styrenes 4a−h were investigated in reactions with alkenyl p-benzoquinone 1a in CH3CN at room temperature. Styrenes 4b−d with electron-donating group underwent this cycloaddition process successfully and produced the corresponding dihydrofuran derivatives 5b−d in good yields as shown in Table 3. For example, when 4-methyl, 4-isopropyl, and 3,4-dimethoxy substituted styrenes were employed, the corresponding products 5b, 5c, and 5d were obtained in 85, 88, and 92% yields, respectively (Table 3). When styrenes 4e and 4f with electron-withdrawing groups were used, the corresponding adducts 5e and 5f were obtained in relatively low yields, as can be seen in Table 3. The reaction of alkenyl p-benzoquinone 1a did not proceed well with αsubstituted styrenes at room temperature; however, the reaction at −30 °C resulted in the formation of 5g and 5h in excellent yields. Subsequently, we examined the substrate scope and limitations of this [3 + 2] cycloaddition reaction. The reactions of 1c with electron-rich and electron-deficient styrenes 4a−h were proved to be synthetically compatible, and the corresponding dihydrofuran derivatives 6 were 77

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

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The Journal of Organic Chemistry Table 3. Scope of Styrenes with Alkenyl p-Benzoquinone 1aa

α-methylstyrenes 4g and 4h also worked well and furnished 7g and 7h in 75 and 79% yields, respectively. To see the utility of the reaction, we performed a gram-scale reaction of alkenyl p-benzoquinone 1a (4 mmol) and styrene (8 mmol). The reaction worked well and afforded the corresponding dihydrobenzofuran 5a in high yield (Scheme 4). Scheme 4. Gram-Scale Synthesis of 5a

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a

STRUCTURE ELUCIDATION The structure of products 3a−h, 5a−h, 6a−h, 7a−d, 7g, and 7h were confirmed by detailed spectral analysis obtained from IR, 1H and 13C NMR, DEPT, and HRMS experiments of pure and isolated products. The connectivity of the protons that are coupled with each other and between protons and carbons 3a−f are identified by two-dimensional 1H−1H COSY and 1H−13C COSY experiments, respectively (Supporting Information). In the 1H NMR of products 3a−d, the two aromatic protons H-9 and H-10 appeared in the range δ 7.13−7.18 ppm as an AB quartet. The olefinic proton H-4 resonates in the range δ 8.43−8.57 ppm. The protons H-4c and H-7a present on the fused carbons of five-membered ring of 3a and 3b resonate at δ 4.24−4.27 ppm (H-4c), and 6.49−6.52 ppm (H-7a), respectively. The coupling constant 6.0 Hz between these two protons showed their cisgeometry. In 13C NMR, the carbons C-2, C-4, C-4c, C-5, C-6, C-7a, C-9, C-10, and C-11 resonate at 156, 144, 45, 33, 67, 112, 115, 117 and 163 ppm, respectively. In case of 3c and 3d, the protons of fused carbons of the five-membered ring resonate at

Reactions were performed with 1a (0.5 mmol) and 4a−h (1.0 mmol) and BF3·OEt2 (1.0 mmol) in CH3CN at rt.

produced in moderate to good yield. As shown in Table 4, 4methylstyrene reacted well to afford dihydrofuran derivative 6b in 81% yield. Similar results were obtained when the reaction was carried out with 4-isopropyl and 3,4-dimethoxy styrenes (4c and 4d). Likewise, the reaction with 4-chloro and 4-bromo styrenes were also compatible, and the desired dihydrofuran derivatives were obtained in good yields (6e, 62% and 6f, 60%). The reaction of 1c with α-substituted styrenes (4g and 4h) was successful and furnished 6g and 6h in excellent yield. The compatibility and generality of the present method were further explored by employing alkenyl p-benzoquinone 1d and styrenes 4 (Table 4). The yields of the product 7 obtained from 1d were comparatively lower than those obtained in previous case, apparently due to the less reactivity of 1d. Although the reactions of 1d worked well with electron-rich styrenes 4b−d, styrenes 4e and 4f equipped with electron-withdrawing groups failed to undergo [3 + 2] cycloaddition with 1d. Furthermore,

Table 4. Scope of Styrenes with Alkenyl p-Benzoquinones 1c and 1da

a

Reactions were performed with 1 (0.5 mmol) and 4 (1.0 mmol) and BF3·OEt2 (1.0 mmol) in CH3CN at rt. 78

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

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The Journal of Organic Chemistry

Figure 2. Selected 1H and 13C NMR chemical shifts (δ in ppm) of 3a−h, and 5a and 5g.

coupling constants obtained from 1H NMR. The H-2 proton appears as a triplet, downfield at 5.65−5.95 ppm because of the adjacent oxygen. The olefinic proton H-8 resonates at 7.84− 8.14 ppm. The meta coupling (J = 1.0−2.5 Hz) of two aromatic protons indicates that the addition of styrene takes place on pbenzoquinone at sixth position. In 13C NMR, one methylene proton, that is, C-3, resonates at 38.1−38.3 ppm which was confirmed by analyzing DEPT 135 spectrum. The 1H−1H COSY and 1H−13C COSY experiments were carried out to identify the protons that are coupled with each other and the connectivity between protons and carbons, respectively. HMBC experiment for 5a further revealed the correlation between C-3 methylene carbon and C-4 indicating that the attack of styrene β-carbon takes place at position-6 on alkenyl p-benzoquinone to produce 5a (Figure S17). Based on the results obtained, a possible mechanism for the formation of 3a−h, 5, 6, and 7 was proposed. The reaction between alkenyl p-benzoquinone 1 and DHF proceeded via domino conjugate addition of 2a to generate cationic intermediate A, which undergoes to tautomerization to form phenolic nucleophile B and subsequently ring closure gives [3 + 2] cycloadduct furo-furocoumarin 3a/3b (Figure 4). The formation of tetrahydro-benzochromene derivatives 3e and 3f can be explained based on the probable mechanism (Figure 5) in which the highly electron-deficient diene 1a undergoes inverse electron-demand Diels−Alder cycloaddition with electron-rich dienophilic ethyl vinyl ether (2c) to produce Diels−Alder adduct C, which further reacts (path 1) with the second molecule of ethyl vinyl ether to generate the target

3.51−3.52 ppm (H-4c) and 6.05−6.06 ppm (H-8a) with a coupling constant of 6.5 Hz between H-4c and H-8a. This small value indicates their cis-relation (Figure 2). NOESY experiment of 3e showed a significant correlation between H-2 and H-3a indicating the cis-geometry of these two protons. Similarly, NOESY correlations between H-5 and H-3a established spatial proximity of these protons in the molecule, which was further confirmed by its single crystal X-ray analysis21 (Figure 3).

Figure 3. NOE correlations related to compounds 3e and 3g.

In case of 3g and 3h, the structure was confirmed on the basis of 1H and 13C NMR, DEPT, and 2D spectral data analysis. In 1H NMR, AB quartet for two protons appeared at 6.90−6.92 ppm, and in 13C NMR, two peaks appear at 193 and 183 ppm, respectively, which indicates the presence of ketonic group. The NOESY experiment of 3g displayed correlations between H-3a and H-9b and H-9a and H-9b, indicating cisgeometry of these protons which was further confirmed by its single crystal X-ray analysis22 (Figure 3). In case of [3 + 2] cycloadducts 5a−i, 6a−i, 7a−d, 7g, and 7h, the given structures were confirmed on the basis of 79

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

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The Journal of Organic Chemistry

Figure 6. Plausible reaction mechanism for the formation of 3g and 3h.

Figure 4. Plausible reaction mechanism for the formation of 3a and 3b.

Figure 7. Plausible reaction mechanism for the formation of dihydrofuran derivatives.

reaction was very regioselective and provided a single diastereomer which indicates the high selectivity of the current high atom economy domino/tandem protocol. The yields of these one-pot reactions are noteworthy and generated polycyclic products with a plethora of functional groups.

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Figure 5. Plausible reaction mechanism for the formation of 3e and 3f.

tricyclic system 3e/3f via the keto−enol tautomerization of the adduct D. In another pathway, the adduct C tautomerizes to form intermediate E where the second molecule of ethyl vinyl ether reacts to deliver the desired product 3e/3f. The formation of tricyclic systems 3g and 3h can be explained on the basis of probable mechanism (Figure 5) in which the highly electron-deficient diene 1a undergoes inverse electron-demand Diels−Alder cycloaddition with electron-rich dienophilic 2-methyl furan (2d) to produce Diels−Alder adduct 3g and 3h. (Figure 6) The possible mechanism for the formation of dihydrofuran derivatives 5, 6, and 7 is depicted in Figure 7. First, BF3·OEt2 coordinates with the carbonyl group of alkenyl p-benzoquinone to enhance the electrophilicity at sixth position, where the Michael attack of β-carbon of styrene takes place to produce intermediate F. The subsequent cyclization delivers target [3 + 2] cycloadduct.

EXPERIMENTAL SECTION

General Information. Unless otherwise noted, chemicals were purchased with the highest purity grade available and were used without further purification. Thin-layer chromatography was performed on Merck precoated 0.25 mm silica gel plates (60F-254) using UV light as visualizing agent. Silica gel (100−200 mesh) was used for column chromatography. IR spectra of the compounds were recorded on FT-IR and are expressed as wavenumber (cm−1). NMR spectra were recorded in CDCl3 and DMSO-d6 using TMS as an internal standard on Brüker AMX-(500 MHz) and JEOL (400 MHz) instrument. Chemical shifts (δ) were reported as parts per million (ppm) in δ scale downfield from TMS. 1H NMR spectra were referenced to CDCl3 (7.26 ppm), and 13C NMR spectra were referenced to CDCl3 (77.0 ppm, the middle peak). Coupling constants were expressed in Hz. The following abbreviations were used to explain the multiplicities: s = singlet, d = doublet, dd = doublet of doublet, ddd = doublet of doublet of doublet, t = triplet, q = quartet, m = multiplet. High-resolution mass spectra (HRMS) were obtained on a Brüker micrOTOF-Q II mass spectrometer (ESI-MS). Characterization Data. General Procedure for the Synthesis of 3a−h. A mixture of 2a/2b (10 mmol) and alkenyl-p-benzoquinone 1a/1b (1 mmol) was stirred at room temperature. Then about 5 mL of hexane was added to the reaction mixture, and the flask was kept at 0 °C for 30 min. During this period a solid was formed, and it was filtered to afford pure product 3a-h. Furo-furocoumarin Derivative 3a. Reaction time: 10 h; Yield: 161 mg (70%) as yellow solid; MP: 208−210 °C; IR (KBr) νmax: 1766,

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CONCLUSION In conclusion, we have synthesized alkenyl p-bezoquinones derivatives and explored their reactivity with several electronrich cyclic and acyclic enol ethers as well as styrene derivatives. Based on the nature of the nucleophile or reaction conditions, it provided the products in diversified pathways. In each case the 80

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

Article

The Journal of Organic Chemistry 1625, 1571, 1245, 1085, 1025, 821 cm−1; 1H NMR (CDCl3, 500 MHz): δ 8.57 (s, 1H), 7.21, 7.12 (ABq, 2H, JAB = 8.7 Hz), 6.52 (d, J = 6.0 Hz, 1H), 4.27 (dd, J = 6.0, 9.0 Hz, 1H), 4.21 (t, J = 8.0 Hz, 1H), 4.00 (s, 3H), 3.71 (ddd, J = 5.0, 9.0, 14.0 Hz, 1H), 2.54−2.44 (m, 1H), 2.13 (dd, J = 4.5, 12.0 Hz, 1H) ppm; 13C NMR (CDCl3, 125 MHz): δ 163.9 (C), 156.5 (C), 155.9 (C), 150.3, (C), 144.6 (CH), 125.0 (C), 118.8 (C), 117.1 (CH), 115.8 (CH), 114.5 (C), 112.3 (CH), 67.3 (CH2), 53.1 (CH3), 45.6 (CH), 33.3 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C15H12O6Na 311.0526; found 311.0519. Furo-furocoumarin Derivative 3b. Reaction time: 9 h; Yield: 154 mg (71%) as yellow solid; MP: 152−154 °C; IR (KBr) νmax: 1713, 1669, 1469, 1243, 1091, 813 cm−1; 1H NMR (CDCl3, 500 MHz): δ 8.50 (s, 1H), 7.18, 7.08 (ABq, 2H, JAB = 9.0 Hz), 6.49 (d, J = 5.5 Hz, 1H), 4.44 (q, J = 7.0 Hz, 2H), 4.24 (dd, J = 5.5, 9.0 Hz, 1H), 4.18 (t, J = 8.5 Hz, 1H), 3.68 (ddd, J = 5.0, 9.0, 14.0 Hz, 1H), 2.50−2.40 (m, 1H), 2.10 (dd, J = 5.0, 12.5 Hz, 1H), 1.42 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (CDCl3, 125 MHz): δ 163.1 (C), 156.3 (C), 155.7 (C), 150.1 (C), 143.8 (CH), 124.9 (C), 119.0 (C), 116.8 (CH), 115.4 (CH), 114.4 (C), 112.2 (CH), 67.2 (CH2), 62.0 (CH2), 45.4 (CH), 33.1 (CH2), 14.1 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H14O6Na 325.0682; found 325.0702. Pyrano-furocoumarin Derivative 3c. Reaction time: 12 h; Yield: 202 mg (67%) as yellow solid; MP: 124−126 °C; IR (KBr) νmax: 1731, 1684, 1621, 1442, 1261, 1072, 725 cm−1; 1H NMR (CDCl3, 500 MHz): δ 8.49 (s, 1H), 7.19, 7.16 (ABq, 2H, JAB = 8.7 Hz), 6.06 (d, J = 6.0 Hz, 1H), 3.99 (s, 3H), 3.96−3.91 (m, 2H), 3.52 (q, J = 7.0 Hz, 1H), 2.28−2.21 (m, 1H), 1.84−1.74 (m, 1H), 1.71−1.60 (m, 2H) ppm; 13C NMR (CDCl3, 125 MHz): δ 163.7 (C), 156.5 (C), 153.6 (C), 149.7, (C), 144.8 (CH), 129.0 (C), 118.4 (C), 116.4 (CH), 116.3 (CH), 114.5 (C), 105.5 (CH), 61.2 (CH2), 52.9 (CH3), 37.0 (CH), 25.4 (CH2), 20.4 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C16H14O6Na 325.0682; found 325.0702. Pyrano-furocoumarin Derivative 3d. Reaction time: 9 h; Yield: 183 mg (65%) as yellow solid; MP: 146−148 °C; IR (KBr) νmax: 1726, 1622, 1460, 1270, 1017, 789 cm−1; 1H NMR (CDCl3, 500 MHz): δ 8.43 (s, 1H), 7.18, 7.14 (ABq, 2H, JAB = 8.7 Hz), 6.05 (d, J = 6.5 Hz, 1H), 4.47−4.41 (m, 2H), 3.95−3.90 (m, 2H), 3.51 (q, J = 7.0 Hz, 1H), 2.28−2.20 (m, 1H), 1.83−1.75 (m, 1H), 1.70−1.58 (m, 2H), 1.43 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (CDCl3, 125 MHz): δ 163.3 (C), 156.6 (C), 153.7 (C), 153.6 (C), 149.7, (C), 144.4 (CH), 129.0 (C), 118.9 (C), 116.3 (CH), 114.7 (C), 105.6 (CH), 62.1 (CH2), 61.3 (CH2), 37.1 (CH), 25.5 (CH2), 20.5 (CH2), 14.2 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C17H16O6Na 339.0839; found 339.0853. Dimethyl 2,5-Diethoxy-7-hydroxy-3,3a,5,6-tetrahydrobenzo[de]chromene-4,4(2H) Dicarboxylate (3e). Reaction time: 12 h; Yield: 274 mg (67%) as cream white solid; MP: 216−218 °C; IR (KBr) νmax: 3464, 1610, 1339, 1250, 1148, 1073, 810 cm−1; 1H NMR (CDCl3, 500 MHz): δ 6.58, 6.55 (ABq, 2H, JAB = 8.75), 5.09 (dd, J = 2.5, 9.5 Hz, 1H), 4.50 (s, 1H), 4.15 (dd, J = 6.5, 10.0 Hz, 1H), 4.10−4.03 (m, 1H), 3.82 (s, 3H), 3.79−3.73 (m, 1H), 3.68−3.64 (m, 1H), 3.62 (s, 3H), 3.59−3.50 (m, 2H), 3.20 (dd, J = 6.5, 17.0 Hz, 1H), 2.89 (dd, J = 10.5, 17.5 Hz, 1H), 2.39 (dt, J = 9.5, 13.0 Hz, 1H), 2.04 (qd, J = 2.5, 13.0 Hz, 1H), 1.28 (t, J = 7.0 Hz, 3H), 1.20 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (CDCl3, 125 MHz): δ 171.0 (C), 168.0 (C), 146.9, (C), 146.7 (C), 120.5 (C), 119.5 (C), 114.6 (CH), 114.4 (CH), 100.4 (CH), 79.6 (CH), 66.2 (CH2), 64.5 (CH2), 61.1 (C), 52.9 (CH3), 52.1 (CH3), 39.9 (CH), 30.4 (CH2), 28.5 (CH2), 15.5 (CH3), 15.2 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H26O8Na 417.1519; found 417.1524. Diethyl 2,5-Diethoxy-7-hydroxy-3,3a,5,6-tetrahydrobenzo[de]chromene-4,4(2H)-Dicarboxylate (3f). Reaction time: 8 h; Yield: 263 mg (60%) as cream white solid; MP: 136−138 °C; IR (KBr) νmax: 3446, 1613, 1461, 1376, 1253, 1150, 1075, 811 cm−1; 1H NMR (CDCl3, 500 MHz): δ 6.56, 6.54 (ABq, 2H, JAB = 8.7 Hz), 5.08 (dd, J = 2.5, 9.5 Hz, 1H), 4.98 (s, 1H), 4.34−4.22 (m, 2H), 4.17−4.10 (m, 2H), 4.09−4.02 (m, 2H), 3.79−3.71 (m, 1H), 3.68−3.61 (m, 1H), 3.57−3.48 (m, 2H), 3.18 (dd, J = 6.5, 17.0 Hz, 1H), 2.91 (dd, J = 10.0, 17.0 Hz, 1H), 2.40 (dt, J = 9.5, 12.5 Hz, 1H), 2.06 (qd, J = 2.5, 12.5 Hz, 1H), 1.33−1.25 (m, 6H), 1.18 (t, J = 7.0 Hz, 3H), 1.08 (t, J = 7.0

Hz, 3H) ppm; 13C NMR (CDCl3, 125 MHz): δ 170.7 (C), 167.5 (C), 147.3, (C), 146.4 (C), 120.7 (C), 119.6 (C), 114.4 (CH), 114.3 (CH), 100.4 (CH), 79.8 (CH), 66.1 (CH2), 64.6 (CH2), 62.0 (CH2), 60.9 (CH2), 39.8 (CH), 30.4 (CH2), 28.6 (CH2), 15.4 (CH3), 15.2 (CH3), 14.1 (CH3), 13.8 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H30O8Na 445.1832; found 445.1828. Dimethyl 2-Methyl-6,9-dioxo-6,9,9a,9b-tetrahydronaphtho[1,2b]furan-4,4(3aH)-dicarboxylate (3g). Reaction time: 15 h; Yield: 258 mg (78%) as yellow solid; MP: 134−136 °C; IR (KBr) νmax: 2956, 2852, 1731, 1684, 1219, 1121, 1073, 1018, 725 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.59 (q, J = 1.0 Hz, 1H), 6.95, 6.87 (ABq, 2H, JAB = 10.5 Hz), 5.75 (dd, J = 4.0, 10.0 Hz, 1H), 4.24 (d, J = 10.0 Hz, 1H), 4.12 (q, J = 1.0 Hz, 1H), 3.84 (s, 3H), 3.68 (s, 3H), 3.61 (t, J = 3.5 Hz, 1H), 1.59 (t, J = 1.5 Hz, 3H) ppm; 13C NMR (CDCl3, 125 MHz): δ 193.7 (C), 183.0 (C), 168.1 (C), 167.1 (C), 158.5 (C), 142.3 (CH), 141.4 (CH), 136.2 (CH), 132.6 (C), 94.2 (CH), 80.6 (CH), 58.6 (C), 53.5 (CH3), 53.1 (CH3), 47.8 (CH), 47.4 (CH), 13.2 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C17H16O7Na 355.0788; found 355.0790. Diethyl 2-Methyl-6,9-dioxo-6,9,9a,9b-tetrahydronaphtho[1,2-b]furan-4,4(3aH)-dicarboxylate (3h). Time: 16 h; Yield: 288 mg (75%) as yellow solid; MP: 202−204 °C; IR (KBr) νmax: 2978, 2930, 1727, 1681, 1251, 1203, 1085, 1013, 730 cm−1; 1H NMR (CDCl3, 500 MHz): δ 7.60 (d, J = 3.0 Hz, 1H), 6.95, 6.86 (ABq, 2H, JAB = 10.5 Hz), 5.75 (dd, J = 4.0, 10.0 Hz, 1H), 4.37−4.26 (m, 2H), 4.25−4.17 (m, 2H), 4.16−4.14 (m, 1H), 4.04 (qd, J = 7.0, 18.5 Hz, 1H), 3.63 (t, J = 3.0 Hz, 1H), 1.59 (s, 3H), 1.32 (t, J = 7.0 Hz, 3H), 1.19 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (CDCl3, 125 MHz): δ 193.8 (C), 183.1 (C), 167.6 (C), 166.6 (C), 158.3 (C), 142.4 (CH), 141.3 (CH), 136.6 (CH), 132.4 (C), 94.3 (CH), 80.7 (CH), 62.5 (CH2), 62.0 (CH2), 58.8 (C), 47.6 (CH), 47.5 (CH), 14.0 (CH3), 13.8 (CH3), 13.2 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H20O7Na 383.1101; found 383.1110. General Procedure for the Synthesis of Derivatives of Dihydrobenzofuran (5, 6, and 7). To a solution of alkenyl pbenzoquinone 1a/1c/1d and styrene derivative 2a−i in CH3CN at rt was added BF3·OEt2, and the reaction mixture was stirred. After completion of the reaction, as checked by TLC, the solvent was removed under vacuo, and the residue was purified by silica gel column chromatography using 30% ethyl acetate in hexanes to furnish the pure dihydrofuran derivatives. Dimethyl 2-((5-Hydroxy-2-phenyl-2,3-dihydrobenzofuran-7-yl)methylene)malonate (5a). Reaction time: 10 min; Yield: 0.152 g (86%) as yellow viscous liquid; IR (KBr) νmax: 3463, 1635, 1556, 1174, 1024, 629 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.89 (s, 1H), 7.40− 7.35 (m, 5H), 6.76 (d, J = 2.8 Hz, 1H), 6.64 (d, J = 2.8 Hz, 1H), 5.72 (t, J = 9.2 Hz, 1H), 3.80 (s, 3H), 3.78 (s, 3H), 3.51 (dd, J = 9.2, 16.4 Hz, 1H), 3.12 (dd, J = 9.2, 16.8 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 167.8 (CO), 164.8 (CO), 153.2 (C), 150.4 (C), 141.0 (C), 137.6 (CH), 128.7 (CH), 128.5 (CH), 128.1 (CH), 125.7 (C), 124.0 (C), 116.3 (CH), 114.5 (C), 112.1 (CH), 84.8 (CH), 52.8 (OCH3), 52.55 (OCH3), 38.25 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H18O6Na 377.0996; found 377.0992. Dimethyl 2-((5-Hydroxy-2-(4-methylphenyl)-2,3-dihydrobenzofuran-7-yl)methylene)-malonate (5b). Reaction time: 10 min; Yield: 0.156 g (85%) as yellow viscous liquid; IR (KBr) νmax: 3852, 1639, 1550, 1459, 1261, 1170, 1079, 1011, 617 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.88 (s, 1H), 7.25 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 2.0 Hz, 1H), 6.63 (d, J = 2.0 Hz, 1H), 5.69 (t, J = 9.0 Hz, 1H) 3.80 (s, 3H), 3.79 (s, 3H), 3.47 (dd, J = 9.0, 16.0 Hz, 1H), 3.13 (dd, J = 8.5, 16.0 Hz, 1H), 2.34 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.0 (CO), 164.8 (CO), 153.4 (C), 150.2 (C), 138.0 (C), 138.0 (C), 137.7 (CH), 129.2 (CH), 129.0 (C), 125.9 (CH), 124.0 (C), 116.3 (CH), 114.5 (C), 112.1 (CH), 84.9 (CH), 52.9 (OCH3), 52.6 (OCH3), 38.3 (CH2), 21.1 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H20O6Na 391.1152; found 391.1148. Dimethyl 2-((5-Hydroxy-2-(4-isopropylphenyl)-2,3-dihydrobenzofuran-7-yl)methylene)-malonate (5c). Reaction time: 10 min; Yield: 0.174 g (88%) as yellow viscous liquid; IR (KBr) νmax: 3442, 1635, 81

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

Article

The Journal of Organic Chemistry 1558, 1464, 1244, 1173, 1070, 611 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.89 (s, 1H), 7.30 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H) 6.76 (s, 1H), 6.64 (d, J = 2.5 Hz, 1H), 6.62 (s, 1H), 5.70 (t, J = 9.0 Hz, 1H), 3.80 (s, 3H), 3.79 (s, 3H), 3.50 (dd, J = 9.0, 16.0 Hz, 1H), 3.16 (dd, J = 8.5, 16.0 Hz, 1H), 2.91 (quin, J = 7.0 Hz, 1H), 1.25 (d, J = 7.0 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.0 (CO), 164.8 (CO), 153.4 (C), 150.2 (C), 149.0 (C), 138.3 (C), 137.6 (CH), 129.0 (C), 126.6 (CH), 126.0 (CH), 124.0 (C), 116.3 (CH), 114.5 (C), 112.0 (CH), 84.9 (CH), 52.8 (OCH3), 52.6 (OCH3), 38.2 (CH2), 33.8 (CH), 23.9 (2*CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C23H24O6Na 419.1465; found 419.1458. Dimethyl 2-((2-(3,4-Dimethoxyphenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)methy-lene)malonate (5d). Reaction time: 10 min; Yield: 0.190 g (92%) as yellow solid; MP: 115−117 °C; IR (KBr) νmax: 3448, 1746, 1636, 1561, 1244, 1126, 1035, 711 cm−1; 1H NMR (400 MHz, CDCl3): δ 7.84 (s, 1H), 6.91 (d, J = 7.6 Hz, 2H), 6.83 (d, J = 8.0 Hz, 1H), 6.76 (s, 1H), 6.63 (s, 1H), 5.65 (t, J = 8.8 Hz, 1H), 3.86 (s, 6H), 3.78 (s, 3H), 3.73 (s, 3H), 3.45 (dd, J = 9.6, 16.0 Hz, 1H), 3.14 (dd, J = 9.2, 16.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 167.7 (CO), 164.9 (CO), 153.2 (C), 150.3 (C), 149.0 (C), 149.0 (C), 137.7 (CH), 133.3 (C), 129.0 (C), 124.3 (C), 118.6 (CH), 116.2 (CH), 114.7 (C), 112.4 (CH), 111.0 (CH), 109.3 (CH), 85.2 (CH), 55.9 (OCH3), 55.9 (OCH3), 52.7 (OCH3), 52.5 (OCH3), 38.2 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H22O8Na 437.1207; found 437.1201. Dimethyl 2-((2-(4-Chlorophenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)methylene)-malonate (5e). Reaction time: 15 min; Yield: 0.128 g (66%) as yellow viscous liquid; IR (KBr) νmax: 3428, 1632, 1559, 1244, 1179, 1070, 920 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.87 (s, 1H), 7.33 (d, J = 9.0 Hz, 2H), 7.29 (d, J = 8.5 Hz, 2H), 6.75 (s, 1H), 6.64 (s, 1H), 6.06 (s, 1H), 5.71 (t, J = 9.0 Hz, 1H), 3.82 (s, 3H), 3.80 (s, 3H), 3.54 (dd, J = 9.5, 16.0 Hz, 1H), 3.09 (dd, J = 8.0, 16.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 167.9 (CO), 164.8 (CO), 153.1 (C), 150.4 (C), 139.6 (C), 137.4 (CH), 133.9 (C), 128.8 (CH), 128.5 (C), 127.2 (CH), 124.4 (C), 116.2 (CH), 114.8 (C), 112.2 (CH), 84.0 (CH), 52.9 (OCH3), 52.7 (OCH3), 38.4 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H17O6ClNa 411.0606; found 411.0609. Dimethyl 2-((2-(4-Bromophenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)methylene)-malonate (5f). Reaction time: 15 min; Yield: 0.138 g (64%) as light yellow solid; MP: 115−117 °C; IR (KBr) νmax: 3447, 1637, 1556, 1417, 1373, 1250, 1170, 1064, 936 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.86 (s, 1H), 7.48 (d, J = 8.5 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 6.74 (d, J = 2.5 Hz, 1H),6.63 (d, J = 2.0 Hz, 1H), 6.31 (s, 1H), 5.69 (t, J = 8.5 Hz, 1H), 3.81 (s, 3H), 3.80 (s, 3H), 3.53 (dd, J = 9.0, 16.0 Hz, 1H), 3.07 (dd, J = 8.5, 15.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 167.9 (CO), 164.8 (CO), 153.0 (C), 150.5 (C), 140.1 (C), 137.4 (CH), 131.7 (CH), 128.4 (C), 127.4 (CH), 124.3 (C), 122.0 (C), 116.3 (CH), 114.7 (C), 112.2 (CH), 84.0 (CH), 52.9 (OCH3), 52.7 (OCH3), 38.3 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H17O6BrNa 455.0101; found 455.0123. Dimethyl 2-((5-Hydroxy-2-methyl-2-phenyl-2,3-dihydrobenzofuran-7-yl)methylene)-malonate (5g). Reaction time: 5 min; Yield: 0.171 g (93%) as yellow viscous liquid; IR (KBr) νmax: 3437, 1632, 1547, 1417, 1297, 1173, 1073 cm−1; 1H NMR (500 MHz, CDCl3): δ 8.04 (s, 1H), 7.43 (d, J = 7.5 Hz, 2H), 7.36 (t, J = 7.5 Hz, 2H), 7.29− 7.26 (m, 1H), 6.71 (d, J = 1.0 Hz, 1H), 6.65 (d, J = 1.0 Hz, 1H)), 3.88 (s, 3H), 3.87 (s, 3H), 3.29 (q, J = 16.0 Hz, 2H) 1.74 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.2 (CO), 164.9 (CO), 152.8 (C), 150.1 (C), 146.0 (C), 137.5 (CH), 128.8 (C), 128.3 (CH), 127.2 (CH), 124.4 (CH), 123.8 (C), 116.6 (CH), 114.7 (C), 111.7 (CH), 90.3 (C), 52.9 (OCH3), 52.6 (OCH3), 44.5 (CH2), 29.3 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H20O6Na 391.1152; found 391.1179. Dimethyl 2-((5-Hydroxy-2-methyl-2-(4-methylphenyl)-2,3-dihydrobenzofuran-7-yl)me-thylene)malonate (5h). Reaction time: 5 min; Yield: 0.181 g (95%) as yellow viscous liquid; IR (KBr) νmax: 3456, 1638, 1541, 1464, 1252, 1082, 1023 cm−1; 1H NMR (500 MHz, CDCl3): δ 8.01 (s, 1H), 7.29 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 2H), 6.78 (s, 1H), 6.70 (d, J = 1.0 Hz, 1H), 6.63 (d, J = 1.0 Hz, 1H),

3.86 (s, 3H), 3.85 (s, 3H), 3.25 (q, J = 15.5 Hz, 2H), 2.32 (s, 3H), 1.70 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.2 (CO), 164.9 (CO), 152.9 (C), 150.0 (C), 143.0 (C),137.6 (C), 136.8 (CH), 128.9 (CH), 128.9 (C), 124.4 (CH), 123.7 (C), 116.6 (CH), 114.6 (C), 111.6 (CH), 90.3 (C), 52.9 (OCH3), 52.6 (OCH3), 44.5 (CH2), 29.2 (CH3), 20.9 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C22H22O6Na 405.1309; found 405.1308. Methyl (E)-3-(5-Hydroxy-2-phenyl-2,3-dihydrobenzofuran-7-yl)acrylate (6a). Reaction time: 10 min; Yield: 0.117 g (79%) as light yellow solid; MP: 166−168 °C; IR (KBr) νmax: 3448, 1639, 1552, 1305, 1085, 1020, 611 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 16.0 Hz, 1H), 7.39−7.37 (m, 4H), 7.34−7.32 (m, 1H), 6.76−6.70 (m, 3H), 5.83 (t, J = 8.5 Hz, 1H), 3.78 (s, 3H), 3.60 (dd, J = 9.5, 16.0 Hz, 1H), 3.16 (dd, J = 8.0, 16.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.5 (CO), 153.2 (C), 150.1 (C), 141.6 (C), 140.6 (CH), 128.8 (C), 128.6 (CH), 128.1 (CH), 125.6 (CH), 119.4 (CH), 116.9 (C), 114.7 (CH), 114.2 (CH), 84.7 (CH), 51.7 (OCH3), 38.3 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H16O4Na 319.0941; found 319.0932. Methyl (E)-3-(5-Hydroxy-2-(4-methylphenyl)-2,3-dihydrobenzofuran-7-yl)acrylate (6b). Reaction time: 10 min; Yield: 0.125 g (81%) as light yellow solid; MP: 143−145 °C; IR (KBr) νmax: 1639, 1553, 1471, 1121, 1077, 1018, 611 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.67 (d, J = 16.0 Hz, 1H), 7.26 (d, J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.75 (d, J = 8.0 Hz, 2H), 6.70 (d, J = 16.0 Hz, 1H), 5.85 (s, 1H), 5.77 (t, J = 8.5 Hz, 1H), 3.77 (s, 3H), 3.54 (dd, J = 9.5, 16.0 Hz, 1H), 3.13 (dd, J = 8.0, 16.0 Hz, 1H) 2.35 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.6 (CO), 153.2 (C), 150.1 (C), 140.8 (CH), 138.5 (C), 137.9 (C), 129.3 (CH), 129.0 (C), 125.7 (CH), 119.2 (CH), 116.9 (C), 114.7 (CH), 114.1 (CH), 84.82 (CH), 51.72 (OCH3), 38.22 (CH2), 21.13 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C19H18O4Na 333.1097; found 333.1126. Methyl (E)-3-(5-Hydroxy-2-(4-isopropylphenyl)-2,3-dihydrobenzofuran-7-yl)acrylate (6c). Reaction time: 10 min; Yield: 0.140 g (83%) as light yellow solid; MP: 147−149 °C; IR (KBr) νmax: 1680, 1554, 1420, 1371, 1209, 1168, 620 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.68 (d, J = 16.0 Hz, 1H), 7.31 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.5 Hz, 2H), 6.76 (d, J = 4.5 Hz, 2H), 6.71 (d, J = 16.0 Hz, 1H), 5.79 (t, J = 9.0 Hz, 1H), 5.66 (s, 1H), 3.78 (s, 3H), 3.56 (dd, J = 9.5, 16.0 Hz, 1H), 3.17 (dd, J = 8.0, 16.0 Hz, 1H), 2.91 (quin, J = 7.0 Hz, 1H), 1.25 (d, J = 7.0 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.5 (CO), 153.3 (C), 150.0 (C), 148.9 (C), 140.7 (CH), 138.9 (C), 129.0 (C), 126.7 (CH), 125.8 (CH), 119.3 (CH), 116.9 (C), 114.7 (CH), 114.1 (CH), 84.9 (CH), 51.7 (OCH3), 38.22 (CH2), 33.8 (CH), 23.9 (2*CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C21H22O4Na 361.1410; found: 361.1417. Methyl (E)-3-(2-(3,4-Dimethoxyphenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)acrylate (6d). Reaction time: 10 min; Yield: 0.142 g (80%) as light yellow solid; MP: 151−153 °C; IR (KBr) νmax: 1639, 1559, 1421, 1330, 1283, 1177, 1024, 620 cm−1; 1H NMR (400 MHz, CDCl3): 7.67 (d, J = 16.0 Hz, 1H), 6.95−6.91 (m, 2H), 6.85 (d, J = 8.0 Hz, 1H), 6.76 (s, 2H), 6.70 (d, J = 16.0 Hz, 1H), 5.76 (t, J = 8.4 Hz, 1H), 3.88 (s, 3H), 3.86 (s, 3H), 3.77 (s, 3H), 3.54 (dd, J = 9.2, 15.6 Hz, 1H), 3.17 (dd, J = 9.6, 17.2 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.4 (CO), 153.2 (C), 150.0 (C), 149.6 (C), 149.1 (C), 140.5 (CH), 133.9 (C), 130.0 (C), 119.4 (CH), 118.3 (CH), 117.0 (C), 114.7 (CH), 114.0 (CH), 111.2 (CH), 109.0 (CH), 85.0 (CH), 55.96 (OCH3), 55.92 (OCH3), 51.68 (OCH3), 38.21(CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C20H20O6Na 379.1152; found: 379.1164. Methyl (E)-3-(2-(4-Chlorophenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)acrylate (6e). Reaction time: 15 min; Yield: 0.102 g (62%) as light yellow solid; MP: 178−181 °C; IR (KBr) νmax: 3451, 1634, 1555, 1303, 1247, 1177, 1071, 1018, 608 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.66 (d, J = 16.0 Hz, 1H), 7.36−7.28 (m, 4H), 6.75 (d, J = 7.5 Hz, 2H), 6.70 (d, J = 16.0 Hz, 1H), 5.80 (t, J = 8.5 Hz, 1H), 5.20 (s, 1H), 3.79 (s, 3H), 3.60 (dd, J = 9.5, 16.0 Hz, 1H), 3.11 (dd, J = 8.0, 16.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.1 (CO), 153.0 (C), 150.1 (C), 140.1 (C), 140.1 (CH), 133.9 (C), 128.8 (CH), 128.5 (C), 127.0 (CH), 119.8 (C), 117.2 (CH), 114.6 (CH), 82

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

Article

The Journal of Organic Chemistry

(E)-3-(5-Hydroxy-2-(4-isopropylphenyl)-2,3-dihydrobenzofuran7-yl)-1-phenylprop-2-en-1-one (7c). Reaction time: 10 min; Yield: 0.134 g (70%) as yellow viscous liquid; IR (KBr) νmax: 3444, 1645, 1559, 1464, 1167, 1079, 1017, 605 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.99 (d, J = 7.5 Hz, 2H), 7.93 (d, J = 15.5 Hz, 1H), 7.83 (d, J = 15.5 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.45 (t, J = 7.5 Hz, 2H), 7.32 (d, J = 8.0 Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 6.99 (d, J = 2 Hz, 1H), 6.81 (s, 1H), 6.64 (s, 1H), 5.87 (t, J = 8.5 Hz, 1H), 3.58 (dd, J = 9.5, 15.5 Hz, 1H), 3.16 (dd, J = 8.0, 16.0 Hz, 1H), 2.90 (quin, J = 7.0 Hz, 1H), 1.24 (d, J = 7.0 Hz, 6H) ppm; 13C NMR (100 MHz, CDCl3): δ 191.6 (CO), 153.5 (C), 150.4 (C), 148.7 (C), 141.2 (CH), 139.1 (C), 138.1 (C), 132.8 (CH), 128.9 (CH), 128.6 (CH), 128.5 (C) 126.7 (CH), 125.4 (CH), 123.8 (CH), 117.5 (C), 115.3 (CH), 115.1 (CH), 84.74 (CH), 38.12 (CH2), 33.82 (CH), 23.94 (2*CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C26H24O3Na 407.1618; found: 407.1615. (E)-3-(2-(3,4-Dimethoxyphenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)-1-phenylprop-2-en-1-one (7d). Reaction time: 10 min; Yield: 0.144 g (72%) as yellow solid; MP: 168−170 °C; IR (KBr) νmax: 3447, 1641, 1559, 1288, 1135, 1026, 626 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.99 (d, J = 7.5 Hz, 2H), 7.88 (d, J = 15.5 Hz, 1H), 7.78 (d, J = 15.5 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 6.96 (d, J = 6.0 Hz, 2H), 6.86 (d, J = 9.0 Hz, 2H), 6.79 (s, 1H), 5.84 (t, J = 8.5 Hz, 1H), 3.88 (s, 3H), 3.85 (s, 3H), 3.58 (dd, J = 9.5, 16 Hz, 1H), 3.19 (dd, J = 8.5, 16.5 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 191.7 (CO), 153.4 (C), 150.4 (C), 149.1 (C), 148.8 (C), 141.2 (CH), 138.1 (C), 134.0 (C), 132.8 (CH), 129.0 (CH), 128.6 (CH), 128.5 (CH) 123.7 (CH), 118.0 (C), 117.6 (C), 115.2 (CH), 115.1 (CH), 111.1 (CH), 108.8 (CH), 84.91 (CH), 55.94 (OCH3), 55.89 (OCH3), 38.08 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C25H22O5Na 425.1359; found: 425.1379. (E)-3-(5-Hydroxy-2-methyl-2-phenyl-2,3-dihydrobenzofuran-7yl)-1-phenylprop-2-en-1-one (7g). Reaction time: 5 min; Yield: 0.133 g (75%) as yellow solid; MP: 168−170 °C; IR (KBr) νmax: 3450, 1641, 1552, 1140, 1028, 620 cm−1; 1H NMR (500 MHz, CDCl3): δ 8.05 (d, J = 7.5 Hz, 2H), 8.00 (d, J = 15.0 Hz, 1H), 7.87 (d, J = 15.5 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 7.50−7.47 (m, 4H), 7.36 (t, J = 7.5 Hz, 2H), 7.27 (t, J = 7.5 Hz, 1H), 6.94 (s, 1H), 6.76 (s, 1H), 3.38 (q, J = 16.0 Hz, 2H), 1.82 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 191.7 (CO), 152.7 (C), 150.3 (C), 146.3 (C), 141.4 (CH), 138.1 (C), 132.8 (C), 130.1 (CH), 128.8 (CH), 128.6 (CH), 128.4 (CH), 127.1 (CH), 124.2 (CH), 123.5 (CH), 117.6 (C), 115.4 (CH), 115.1 (CH), 90.63 (C), 44.29 (CH2), 29.69 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H20O3Na 379.1305; found: 379.1317. (E)-3-(5-Hydroxy-2-methyl-2-p-tolyl-2,3-dihydrobenzofuran-7yl)-1-phenylprop-2-en-1-one (7h). Reaction time: 5 min; Yield: 0.146 g (79%) as yellow viscous solid; IR (KBr) νmax: 3451, 1643, 1553, 1461, 1297, 1170, 1073, 1011, 612 cm−1; 1H NMR (500 MHz, CDCl3): δ 8.06−8.03 (m, 2H), 8.00 (s, 1H), 7.89 (d, J = 17.0 Hz, 1H), 7.58 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 2H), 7.37 (t, J = 8.5 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.96 (s, 1H), 6.76 (s, 1H), 6.43 (s, 1H), 3.36 (q, J = 15.0 Hz, 2H), 2.34 (s, 3H)1.81 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 191.7 (CO), 152.8 (C), 150.3 (C), 143.4 (C), 141.5 (CH), 138.2 (C), 136.8 (C), 132.8 (CH), 129.06 (CH), 129.02 (C), 128.9 (CH), 128.5 (CH), 124.2 (CH), 123.5 (CH), 117.6 (C), 115.4 (CH), 115.1 (CH), 90.63 (C), 44.30 (CH2), 29.66 (CH3), 20.92 (CH3) ppm; HRMS (ESI-TOF): m/z [M + H]+ calcd for C25H23O3 371.1641; found: 371.1637.

114.2 (CH), 84.0 (CH), 51.7 (OCH3), 38.3 (CH2) ppm; HRMS (ESITOF): m/z [M + Na]+ calcd for C18H15O4ClNa 353.0551; found: 353.0550. Methyl (E)-3-(2-(4-Bromophenyl)-5-hydroxy-2,3-dihydrobenzofuran-7-yl)acrylate (6f). Reaction time: 15 min; Yield: 0.112 g (60%) as light yellow solid; MP: 200−202 °C; IR (KBr) νmax: 3446, 1638, 1550, 1244, 1176, 1079, 622 cm−1; 1H NMR (400 MHz, CDCl3): δ 8.28 (s, 1H), 7.58 (d, J = 16.0 Hz, 1H), 7.42 (d, J = 8.4 Hz, 2H), 7.19 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 2.4 Hz, 2H), 6.58 (d, J = 16.0 Hz, 1H), 5.68 (t, J = 8.8 Hz, 1H), 3.70 (s, 3H), 3.51 (dd, J = 9.6, 16.0 Hz, 1H), 3.01 (dd, J = 8.0, 16.0 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3): δ 167.8 (CO), 152.0 (C), 151.3 (C), 140.7 (CH), 140.3 (C), 131.5 (CH), 127.8 (C), 127.1 (CH), 121.6 (C), 119.0 (CH), 116.9 (C), 114.6 (CH), 113.9 (CH), 83.57 (CH), 51.38 (OCH3), 38.16 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C18H15O4BrNa 397.0046; found: 397.0046. Methyl (E)-3-(5-Hydroxy-2-methyl-2-phenyl-2,3-dihydrobenzofuran-7-yl)acrylate (6g). Reaction time: 10 min; Yield: 0.130 g (84%) as light yellow solid; MP: 119−121 °C; IR (KBr) νmax: 3441, 1686, 1555, 1377, 1298, 1203, 1097, 621 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.73 (d, J = 16.0 Hz, 1H), 7.41 (d, J = 7.5 Hz, 2H), 7.32 (t, J = 7.5 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1H), 6.81−6.76 (m, 2H), 6.70 (s, 1H), 6.31 (s, 1H), 3.81 (s, 3H), 3.32 (q, J = 15.5 Hz, 2H), 1.75 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.7 (CO), 152.4 (C), 150.0 (C), 146.3 (C), 142.0 (CH), 128.8 (C), 128.4 (CH), 127.1 (CH), 124.3 (CH), 119.0 (CH), 117.0 (C), 115.0 (CH), 114.2 (CH), 90.5 (C), 51.8 (OCH3), 44.4 (CH2), 29.4 (CH3) ppm; HRMS (ESI-TOF): m/z [M + H]+ calcd for C19H19O4 311.1278; found: 311.1301. Methyl (E)-3-(5-Hydroxy-2-methyl-2-p-tolyl-2,3-dihydrobenzofuran-7-yl)acrylate (6h). Reaction time: 10 min; Yield: 0.144 g (89%) as light yellow solid; MP: 159−161 °C; IR (KBr) νmax: 3442, 1631, 1556, 1297, 1172, 1028, 622 cm−1; 1H NMR (500 MHz, CDCl3): δ 7.74 (d, J = 16.0 Hz, 1H), 7.32 (d, J = 8.5 Hz, 2H), 7.15 (d, J = 8.0 Hz, 2H), 6.80 (d, J = 16.0 Hz, 1H), 6.77 (d, J = 2.0 Hz, 1H), 6.71 (d, J = 2.0 Hz, 1H), 3.82 (s, 3H), 3.32 (q, J = 15.5 Hz, 2H), 2.33 (s, 3H), 1.76 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 168.8 (CO), 152.5 (C), 150.0 (C), 143.3 (C), 141.1(CH), 136.8 (C), 129.0 (CH), 128.9 (C), 124.3 (CH), 119.0 (CH), 117.0 (C), 115.0 (CH), 114.1 (CH), 90.5 (C), 51.7 (OCH3), 44.4 (CH2), 29.4 (CH3), 20.9 (CH3) ppm; HRMS (ESITOF): m/z [M + Na]+ calcd for C20H20O4 Na 347.1254; found: 347.1254. (E)-3-(5-Hydroxy-2-phenyl-2,3-dihydrobenzofuran-7-yl)-1-phenylprop-2-en-1-one (7a). Reaction time: 10 min; Yield: 0.118 g (69%) as light yellow solid; MP: 174−177 °C; IR (KBr) νmax: 3431, 1647, 1563, 1370, 1270, 1173, 1088, 610 cm−1; 1H NMR (400 MHz, CDCl3+DMSO-d6): δ 8.60 (d, J = 13.6 Hz, 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.88−7.74 (m, 2H), 7.57−7.54 (m, 1H), 7.50−7.33 (m, 6H), 7.32 (d, J = 7.2 Hz, 1H), 6.85 (s, 1H), 6.80 (s, 1H), 5.90 (t, J = 8.0 Hz, 1H), 3.64 (dd, J = 10.4, 15.6 Hz, 1H), 3.16 (dd, J = 7.6, 15.6 Hz, 1H) ppm; 13C NMR (100 MHz, CDCl3+DMSO-d6): δ 191.0 (CO), 152.7 (C), 151.6 (C), 141.9 (C), 140.7 (CH), 138.3 (C), 132.6 (CH), 128.6 (CH), 128.5 (CH), 128.4 (CH), 127.9 (CH), 125.4 (CH), 123.5 (CH), 117.5 (C), 115.2 (CH), 114.4 (CH), 84.4 (CH), 38.3 (CH2) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C23H18O3Na 365.1148; found: 365.1165. (E)-3-(5-Hydroxy-2-(4-methylphenyl)-2,3-dihydrobenzofuran-7yl)-1-phenylprop-2-en-1-one (7b). Reaction time: 10 min; Yield: 0.119 g (67%) as light yellow solid; MP: 159−161 °C; IR (KBr) νmax: 3453, 1642, 1560, 1244, 1024, 968, 616 cm−1; 1H NMR (500 MHz, CDCl3): δ 8.00 (d, J = 7.5 Hz, 2H), 7.92 (d, J = 15.5 Hz, 1H), 7.82 (d, J = 16.0 Hz, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.46 (t, J = 7.5 Hz, 2H), 7.30 (d, J = 8.0 Hz, 2H), 7.19 (d, J = 8.0 Hz, 2H), 6.96 (s, 1H), 6.80 (s, 1H), 6.08 (s, 1H), 5.88 (t, J = 8.5 Hz, 1H), 3.60 (dd, J = 9.5, 16.0 Hz, 1H), 3.16 (dd, J = 8.0, 16.0 Hz, 1H), 2.36 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3): δ 191.6 (CO), 153.5 (C), 150.3 (C), 141.1 (C), 138.7 (CH), 138.1 (C), 137.8 (C), 132.7 (CH), 129.3 (CH), 129.0 (CH), 128.6 (CH), 125.4 (CH), 123.9 (CH), 117.6 (C), 115.2 (CH), 115.0 (CH), 84.80 (CH), 38.19 (CH2), 21.14 (CH3) ppm; HRMS (ESI-TOF): m/z [M + Na]+ calcd for C24H20O3Na 379.1305; found: 379.1302.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b02377. ORTEP plot and crystallographic data for 3b (CIF) ORTEP plot and crystallographic data for 3e (CIF) ORTEP plot and crystallographic data for 3g (CIF) Spectral data for compounds 3a−h, 5a, and 5g; 1H and 13 C NMR spectra for all products 3, 5, 6, and 7; 1H−1H 83

DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84

Article

The Journal of Organic Chemistry

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and 1H−13C (HSQC/HMBC) COSY spectra of 3a, 3c, 3e, 3g, and 5a (PDF)

Winzer, A.; Kühner, S.; Little, S.; Yardley, V.; Vezin, H.; Palfey, B.; Schirmer, R. H.; Davioud-Charvet, E. J. Am. Chem. Soc. 2006, 128, 10784. (15) (a) Liao, C.-C.; Peddinti, R. K. Acc. Chem. Res. 2002, 35, 856. (b) Surasani, S. R.; Parumala, S. K. R.; Peddinti, R. K. Org. Biomol. Chem. 2014, 12, 5656. (16) (a) Bisht, S.; Peddinti, R. K. Tetrahedron 2017, 73, 2591. (b) Sharma, S.; Parumala, S. K. R.; Peddinti, R. K. Synlett 2017, 28, 239. (c) Sharma, S.; Naganaboina, R. T.; Peddinti, R. K. RSC Adv. 2015, 5, 100060. (d) Parumala, S. K. R.; Surasani, S. R.; Peddinti, R. K. New J. Chem. 2014, 38, 5268. (e) Parumala, S. K. R.; Peddinti, R. K. Org. Lett. 2013, 15, 3546. (17) 3b: CCDC No. 1549318. (18) (a) Kende, A. S.; Deng, W.-P.; Zhong, M.; Guo, X.-C. Org. Lett. 2003, 5, 1785. (b) Shang, S.; Long, S. Chem. Nat. Compd. 2008, 44, 186. (c) Feng, W.-S.; Zang, X.-Y.; Zheng, X.-K.; Wang, Y.-Z.; Chen, H.; Li, Z. J. Asian Nat. Prod. Res. 2010, 12, 557. (19) (a) Xie, P.; Li, E.; Zheng, J.; Li, X.; Huang, Y.; Chen, R. Adv. Synth. Catal. 2013, 355, 161. (b) Hata, K.; He, Z.; Daniliu, C. G.; Itami, K.; Studer, A. Chem. Commun. 2014, 50, 463. (c) Zhou, Z.; Liu, G.; Chen, Y.; Lu, X. Org. Lett. 2015, 17, 5874. (20) (a) Dohi, T.; Hu, Y.; Kamitanaka, T.; Kita, Y. Tetrahedron 2012, 68, 8424. (b) Meng, L.; Zhang, G.; Liu, C.; Wu, K.; Lei, A. Angew. Chem., Int. Ed. 2013, 52, 10195. (c) Zhang, L.; Li, Z.; Fan, R. Org. Lett. 2013, 15, 2482. (d) Zhao, Y.; Huang, B.; Yang, C.; Li, B.; Xia, W. Synthesis 2015, 47, 2731. (21) 3e: CCDC No. 1574602. (22) 3g: CCDC No. 1585911.

AUTHOR INFORMATION

Corresponding Author

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

Rama Krishna Peddinti: 0000-0001-7340-1516 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We sincerely thank CSIR and SERB, New Delhi for financial support and DST-FIST program for HRMS facility. S.B. thanks CSIR, and R.R. thanks DST for research fellowships.

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DOI: 10.1021/acs.joc.7b02377 J. Org. Chem. 2018, 83, 75−84