1 Introduction
Carbene transfer reactions are among the most important reactions in organic synthesis, providing multiple efficient protocols to construct a wide variety of C—C and C—X bonds. This area has been mainly dominated by transition-metal catalysis in the past decades.[1] And the transition-metal catalyzed insertion reactions of carbene into O—H bonds have been developed as an important way to synthesize ethers.[2] Recently, visible-light-mediated carbene transfer reactions have attracted a lot of attention due to their mild conditions, simple operation and tolerance for moisture and oxygen.[3] Many classical carbene transfer reactions have been reexamined under the irradiation of visible-light. Among them, visible-light-mediated O—H functionalization reactions of alcohols with electron donating group (EDG)/electron withdrawing group (EWG) diazo compounds have gradually become a good complement to transition-metal catalyzed protocols.[4] In 2020, Koenigs and coworkers reported the visible-light-mediated O—H functionalization reactions of acidic fluorinated alcohols with two EDG/EWG diazo compounds, aryldiazoacetates[4b] and 3-diazooxindoles[4c] successively (Scheme 1a). However, similar reactions with other less acidic alcohols, especially those with reactive functional groups like alkenyl or alkynyl, have rarely been studied due to the inevitable side reactions involving cycloaddition.[5] Very recently, our group[6a] achieved the visible-light-mediated O—H functionalization reactions of acetylenic alcohols with 3-diazooxindoles. And the products could be easily transformed into spirooxindole-fused oxacycles via intramolecular cyclization reactions (Scheme 1b). Nevertheless, aryldiazoacetates were not well tolerated in the reaction.
With our continuous interest in developing practical methods to construct spirooxindoles and visible-light-mediated carbene transfer reactions.[6] Herein, we developed the visible-light-mediated O—H functionalization reactions of alkenyl alcohols with EDG/EWG diazo compounds. Both aryldiazoacetates and 3-diazooxindoles were compatible with this reaction. Similarly, the O—H functionalization product from alkenyl alcohol and 3-diazo- oxindole could be converted into spirooxindole-fused oxacycle through epoxidation and the following intramolecular cyclization reactions.
2 Results and discussion
The study was initiated by investigating the reaction of phenyldiazoacetate (1a) with 3-buten-1-ol (2a) in dichloroethane (DCE) under the irradiation of blue LEDs (470 nm) at room temperature in N2 atmosphere. When the reaction was conducted with a 1∶1 ratio of 1a and 2a, the O—H insertion product 3a could be isolated in very low yield (Table 1, Entry 1). It was found that the reaction yield increased with increasing equivalent of 2a,[6b] and the highest yield could be obtained when 10 equiv. of 2a was used (Table 1, Entry 5). Optimization of the concentration of 1a showed that 0.4 mol/L was the optimal concentration and the product could be afforded in 73% yield (Table 1, Entry 9). When alkenyl alcohol 2a was used as the solvent, the yield was reduced to 56% (Table 1, Entry 11). A control experiment in the dark showed that visible-light irradiation was essential to the reaction (Table 1, Entry 12).
Table 1 Optimization of reaction conditionsa |
| Entry | n(1a)∶n(2a) | c(1a)/(mol/L) | t/h | Yieldb/% |
|---|---|---|---|---|
| 1 | 1∶1 | 0.1 | 16 | 27 |
| 2 | 1∶3 | 0.1 | 14 | 31 |
| 3 | 1∶5 | 0.1 | 12 | 42 |
| 4 | 1∶7 | 0.1 | 14 | 54 |
| 5 | 1∶10 | 0.1 | 17 | 64 |
| 6 | 1∶20 | 0.1 | 14 | 60 |
| 7 | 1∶10 | 0.05 | 11 | 46 |
| 8 | 1∶10 | 0.2 | 14 | 68 |
| 9 | 1∶10 | 0.4 | 15 | 73 |
| 10 | 1∶10 | 0.8 | 16 | 64 |
| 11 | 2a as solvent | — | 11 | 56 |
| 12c | 1∶10 | 0.4 | 48 | NR |
a Unless otherwise noted, 1a (0.2 mmol) and 2a were dissolved in DCE, and the mixture was stirred at room temperature in N2 atmosphere under irradiation of blue LEDs (470 nm, 5 W). b Isolated yields. c The reaction was carried out in the dark. |
With the optimized conditions in hand, the substrate scope of this O—H functionalization reaction was investigated. As shown in Table 2, the scope of the aryldiazoacetate 1 was first examined. When the benzyl group of 1a was changed to other alkyl substituents, the corresponding products could be afforded smoothly, albeit in lower yields (3b~3e). The main side product was determined as the transesterification product 3b'. Then aryldiazoacetates with different substituents on the phenyl ring were investigated under the optimal reaction conditions. Reactions of aryldiazoacetates with halogen or methyl substituents smoothly proceeded while lower yields were obtained with nitro- or trifluoromethyl-substituted substrates (3f~3o). To our delight, upon replacement of the phenyl in the diazo compounds with 2-naphthyl or 3-pyridyl, the O—H functionalization products could be delivered in moderated yields (3p~3q).
Table 2 Scope of aryldiazoacetates |
 |
a Reaction conditions: 1 (0.2 mmol) and 2a (2 mmol) were dissolved in DCE (0.5 mL), and the mixture was stirred at room temperature in an N2 atmosphere under irradiation of blue LEDs (470 nm, 5 W). Yields refer to isolated products. |
Next, the scope of alkenyl alcohols was investigated under the optimal reaction conditions (Table 3). Reactions of 1a with 2-propen-1-ol and 4-penten-1-ol, the homo-logues of 3-buten-1-ol, gave the desired products in moderate yields (3r and 3s). Alkyl or chloro-substituted terminal alkenyl alcohols were also tolerated in this reaction, delivering the O—H functionalization products in low to moderate yields (3t~3x). As expected, the diastereoselectivities of the reaction products from the racemic secondary alcohols were very low (3w and 3x). When non-ter- minal alkenyl alcohols were used in the reaction, the desired products were obtained in low yields, which is probably because of the large steric hindrance (3y~3ab).
Table 3 Scope of alkenyl alcoholsa |
 |
a Reaction conditions: 1a (0.2 mmol) and 2 (2 mmol) were dissolved in DCE (0.5 mL), and the mixture was stirred at room temperature in an N2 atmosphere under irradiation of blue LEDs (470 nm, 5 W). Yields refer to isolated products. The dr value was determined by ¹H NMR spectroscopy of crude mixture. |
Then the visible-light-mediated O—H functionalization reaction of 3-diazooxindole with alkenyl alcohol was investigated. The optimal conditions of this reaction were easily obtained after making slight adjustments to the reaction conditions in Table 1. As shown in Table 4, the scope of 3-diazooxindole was first examined under these condi-tions. Reaction of N-methyl 3-diazooxindole 4a with 3-buten-1-ol delivered the O—H functionalization product in moderate yield (5a). When the N-methyl substituent in 3-diazooxindole was replaced with NH or NBn substituent, the desired products were afforded in lower yields (5b and 5c). Next, 3-diazooxindoles with different substituents on the phenyl ring were studied under the optimal reaction conditions. In general, substrates with electron-donating methyl substituents gave higher yields than those with electron-withdrawing fluoro or chloro substituents (5l~5n vs 5d~5k). The position of these halogen substituents also has a great impact on the reaction. Reactions with 6-fluoro- or 6-chloro-substituted 3-diazooxindole gave the products in higher yields than those with other halogen substituted substrates (5d~5k). It is worth noting that the drastic reduction in yields of the reactions of 3-diazooxindole was mainly due to the formation of cycloaddition products.
Table 4 Scope of the O—H functionalization reaction of 3-diazooxindole with alkenyl alcohola |
 |
a Reaction conditions: 4 (0.2 mmol) and 2 (2 mmol) were dissolved in DCE (2 mL), and the mixture was stirred at room temperature in an N2 atmosphere under irradiation of blue LEDs (470 nm, 5 W). Yields refer to isolated products. The dr value was determined by ¹H NMR spectroscopy of crude mixture. |
The scope of alkenyl alcohols was also examined with 3-diazooxindole 4a under the optimized reaction conditions (Table 4). When 2-propen-1-ol or 4-penten-1-ol was used in the reaction, the product could be obtained in moderate yield (5o and 5p). Dienol was also tolerated in this reaction (5q). Reactions with methyl or chloro-substituted terminal alkenyl alcohols gave the O—H functionalization products in moderate yields (5r and 5s). Non-terminal alkenyl alcohols were also investigated under the optimal reaction conditions. The corresponding O—H functionalization products could be afforded in low to moderate yields (5t~5w).
To demonstrate the utility of this photochemical O—H functionalization reaction, cholesterol was used in the reaction with aryldiazoacetate 1a under the standard conditions, and the desired product 3ac was successfully obtained, albeit in very low yield probably due to the big steric hindrance (Scheme 2a).
Further transformations of the O—H functionalization products were also studied. Treating 5a with m-chloro- perbenzoic acid (m-CPBA)/KF gave the epoxidation product 6a in moderate yield,[7] and the following cyclization reaction of 6a with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) delivered the spirooxindole-fused oxacycle 7a smoothly (Scheme 2b).[6c] Spirooxindole-fused oxacycles are important structural motifs that have been proved to have multiple biological activities.[8] Under the same conditions, epoxidation product 8a could be successfully isolated in moderate yield from the O—H functionalization product of aryldiazoacetate 1a (Scheme 2c). However, the intramolecular cyclization reaction of 8a with DBU was failed.
Next, the mechanistic investigation of this visible-light- mediated O—H functionalization reaction was focused on. The radical trapping experiments were conducted under the standard conditions. When 1 equiv. of 2,2,6,6-tetramethyl- piperidoxyl (TEMPO) or butylated hydroxytoluene (BHT) was added into the reaction mixture of 1a and 2a, the desired products could be obtained smoothly, albeit with prolonged time (Scheme 3). This result suggested that singlet carbene was probably involved in the reaction.
Finally, based on the experimental results and literature reports,[3-4] a plausible mechanism for this photochemical O—H functionalization reaction is postulated in Scheme 4. Upon irradiation with blue LEDs, aryldiazoacetate 1a is transformed to its excited state 1a*. The following expulsion of dinitrogen give a singlet carbene 1A, which could be transformed to 3A through the intersystem crossing (ISC). Then, the O—H functionalization reaction between the electrophilic singlet carbene 1A and alkenyl alcohol gave the product 3a.
3 Conclusions
In conclusion, we have developed the visible-light- mediated O—H functionalization reaction of alkenyl alcohols with aryldiazoacetates and 3-diazooxindoles. A range of multifunctional ethers were produced in low to high yields. This methodology was successfully applied to the O—H functionalization reaction of cholesterol. Due to the mild and simple conditions, this photochemical reaction may have wide applications on the late-functionalization of complex molecules. Furthermore, the O—H functionalization product could be transformed into spirooxindole-fused oxacycle through epoxidation and the following intramolecular cyclization reactions.
4 Experimental section
4.1 General information
All glassware was thoroughly oven-dried. Chemicals and solvents were either purchased from commercial suppliers or purified by standard techniques. Thin-layer chromatography plates were visualized by exposure to ultraviolet light and/or staining with phosphomolybdic acid followed by heating on a hot plate. Flash chromatography was carried out using silica gel (160~200 mesh). 1H NMR and 13C NMR spectra were recorded using Bruker AV- 300/AV-400/AV-500 spectrometers with CDCl3 or (CD3)2SO (DMSO-d6) as the solvent at room temperature, TMS served as internal standard (δ 0) for 1H NMR and CDCl3 was used as an internal standard (δ 77.00) for 13C NMR. High resolution mass spectra (HRMS) were acquired on a Thermo Orbitrap Elite instrument (Agilent, Palo Alto, CA, USA). All reactions involving heating were carried out in an oil bath. Irradiation was carried out with a 6W LED (spectral distribution of 465~475 nm with a maximum intensity at 470 nm). Photochemical reactions were performed in Schlenk tube or flask. The distance from the diode to the irradiation vessel was about 25 mm. Cooling was realized with a fan.
Diazo compounds should only be handled in a well- ventilated fume cupboard using an additional blast shield. During the preparation of this manuscript, no incidents occurred, yet the reader should be aware of hazards of the herein used diazo compounds. General safety precautions should be followed, and strict risk assessment and proper safety precautions are recommended.
4.2 General procedure of visible-light-mediated O—H functionalization reactions of alkenyl alcohols with aryldiazoacetates and analytical data of the products
In a reaction vial (10 mL), aryldiazoacetate 1 (0.2 mmol) and alkenyl alcohol 2 (2 mmol) were dissolved in DCE (0.5 mL). The vial was capped under nitrogen and closed tightly. The mixture was stirred at room temperature under irradiation with blue LEDs (470 nm, 5 W) for a given time. Then the reaction mixture was concentrated and directly purified by flash column chromatography (eluted with EtOAc/petroleum ether, V∶V=1∶10) to give product 3.
Benzyl 2-(but-3-en-1-yloxy)-2-phenylacetate (3a): Colorless oil, 73% yield (43 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.44~7.41 (m, 2H), 7.34~7.29 (m, 3H), 7.29~7.25 (m, 3H), 7.21~7.18 (m, 2H), 5.84~5.74 (m, 1H), 5.16~5.08 (m, 2H), 5.08~5.03 (m, 1H), 5.02~4.98 (m, 1H), 4.90 (s, 1H), 3.60~3.54 (m, 1H), 3.50~3.44 (m, 1H), 2.42~2.36 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 170.8, 136.5, 135.6, 134.8, 128.7, 128.7, 128.6, 128.3, 128.0, 127.3, 116.8, 81.1, 69.3, 66.8, 34.1; HRMS (ESI) calcd for C19H21O3 [M＋H]＋ 297.1485, found 297.1478.
Methyl 2-(but-3-en-1-yloxy)-2-phenylacetate (3b): Colorless oil, 54% yield (24 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.46~7.43 (m, 2H), 7.39~7.30 (m, 3H), 5.88~5.77 (m, 1H), 5.12~5.07 (m, 1H), 5.05~5.02 (m, 1H), 4.89 (s, 1H), 3.71 (s, 3H), 3.62~3.57 (m, 1H), 3.52~3.46 (m, 1H), 2.45~2.40 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 171.4, 136.6, 134.7, 128.7, 128.7, 127.2, 116.7, 81.1, 69.3, 52.3, 34.1; HRMS (ESI) calcd for C13H17O3 [M＋H]＋ 221.1172, found 221.1168.
But-3-en-1-yl 2-(but-3-en-1-yloxy)-2-phenylacetate (3b'): Colorless oil, 20% yield (10.2 mg), Rf=0.7. 1H NMR (400 MHz, CDCl3) δ: 7.46~7.44 (m, 2H), 7.37~7.32 (m, 3H), 5.87~5.80 (m, 1H), 5.70~5.63 (m, 1H), 5.12~4.97 (m, 4H), 4.87 (s, 1H), 4.17 (t, J=6.6 Hz, 2H), 3.63~3.58 (m, 1H), 3.52~3.46 (m, 1H), 2.45~2.39 (m, 2H), 2.36~2.30 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 171.0, 136.7, 134.8, 133.7, 128.7, 128.6, 127.3, 117.5, 116.8, 81.1, 69.3, 64.2, 34.2, 33.1; HRMS (ESI) calcd for C16H21O3 [M＋H]＋ 261.1485, found 261.1483.
Ethyl 2-(but-3-en-1-yloxy)-2-phenylacetate (3c): Colorless oil, 66% yield (31 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.47~7.44 (m, 2H), 7.38~7.32 (m, 3H), 5.87~5.78 (m, 1H), 5.13~5.07 (m, 1H), 5.05~5.02 (m, 1H), 4.87 (s, 1H), 4.22~4.12 (m, 2H), 3.63~3.57 (m, 1H), 3.52~3.47 (m, 1H), 2.45~2.40 (m, 2H), 1.21 (t, J=7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 171.1, 136.7, 134.9, 128.7, 127.2, 116.8, 81.2, 69.3, 61.3, 34.2, 14.2; HRMS (ESI) calcd for C14H19O3 [M＋H]＋ 235.1329, found 235.1325.
tert-Butyl 2-(but-3-en-1-yloxy)-2-phenylacetate (3d): Colorless oil, 46% yield (24 mg), Rf=0.4. 1H NMR (400 MHz, CDCl3) δ: 7.45~7.42 (m, 2H), 7.37~7.30 (m, 3H), 5.88~5.81 (m, 1H), 5.13~5.07 (m, 1H), 5.05~5.01 (m, 1H), 4.75 (s, 1H), 3.63~3.58 (m, 1H), 3.51~3.45 (m, 1H), 2.45~2.39 (m, 2H), 1.39 (s, 9H); 13C NMR (100 MHz, CDCl3) δ: 170.2, 137.2, 135.0, 128.5, 128.4, 127.2, 116.6, 81.8, 81.5, 69.1, 34.2, 28.0; HRMS (ESI) calcd for C16H23O3 [M＋H]＋ 263.1642, found 263.1638.
Isobutyl 2-(but-3-en-1-yloxy)-2-phenylacetate (3e): Colorless oil, 51% yield (27 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.47~7.45 (m, 2H), 7.38~7.31 (m, 3H), 5.87~5.80 (m, 1H), 5.12~5.07 (m, 1H), 5.05~5.02 (m, 1H), 4.88 (s, 1H), 3.94~3.85 (m, 2H), 3.64~3.58 (m, 1H), 3.53~3.47 (m, 1H), 2.46~2.40 (m, 2H), 1.91~1.84 (m, 1H), 0.82 (dd, J=6.7, 1.2 Hz, 6H); 13C NMR (100 MHz, CDCl3) δ: 171.1, 136.9, 134.9, 128.7, 128.6, 127.3, 116.8, 81.2, 71.2, 69.3, 34.2, 27.8, 19.0; HRMS (ESI) calcd for C16H23O3 [M＋H]＋ 263.1642, found 263.1641.
Benzyl 2-(but-3-en-1-yloxy)-2-(2-fluorophenyl)acetate (3f): Colorless oil, 64% yield (40 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.44~7.39 (m, 2H), 7.34~7.29 (m, 3H), 7.26~7.20 (m, 4H), 5.80~5.73 (m, 1H), 5.31 (s, 1H), 5.16 (s, 2H), 5.09~5.04 (m, 1H), 5.00~4.97 (m, 1H), 3.66~3.60 (m, 1H), 3.52~3.47 (m, 1H), 2.31~2.26 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 169.6, 161.0, 158.5, 135.7, 135.0, 130.8, 130.7, 129.2, 129.1, 128.4, 128.1, 127.6, 124.7, 124.6, 124.1, 124.0, 116.6, 115.6, 115.4, 74.0, 74.0, 68.8, 66.1, 33.5; HRMS (ESI) calcd for C19H20FO3 [M＋H]＋ 315.1391, found 315.1390.
Benzyl 2-(but-3-en-1-yloxy)-2-(3-fluorophenyl)acetate (3g): Colorless oil, 72% yield (45 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.45~7.42 (m, 1H), 7.34~7.30 (m, 3H), 7.26~7.22 (m, 3H), 7.21~7.17 (m, 2H), 5.83~5.76 (m, 1H), 5.17 (s, 1H), 5.15 (s, 2H), 5.11~5.06 (m, 1H), 5.03~4.99 (m, 1H), 3.59~3.55 (m, 1H), 3.50~3.46 (m, 1H), 2.34~2.29 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 170.0, 160.9, 139.5, 139.4, 135.7, 135.2, 130.7, 130.6, 128.5, 128.2, 127.8, 123.2, 123.2, 116.7, 115.5, 115.3, 114.0, 113.8, 79.1, 68.6, 66.2, 33.5; HRMS (ESI) calcd for C19H20FO3 [M＋H]＋ 315.1391, found 315.1398.
Benzyl 2-(but-3-en-1-yloxy)-2-(4-fluorophenyl)acetate (3h): Colorless oil, 67% yield (42 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.45~7.42 (m, 2H), 7.33~7.30 (m, 3H), 7.25~7.18 (m, 4H), 5.81~5.74 (m, 1H), 5.14~5.13 (m, 3H), 5.10~5.05 (m, 1H), 5.02~4.98 (m, 1H), 3.57~3.53 (m, 1H), 3.47~3.43 (m, 1H), 2.32~2.27 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 170.2, 163.3, 160.8, 135.7, 135.1, 133.0, 133.0, 129.3, 129.2, 128.4, 128.1, 127.7, 116.6, 115.5, 115.2, 79.1, 68.3, 66.0, 33.5; HRMS (ESI) calcd for C19H20FO3 [M＋H]＋ 315.1391, found 315.1394.
Benzyl 2-(but-3-en-1-yloxy)-2-(2-chlorophenyl)acetate (3i): Colorless oil, 65% yield (43 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.50~7.48 (m, 1H), 7.45~7.43 (m, 1H), 7.40~7.36 (m, 2H), 7.35~7.29 (m, 3H), 7.26~7.23 (m, 2H), 5.81~5.74 (m, 1H), 5.37 (s, 1H), 5.17 (s, 2H), 5.09~5.05 (m, 1H), 5.01~4.98 (m, 1H), 3.66~3.62 (m, 1H), 3.53~3.49 (m, 1H), 2.32~2.27 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 169.5, 135.7, 135.1, 134.5, 132.7, 130.4, 129.6, 129.1, 128.4, 128.1, 127.7, 127.6, 116.7, 77.1, 69.1, 66.2, 33.6; HRMS (ESI) calcd for C19H19ClNaO3 [M＋Na]＋ 353.0915, found 353.0914.
Benzyl 2-(but-3-en-1-yloxy)-2-(3-chlorophenyl)acetate (3j): Colorless oil, 71% yield (47 mg), Rf=0.5. 1H NMR (300 MHz, DMSO-d6) δ: 7.42~7.41 (m, 3H), 7.37~7.31 (m, 4H), 7.25~7.22 (m, 2H), 5.85~5.72 (m, 1H), 5.15 (s, 3H), 5.08 (dd, J1=23.2 Hz, J2=2.6 Hz, 1H), 5.00 (d, J=10.4 Hz, 1H), 3.62~3.55 (m, 1H), 3.51~3.43 (m, 1H), 2.31 (q, J1=13.4 Hz, J2=6.7 Hz, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 169.9, 139.1, 135.6, 135.1, 133.1, 130.5, 128.5, 128.4, 128.1, 127.8, 126.9, 125.7, 116.6, 79.0, 68.5, 66.2, 33.5; HRMS (ESI) calcd for C19H19ClNaO3 [M＋Na]＋ 353.0915, found 353.0912.
Benzyl 2-(but-3-en-1-yloxy)-2-(4-chlorophenyl)acetate (3k), Colorless oil, 67% yield (44 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.46~7.40 (m, 4H), 7.33~7.30 (m, 3H), 7.25~7.23 (m, 2H), 5.81~5.73 (m, 1H), 5.14~5.13 (m, 3H), 5.10~5.05 (m, 1H), 5.01~4.98 (m, 1H), 3.59~3.54 (m, 1H), 3.48~3.42 (m, 1H), 2.32~2.27 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 170.1, 135.8, 135.7, 135.2, 133.2, 129.0, 128.6, 128.5, 128.2, 127.8, 116.7, 79.1, 68.5, 66.2, 33.6; HRMS (ESI) calcd for C19H19ClNaO3 [M＋Na]＋ 353.0915, found 353.0918.
Benzyl 2-(but-3-en-1-yloxy)-2-(3-nitrophenyl)acetate (3l): yellow oil, 58% yield (40 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 8.24~8.20 (m, 2H), 7.86~7.84 (m, 1H), 7.69 (t, J=7.8 Hz, 1H), 7.33~7.29 (m, 3H), 7.26~7.23 (m, 2H), 5.83~5.76 (m, 1H), 5.38 (s, 1H), 5.16 (s, 2H), 5.11~5.06 (m, 1H), 5.03~4.99 (m, 1H), 3.65~3.62 (m, 1H), 3.54~3.50 (m, 1H), 2.35~2.30 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 169.7, 147.8, 138.9, 135.6, 135.1, 133.6, 130.3, 128.4, 128.2, 127.9, 123.5, 121.7, 116.8, 78.6, 68.8, 66.5, 33.5; HRMS (ESI) calcd for C19H19NNaO5 [M＋Na]＋ 364.1155, found 364.1151.
Benzyl 2-(but-3-en-1-yloxy)-2-(3-(trifluoromethyl)- phenyl)acetate (3m): yellow oil, 48% yield (35 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.73 (s, 1H), 7.64 (d, J=7.8 Hz, 1H), 7.59 (d, J=7.7 Hz, 1H), 7.47 (t, J=7.8 Hz, 1H), 7.33~7.29 (m, 3H), 7.23~7.21 (m, 2H), 5.85~5.77 (m, 1H), 5.16 (s, 2H), 5.13~5.07 (m, 1H), 5.06~5.03 (m, 1H), 4.97 (s, 1H), 3.69~3.63 (m, 1H), 3.53~3.48 (m, 1H), 2.46~2.40 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 170.2, 137.6, 135.3, 134.6, 130.5, 129.2, 128.7, 128.6, 128.2, 125.6, 125.5, 124.1, 117.0, 80.5, 69.7, 67.2, 34.1; HRMS (ESI) calcd for C20H19F3NaO3 [M＋Na]＋ 387.1178, found 387.1176.
Benzyl 2-(but-3-en-1-yloxy)-2-(m-tolyl)acetate (3n): Colorless oil, 66% yield (41 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.34~7.29 (m, 3H), 7.25~7.22 (m, 3H), 7.19~7.14 (m, 3H), 5.83~5.73 (m, 2H), 5.14 (s, 2H), 5.10~5.05 (m, 1H), 5.04 (s, 1H), 5.02~4.98 (m, 1H), 3.58~3.52 (m, 1H), 3.47~3.41 (m, 1H), 2.33~2.28 (m, 2H), 2.28 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.4, 137.7, 136.7, 135.8, 135.2, 129.2, 128.4, 128.1, 127.8, 127.7, 124.4, 116.6, 80.0, 68.4, 65.9, 33.6, 21.0; HRMS (ESI) calcd for C20H22NaO3 [M＋Na]＋ 333.1461, found 333.1463.
Benzyl 2-(but-3-en-1-yloxy)-2-(p-tolyl)acetate (3o): Colorless oil, 73% yield (45 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.34~7.28 (m, 5H), 7.25~7.23 (m, 2H), 7.18~7.16 (m, 2H), 5.83~5.73 (m, 1H), 5.16~5.05 (m, 3H), 5.04 (s, 1H), 5.01~4.98 (m, 1H), 3.57~3.51 (m, 1H), 3.46~3.40 (m, 1H), 2.32~2.27 (m, 5H); 13C NMR (100 MHz, DMSO-d6) δ: 170.5, 137.9, 135.8, 135.2, 133.8, 129.1, 128.4, 128.1, 127.8, 127.2, 116.6, 79.8, 68.2, 65.9, 33.6, 20.8; HRMS (ESI) calcd for C20H22NaO3 [M＋Na]＋ 333.1461, found 333.1460.
Benzyl 2-(but-3-en-1-yloxy)-2-(naphthalen-2-yl)acetate (3p): Colorless oil, 50% yield (35 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.91 (s, 1H), 7.84~7.81 (m, 3H), 7.58~7.55 (m, 1H), 7.51~7.46 (m, 2H), 7.29~7.20 (m, 5H), 5.88~5.78 (m, 1H), 5.21~5.01 (m, 5H), 3.67~3.61 (m, 1H), 3.57~3.51 (m, 1H), 2.47~2.42 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 170.8, 135.6, 134.8, 133.9, 133.5, 133.2, 128.6, 128.6, 128.4, 128.3, 128.2, 127.8, 126.8, 126.5, 126.4, 124.8, 116.8, 81.3, 69.4, 66.9, 34.2; HRMS (ESI) calcd for C23H22NaO3 [M＋Na]＋ 369.1461, found 369.1458.
Benzyl 2-(but-3-en-1-yloxy)-2-(pyridin-3-yl)acetate (3q): yellow oil, 46% yield (27 mg), Rf=0.4. 1H NMR (400 MHz, CDCl3) δ: 8.68~8.57 (m, 2H), 7.78 (d, J=7.9 Hz, 1H), 7.35~7.28 (m, 4H), 7.27~7.23 (m, 2H), 5.86~5.76 (m, 1H), 5.20~5.02 (m, 4H), 4.95 (s, 1H), 3.69~3.64 (m, 1H), 3.53~3.48 (m, 1H), 2.41 (q, J=6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 170.2, 150.1, 148.9, 135.2, 134.7, 134.6, 132.4, 128.7, 128.6, 128.3, 123.7, 117.0, 79.0, 69.8, 67.3, 34.1; HRMS (ESI) calcd for C18H20NO3 [M＋H]＋ 298.1438, found 298.1435.
Benzyl 2-(allyloxy)-2-phenylacetate (3r): Colorless oil, 50% yield (28 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.44~7.35 (m, 5H), 7.33~7.29 (m, 3H), 7.25~7.22 (m, 2H), 5.96~5.86 (m, 1H), 5.29~5.24 (m, 1H), 5.18~5.09 (m, 4H), 4.11~4.05 (m, 1H), 4.02~3.96 (m, 1H); 13C NMR (100 MHz, DMSO-d6) δ: 170.3, 136.6, 135.8, 134.4, 128.6, 128.6, 128.4, 128.1, 127.7, 127.2, 117.3, 79.4, 69.9, 66.0; HRMS (ESI) calcd for C18H18NaO3 [M＋Na]＋ 305.1148, found 305.1149.
Benzyl 2-(pent-4-en-1-yloxy)-2-phenylacetate (3s): Colorless oil, 56% yield (35 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.42~7.35 (m, 5H), 7.33~7.29 (m, 3H), 7.24~7.21 (m, 2H), 5.82~5.75 (m, 1H), 5.13~5.13 (m, 2H), 5.06 (s, 1H), 5.00~4.95 (m, 1H), 4.94~4.91 (m, 1H), 3.53~3.48 (m, 1H), 3.43~3.39 (m, 1H), 2.09~2.03 (m, 2H), 1.65~1.58 (m, 2H); 13C NMR (100 MHz, DMSO-d6) δ: 170.4, 138.1, 136.8, 135.7, 128.5, 128.5, 128.4, 128.0, 127.7, 127.1, 115.0, 80.0, 68.5, 65.9, 29.7, 28.3; HRMS (ESI) calcd for C20H23O3 [M＋H]＋ 311.1642, found 311.1639.
Benzyl 2-((2-methylallyl)oxy)-2-phenylacetate (3t): Colorless oil, 49% yield (29 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.42~7.34 (m, 5H), 7.33~7.29 (m, 3H), 7.25~7.22 (m, 2H), 5.18~5.11 (m, 2H), 5.06 (s, 1H), 4.94 (s, 1H), 4.88 (s, 1H), 3.92 (q, J=12.5 Hz, 2H), 1.67 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.3, 141.5, 136.6, 135.8, 128.6, 128.6, 128.4, 128.1, 127.8, 127.2, 112.5, 79.2, 72.7, 66.0, 19.3; HRMS (ESI) calcd for C19H21O3 [M＋H]＋ 297.1485, found 297.1487.
Benzyl 2-((2-chloroallyl)oxy)-2-phenylacetate (3u): Colorless oil, 48% yield (30 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.43~7.41 (m, 2H), 7.35~7.31 (m, 3H), 7.29~7.25 (m, 3H), 7.21~7.17 (m, 2H), 5.44 (q, J=1.4 Hz, 1H), 5.35 (s, 1H), 5.18~5.08 (m, 2H), 5.00 (s, 1H), 4.14~4.04 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 170.2, 137.2, 135.7, 135.4, 129.1, 128.8, 128.6, 128.4, 128.1, 127.5, 114.5, 79.9, 71.6, 67.0; HRMS (ESI) calcd for C18H18ClO3 [M＋H]＋ 317.0939, found 317.0935.
Benzyl 2-((3-methylbut-3-en-1-yl)oxy)-2-phenylacetate (3v): Colorless oil, 39% yield (24 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.40~7.35 (m, 5H), 7.33~7.29 (m, 3H), 7.24~7.22 (m, 2H), 5.14 (s, 2H), 5.10 (s, 1H), 4.73~4.70 (m, 2H), 3.66~3.60 (m, 1H), 3.54~3.48 (m, 1H), 2.26 (t, J=6.7 Hz, 2H), 1.67 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.4, 142.4, 136.7, 135.7, 128.5, 128.5, 128.4, 128.0, 127.7, 127.1, 111.6, 79.9, 67.5, 65.9, 37.1, 22.4; HRMS (ESI) calcd for C20H22NaO3 [M＋Na]＋ 333.1461, found 333.1463.
Benzyl 2-(but-3-en-2-yloxy)-2-phenylacetate (3w, one isomer): Colorless oil, 18% yield (11 mg), Rf=0.5. 1H NMR (400 MHz, DMSO-d6) δ: 7.39~7.30 (m, 8H), 7.25~7.23 (m, 2H), 5.77~5.68 (m, 1H), 5.18~5.11 (m, 4H), 5.03 (s, 1H), 4.02~3.98 (m, 1H), 1.23 (d, J=6.3 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.8, 139.3, 136.8, 135.8, 128.5, 128.4, 128.1, 127.8, 127.2, 117.0, 77.4, 75.7, 66.1, 21.1; HRMS (ESI) calcd for C19H20NaO3 [M＋Na]＋ 319.1304, found 319.1305.
Benzyl 2-(but-3-en-2-yloxy)-2-phenylacetate (3w', another isomer): Colorless oil, 23% yield (14 mg), Rf=0.4. 1H NMR (400 MHz, DMSO-d6) δ: 7.42~7.34 (m, 5H), 7.33~7.29 (m, 3H), 7.22~7.20 (m, 2H), 5.79~5.70 (m, 1H), 5.21~5.16 (m, 1H), 5.13~5.04 (m, 3H), 5.04 (s, 1H), 3.91~3.87 (m, 1H), 1.18 (d, J=6.4 Hz, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.5, 139.5, 137.0, 135.8, 128.6, 128.6, 128.4, 128.1, 127.8, 127.2, 116.8, 77.7, 75.6, 65.9, 20.9; HRMS (ESI) calcd for C19H20NaO3 [M＋Na]＋ 319.1304, found 319.1306.
Benzyl 2-(pent-1-en-3-yloxy)-2-phenylacetate (3x, one isomer): Colorless oil, 20% yield (12 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.42~7.40 (m, 2H), 7.32~7.24 (m, 6H), 7.22~7.18 (m, 2H), 5.65~5.56 (m, 1H), 5.19~5.16 (m, 1H), 5.12~5.07 (m, 3H), 5.01 (s, 1H), 3.74~3.68 (m, 1H), 1.76~1.68 (m, 1H), 1.57~1.50 (m, 1H), 0.91 (t, J=7.5 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.6, 138.0, 137.0, 135.8, 128.6, 128.6, 128.4, 128.1, 127.3, 118.6, 82.3, 77.8, 66.7, 28.5, 9.8; HRMS (ESI) calcd for C20H22NaO3 [M＋Na]＋ 333.1461, found 333.1455.
Benzyl 2-(pent-1-en-3-yloxy)-2-phenylacetate (3x', another isomer): Colorless oil, 23% yield (14 mg), Rf=0.4. 1H NMR (400 MHz, DMSO-d6) δ: 7.40~7.30 (m, 8H), 7.26~7.23 (m, 2H), 5.70~5.61 (m, 1H), 5.24~5.13 (m, 4H), 5.01 (s, 1H), 3.80~3.75 (m, 1H), 1.67~1.57 (m, 1H), 1.55~1.45 (m, 1H), 0.89~0.85 (m, 3H); 13C NMR (100 MHz, DMSO-d6) δ: 170.7, 137.8, 136.9, 135.8, 128.5, 128.4, 128.1, 127.8, 127.1, 118.3, 81.2, 77.2, 66.0, 27.8, 9.5; HRMS (ESI) calcd for C20H22NaO3 [M＋Na]＋ 333.1461, found 333.1458.
Benzyl (E)-2-(but-2-en-1-yloxy)-2-phenylacetate (3y): Colorless oil, 30% yield (18 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.43~7.41 (m, 2H), 7.34~7.25 (m, 6H), 7.22~7.18 (m, 2H), 5.69~5.62 (m, 1H), 5.60~5.53 (m, 1H), 5.17~5.06 (m, 2H), 4.95 (s, 1H), 3.96 (d, J=6.3 Hz, 2H), 1.68~1.65 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 170.9, 136.5, 135.6, 131.0, 128.7, 128.7, 128.6, 128.3, 128.1, 128.1, 127.5, 127.5, 126.7, 79.5, 70.3, 66.8, 17.9; HRMS (ESI) calcd for C19H21O3 [M＋H]＋ 297.1485, found 297.1477.
Benzyl 2-((3-methylbut-2-en-1-yl)oxy)-2-phenylacetate (3z): Colorless oil, 40% yield (25 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.47~7.44 (m, 2H), 7.37~7.28 (m, 6H), 7.24~7.21 (m, 2H), 5.39~5.36 (m, 1H), 5.21~5.09 (m, 2H), 4.96 (s, 1H), 4.09~4.01 (m, 2H), 1.73 (s, 3H), 1.58 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 171.1, 138.5, 136.7, 135.7, 128.7, 128.7, 128.6, 128.3, 128.2, 127.5, 120.3, 79.7, 66.8, 66.0, 26.0, 18.2; HRMS (ESI) calcd for C20H22NaO3 [M＋Na]＋ 333.1461, found 333.1457.
Benzyl 2-(cyclopent-3-en-1-yloxy)-2-phenylacetate (3aa): Colorless oil, 36% yield (22 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.43~7.41 (m, 2H), 7.32~7.25 (m, 6H), 7.21~7.18 (m, 2H), 5.64~5.59 (m, 2H), 5.15~5.07 (m, 2H), 4.98 (s, 1H), 4.29~4.24 (m, 1H), 2.60~2.38 (m, 4H); 13C NMR (100 MHz, CDCl3) δ: 171.2, 136.8, 135.7, 128.7, 128.6, 128.4, 128.3, 128.3, 128.1, 127.4, 79.4, 78.6, 66.8, 39.3, 39.3; HRMS (ESI) calcd for C20H20NaO3 [M＋Na]＋ 331.1304, found 331.1304.
Benzyl 2-(cyclopent-3-en-1-ylmethoxy)-2-phenylacetate (3ab): Colorless oil, 38% yield (25 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.47~7.45 (m, 2H), 7.38~7.29 (m, 6H), 7.24~7.21 (m, 2H), 5.63 (s, 2H), 5.19~5.11 (m, 2H), 4.92 (s, 1H), 3.48~3.44 (m, 1H), 3.39~3.35 (m, 1H), 2.70~2.61 (m, 1H), 2.52~2.45 (m, 2H), 2.20~2.06 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 171.0, 136.8, 135.7, 129.7, 129.5, 128.7, 128.7, 128.6, 128.3, 128.1, 127.3, 81.3, 74.3, 66.8, 36.8, 36.1, 36.0; HRMS (ESI) calcd for C21H22NaO3 [M＋Na]＋ 345.1461, found 345.1462.
Benzyl-2-(((3S,8S,9S,10R,13R,14S,17R)-10,13-dimethyl- 17-((R)-6-methylheptan-2-yl)-2,3,4,7,8,9,10,11,12,13,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-3-yl)oxy)-2-phenylacetate (3ac): Colorless oil, 22% yield (27 mg), Rf=0.5. m.p. 99~102 ℃; 1H NMR (400 MHz, CDCl3) δ: 7.49~7.47 (m, 4H), 7.37~7.30 (m, 12H), 7.24~7.22 (m, 4H), 5.33~5.29 (m, 2H), 5.19~5.14 (m, 4H), 5.11 (s, 2H), 3.30~3.27 (m, 2H), 2.42~2.33 (m, 4H), 2.03~1.95 (m, 5H), 1.89~1.81 (m, 5H), 1.64~1.25 (m, 30H), 1.18~1.06 (m, 13H), 1.00 (s, 14H), 0.97~0.92 (m, 8H), 0.89~0.87 (m, 13H), 0.68 (s, 6H); 13C NMR (100 MHz, CDCl3) δ: 171.5, 171.4, 140.7, 140.7, 137.2, 137.2, 135.7, 128.7, 128.6, 128.6, 128.3, 128.1, 128.1, 127.3, 122.0, 78.6, 78.6, 78.5, 78.4, 66.8, 66.8, 56.9, 56.2, 50.2, 42.4, 39.9, 39.6, 39.1, 37.3, 36.9, 36.3, 35.9, 32.1, 32.0, 32.0, 28.4, 28.4, 28.1, 24.4, 23.9, 23.0, 22.7, 21.2, 19.5, 18.8, 12.0; HRMS (ESI) calcd for C42H58NaO3 [M＋Na]＋ 633.4278, found 633.4274.
4.3 General procedure of visible-light-mediated O—H functionalization reactions of alkenyl alcohols with 3-diazooxindoles and analytical data of the products
In a reaction vial (10 mL), 3-diazooxindole 4 (0.2 mmol) and alkenyl alcohol 2 (2 mmol) were dissolved in DCE (2 mL). The vial was capped under nitrogen and closed tightly. The mixture was stirred at room temperature under irradiation with blue LEDs (470 nm, 5 W) for a given time. Then the reaction mixture was concentrated and directly purified by flash column chromatography (eluted with EtOAc/petroleum ether, V∶V=1∶3) to give product 5.
3-(But-3-en-1-yloxy)-1-methylindolin-2-one (5a): Yellow oil, 60% yield (26 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J=7.3 Hz, 1H), 7.33 (t, J=7.7 Hz, 1H), 7.08 (t, J=7.5 Hz, 1H), 6.80 (d, J=7.8 Hz, 1H), 5.88~5.78 (m, 1H), 5.14-5.09 (m, 1H), 5.07-5.03 (m, 1H), 4.91 (s, 1H), 3.86~3.81 (m, 1H), 3.68~3.62 (m, 1H), 3.17 (s, 3H), 2.44~2.38 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.7, 144.3, 134.9, 130.0, 125.4, 125.2, 123.0, 116.8, 108.5, 76.0, 68.1, 34.4, 26.2; HRMS (ESI) calcd for C13H16NO2 [M＋H]＋ 218.1176, found 218.1173.
3-(But-3-en-1-yloxy)indolin-2-one (5b): Yellow oil, 50% yield (20 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 8.73 (s, 1H), 7.37 (d, J=7.4 Hz, 1H), 7.29~7.25 (m, 1H), 7.08~7.04 (m, 1H), 6.88 (d, J=7.8 Hz, 1H), 5.89~5.79 (m, 1H), 5.15~5.10 (m, 1H), 5.07~5.04 (m, 1H), 4.97 (s, 1H), 3.83~3.78 (m, 1H), 3.70~3.64 (m, 1H), 2.45~2.40 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 177.2, 141.4, 134.9, 130.1, 125.8, 125.6, 123.1, 116.9, 110.5, 76.4, 68.0, 34.4; HRMS (ESI) calcd for C12H14NO2 [M＋H]＋ 204.1019, found 204.1015.
1-Benzyl-3-(but-3-en-1-yloxy)indolin-2-one (5c): Red oil, 41% yield (24 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J=7.3 Hz, 1H), 7.32~7.23 (m, 5H), 7.19 (t, J=7.7 Hz, 1H), 7.03 (t, J=7.5 Hz, 1H), 6.68 (d, J=7.8 Hz, 1H), 5.88~5.81 (m, 1H), 5.15~5.09 (m, 1H), 5.08~5.04 (m, 1H), 5.00 (s, 1H), 4.86 (d, J=2.8 Hz, 2H), 3.90~3.85 (m, 1H), 3.72~3.67 (m, 1H), 2.45~2.40 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.8, 143.4, 135.6, 134.9, 129.9, 128.9, 127.8, 127.4, 125.5, 125.2, 123.1, 116.8, 109.5, 76.0, 68.2, 43.8, 34.4; HRMS (ESI) calcd for C19H20NO2 [M＋H]＋ 294.1489, found 294.1488.
3-(But-3-en-1-yloxy)-4-fluoro-1-methylindolin-2-one (5d): Colorless oil, 28% yield (13 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.34~7.28 (m, 1H), 6.77 (t, J=8.6 Hz, 1H), 6.61 (d, J=7.8 Hz, 1H), 5.90~5.80 (m, 1H), 5.12 (dd, J1=17.2 Hz, J2=1.9 Hz, 1H), 5.02 (d, J=10.7 Hz, 1H), 5.01 (s, 1H), 3.93~3.88 (m, 1H), 3.78~3.72 (m, 1H), 3.17 (s, 3H), 2.43 (q, J=6.8 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 173.9, 161.1, 158.6, 146.6, 134.8, 132.2, 132.1, 116.8, 111.1, 111.0, 110.8, 104.6, 104.6, 74.5, 69.4, 34.3, 26.6; HRMS (ESI) calcd for C13H15FNO2 [M＋H]＋ 236.1082, found 236.1080.
3-(But-3-en-1-yloxy)-5-fluoro-1-methylindolin-2-one (5e): Colorless oil, 37% yield (17 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.14 (dd, J1=7.5, J2=1.6 Hz, 1H), 7.03 (td, J1=8.9, J2=2.7 Hz, 1H), 6.72 (dd, J1=8.5, J2=4.0 Hz, 1H), 5.88~5.78 (m, 1H), 5.15~5.10 (m, 1H), 5.08~5.05 (m, 1H), 4.89 (s, 1H), 3.89~3.84 (m, 1H), 3.69~3.64 (m, 1H), 3.16 (s, 3H), 2.41 (q, J=6.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.4, 160.7, 158.3, 140.2, 140.2, 134.8, 126.8, 126.7, 117.0, 116.4, 116.1, 113.7, 113.4, 109.0, 109.0, 76.0, 76.0, 68.5, 34.4, 26.3; HRMS (ESI) calcd for C13H15FNO2 [M＋H]＋ 236.1082, found 236.1079.
3-(But-3-en-1-yloxy)-6-fluoro-1-methylindolin-2-one (5f): Colorless oil, 51% yield (24 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.33~7.30 (m, 1H), 6.77~6.72 (m, 1H), 6.54 (dd, J1=8.8, J2=2.3 Hz, 1H), 5.86~5.77 (m, 1H), 5.14~5.09 (m, 1H), 5.07~5.03 (m, 1H), 4.85 (s, 1H), 3.89~3.83 (m, 1H), 3.68~3.62 (m, 1H), 3.15 (s, 3H), 2.43~2.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 175.0, 165.5, 163.0, 146.1, 146.0, 134.8, 126.7, 126.6, 120.6, 120.6, 116.9, 109.2, 109.0, 97.5, 97.3, 75.4, 68.3, 34.3, 26.3; HRMS (ESI) calcd for C13H15FNO2 [M＋H]＋ 236.1082, found 236.1079.
3-(But-3-en-1-yloxy)-7-fluoro-1-methylindolin-2-one (5g): Colorless oil, 24% yield (11 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.17 (d, J=7.0 Hz, 1H), 7.08~6.98 (m, 2H), 5.88~5.78 (m, 1H), 5.12 (dd, J1=17.2, J2=1.8 Hz, 1H), 5.06 (d, J=10.2 Hz, 1H), 4.89 (s, 1H), 3.88~3.83 (m, 1H), 3.69~3.63 (m, 1H), 3.38 (d, J=2.7 Hz, 3H), 2.41 (q, J=6.8 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ: 174.3, 149.1, 146.6, 134.8, 130.8, 128.0, 128.0, 123.7, 123.6, 121.3, 121.2, 118.1, 117.9, 116.9, 75.9, 75.8, 68.3, 34.4, 28.8, 28.7; HRMS (ESI) calcd for C13H15FNO2 [M＋H]＋ 236.1082, found 236.1077.
3-(But-3-en-1-yloxy)-4-chloro-1-methylindolin-2-one (5h): Colorless oil, 26% yield (13 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.29~7.25 (m, 1H), 7.03 (d, J=8.2 Hz, 1H), 6.69 (d, J=7.8 Hz, 1H), 5.92~5.82 (m, 1H), 5.15~5.10 (m, 1H), 5.06~5.03 (m, 1H), 4.92 (s, 1H), 3.95~3.89 (m, 1H), 3.72~3.66 (m, 1H), 3.16 (s, 3H), 2.44 (q, J=6.6 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.0, 146.0, 135.0, 132.7, 131.4, 123.8, 122.7, 116.7, 106.8, 75.8, 69.2, 34.4, 26.4; HRMS (ESI) calcd for C13H15ClNO2 [M＋H]＋ 252.0786, found 252.0784.
3-(But-3-en-1-yloxy)-5-chloro-1-methylindolin-2-one (5i): Colorless oil, 28% yield (14 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.36~7.35 (m, 1H), 7.32~7.29 (m, 1H), 6.73 (d, J=8.3 Hz, 1H), 5.88~5.78 (m, 1H), 5.16~5.10 (m, 1H), 5.09~5.05 (m, 1H), 4.88 (s, 1H), 3.91~3.85 (m, 1H), 3.69~3.64 (m, 1H), 3.16 (s, 3H), 2.44~2.38 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 174.3, 142.8, 134.7, 129.9, 128.5, 126.9, 125.9, 117.0, 109.4, 75.8, 68.6, 34.3, 26.3; HRMS (ESI) calcd for C13H15ClNO2 [M＋H]＋ 252.0786, found 252.0784.
3-(But-3-en-1-yloxy)-6-chloro-1-methylindolin-2-one (5j): Colorless oil, 47% yield (24 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.29 (d, J=7.9 Hz, 1H), 7.06~7.04 (m, 1H), 6.80 (d, J=1.8 Hz, 1H), 5.87~5.77 (m, 1H), 5.14~5.09 (m, 1H), 5.07~5.04 (m, 1H), 4.86 (s, 1H), 3.88~3.82 (m, 1H), 3.68~3.62 (m, 1H), 3.15 (s, 3H), 2.43~2.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.7, 145.6, 135.9, 134.8, 126.3, 123.6, 122.9, 116.9, 109.3, 75.5, 68.4, 34.3, 26.3; HRMS (ESI) calcd for C13H15ClNO2 [M＋H]＋ 252.0786, found 252.0783.
3-(But-3-en-1-yloxy)-7-chloro-1-methylindolin-2-one (5k): Colorless oil, 18% yield (9 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.28~7.24 (m, 2H), 7.01~6.97 (m, 1H), 5.88~5.78 (m, 1H), 5.12 (dd, J1=17.2, J2=1.7 Hz, 1H), 5.06 (d, J =10.2 Hz, 1H), 4.86 (s, 1H), 3.88~3.83 (m, 1H), 3.68~3.63 (m, 1H), 3.54 (s, 3H), 2.40 (q, J=6.7 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.9, 140.1, 134.8, 132.3, 128.0, 123.9, 123.9, 116.9, 115.9, 75.4, 68.3, 34.4, 29.6; HRMS (ESI) calcd for C13H15ClNO2 [M＋H]＋ 252.0786, found 252.0778.
3-(But-3-en-1-yloxy)-1,5-dimethylindolin-2-one (5l): Colorless oil, 53% yield (25 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.20 (s, 1H), 7.12 (d, J=8.0 Hz, 1H), 6.68 (d, J=7.9 Hz, 1H), 5.89~5.79 (m, 1H), 5.15~5.09 (m, 1H), 5.07~5.03 (m, 1H), 4.87 (s, 1H), 3.88~3.83 (m, 1H), 3.68~3.62 (m, 1H), 3.15 (s, 3H), 2.44~2.38 (m, 2H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.6, 141.9, 134.9, 132.6, 130.2, 126.2, 125.2, 116.8, 108.2, 76.1, 68.2, 34.4, 26.2, 21.2; HRMS (ESI) calcd for C14H18NO2 [M＋H]＋ 232.1332, found 232.1332.
3-(But-3-en-1-yloxy)-1,7-dimethylindolin-2-one (5m): Colorless oil, 50% yield (23 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.21 (d, J=7.2 Hz, 1H), 7.05 (d, J=7.7 Hz, 1H), 6.96 (t, J=7.5 Hz, 1H), 5.88~5.78 (m, 1H), 5.14~5.08 (m, 1H), 5.06~5.03 (m, 1H), 4.84 (s, 1H), 3.84~3.79 (m, 1H), 3.65~3.60 (m, 1H), 3.44 (s, 3H), 2.54 (s, 3H), 2.43~2.37 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 175.4, 141.9, 135.0, 133.7, 125.8, 123.3, 123.0, 120.1, 116.7, 75.5, 67.9, 34.4, 29.5, 19.1; HRMS (ESI) calcd for C14H18NO2 [M＋H]＋ 232.1332, found 232.1331.
3-(But-3-en-1-yloxy)-1,5,7-trimethylindolin-2-one (5n): Colorless oil, 57% yield (28 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.02 (s, 1H), 6.85 (s, 1H), 5.88~5.78 (m, 1H), 5.14~5.09 (m, 1H), 5.06~5.03 (m, 1H), 4.80 (s, 1H), 3.86~3.81 (m, 1H), 3.65~3.59 (m, 1H), 3.41 (s, 3H), 2.49 (s, 3H), 2.43~2.37 (m, 2H), 2.27 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.3, 139.5, 135.0, 134.1, 132.5, 125.9, 124.0, 119.8, 116.7, 75.6, 67.9, 34.4, 29.5, 20.8, 18.9; HRMS (ESI) calcd for C15H20NO2 [M＋H]＋ 246.1489, found 246.1488.
3-(Allyloxy)-1-methylindolin-2-one (5o): Colorless oil, 61% yield (25 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J=7.3 Hz, 1H), 7.35~7.30 (m, 1H), 7.10~7.06 (m, 1H), 6.80 (d, J=7.8 Hz, 1H), 6.03~5.93 (m, 1H), 5.37~5.31 (m, 1H), 5.24~5.21 (m, 1H), 4.92 (s, 9H), 4.39~4.34 (m, 1H), 4.29~4.24 (m, 1H), 3.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.8, 144.3, 134.2, 130.1, 125.4, 125.3, 123.0, 118.2, 108.5, 74.9, 70.0, 26.1; HRMS (ESI) calcd for C12H14NO2 [M＋H]＋ 204.1019, found 204.1016.
1-Methyl-3-(pent-4-en-1-yloxy)indolin-2-one (5p): Colorless oil, 42% yield (19 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J=7.1 Hz, 1H), 7.33 (t, J=7.8 Hz, 1H), 7.08 (t, J=8.0 Hz, 1H), 6.80 (d, J=7.8 Hz, 1H), 5.86~5.75 (m, 1H), 5.05~4.99 (m, 1H), 4.97~4.93 (m, 1H), 4.88 (s, 1H), 3.83~3.77 (m, 1H), 3.63~3.58 (m, 1H), 3.17 (s, 3H), 2.19~2.12 (m, 2H), 1.77~1.72 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.8, 144.3, 138.2, 130.0, 126.0, 125.3, 123.0, 115.0, 108.5, 76.0, 68.4, 30.3, 29.2, 26.2; HRMS (ESI) calcd for C14H18NO2 [M＋H]＋ 232.1332, found 232.1329.
1-Methyl-3-(penta-1,4-dien-3-yloxy)indolin-2-one (5q): Colorless oil, 48% yield (22 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.35~7.29 (m, 2H), 7.08~7.04 (m, 1H), 6.78 (d, J=7.8 Hz, 1H), 5.98~5.83 (m, 1H), 5.41~5.30 (m, 3H), 5.22~5.18 (m, 1H), 5.11 (t, J=6.8 Hz, 1H), 4.95 (s, 1H), 3.14 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.5, 144.3, 137.3, 136.7, 129.9, 126.0, 125.3, 122.9, 119.3, 117.1, 108.4, 81.1, 72.4, 26.1; HRMS (ESI) calcd for C14H16NO2 [M＋H]＋ 230.1176, found 230.1174.
1-Methyl-3-((2-methylallyl)oxy)indolin-2-one (5r): Colorless oil, 43% yield (19 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.37 (d, J=7.3 Hz, 1H), 7.32 (t, J=7.8 Hz, 1H), 7.07 (t, J=7.5 Hz, 1H), 6.79 (d, J=7.8 Hz, 1H), 5.06 (s, 1H), 4.94 (s, 1H), 4.89 (s, 1H), 4.22 (s, 2H), 3.16 (s, 3H), 1.81 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.8, 144.3, 141.6, 130.0, 125.4, 125.3, 122.9, 113.4, 108.4, 74.7, 72.9, 26.1, 19.7; HRMS (ESI) calcd for C13H16NO2 [M＋H]＋ 218.1176, found 278.1174.
1-Methyl-3-((3-methylbut-2-en-1-yl)oxy)indolin-2-one (5s): Colorless oil, 44% yield (21 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.42 (d, J=7.4 Hz, 1H), 7.34 (t, J=7.8 Hz, 1H), 7.09 (td, J1=7.5, J2=1.0 Hz, 1H), 6.80 (d, J=7.8 Hz, 1H), 5.62 (d, J=1.3 Hz, 1H), 5.44 (s, 1H), 4.91 (s, 1H), 4.53~4.38 (m, 2H), 3.16 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 174.5, 144.3, 137.6, 130.3, 125.6, 124.8, 123.2, 115.2, 108.5, 74.5, 71.5, 26.1; HRMS (ESI) calcd for C12H12ClNNaO2 [M＋Na]＋ 260.0449, found 260.0452.
(E)-3-(But-2-en-1-yloxy)-1-methylindolin-2-one (5t): Colorless oil, 33% yield (14 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J=7.3 Hz, 1H), 7.32 (t, J=7.7 Hz, 1H), 7.07 (td, J1=7.5, J2=1.0 Hz, 1H), 6.79 (d, J=7.8 Hz, 1H), 5.82~5.73 (m, 1H), 5.69~5.61 (m, 1H), 4.91 (s, 1H), 4.32~4.27 (m, 1H), 4.21~4.16 (m, 1H), 3.17 (s, 3H), 1.72~1.70 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 175.0, 144.3, 131.3, 130.0, 127.0, 125.5, 125.4, 123.0, 108.4, 74.7, 69.8, 26.1, 18.0; HRMS (ESI) calcd for C13H15NNaO2 [M＋Na]＋ 240.0995, found 240.0992.
1-Methyl-3-((3-methylbut-2-en-1-yl)oxy)indolin-2-one (5u): Colorless oil, 41% yield (19 mg), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J=7.3 Hz, 1H), 7.32 (t, J=7.7 Hz, 1H), 7.08 (t, J=7.6 Hz, 1H), 6.80 (d, J=7.7 Hz, 1H), 5.44~5.40 (m, 1H), 4.91 (s, 1H), 4.34~4.23 (m, 2H), 3.17 (s, 3H), 1.75 (s, 3H), 1.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ: 175.1, 144.4, 139.2, 129.9, 125.6, 125.4, 123.0, 120.4, 108.4, 74.7, 65.3, 26.1, 26.0, 18.2; HRMS (ESI) calcd for C14H17NNaO2 [M＋Na]＋ 254.1151, found 254.1144.
3-(Cyclopent-3-en-1-yloxy)-1-methylindolin-2-one (5v): Colorless oil, 41% yield (19 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.35~7.29 (m, 2H), 7.06 (td, J1=7.5, J2=1.0 Hz, 1H), 6.78 (d, J=7.8 Hz, 1H), 5.70 (s, 2H), 4.90~4.85 (m, 2H), 3.16 (s, 3H), 2.73~2.52 (m, 4H); 13C NMR (100 MHz, CDCl3) δ: 175.3, 144.1, 129.9, 128.8, 128.0, 126.0, 125.3, 123.0, 108.4, 79.6, 74.5, 40.4, 39.7, 26.2; HRMS (ESI) calcd for C14H15NNaO2 [M＋Na]＋ 252.0995, found 252.0991.
3-(Cyclopent-3-en-1-ylmethoxy)-1-methylindolin-2-one (5w): Colorless oil, 40% yield (19 mg), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.38 (d, J=7.3 Hz, 1H), 7.33 (t, J=8.0 Hz, 1H), 7.09 (t, J=8.0 Hz, 1H), 6.80 (d, J=7.8 Hz, 1H), 5.64 (s, 2H), 4.92 (s, 1H), 3.66 (t, J=8.0 Hz, 1H), 3.48 (t, J=8.0 Hz, 1H), 3.18 (s, 3H), 2.68~2.58 (m, 1H), 2.53~2.45 (m, 2H), 2.18~2.10 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.7, 144.3, 130.0, 129.7, 129.6, 125.3, 125.3, 123.0, 108.4, 76.1, 73.0, 67.4, 39.4, 37.0, 36.1, 36.1, 35.7, 26.2; HRMS (ESI) calcd for C15H17NNaO2 [M＋ Na]＋ 266.1151, found 266.1147.
4.4 Procedure for the epoxidation of 3a and 5a, and analytical data of the products
To a sealed tube was added a solution of 5a or 3a (0.1 mmol) in dichloromethane (DCM, 0.75 mL), and a solution of m-CPBA (27 mg, 0.12 mmol) and KF (7 mg, 0.12 mmol) in DCM (0.5 mL). The tube was sealed and the mixture was stirred at room temperature for 24 h. The resulting solution was concentrated in vacuo. Then the reaction mixture was concentrated and directly purified by flash column chromatography (eluted with EtOAc/petro- leum ether, V∶V=1∶3) to give product 6a or 8a.
1-Methyl-3-(2-(oxiran-2-yl)ethoxy)indolin-2-one (6a): Colorless oil, 60% yield (22 mg, mixture of two isomers, dr =1∶1), Rf=0.6. 1H NMR (400 MHz, CDCl3) δ: 7.39 (d, J=7.3 Hz, 2H), 7.33 (t, J=7.8 Hz, 2H), 7.09 (td, J=7.5, 2.5 Hz, 2H), 6.81 (d, J=7.8 Hz, 2H), 4.91 (d, J=11.0 Hz, 2H), 4.01~3.90 (m, 2H), 3.81~3.70 (m, 2H), 3.18 (s, 6H), 3.10~3.06 (m, 2H), 2.79 (t, J=4.5 Hz, 2H), 2.55~2.53 (m, 2H), 1.97~1.91 (m, 2H), 1.83~1.78 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 174.6, 174.6, 144.3, 133.5, 130.1, 125.3, 125.1, 124.9, 123.1, 108.5, 76.1, 66.0, 65.4, 50.0, 50.0, 47.3, 33.1, 33.1, 29.8, 26.2; HRMS (ESI) calcd for C13H16NO3 [M＋H]＋ 234.1125, found 234.1125.
Benzyl 2-(2-(oxiran-2-yl)ethoxy)-2-phenylacetate (8a): Colorless oil, 58% yield (18 mg, mixture of two isomers, dr=1∶1), Rf=0.5. 1H NMR (400 MHz, CDCl3) δ: 7.46~7.44 (m, 4H), 7.38~7.29 (m, 12H), 7.23~7.21 (m, 4H), 5.20~5.11 (m, 4H), 4.94 (s, 2H), 3.73~3.67 (m, 2H), 3.63~3.58 (m, 2H), 3.10~3.07 (m, 2H), 2.78~2.75 (m, 2H), 2.57~2.50 (m, 2H), 1.98~1.94 (m, 2H), 1.83~1.78 (m, 2H); 13C NMR (100 MHz, CDCl3) δ: 170.8, 136.4, 135.5, 128.9, 128.8, 128.7, 128.4, 128.1, 127.3, 127.3, 81.3, 81.1, 66.9, 66.7, 66.6, 50.0, 50.0, 47.3, 47.3, 33.0, 32.8; HRMS (ESI) calcd for C19H20NaO4 [M＋Na]＋ 335.1254, found 335.1253.
4.5 Procedure for the annulation of 6a with DBU and analytical data of the product
To a solution of 6a (62.5 mg, 0.2 mmol) in CH3CN (2 mL) was added DBU (182.7 mg, 1.2 mmol). The mixture was stirred at room temperature for 12 h. Then the reaction mixture was concentrated and directly purified by flash column chromatography (eluted with EtOAc/petroleum ether, V∶V=1∶3) to give product 7a.
3-(Hydroxymethyl)-1'-methyl-4,5-dihydro-3H-spiro-[furan-2,3'-indolin]-2'-one (7a): Colorless oil, 50% yield (24 mg, the main isomer), Rf=0.7. 1H NMR (400 MHz, CDCl3) δ: 7.90 (dd, J=8.0, 1.7 Hz, 1H), 7.63 (s, 1H), 7.41~7.36 (m, 1H), 6.67 (d, J=8.5 Hz, 1H), 6.59 (t, J=8.0 Hz, 1H), 4.46~4.37 (m, 2H), 3.13~3.08 (m, 1H), 2.91 (s, 3H), 2.82 (t, J=4.5 Hz, 1H), 2.57 (dd, J=5.0, 2.7 Hz, 1H), 2.09~2.01 (m, 1H), 1.97~1.89 (m, 1H); 13C NMR (100 MHz, CDCl3) δ: 168.6, 152.2, 134.9, 131.6, 114.5, 110.9, 109.8, 61.2, 49.9, 47.1, 32.2, 29.7; HRMS (ESI) calcd for C13H15NNaO3 [M＋Na]＋ 256.0944, found 256.0943.
Supporting Information 1H NMR and 13C NMR spectra of all products. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.
(Zhao, C.)