Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with

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Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with Internal Alkynes via C−H Functionalization in Poly(ethylene glycol) Li-Ming Tao,* Chuan-Hua Li, Jun Chen, and Hui Liu Hunan Provincial Key Laboratory of Xiangnan Rare-Precious Metals Compounds Research and Application, Xiangnan University, Chenzhou 423000, China

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ABSTRACT: A novel Co(III)-catalyzed oxidative annulation of aromatic aldehydes with internal alkynes for accessing isocoumarins is described, which is achieved by oxidation, weak chelation-assisted C−H bond functionalization, and annulation cascades with excellent functional group compatibility, high atom economy, and step efficiency. By using environmentally benign and inexpensive poly(ethylene glycol)-400 (PEG-400), the Co/Cu/PEG-400 system could be recycled and reused.

1. INTRODUCTION Isocoumarins are a very important class of O-heterocyclic compounds that are found in a wide range of natural products and pharmaceuticals.1,2 For these reasons, tremendous attention has been attracted on the development of efficient strategies for assembling isocoumarins. Among them, the annulation reaction with unsaturated hydrocarbons (e.g., alkynes and alkenes) via weak chelation-assisted C−H bond functionalization is particularly attractive due to its high atom and step economy.2,3 Generally, these transformations focus on transition metal-catalyzed annulation of aromatic acids and their derivatives with internal alkynes,2−5 where the carboxyl group serves as the weak chelation group4,5 to selectively enable functionalization of its ortho-C(sp2)−H bond, leading to isocoumarins (Scheme 1a). However, most of such transformations are restricted by the requirement of noble metal catalysts (e.g., Rh, Ru, and Pd) and toxic solvents,5 and

examples using abundant, nontoxic, air-stable cobalt catalysts are rare.4 To our knowledge, only a paper that employs aldehydes as the weak chelation carboxyl group precursors using the N-heterocyclic carbene/rhodium(III) catalysis has been reported (Scheme 1b).5e In view of significant economic and environmental reasons from both academic and industrial perspectives, development of efficient routes, especially including recyclable catalytic process, to access isocoumarins is therefore appealing. Herein, we report a cobalt(III)-catalyzed oxidative [4 + 2] annulation of aromatic aldehydes with internal alkynes. The reaction allows the formation of isocoumarins through a sequence of oxidation of aldehydes6 and weak chelationassisted C−H bond functionalization and annulation (Scheme 1c). Importantly, this reaction employs an abundant, nontoxic, air-stable cobalt catalyst and environmentally benign, inexpensive PEG-400 medium7 to allow the Co/Cu/PEG-400 system recycle and reuse.

Scheme 1. Synthesis of Isocoumarins via Annulations

2. RESULTS AND DISCUSSION At the outset of our investigation, the reaction between benzaldehyde 1a and diphenylethyne 2a was chosen to explore the optimal reaction conditions (Table 1). The reaction of 1a with 2a in the presence of Cp*Co(CO)I2 (10 mol %), CuO (2 equiv), and O2 (1 atm) was performed in PEG-400 (2 g) at 100 °C, affording the target 3,4-diphenyl-1H-isochromen-1one 3aa in 83% yield (entry 1). Notably, both Cp*Co(CO)I2 and CuO played a key role in the reaction as the absence of one resulted in no reaction (entries 2 and 8). A lower amount of Cp*Co(CO)I2 (5 mol %) had a negative effect even after prolonging the reaction time (entry 3), whereas a higher amount of Cp*Co(CO)I2 (15 mol %) gave identical results to that proceeded at 10 mol % loading (entry 4). Other Co Received: February 27, 2019

© XXXX American Chemical Society

A

DOI: 10.1021/acs.joc.9b00580 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry Table 1. Screening of the Reaction Conditionsa

Table 2. Variations of the Aromatic Aldehydes (1) and Alkynes (2)a

entry

variation from the standard conditions

yield (%)

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

none without Cp*Co(CO)I2 Cp*Co(CO)I2 (5 mol %) Cp*Co(CO)I2 (15 mol %) [Cp*CoI2]2 instead of Cp*Co(CO)I2 Co(acac)3 instead of Cp*Co(CO)I2 CoI2 instead of Cp*Co(CO)I2 without CuO CuO (1.5 equiv) Cu(OAc)2 instead of CuO CuCl2 instead of CuO Cu2O instead of CuO without molecular sieves at 80 °C at 110 °C air instead of O2 argon instead of O2 toluene (3 mL) instead of PEG-400 DMF (3 mL) instead of PEG-400 none

83 0 51/55b 85 38 15 trace trace 76 13 6 trace 71 55 81 58 7 31 65 79

a

Reaction conditions: 1a (0.6 mmol), 2a (0.3 mmol), Cp*Co(CO)I2 (10 mol %), CuO (2 equiv), O2 (1 atm), molecular sieves (100 mg), PEG-400 (2 g), 100 °C, and 24 h. Some by-products, including benzoic acid, were observed as determined by GC−MS analysis. bFor 48 h. c1a (2 mmol), 2a (1 mmol), PEG-400 (8 g), and 48 h.

a

Reaction conditions: 1 (0.6 mmol), 2 (0.3 mmol), Cp*Co(CO)I2 (10 mol %), CuO (2 equiv), O2 (1 atm), molecular sieves (100 mg), PEG-400 (2 g), 100 °C, and 24 h. bThe regioselectivity ratio is >99:1.

catalysts, such as [Cp*CoI2]2, Co(acac)3, and CoI2, were tested (entries 5−7), and they all were less efficient than Cp*Co(CO)I2. A lower loading (1.5 equiv) CuO decreased the yield to 76% (entry 9). Three other Cu salts, including Cu(OAc)2, CuCl2, and Cu2O, proved to be inferior to CuO (entries 10−12). We found that the reaction could be promoted by molecular sieves (entry 1 vs entry 13). Extensive optimization revealed that 100 °C was the best option as a lower temperature (90 °C) diminished the yield and a higher temperature (110 °C) had no further improvement of the yield (entries 14 and 15). The reaction stunted the formation of 3aa with moderate yield when using air-replaced O2 (entry 16), and replacement of O2 by argon led to a lower yield (entry 17). Two conventional solvents, toluene and DMF, were tested, and they both were less reactive than PEG-400 (entries 18 and 19). Gratifyingly, the reaction was applicable to a 1 mmol scale of diphenylethyne 2a, giving 3aa in a good yield (entry 20). Having established the optimized reaction conditions, we turned our attention to investigate the substrate scope of this annulation reaction (Table 2). The optimal conditions were compatible with a wide range of internal alkynes 2a−2e and 2g−2l, including diaryl, dialkyl, and alkylarylacetylenes (products 3ab−3ae and 3ga−3al), but unsuitable for bulky ortho-substituted diaryl acetylene 2f and terminal alkyne 2m (products 3fa and 3ma). For symmetric diarylacetylenes, a number of substituents, namely, Me, MeO, and Cl, on the aryl ring were well tolerated, and the electron properties affected their reactivity (products 3ab−3ae). While alkynes, possessing an electron-donating group (e.g., Me and MeO) at para or meta position, afforded 3ab, 3ac, and 3ae in 81−87% yields,

alkynes with a weak electron-donating Cl group provided 3ad in diminishing yield. A heteroarylacetylene, 1,2-di(thiophen-2yl)ethyne, was found to be suitable for assembling 3ag in a moderate yield. For dialkylacetylenes, the reaction was efficiently executed to afford 3ah and 3ai in high yields. Gratifyingly, unsymmetrical alkylacetylenes were suitable substrates and regioselectively furnished 3aj−3al in good yields. It should be noted that this reaction can be applicable to construction of estrone-containing 1H-isochromen-1-one 3al, in which the estrone unit has unique bioactive properties.8 Unfortunately, the reaction failed to annulation with terminal alkyne (3am). Subsequently, a variety of aromatic aldehydes 1b−1k with diphenylethyne 2a were investigated under the optimal conditions (products 3ba−3ka). We found that several substituents, including Me, MeO, Br, Cl, CN, and MeCO, on the aryl ring were perfectly tolerated. Aldehydes possessing a Me group at para, meta, or ortho position were all converted efficiently into the corresponding products 3ba, 3ha, and 3ia. To our delight, halogens, such as bromide and chloride, were tolerated well, giving 3da and 3ea, respectively, in satisfactory yields. Aldehydes 1f−1g bearing an electron-withdrawing CN or acetyl group were viable for the synthesis of 3fa−3ga, albeit with diminishing yield. Using diMeO-substituted aldehyde enable the formation of 3ja in 74% yield. The optimal conditions were also compatible with thiophene-2-carbaldehyde, giving 3ka in a moderate yield. The recycle experiments of benzaldehyde 1a with diphenylethyne 2a were performed on the Cp*Co(CO)I2/ B

DOI: 10.1021/acs.joc.9b00580 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry CuO/molecular sieves/PEG 400 system (Scheme 2, eq 1).7 A constant rate of conversion was observed under the optimal

4. EXPERIMENTAL SECTION 4.1. General Considerations. The 1H and 13C NMR spectra were recorded in CDCl3 solvent on an NMR spectrometer using TMS as the internal standard. High-resolution mass spectrometry (HRMS) was measured on an electrospray ionization (ESI) apparatus using time-of-flight (TOF) mass spectrometry. Melting points are uncorrected. 4.2. Typical Experimental Procedure for Cobalt(III)-Catalyzed Oxidative Annulation of Benzaldehydes with Internal Alkynes. A mixture of benzaldehydes 1 (0.6 mmol), alkynes 2 (0.3 mmol), Cp*Co(CO)I2 (10 mol %), CuO (2 equiv), O2 (1 atm), molecular sieves (100 mg), and PEG-400 (2 g) was prepared in a 25 mL Schlenk tube and heated to 100 °C (oil bath temperature). The reaction mixture was stirred at 100 °C for 24 h until complete consumption of the starting material, as monitored by thin-layer chromatography (TLC) and/or gas chromatography−mass spectrometry (GC−MS) analysis. After the reaction was finished, the reaction was allowed to cool to room temperature and extracted with hexane/ diethyl ether (10:1; 5 × 10 mL). The combined organic layer was washed with brine (3 × 5 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate = 25:1) to afford the desired 1H-isochromen-1-ones 3. After extracting with diethyl ether/hexane (1:1), the mixture of Cp*Co(CO)I2, CuO, PEG-400, and molecular sieves was solidified (cooled and then evaporated under vacuo) and subjected to a second run of the annulation reaction by charging with the same substrates (aldehyde 1, alkyne 2, and O2). 4.3. Synthesis Experimental Procedure for a Scale up to 1 mmol of Diphenylethyne 2a. A mixture of benzaldehyde 1a (2 mmol), diphenylethyne 2a (1 mmol), Cp*Co(CO)I2 (10 mol %), CuO (2 equiv), O2 (1 atm), molecular sieves (200 mg), and PEG-400 (8 g) was prepared in a 25 mL Schlenk tube and heated to 100 °C (oil bath temperature). The reaction mixture was stirred at 100 °C for 48 h until complete consumption of the starting material, as monitored by TLC and/or GC−MS analysis. After the reaction was finished, the reaction was allowed to cool to room temperature and extracted with hexane/diethyl ether (10:1; 5 × 15 mL). The combined organic layer was washed with brine (3 × 5 mL), dried over anhydrous Na2SO4, and concentrated in vacuo. The resulting residue was purified by silica gel column chromatography (hexane/ethyl acetate = 25:1) to afford the desired 1H-isochromen-1-one 3aa (235.4 mg, 79% yield). 4.3.1. 3,4-Diphenyl-1H-isochromen-1-one (3aa).5m,9a 74.2 mg, 83% yield; white solid; mp 171.8−173.5 °C (lit.5m,9a 172−174 °C); 1 H NMR (500 MHz, CDCl3): δ (ppm) 8.41−8.40 (m, 1H), 7.65− 7.62 (m, 1H), 7.53−7.50 (m, 1H), 7.43−7.40 (m, 3H), 7.33 (t, J = 7.0 Hz, 2H), 7.27−7.25 (m, 3H), 7.22−7.17 (m, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.3, 151.0, 138.9, 134.7, 134.3, 133.0, 131.2, 129.6, 129.2, 129.1, 129.0, 128.2, 128.1, 127.9, 125.4, 120.4, 116.9; LRMS (EI, 70 eV) m/z (%): 298 (M+, 100), 270 (25), 221 (33), 165 (26), 105 (88). 4.3.2. 3,4-Di-p-tolyl-1H-isochromen-1-one (3ab).5m 83.1 mg, 85% yield; light yellow solid; mp 152.5−154.3 °C (lit.5m 153−155 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.39 (d, J = 7.5 Hz, 1H), 7.61 (t, J = 7.5 Hz, 1H), 7.49 (t, J = 7.5 Hz, 1H), 7.26−7.19 (m, 5H), 7.14 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.0 Hz, 2H), 2.42 (s, 3H), 2.29 (s, 3H); 13 C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 151.0, 139.3, 139.0, 137.8, 134.6, 131.4, 131.0, 130.2, 129.8, 129.5, 129.1, 128.6, 127.8, 125.3, 120.3, 116.3, 21.4, 21.3; LRMS (EI, 70 eV) m/z (%): 326 (M+, 100), 298 (45), 235 (25), 178 (18), 119 (51). 4.3.3. 3,4-Bis(4-methoxyphenyl)-1H-isochromen-1-one (3ac).9b 107.0 mg, 87% yield; light yellow solid; mp 156.8−158.3 °C (lit.9b 158.4−159.7 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.38−8.36 (m, 1H), 7.63−7.59 (m, 1H), 7.49−7.46 (m, 1H), 7.30−7.28 (m, 2H), 7.21−7.16 (m, 3H), 6.96 (d, J = 8.5 Hz, 2H), 6.72 (d, J = 9.0 Hz, 2H), 3.86 (s, 3H), 3.76 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 159.9, 159.3, 150.9, 139.5, 134.6, 132.3, 130.7, 129.5, 127.7, 126.6, 125.4, 125.2, 120.2, 115.4, 114.6, 113.3, 55.3, 55.2;

Scheme 2. Recycle Experiments and Control Experiments

conditions without the addition Cp*Co(CO)I2, CuO, and PEG-400 in the every cycles. To our delight, the reaction is still efficient after recycling for three times by replenishing it with oxygen every time. The yield slightly decreased because there are some losses of the Co catalyst in every recycle process. Notably, using benzoic acid 1k to react with alkyne 2a afforded 3aa in 86% yield under the optimal conditions (Scheme 2, eq 2). The possible mechanisms for this annulation protocol are proposed (Scheme 3).2−5 Aldehyde 1a is oxidized and Scheme 3. Possible Mechanisms

transformed into the acid intermediate A by the Co(III)/ CuO/O2 system. Subsequently, insertion of the active Co(III) species into C−H bond of the acid intermediate A forms the intermediate B.2,4 Coordination of the intermediate B with alkyne 2a results in the formation of the intermediate C, which sequentially undergoes cis-addition to afford the intermediate D.4 Annulation and reductive elimination of the intermediate D provides the desired product 3aa and the Co(I) species. Oxidation of the Co(I) species by the Cu(II) species regenerates the active Co(III) species. We also cannot rule out the reaction via the peroxide intermediate E.

3. CONCLUSIONS In summary, we have reported the first recyclable Co(III)/ CuO/PEG-400 system for oxidative annulation of aromatic aldehydes with internal alkynes involving C−H functionalization. By using both abundant, nontoxic, air-stable Cp*Co(III) catalyst and environmentally benign and inexpensive PEG-400, diverse functional groups were tolerated, and the resulting isocoumarins were obtained in good yields and excellent selectivity. Most importantly, the Co(III)/CuO/PEG-400 system were recycled and reused three times and showed high efficiency every time. C

DOI: 10.1021/acs.joc.9b00580 J. Org. Chem. XXXX, XXX, XXX−XXX

Article

The Journal of Organic Chemistry LRMS (EI, 70 eV) m/z (%): 410 (M+, 96), 354 (100), 297 (17), 221 (25), 161 (33). 4.3.4. 3,4-Bis(4-chlorophenyl)-1H-isochromen-1-one (3ad).9a 85.6 mg, 78% yield; light yellow solid; mp 171.0−172.5 °C (lit.9a 172.6−173.6 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.40 (d, J = 7.5 Hz, 1H), 7.68−7.65 (m, 1H), 7.55 (t, J = 7.5 Hz, 1H), 7.43 (d, J = 8.5 Hz, 2H), 7.26 (d, J = 8.5 Hz, 2H), 7.20 (t, J = 8.5 Hz, 4H), 7.16 (d, J = 8.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ (ppm) 161.8, 150.0, 138.2, 135.3, 135.0, 134.5, 132.5, 131.1, 130.5, 129.8, 129.6, 128.6, 128.4, 125.1, 120.4, 116.1; LRMS (EI, 70 eV) m/z (%): 366 (M+, 100), 338 (54), 303 (38), 239 (42), 139 (76). 4.3.5. 3,4-Di-m-tolyl-1H-isochromen-1-one (3ae).9a 79.2 mg, 81% yield; white solid; mp 120.1−122.8 °C; 1H NMR (500 MHz, CDCl3): δ (ppm) 8.40 (d, J = 7.5 Hz, 1H), 7.63 (t, J = 7.5 Hz, 1H), 7.51 (t, J = 7.5 Hz, 1H), 7.30 (d, J = 7.5 Hz, 2H), 7.21 (t, J = 5.5 Hz, 2H), 7.06 (t, J = 13.5 Hz, 5H), 2.35 (s, 3H), 2.24 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 150.9, 139.1, 138.7, 137.5, 134.6, 134.3, 132.8, 131.7, 129.7, 129.7, 129.5, 128.9, 128.8, 128.3, 128.0, 127.6, 126.4, 125.5, 120.4, 116.9, 21.5, 21.4; LRMS (EI, 70 eV) m/z (%): 326 (M+, 95), 298 (45), 235 (38), 178 (30), 119 (100). 4.3.6. 3,4-Di(thiophen-2-yl)-1H-isochromen-1-one (3ag). 56.7 mg, 61% yield; yellow solid; mp 183.9−185.0 °C; 1H NMR (500 MHz, CDCl3): δ (ppm) 8.34−8.32 (m, 1H), 7.66−7.63 (m, 2H), 7.50−7.46 (m, 1H), 7.41−7.40 (m, 1H), 7.33−7.32 (m, 1H), 7.29− 7.26 (m, 1H), 7.16−7.12 (m, 2H), 6.99−6.97 (m, 1H); 13C NMR (125 MHz, CDCl3): δ (ppm) 161.2, 148.2, 139.7, 135.0, 134.6, 133.7, 130.8, 130.0, 129.5, 129. 5, 129.0, 128.4, 128.0, 127.0, 125.2, 119.7, 107.2; IR (KBr): νCO 1732 cm−1; LRMS (EI, 70 eV) m/z (%): 310 (M+, 81), 282 (100), 253 (66), 221 (32), 111 (30); HRMS m/z (ESI) calcd for C17H11O2S2 [M + H]+, 311.0200; found, 311.0221. 4.3.7. 3,4-Diethyl-1H-isochromen-1-one (3ah).9a 50.3 mg, 83% yield; white solid; mp 57.0−59.5 °C (lit.9a 59−64 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.32 (d, J = 8.0 Hz, 1H), 7.76−7.72 (m, 1H), 7.55 (d, J = 8.5 Hz, 1H), 7.46 (t, J = 8.0 Hz, 1H), 2.68−2.60 (m, 4H), 1.29 (t, J = 7.5 MHz,3H), 1.21 (t, J = 7.5 MHz,3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 163.0, 155.0, 137.8, 134.6, 130.9, 127.1, 122.5, 120.9, 113.1, 24.1, 19.3, 14.4, 12.6; LRMS (EI, 70 eV) m/z (%): 202 (M+, 100), 187 (92), 259 (30), 131 (83), 115 (46). 4.3.8. 3,4-Dibutyl-1H-isochromen-1-one (3ai).5g 61.9 mg, 80% yield; colorless oil; 1H NMR (500 MHz, CDCl3): δ (ppm) 8.32−8.30 (m, 1H), 7.75−7.71 (m, 1H), 7.52 (d, J = 8.0 Hz, 1H), 7.47−7.44 (m, 1H), 2.62−2.57 (m, 4H), 1.73−1.67 (m, 2H), 1.56−1.51 (m, 2H), 1.48−1.39 (m, 4H), 1.00−0.94 (m, 6H); 13C NMR (125 MHz, CDCl3): δ (ppm) 163.0, 154.2, 138.0, 134.6, 129.8, 127.0, 122.68, 120.8, 112.3, 31.9, 30.6, 30.0, 25.9, 22.9, 22.5, 14.0, 13.9; LRMS (EI, 70 eV) m/z (%): 258 (M+, 42), 215 (45), 173 (100), 145 (20), 131 (20). 4.3.9. 4-Methyl-3-phenyl-1H-isochromen-1-one (3aj).5g 49.6 mg, 70% yield; white solid; mp 91.2−93.8 °C (lit.5g 92−94 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.39−8.37 (m, 1H), 7.82−7.79 (m, 1H), 7.64 (d, J = 8.0 Hz, 1H), 7.60−7.58 (m, 2H), 7.57−7.53 (m, 1H), 7.48−7.44 (m, 3H), 2.32 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.6, 151.2, 138.8, 134.8, 133.3, 129.8, 129.5, 129.4, 128.3, 128.0, 123.4, 120.8, 109.2, 13.6; LRMS (EI, 70 eV) m/z (%): 236 (M+, 93), 208 (100), 178 (25), 105 (31), 77 (52). 4.3.10. 4-Cyclopropyl-3-phenyl-1H-isochromen-1-one (3ak).9b 56.6 mg, 72% yield; light yellow solid; mp 114.5−116.0 °C (lit.9b 115−117 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.33 (d, J = 8.0 Hz, 1H), 8.12 (d, J = 8.0 Hz, 1H), 7.82−7.79 (m, 1H), 7.75−7.73 (m, 2H), 7.53 (t, J = 7.5 Hz, 1H), 7.47−7.43 (m, 3H), 1.94−1.89 (m, 1H), 1.00−0.93 (m, 2H), 0.21−0.17 (m, 2H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 153.5, 139.7, 134.5, 133.2, 129.5 (2C), 129.4, 127.9, 124.6, 120.6, 114.6, 10.0, 9.1; LRMS (EI, 70 eV) m/z (%): 262 (M+, 72), 233 (21), 217 (52), 185 (63), 105 (100). 4.3.11. 4-Cyclopropyl-3-((8R,9S,13S,14S)-13-methyl-17-oxo7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-3-yl)-1H-isochromen-1-one (3al). 90.7 mg, 69% yield; light yellow solid; mp 225.3−227.9 °C; 1H NMR (500 MHz, CDCl3): δ (ppm) 8.33 (d, J = 8.0 Hz, 1H), 8.11 (d, J = 8.0 Hz, 1H), 7.80 (t, J = 7.5 Hz, 1H), 7.55−7.51 (m, 3H), 7.35 (d, J = 8.0 Hz, 1H), 2.99−

2.97 (m, 2H), 2.56−2.52 (m, 1H), 2.51−2.46 (m, 1H), 2.38 (t, J = 10.5 Hz, 1H), 2.21−1.91 (m, 6H), 1.70−1.65 (m, 3H), 1.59−1.49 (m, 4H), 0.99−0.87 (m, 5H), 0.26−0.21 (m, 2H); 13C NMR (125 MHz, CDCl3): δ (ppm) 220.9, 162.6, 153.6, 141.2, 139.9, 136.1, 134.5, 130.6, 129.8, 129.5, 127.7, 127.1, 124.7, 124.5, 120.5, 114.2, 50.6, 48.0, 44.6, 38.0, 35.9, 31.6, 29.4, 26.5, 25.6, 21.6, 13.9, 10.2, 10.1, 9.2; IR (KBr): νCO 1741, 1735 cm−1; HRMS m/z (ESI) calcd for C30H31O3 [M + H]+, 439.2273; found, 439.2281. 4.3.12. 6-Methyl-3,4-diphenyl-1H-isochromen-1-one (3ba).5m,9a 79.6 mg, 85% yield; white solid; mp 184.3−187.0 °C (lit.9a 186−188 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.30 (d, J = 8.0 Hz, 1H), 7.42 (t, J = 5.5 Hz, 3H), 7.35−7.31 (m, 3H), 7.26−7.24 (m, 2H), 7.22−7.17 (m, 3H), 6.97 (s, 1H), 2.37 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.4, 151.0, 145.8, 138.9, 134.4, 133.1, 131.3, 129.6, 129.5, 129.3, 129.1, 128.9, 128.1, 127.8, 125.3, 118.1, 116.9, 22.3; LRMS (EI, 70 eV) m/z (%): 312 (M+, 100), 284 (30), 235 (23), 178 (20), 105 (45). 4.3.13. 6-Methoxy-3,4-diphenyl-1H-isochromen-1-one (3ca).9a 81.7 mg, 83% yield; white solid; mp 175.5−177.0 °C (lit.9a 178− 180 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.34 (d, J = 8.5 Hz, 1H), 7.40 (t, J = 7.0 Hz, 3H), 7.32 (d, J = 7.5 Hz, 2H), 7.26−7.25 (m, 2H), 7.23−7.17 (m, 3H), 7.07−7.05 (m, 1H), 6.58 (d, J = 2.0 Hz, 1H), 3.75 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 164.7, 162.1, 151.5, 141.2, 134.4, 133.0, 131.9, 131.2, 129.3, 129.1, 129.0, 128.2, 127.8, 116.8, 115.7, 113.7, 108.5, 55.5; LRMS (EI, 70 eV) m/z (%): 328 (M+, 100), 300 (25), 251 (30), 152 (22), 105 (60). 4.3.14. 6-Bromo-3,4-diphenyl-1H-isochromen-1-one (3da).5m 73.3 mg, 65% yield; white solid; mp 199.0−202.6 °C (lit.5m 198− 200 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.25−8.23 (m, 1H), 7.63 (d, J = 8.5 Hz, 1H), 7.43 (d, J = 5.0 Hz, 3H), 7.33−7.30 (m, 3H), 7.24 (t, J = 5.5 Hz, 3H), 7.21−7.18 (m, 2H); 13C NMR (125 MHz, CDCl3): δ (ppm) 161.7, 152.2, 140.4, 133.6, 132.6, 131.5, 131.2, 131.1, 130.5, 129.3, 129.3, 129.3, 128.5, 128.1, 128.0, 119.1, 116.0; LRMS (EI, 70 eV) m/z (%): 376 (M+, 38), 348 (9), 299 (18), 163 (41), 105 (100). 4.3.15. 6-Chloro-3,4-diphenyl-1H-isochromen-1-one (3ea).9a 72.7 mg, 73% yield; white solid; mp 167.2−171.7 °C (lit.9a 168− 170 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.33 (d, J = 8.5 Hz, 1H), 7.48−7.42 (m, 4H), 7.32−7.31 (m, 2H), 7.26−7.24 (m, 3H), 7.21−7.18 (m, 2H), 7.16 (d, J = 2.0 Hz, 1H); 13C NMR (125 MHz, CDCl3): δ (ppm) 161.5, 152.2, 141.7, 140.4, 133.6, 132.6, 131.3, 131.1, 129.3 (3C), 128.6, 128.5, 128.0, 125.0, 118.7, 116.1;LRMS (EI, 70 eV) m/z (%): 332 (M+, 89), 304 (20), 255 (28), 163 (32), 105 (100). 4.3.16. 1-Oxo-3,4-diphenyl-1H-isochromene-6-carbonitrile (3fa).9a 63.0 mg, 65% yield; light yellow solid; mp 174.6−177.2 °C (lit.9a 176−178 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.48 (d, J = 8.0 Hz, 1H), 7.74−7.72 (m, 1H), 7.50−7.46 (m, 4H), 7.34−7.32 (m, 2H), 7.28−7.20 (m, 5H); 13C NMR (125 MHz, CDCl3): δ (ppm) 160.7, 152.8, 139.5, 132.9, 132.1, 131.0, 130.5, 130.2, 129.7, 129.7, 129.6, 129.3, 128.9, 128.1, 123.0, 118.2, 117.7, 115.7; LRMS (EI, 70 eV) m/z (%): 323 (M+, 100), 295 (21), 246 (20), 105 (65). 4.3.17. 6-Acetyl-3,4-diphenyl-1H-isochromen-1-one (3ga).9a 71.4 mg, 70% yield; light yellow solid; mp 173.1−174.9 °C; 1H NMR (500 MHz, CDCl3): δ 8.48 (d, J = 8.0 Hz, 1H), 8.04−8.02 (m, 1H), 7.76 (s, 1H), 7.49−7.41 (m, 3H), 7.36−7.31 (m, 2H), 7.30−7.24 (m, 3H), 7.23−7.17 (m, 2H), 2.53 (s, 3H); 13C NMR (125 MHz, CDCl3): δ 197.4, 161.5, 151.8, 141.6, 139.2, 133.6, 132.5, 131.1, 130.2, 129.3 (3C), 128.6, 128.0, 126.9, 125.4, 123.2, 116.8, 27.0; LRMS (EI, 70 eV) m/z (%): 340 (M+, 100), 312 (20), 239 (27), 105 (81), 111 (31). 4.3.18. 7-Methyl-3,4-diphenyl-1H-isochromen-1-one (3ha).5m,9a 78.6 mg, 84% yield; white solid; mp 169.6−172.1 °C (lit.5m,9a 171− 173 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 8.20 (d, J = 0.5 Hz, 1H), 7.45−7.38 (m, 4H), 7.33−7.31 (m, 2H), 7.25−7.23 (m, 2H), 7.21−7.17 (m, 3H), 7.09 (d, J = 8.5 Hz, 1H), 2.46 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 150.1, 138.5, 136.4, 136.0, 134.5, 133.0, 131.2, 129.3, 129.2, 129.1, 128.8, 128.1, 127.9, 125.4, 120.3, 116.9, 21.3; LRMS (EI, 70 eV) m/z (%): 312 (M+, 100), 284 (28), 235 (40), 178 (25), 105 (80). D

DOI: 10.1021/acs.joc.9b00580 J. Org. Chem. XXXX, XXX, XXX−XXX

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The Journal of Organic Chemistry 4.3.19. 8-Methyl-3,4-diphenyl-1H-isochromen-1-one (3ia).5m 72.1 mg, 77% yield; white solid; mp 142.0−144.6 °C (lit.5m 143− 144 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 7.45 (t, J = 7.8 Hz, 1H), 7.42−7.38 (m, 3H), 7.31 (t, J = 7.5 Hz, 3H), 7.25−7.23 (m, 2H), 7.22−7.16 (m, 3H), 7.00 (d, J = 8.0 Hz, 1H), 2.91 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 161.6, 150.6, 143.5, 140.5, 135.0, 133.8, 133.0, 131.4, 131.1, 129.1, 129.1, 128.8, 128.0, 127.8, 123.7, 118.9, 117.0, 23.6; LRMS (EI, 70 eV) m/z (%): 312 (M+, 100), 284 (34), 235 (20), 178 (23), 105 (86). 4.3.20. 5,7-Dimethoxy-3,4-diphenyl-1H-isochromen-1-one (3ja).5m 79.5 mg, 74% yield; white solid; mp 157.8−160.3 °C (lit.5m 159−161 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 7.49 (d, J = 2.5 Hz, 1H), 7.24−7.21 (m, 5H), 7.18−7.11 (m, 5H), 6.68 (d, J = 2.6 Hz, 1H), 3.93 (s, 3H), 3.32 (s, 3H); 13C NMR (125 MHz, CDCl3): δ (ppm) 162.5, 160.3, 157.6, 149.0, 137.6, 133.6, 130.7, 129.5, 128.3, 127.6, 127.4, 126.7, 122.9, 122.1, 115.5, 106.9, 102.1, 55.9, 55.8; LRMS (EI, 70 eV) m/z (%): 358 (M+, 100), 315 (20), 253 (60), 105 (45). 4.3.21. 4,5-Diphenyl-7H-thieno[2,3-c]pyran-7-one (3ka).9a 42.0 mg, 46% yield; light yellow solid; mp 146.2−149.0 °C (lit.9a 146−148 °C); 1H NMR (500 MHz, CDCl3): δ (ppm) 7.78−7.77 (m, 1H), 7.40−7.38(m, 4H), 7.35 (d, J = 8.0 Hz, 2H), 7.28−7.27 (m, 2H), 7.22−7.19 (m, 2H), 6.96 (m, 1H); 13C NMR (125 MHz, CDCl3): δ (ppm) 158.2, 153.4, 149.5, 136.3, 134.9, 132.4, 130.3, 129.3, 129.2, 129.1, 128.2, 128.0, 125.2, 122.8, 115.9; LRMS (EI, 70 eV) m/z (%): 304 (M+, 100), 276 (21), 227 (41), 171 (25), 105 (50).

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(2) For reviews on the synthesis of isocoumarins via C-H functionalization, see: (a) Datsenko, V. P.; Nelyubina, Y. V.; Smol’yakov, A. F.; Loginov, D. A. Cyclooctadiene iridium complexes [Cp*Ir(COD)X]+ (X = Cl, Br, I): Synthesis and application for oxidative coupling of benzoic acid with alkynes. J. Organomet. Chem. 2018, 874, 7−12. (b) Saikiaa, P.; Gogoi, S. Isocoumarins: General Aspects and Recent Advances in their Synthesis. Adv. Synth. Catal. 2018, 360, 2063−2075. (3) For selective reviews on the annulation reaction involving C-H functionalization using Co catalysis, see: (a) Chirila, P. G.; Whiteoak, C. J. Recent advances using[Cp*Co(CO)I2] catalysts as a powerful tool for C−H functionalisation. Dalton Trans. 2017, 46, 9721−9739. (b) Ujwaldev, S. M.; Harry, N. A.; Divakar, M. A.; Anilkumar, G. Cobalt-catalyzed C−H activation: recent progress in heterocyclic chemistry. Catal. Sci. Technol. 2018, 8, 5983−6018. (c) Prakash, S.; Kuppusamy, R.; Cheng, C.-H. Cobalt-Catalyzed Annulation Reactions via C-H Bond Activation. ChemCatChem 2018, 10, 683−705. Using diverse transition-metal catalysis, see: (d) Song, G.; Wang, F.; Li, X. C−C, C−O and C−N bond formation via rhodium(III)-catalyzed oxidative C−H activation. Chem. Soc. Rev. 2012, 41, 3651−3678. (e) Ackermann, L. Carboxylate-Assisted Ruthenium-Catalyzed Alkyne Annulations by C−H/Het−H Bond Functionalizations. Acc. Chem. Res. 2013, 47, 281−295. (f) De Sarkar, S.; Liu, W.; Kozhushkov, S. I.; Ackermann, L. Weakly Coordinating Directing Groups for Ruthenium(II)-Catalyzed C−H Activation. Adv. Synth. Catal. 2014, 356, 1461−1479. (g) Gulías, M.; Mascareñas, J. L. Metal-Catalyzed Annulations through Activation and Cleavage of C−H Bonds. Angew. Chem. Int. Ed. 2016, 55, 11000−11019. (h) Wang, Z.; Xie, P.; Xia, Y. Recent progress in Ru(II)-catalyzed C−H activations with oxidizing directing groups. Chin. Chem. Lett. 2018, 29, 47−53. (i) da Silva Júnior, E. N.; Jardim, G. A.; Gomes, R. S.; Liang, Y.-F.; Ackermann, L. Weakly-coordinating N-oxide and carbonyl groups for metal-catalyzed C−H activation: the case of A-ring functionalization. Chem. Commun. 2018, 54, 7398−7411. (4) For papers on the Co catalysis, see: (a) Mandal, R.; Sundararaju, B. Cp*Co(III)-Catalyzed Annulation of Carboxylic Acids with Alkynes. Org. Lett. 2017, 19, 2544−2547. (b) Nguyen, T. T.; Grigorjeva, L.; Daugulis, O. Cobalt-Catalyzed Coupling of Benzoic Acid C−H Bonds with Alkynes, Styrenes, and 1,3-Dienes. Angew. Chem. Int. Ed. 2018, 57, 1688−1691. (5) For papers on other transition-metal catalysis, see: (a) Ueura, K.; Satoh, T.; Miura, M. An Efficient Waste-Free Oxidative Coupling via Regioselective C−H Bond Cleavage: Rh/Cu-Catalyzed Reaction of Benzoic Acids with Alkynes and Acrylates under Air. Org. Lett. 2007, 9, 1407−1409. (b) Ueura, K.; Satoh, T.; Miura, M. Rhodium- and Iridium-Catalyzed Oxidative Coupling of Benzoic Acids with Alkynes via Regioselective C−H Bond Cleavage. J. Org. Chem. 2007, 72, 5362−5367. (c) Shimizu, M.; Hirano, K.; Satoh, T.; Miura, M. WasteFree Synthesis of Condensed Heterocyclic Compounds by RhodiumCatalyzed Oxidative Coupling of Substituted Arene or Heteroarene Carboxylic Acids with Alkynes. J. Org. Chem. 2009, 74, 3478−3483. (d) Mochida, S.; Hirano, K.; Satoh, T.; Miura, M. Synthesis of Functionalized α-Pyrone and Butenolide Derivatives by RhodiumCatalyzed Oxidative Coupling of Substituted Acrylic Acids with Alkynes and Alkenes. J. Org. Chem. 2009, 74, 6295−6298. (e) Youn, S. W.; Yoo, H. J. One-Pot Sequential N-Heterocyclic Carbene/ Rhodium(III) Catalysis: Synthesis of Fused Polycyclic Isocoumarins. Adv. Synth. Catal. 2017, 359, 2176−2183. (f) Ackermann, L.; Pospech, J.; Graczyk, K.; Rauch, K. Versatile Synthesis of Isocoumarins and α-Pyrones by Ruthenium-Catalyzed Oxidative C− H/O−H Bond Cleavages. Org. Lett. 2012, 14, 930−933. (g) Yu, Y.; Huang, L.; Wu, W.; Jiang, H. Palladium-Catalyzed Oxidative Annulation of Acrylic Acid and Amide with Alkynes: A Practical Route to Synthesize α-Pyrones and Pyridones. Org. Lett. 2014, 16, 2146−2149. (h) Warratz, S.; Kornhass, C.; Cajaraville, A.; Niepoetter, B.; Stalke, D.; Ackermann, L. Ruthenium(II)-Catalyzed C-H Activation/Alkyne Annulation by Weak Coordination with O2 as the Sole Oxidant. Angew. Chem., Int. Ed. 2015, 54, 5513−5517. (i) Yu, J.-L.; Zhang, S.-Q.; Hong, X. Mechanisms and Origins of Chemo- and

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S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.9b00580. Spectra of products (PDF)

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Li-Ming Tao: 0000-0001-9258-0441 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS We thank the Key Scientific Research Project of Hunan Provincial Education Department of China (nos. 15A175 and 15A176) and the Science and Technology Plan Project of Chenzhou City (nos. CZ2014038 and CKJ2016020) for the financial support.

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REFERENCES

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The Journal of Organic Chemistry

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DOI: 10.1021/acs.joc.9b00580 J. Org. Chem. XXXX, XXX, XXX−XXX