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Article

9,10-Phenanthrenedione as Visible-Light Photoredox Catalyst: A Green Methodology for the Functionalization of 3,4-Dihydro-1,4-Benzoxazin-2-Ones through a Friedel-Crafts Reaction

by
Jaume Rostoll-Berenguer
,
Gonzalo Blay
,
José R. Pedro
* and
Carlos Vila
*
Departament de Química Orgànica, Facultat de Química, Universitat de València, Dr. Moliner 50, 46100 Burjassot, València, Spain
*
Authors to whom correspondence should be addressed.
Catalysts 2018, 8(12), 653; https://doi.org/10.3390/catal8120653
Submission received: 12 November 2018 / Revised: 1 December 2018 / Accepted: 6 December 2018 / Published: 12 December 2018
(This article belongs to the Special Issue Photocatalytic Organic Synthesis)
Browse Figures
Versions Notes

Abstract

:
A visible-light photoredox functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones through a Friedel-Crafts reaction with indoles using an inexpensive organophotoredox catalyst is described. The reaction uses a dual catalytic system that is formed by a photocatalyst simple and cheap, 9,10-phenanthrenedione, and a Lewis acid, Zn(OTf)2. 5W white LEDs are used as visible-light source and oxygen from air as a terminal oxidant, obtaining the corresponding products with good yields. The reaction can be extended to other electron-rich arenes. Our methodology represents one of the most valuable and sustainable approach for the functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones, as compared to the reported procedures. Furthermore, several transformations were carried out, such as the synthesis of the natural product cephalandole A and a tryptophol derivative.

Graphical Abstract

1. Introduction

Visible-light (sunlight) is a safe, renewable, abundant, inexpensive, and non-polluting source of energy, which means that sunlight is the most “green” energy source that we can use. Therefore, the development of methodologies using visible-light has become one of the greatest challenges in the scientific community in the last century [1,2]. In this context, the development of methodologies to increase the use of visible-light to control chemical reactivity and achieve molecular complexity with higher levels of efficiency have become a hot topic in the last years and many challenging organic reactions have been described [3,4,5,6,7,8,9]. For this purpose, intensive research has been devoted to develop photoredox catalysts that are capable of absorbing visible light and transfer this energy to the organic molecules. Many elegant works on photocatalysis have been reported using transition metal ruthenium or iridium polypyridyl complexes as efficient photosensitizers [10,11,12,13]. However, these transition metals are expensive and they have potential toxicity that has limited their usefulness. Therefore, for the development of more sustainable visible-light photoredox methodologies the use of organic dyes is more convenient due to the low cost, high availability, and low toxicity that offer this kind of catalyst. However, some of the organophotoredox catalysts are expensive, such as pyrilium [14,15,16,17,18] or acridinium [19,20,21,22,23,24] salts (Figure 1). Organic dyes, such as Rose Bengal and Eosin Y, are more convenient due to their lower cost [25,26,27,28,29,30,31]. Nevertheless, the development of new methodologies using simpler organophotoredox catalysts that improve the sustainability of the “green” chemical process is highly desirable. In this context, α-diketones represent a class of compounds that can exhibit absorption bands in the visible range and that have been used for photochemical processes [32,33,34]. For example, 9,10-phenanthrenedione is an inexpensive organic compound with very low molecular weight (Figure 1) when compared with other organophotoredox catalysts. This α-diketone has absorption bands in the visible region (412 and 505 nm in acetonitrile, see Supplementary Materials for further details) and therefore could be excited by visible-light. However, it has been rarely used in visible-light photochemical processes [35,36,37].
On the other hand, tertiary amines represent an important class of compounds in organic synthesis, where functionalization is of great interest for the chemical community, medicinal chemistry, pharmaceutical, and agrochemical industry. In this context, the combination of visible-light catalysis and C-H bond functionalization adjacent to a tertiary amine has been successfully developed in the last years [38,39,40,41]. Normally, this sp3-C-H functionalization involves the oxidation of the amine to iminium ion, which can be attacked by various kind of nucleophiles. Nonetheless, the major number of examples are regarded to the functionalization of N-aryl tetrahydroisoquinolines [42,43,44,45,46,47,48,49,50,51,52], N,N-dimethylanilines [53,54,55,56,57], and N-aryl glycine derivatives [58,59,60,61,62]. Hence, exploring other substrates is highly desirable. In this context, 1,4-dibenzoxazinone skeleton is present in a wide number of compounds with biological activities and its functionalization could be significant and interesting for medicinal chemistry [63,64,65,66,67,68,69]. Very recently, Huo described the iron catalyzed sp3-C-H functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones [70,71] using as a terminal oxidant tert-Butyl hydroperoxide (TBHP) [70] or 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) [71]. We envisioned that this functionalization could be achieved by a visible-light photochemical process. Herein, continuing with our interest in the synthesis of multisubstituted 1,4-dihydrobenzoxazin-2-ones [72] and the Friedel-Crafts reactions with indoles [73,74,75], we described the visible-light photoredox Friedel-Crafts reaction of indoles with benzoxazin-2-ones using as catalyst a simple and cheap diketone such as the 9,10-phenanthrenedione, and oxygen as terminal oxidant. During our experimental work and the preparation of manuscript, a photoredox functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones was reported [76,77]. In both cases, the expensive Ru(bpy)2Cl2 was used as photocatalyst. Besides, unlike the photoredox catalytic system described earlier [76], the results that were obtained with our method are not affected by the steric hindrance around the C3 carbon atom of the indole skeleton. The second paper [77] deals with the functionalization of 3,4-dihydro-1,4-quinoxalin-2(1H)-one skeleton and only one example of 3,4-dihydro-1,4-benzoxazin-2-ones was reported with low yield (44%).

2. Results

Initially, we choose the Friedel-Crafts reaction between indole 1a and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one 2a in acetonitrile at room temperature under air atmosphere and the irradiation of white LEDs (5W). Under these conditions, a survey of photocatalyst were screened, and the results are summarized in Table 1. In a preliminary study of the photocatalyst (entries 1–6), Ru(bpy)2Cl2 (A), Rose Bengal (B), Fukuzumi photocatalyst (E), and 9,10-phenanthrenedione (F) afforded product 3aa with similar yields, around 30%, after 24 h. With these catalysts, we decided to change the molar ratio of 1a:2a from 0.15:0.1 to 0.1:0.15 (entries 7–10). The best yield for compound 3aa was obtained when Rose Bengal (B) and 9,10-phenanthrenedione (F) were used as photocatalyst (53% yield in both cases). In view of the good performance of the photocatalyst F, we decided to carry out the reaction using another α-diketone, such as benzyl (G), however the yield of 3aa drop to only 15%. In view of the results, we decided to continue the optimization of the reaction conditions using 9,10-phenanthrenedione as a photocatalyst, due to its low molecular weight and its lower price in relation to the other photocatalysts tested.
In order to improve the yield of 3aa, we decided to investigate a dual catalytic protocol combining Brønsted or Lewis acid catalysis and visible-light photoredox catalysis [58] (Table 2). For this purpose, different Brønsted acids, such as PhCO2H or AcOH, were tested, however product 3aa was obtained with lower yield (entries 2 and 3, respectively). After we decided to test Zn salts as Lewis acid, obtaining an improvement of the catalytic performance when we used 10 mol% of Zn(OTf)2. In these conditions, the functionalized benzoxazinone 3aa was obtained in 76% after 9 h (entry 5). Other Lewis acids, such as Fe(OTf)2, Cu(OTf)2, and Sc(OTf)3 were evaluated (entries 6–8), obtaining lower yields for the corresponding product 3aa. The lowering of the catalyst loading of Zn(OTf)2 to 5 mol% did not influence in the yield of product 3aa (entry 10). Subsequently, different solvents such as toluene, CH2Cl2, DMF, THF, or MeOH were screened (entries 11–14), obtaining the functionalized benzoxazinone 3aa with much lower yields. We could diminish the photocatalyst and Lewis acid loadings maintaining the yield of product 3aa (entries 15 and 16). Finally, some control experiments were carried out. Thus, in the absence of visible-light (entry 19) or 9,10-phenanthrenedione (entry 20), the product 3aa was not detected or the conversion was very low.
With the optimized reaction conditions in hand (entry 13, Table 2), the scope of the Friedel-Crafts reaction was explored with a range of indoles 1 with several substituents in different positions (Scheme 1). Indoles bearing electron-donating (Me, Ph, OMe, OH) or electron-withdrawing (F, Cl, Br) groups furnished the corresponding functionalized benzoxazinones 3 in 54–80% yield, independently of the position or the electronic character of the substituents. Moreover, disubstituted indoles, such as 1n–1p, afforded the corresponding products 3na–3pa, with high yields (up to 77%). It is interesting to note the good results that were obtained with 2- and 4-substituted indoles, despite the steric hindrance around the reactive carbon atom. Thus, for example, 2-methyl- and 4-methylindol gave the corresponding reaction products with yields of 58% and 64%, respectively (versus 13% and 26% described in the literature [76]). Also 2-phenyl-, 4-fluoro-, and 1,2-dimethylindole give yields of 80%, 79%, and 70%, respectively.
Afterwards, we examined the scope of the Friedel-Crafts alkylation with a range of 3,4-dihydro-1,4-benzoxazin-2-ones 2 using indole 1a as nucleophile (Scheme 2). An assortment of derivatives with different groups on the benzyl moiety reacted smoothly in the optimized reaction conditions, obtaining the corresponding products 3ab–3ad with good yields (56–88%). A thienylmethyl group on the nitrogen of the benzoxazinone 1e could be used in the Friedel-Crafts reaction obtaining the corresponding product 3ae with a high yield (77%). Additionally, 3,4-dihydro-1,4-benzoxazin-2-ones 1g and 1h, with methyl substituents at 6 and 7 positions worked well in this Friedel-Crafts reaction.
We also extended our methodology to other electron-rich arenes, such as pyrrole (4a), N-methylpyrrole (4b), and 1,3,5-trimethoxybenzene (5) (Scheme 3), which were reacted with 3,4-dihydro-1,4-benzoxazin-2-ones 2a under the optimized reaction conditions, obtaining the corresponding functionalized benzoxazinones 6a, 6b, and 7 with good yields (55–83%). Again, it is interesting to note the good result obtained with 1,3,5-trimethoxybenzene, a starting material with a large steric hindrance. The reaction product was obtained with a yield of 83% (versus 23% described in the literature [76]).
Furthermore, in order to demonstrate the sustainability of our visible-light photoredox methodology, the reaction was performed using sun-light (Scheme 4). Therefore, when the Friedel-Crafts reaction was placed outdoors under sun-light irradiation, the corresponding product 3aa was obtained with 87% yield in 5 h.
Based on previous literature reports [3,70] and control experiments (see Supplementary Materials for further details) a possible mechanism for the reaction is proposed in Scheme 5. Initially, under visible-light irradiation, 9,10-phenanthrenedione F is excited to F*. Subsequently, this excited state, by a single-electron transfer (SET), transforms 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one 2a into a nitrogen radical cation I, with the consequent reduction of F* to the radical anion F.-, which can be oxidized by molecular oxygen (O2) regenerating the photocatalyst F. On the other hand, deprotonation of the nitrogen radical cation I can generate the α-amino radical II, which can be further oxidized to the iminium ion III. After the nucleophilic attack of indole 1a to the iminium ion III, product 3aa is obtained. The radical mechanism was confirmed by an experiment control using a radical scavenger (TEMPO). Under these conditions, a trace amount of product 3aa was observed by 1H NMR of the crude reaction mixture and the corresponding adduct formed from radical II and TEMPO was detected by HRMS. In this mechanism, the O2 is the terminal oxidant that is reduced in H2O2. The role of molecular oxygen was also studied in a control experiment. When we performed the photocatalyzed Friedel-Crafts reaction under argon atmosphere, the conversion to product 3aa was very low (12%). However, the role of Zn(OTf)2 is not clear, with this Lewis acid, the reaction is accelerated, activating either the electrophile or the nucleophile, or both.
To showcase the utility of our catalytic protocol, we performed several synthetic transformations (Scheme 6). Compound 3aa was catalytically deprotected using H2 and 10% Pd/C in THF/EtOH, and then the addition of 1 equivalent of DDQ for 1 h, allowed us to obtain the natural product cephalandole A [78] (8) in 91% yield in a one-pot reaction. Moreover, compounds 3 can be used to prepare tryptophol derivatives by a reduction of the carbonyl group of the benzoxazin-2-one. Tryptophols are a class of indoles bearing a 3-(hydroxyethyl) side chain. These class of compounds have been isolated from a variety of natural sources, and some of them possess biological activity [79,80,81,82]. Therefore, compound 3aa has been reduced with LiAlH4 affording tryptophol derivative 9 with 57% yield.

3. Materials and Methods

3.1. General Information

Reactions were carried out in 5 mL vials under air, unless otherwise indicated. Commercial reagents were used as purchased. Reactions were monitored by thin-layer chromatography (TLC) analysis using Merck Silica Gel 60 F-254 (Sigma-Aldrich, St. Louis, MO, USA) thin layer plates and these are visualized using both an UV lamp (254 nm) and then a CAM solution (an aqueous solution of ceric ammonium molybdate). Flash column chromatography was performed on Merck Silica Gel 60 (Sigma-Aldrich, St. Louis, MO, USA), 0.040–0.063 mm. NMR (Nuclear Magnetic Resonance) spectra were run in a Bruker DPX300 spectrometer (Bruker, Billerica, MA, USA) at 300 MHz for 1H and 75 MHz for 13C using residual nondeuterated solvent as internal standard (CHCl3: δ 7.26 and δ 77.00 ppm, respectively, MeOH: δ 3.34 ppm and δ 49.87 ppm, respectively, Acetone: δ 2.05 ppm and δ 29.84 ppm, respectively). Chemical shifts are given in ppm. The carbon multiplicity was established by DEPT (Distortionless Enhancement by Polarization Transfer) experiments. High resolution mass spectra (HRMS-ESI) were recorded on a TRIPLETOFT5600 spectrometer (AB Sciex, Warrington, UK), equipped with an electrospray source with a capillary voltage of 4.5 kV (ESI).
All photocatalysts, indoles, and related arenes were commercially available. 3,4-dihydro-benzoxazin-2-ones derivatives 2a, 2b, and 2c were synthesized according to a procedure that was published in the literature and the spectroscopic data (1H-NMR and 13C-NMR) match with those reported. 3,4-dihydro-benzoxazin-2-ones derivatives 2d, 2e, 2f, 2g, and 2h were synthesized according to the same procedure and were characterized by 1H-NMR, 13C-NMR, and HRMS (see Supplementary Materials for further details).

3.2. General Procedure: Friedel-Crafts Reaction between 4-Benzyl-3,4-Dihydro-1,4-Benzoxazin-2-Ones and Indoles, Pyrroles and 1,3,5-Trimethoxybenzene

In a 5 mL vial were placed the proper aromatic compound (1, 4, or 5, 0.10 mmol), the proper 4-benzyl-3,4-dihydro-1,4-benzoxazin-2-one (2, 0.15 mmol), Zn(OTf)2 (1.0 mg, 0.0025 mmol, 2.5 mol%), and 9,10-phenanthrenedione (F, 1.0 mg, 0.005 mmol, 5 mol%). Subsequently, the mixture was dissolved in non-dried acetonitrile (1 mL) and was placed at two centimetres from the white LEDs. The reaction was monitored by TLC and was stopped when the corresponding indole was consumed (NOTE: It is important to analyse frequently the conversion and to stop the reaction in the precise moment to avoid product decomposition. The reaction should not be left overnight under irradiation conditions). The resulted reaction mixture was purified by column chromatography using hexane:EtOAc mixtures (from 95:5 to 85:15) to afford pure product 3, 6, or 7.

3.3. Characterization Data for Compounds 3, 6 and 7

4-Benzyl-3-(1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3aa)
Catalysts 08 00653 i003
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3aa was obtained (26.6 mg, 0.075 mmol, 75% yield) after 10 h as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 8.12 (s, 1H), 7.51 (d, J = 7.9 Hz, 1H), 7.38–7.27 (m, 5H), 7.24–7.17 (m, 1H), 7.16–7.04 (m, 3H), 6.91 (td, J = 7.7, 1.4 Hz, 1H), 6.82 (dd, J = 8.0, 1.2 Hz, 1H), 6.72 (d, J = 2.6 Hz, 1H), 5.41 (s, 1H), 4.62 (d, J = 14.9 Hz, 1H), 4.15 (d, J = 14.8 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.56 (C), 141.84 (C), 136.08 (C), 135.78 (C), 134.13 (C), 128.81 (CH), 127.77 (CH), 126.05 (C), 125.37 (CH), 122.87 (CH), 122.79 (CH), 120.41 (CH), 119.85 (CH), 119.09 (CH), 116.53 (CH), 113.87 (CH), 111.27 (CH), 108.69 (C), 55.86 (CH), 51.55 (CH2). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(1-methyl-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ba)
Catalysts 08 00653 i004
Using N-methylindole (1b, 13.1 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ba was obtained (21.2 mg, 0.058 mmol, 58% yield) after 15 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.48 (dt, J = 8.0, 1.0 Hz, 1H), 7.38–7.21 (m, 7H), 7.16–7.10 (m, 2H), 7.10–7.04 (m, 1H), 6.92 (td, J = 7.7, 1.5 Hz, 1H), 6.82 (dd, J = 8.0, 1.4 Hz, 1H), 6.59 (d, J = 0.6 Hz, 1H), 5.40 (d, J = 0.6 Hz, 1H), 4.61 (d, J = 14.9 Hz, 1H), 4.16 (d, J = 14.9 Hz, 1H), 3.64 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.5 (C), 141.8 (C), 136.7 (C), 136.2 (C), 134.1 (C), 128.8 (CH), 127.8 (CH), 127.7 (CH), 127.2 (CH), 126.7 (C), 125.3 (CH), 122.4 (CH), 120.0 (CH), 119.8 (CH), 119.2 (CH), 116.6 (CH), 113.8 (CH), 109.4 (CH), 107.1 (C), 55.8 (CH), 51.5 (CH2), 32.9 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(2-methyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ca)
Catalysts 08 00653 i005
Using 2-methylindole (1c, 13.1 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ca was obtained (21.2 mg, 0.058 mmol, 58% yield) after 11 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.98 (bs, 1H), 7.29–7.22 (m, 4H), 7.18 (dd, J = 7.9, 1.5 Hz, 1H), 7.16–7.03 (m, 5H), 6.95 (ddd, J = 8.1, 6.9, 1.1 Hz, 1H), 6.89 (td, J = 7.7, 1.4 Hz, 1H), 6.80 (dd, J = 8.1, 1.4 Hz, 1H), 5.34 (s, 1H), 4.59 (d, J = 16.1 Hz, 1H), 3.98 (d, J = 16.1 Hz, 1H), 2.02 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 166.0 (C), 140.7 (C), 136.6 (C), 135.4 (C), 135.2 (C), 134.6 (C), 128.7 (CH), 127.3 (CH), 127.2 (CH), 126.5 (C), 125.5 (CH), 121.7 (CH), 120.2 (CH), 119.1 (CH), 118.7 (CH), 117.0 (CH), 113.2 (CH), 110.5 (CH), 106.0 (C), 55.8 (CH), 49.9 (CH2), 11.6 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(4-methyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3da)
Catalysts 08 00653 i006
Using 4-methylindole (1d, 13.1 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3da was obtained (23.6 mg, 0.064 mmol, 64% yield) after 12 h as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.07 (bs, 1H), 7.34–7.29 (m, 3H), 7.21 (dd, J = 6.6, 3.0 Hz, 2H), 7.19–7.04 (m, 4H), 6.97–6.83 (m, 3H), 6.64 (d, J = 2.5 Hz, 1H), 5.70 (s, 1H), 4.63 (d, J = 14.4 Hz, 1H), 4.07 (d, J = 14.4 Hz, 1H), 2.48 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.8 (C), 141.5 (C), 136.0 (C), 135.7 (C), 134.6 (C), 130.8 (C), 128.8 (CH), 128.1 (CH), 127.8 (CH), 125.4 (CH), 124.8 (C), 122.7 (CH), 122.6 (C), 122.4 (CH), 119.7 (CH), 116.5 (CH), 113.4 (CH), 110.2 (C), 109.2 (CH), 55.3 (CH), 51.0 (CH2), 20.5 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(4-fluoro-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ea)
Catalysts 08 00653 i007
Using 4-fluoroindole (1e, 13.5 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ea was obtained (29.4 mg, 0.079 mmol, 79% yield) after 14 h as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 8.28 (s, 1H), 7.14 (dd, J = 7.9, 1.6 Hz, 1H), 7.11–7.08 (m, 2H), 7.00 (td, J = 7.7, 1.6 Hz, 1H), 6.89 (td, J = 7.7, 1.5 Hz, 1H), 6.85–6.77 (m, 1H), 6.74–6.63 (m, 2H), 5.71 (s, 1H), 4.46 (d, J = 15.5 Hz, 1H), 4.35 (d, J = 15.5 Hz, 1H); 19F NMR (282 MHz, CDCl3) δ -121.20 (s); 13C NMR (75 MHz, CDCl3) δ 164.9 (C), 156.6 (d, JC-F = 246.6 Hz, C), 141.8 (C), 138.2 (d, JC-F = 10.9 Hz, C), 136.5 (C), 133.7 (C), 128.7 (CH), 127.4 (CH), 127.2 (CH), 125.3 (CH), 123.3 (d, JC-F = 7.9 Hz, CH), 123.1 (CH), 119.8 (CH), 116.4 (CH), 115.2 (d, JC-F = 19.4 Hz, C), 114.7 (CH), 107.7 (d, JC-F = 3.9 Hz, C), 107.6 (d, JC-F = 3.8 Hz, CH), 105.8 (d, JC-F = 19.6 Hz, CH), 56.8 (d, JC-F = 3.2 Hz, CH), 51.7 (d, JC-F = 1.5 Hz, CH2); HRMS (ESI) m/z: 373,1342 [M + H]+, C23H18FN2O2 required 373,1347.
4-Benzyl-3-(5-methyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3fa)
Catalysts 08 00653 i008
Using 5-methylindole (1f, 13.1 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3fa was obtained (23.2 mg, 0.063 mmol, 63% yield) after 11 h as a brown oil. 1H NMR (300 MHz, CDCl3) δ 8.01 (bs, 1H), 7.37–7.27 (m, 5H), 7.24 (dd, J = 1.6, 0.8 Hz, 1H), 7.20 (dd, J = 8.3, 0.7 Hz, 1H), 7.12 (dd, J = 7.9, 1.5 Hz, 1H), 7.04 (ddd, J = 9.4, 8.0, 1.6 Hz, 2H), 6.92 (td, J = 7.7, 1.5 Hz, 1H), 6.82 (dd, J = 8.0, 1.4 Hz, 1H), 6.67 (d, J = 2.5 Hz, 1H), 5.37 (d, J = 0.7 Hz, 1H), 4.61 (d, J = 14.8 Hz, 1H), 4.12 (d, J = 14.8 Hz, 1H), 2.41 (s, 2H); 13C NMR (75 MHz, CDCl3) δ 164.6 (C), 141.9(C), 136.1 (C), 134.3 (C), 134.1 (C), 129.7 (C), 128.8 (CH), 127.9 (CH), 127.8 (CH), 126.4 (C), 125.3 (CH), 124.4 (CH), 122.9 (CH), 119.8 (CH), 118.7 (CH), 116.5 (CH), 113.9 (CH), 110.9 (CH), 108.2 (C), 55.8 (CH), 51.5 (CH2), 21.4 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(5-methoxy-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ga)
Catalysts 08 00653 i009
Using 5-methoxyindole (1g, 14.7 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ga was obtained (26.1 mg, 0.068 mmol, 68% yield) after 11 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.05 (bs, 1H), 7.40–7.27 (m, 5H), 7.19 (dd, J = 8.8, 0.7 Hz, 1H), 7.13 (dd, J = 7.9, 1.5 Hz, 1H), 7.08 (ddd, J = 8.0, 7.5, 1.5 Hz, 1H), 6.91 (ddd, J = 7.5, 1.5 Hz, 1H), 6.88–6.79 (m, 3H), 6.72 (dd, J = 2.6, 0.6 Hz, 1H), 5.34 (d, J = 0.6 Hz, 1H), 4.62 (dd, J = 14.7, 0.8 Hz, 1H), 4.10 (d, J = 14.7 Hz, 1H), 3.72 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.7 (C), 154.6 (C), 141.8 (C), 136.1 (C), 134.3 (C), 130.8 (C), 128.8 (CH), 127.9 (CH), 127.8 (CH), 126.4 (C), 125.5 (CH), 123.7 (CH), 119.8 (CH), 116.6 (CH), 113.7 (CH), 113.6 (CH), 112.1 (CH), 108.7 (C), 100.3 (CH), 55.8 (CH), 55.7 (CH3), 51.3 (CH2). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(5-hydroxy-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ha)
Catalysts 08 00653 i010
Using 5-hydroxyindole (1h, 13.3 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ha was obtained (24.4 mg, 0.066 mmol, 66% yield) after 11 h as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 8.05 (bs, 1H), 7.38–7.23 (m, 5H), 7.13 (d, J = 8.7 Hz, 1H), 7.11–7.02 (m, 2H), 6.89 (td, J = 7.7, 1.4 Hz, 1H), 6.86–6.79 (m, 2H), 6.76 (dd, J = 8.7, 2.3 Hz, 1H), 6.67 (d, J = 2.5 Hz, 1H), 5.28 (s, 1H), 4.60 (d, J = 14.9 Hz, 1H), 4.12 (d, J = 14.9 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.7 (C), 150.1 (C), 141.7 (C), 136.1 (C), 134.1 (C), 131.0 (C), 128.8 (CH), 127.8 (CH), 126.7 (C), 125.4 (CH), 123.8 (CH), 119.8 (CH), 116.6 (CH), 113.9 (CH), 112.8 (CH), 112.0 (CH), 108.0 (C), 103.6 (CH), 56.0 (CH), 51.6 (CH2); HRMS (ESI) m/z: 371,1393 [M + H]+, C23H19N2O3 required 371,1390.
4-Benzyl-3-(5-bromo-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ia)
Catalysts 08 00653 i011
Using 5-bromoindole (1i, 19.6 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ia was obtained (23.4 mg, 0.054 mmol, 54% yield) after 14 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.21 (s, 1H), 7.54 (d, J = 1.8 Hz, 1H), 7.40–7.32 (m, 3H), 7.32–7.24 (m, 3H), 7.17 (d, J = 8.6 Hz, 1H), 7.15–7.05 (m, 2H), 6.93 (td, J = 7.7, 1.4 Hz, 1H), 6.84 (dd, J = 8.0, 1.3 Hz, 1H), 6.71 (d, J = 2.6 Hz, 1H), 5.29 (s, 1H), 4.62 (d, J = 14.6 Hz, 1H), 4.06 (d, J = 14.6 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.46 (C), 141.84 (C), 135.73 (C), 134.39 (C), 134.02 (C), 128.89 (CH), 127.95 (CH), 127.73 (CH), 126.45 (C), 125.75 (CH), 125.51 (CH), 124.02 (CH), 121.78 (CH), 120.15 (CH), 116.60 (CH), 114.07 (CH), 113.75 (C), 112.73 (CH), 108.37 (C), 55.32 (CH), 51.54 (CH2). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(6-methyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ja)
Catalysts 08 00653 i012
Using 6-methylindole (1j, 13.1 mg, 0,1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ja was obtained (28.3 mg, 0.077 mmol, 77% yield) after 14 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 7.98 (bs, 1H), 7.43–7.26 (m, 6H), 7.16–7.07 (m, 2H), 7.06 (td, J = 7.7, 1.6 Hz, 1H), 6.96 (dd, J = 8.2, 1.4 Hz, 1H), 6.91 (td, J = 7.7, 1.5 Hz, 1H), 6.81 (dd, J = 8.0, 1.4 Hz, 1H), 6.66 (d, J = 2.5 Hz, 1H), 5.37 (d, J = 0.7 Hz, 1H), 4.61 (d, J = 14.8 Hz, 1H), 4.15 (d, J = 14.8 Hz, 1H), 2.44 (s, 3H): 13C NMR (75 MHz, CDCl3) δ 164.6 (C), 141.9 (C), 136.3 (C), 136.1 (C), 134.2 (C), 132.7 (C), 128.8 (CH), 127.8 (CH), 127.7 (CH), 125.3 (CH), 123.9 (C), 122.3 (CH), 122.2 (CH), 119.8 (CH), 118.7 (CH), 116.5 (CH), 113.8 (C), 111.2 (CH), 108.6 (C), 56.0 (CH), 51.5 (CH2), 21.6 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(7-methyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ka)
Catalysts 08 00653 i013
Using 7-methylindole (1k, 13.1 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ka was obtained (26.1 mg, 0.071 mmol, 71% yield) after 14 h as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.03 (s, 1H), 7.33 (m, 6H), 7.12 (dd, J = 7.9, 1.5 Hz, 1H), 7.09–6.98 (m, 3H), 6.91 (td, J = 7.7, 1.4 Hz, 1H), 6.81 (dd, J = 8.1, 1.4 Hz, 1H), 6.73 (d, J = 2.6 Hz, 1H), 5.39 (d, J = 0.7 Hz, 1H), 4.61 (d, J = 14.9 Hz, 1H), 4.16 (d, J = 14.9 Hz, 1H), 2.42 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.5 (C), 141.9 (C), 136.1 (C), 135.4 (C), 134.2 (C), 128.8 (CH), 127.8 (CH), 127.8 (CH), 125.7 (C), 125.3 (CH), 123.3 (CH), 122.6 (CH), 120.7 (CH), 120.5 (C), 119.8 (CH), 116.8 (CH), 116.5(CH), 113.9 (CH), 109.2 (C), 56.0 (CH), 51.6 (CH2), 16.4 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(7-chloro-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3la)
Catalysts 08 00653 i014
Using 7-chloroindole (1l, 15.2 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3la was obtained (22.9 mg, 0.059 mmol, 59% yield) after 16 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.29 (bs, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.36–7.24 (m, 5H), 7.21 (dd, J = 7.6, 0.7 Hz, 1H), 7.15–7.02 (m, 3H), 6.92 (td, J = 7.7, 1.4 Hz, 1H), 6.85 (dd, J = 8.0, 1.3 Hz, 1H), 6.80 (d, J = 2.6 Hz, 1H), 5.35 (s, 1H), 4.64 (d, J = 14.7 Hz, 1H), 4.12 (d, J = 14.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.20 (C), 141.83 (C), 135.83 (C), 134.00 (C), 133.15 (C), 128.87 (CH), 127.88 (CH), 127.45 (C), 125.48 (CH), 123.41 (CH), 122.22 (CH), 121.29 (CH), 120.13 (CH), 117.93 (CH), 116.76 (C), 116.64 (CH), 113.92 (CH), 110.01 (C), 55.73 (CH), 51.63 (CH2). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(2-phenyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ma)
Catalysts 08 00653 i015
Using 2-phenylindole (1m, 19.3 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ma was obtained (34.4 mg, 0.080 mmol, 80% yield) after 14 h as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.27 (bs, 1H), 7.54–7.46 (m, 2H), 7.42–7.32 (m, 4H), 7.22–7.14 (m, 3H), 7.11–7.05 (m, 3H), 7.04–6.96 (m, 2H), 6.96–6.91 (m, 2H), 6.90–6.82 (m, 1H), 6.69 (dd, J = 8.1, 1.4 Hz, 1H), 5.57 (s, 1H), 4.42 (d, J = 16.2 Hz, 1H), 3.87 (d, J = 16.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 166.2 (C), 140.5 (C), 139.4 (C), 136.4 (C), 135.9 (C), 134.2 (C), 131.3 (C), 129.0 (CH), 128.9 (CH), 128.7 (CH), 128.4 (CH), 127.0 (CH), 126.9 (CH), 126.3 (C), 125.5 (CH), 122.9 (CH), 120.7 (CH), 120.0 (CH), 118.9 (CH), 116.9 (CH), 113.1 (CH), 111.1 (CH), 107.6 (C), 56.1 (CH), 50.0 (CH2). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(1,2-dimethyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3na)
Catalysts 08 00653 i016
Using 1,2-dimethylindole (1n, 14.5 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3na was obtained (26.7 mg, 0.070 mmol, 70% yield) after 12 h as a brown oil. 1H NMR (300 MHz, CDCl3) δ 7.31–7.22 (m, 4H), 7.19–7.14 (m, 3H), 7.14–7.08 (m, 2H), 7.05 (ddd, J = 8.1, 7.4, 1.6 Hz, 1H), 6.96 (ddd, J = 8.0, 6.9, 1.1 Hz, 1H), 6.88 (ddd, J = 7.9, 7.5, 1.4 Hz, 1H), 6.78 (dd, J = 8.1, 1.4 Hz, 1H), 5.38 (d, J = 0.5 Hz, 1H), 4.57 (d, J = 16.2 Hz, 1H), 3.99 (d, J = 16.2 Hz, 1H), 3.63 (s, 3H), 2.12 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 166.1 (C), 140.9 (C), 140.7 (C), 137.0 (C), 136.8 (C), 134.6 (C), 128.7 (CH), 127.2 (CH), 127.1 (CH), 125.8 (C), 125.5 (CH), 121.3 (CH), 120.0 (CH), 119.0 (CH), 118.6 (CH), 117.0 (CH), 113.2 (CH), 109.0 (CH), 105.3 (C), 56.2 (CH), 49.9 (CH2), 29.6 (CH3), 10.3 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(5-methoxy-7-methyl-1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3oa)
Catalysts 08 00653 i017
Using 5-methoxy-7-methylindole (1o, 16.1 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3oa was obtained (27.9 mg, 0.070 mmol, 70% yield) after 11 h as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 7.98 (bs, 1H), 7.40–7.27 (m, 5H), 7.13 (dd, J = 7.9, 1.5 Hz, 1H), 7.07 (td, J = 7.7, 1.5 Hz, 1H), 6.91 (td, J = 7.7, 1.4 Hz, 1H), 6.82 (dd, J = 8.1, 1.3 Hz, 1H), 6.74–6.62 (m, 3H), 5.33 (s, 1H), 4.61 (d, J = 14.8 Hz, 1H), 4.10 (d, J = 14.7 Hz, 1H), 3.71 (s, 3H), 2.36 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.7 (C), 154.7 (C), 141.8 (C), 136.1 (C), 134.3 (C), 130.6 (C), 128.8 (CH), 127.9 (CH), 127.8 (CH), 125.8 (C), 125.4 (CH), 123.3 (CH), 121.6 (C), 119.8 (CH), 116.5 (CH), 114.1 (CH), 113.8 (CH), 109.1 (C), 97.8 (CH), 55.8 (CH), 55.6 (CH3), 51.2 (CH2), 16.4 (CH3); HRMS (ESI) m/z: 399,1708 [M + H]+, C25H23N2O3 required 399,1703.
3-(1H-benzo[g]indol-3-yl)-4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3pa)
Catalysts 08 00653 i018
Using 1H-benzo[g]indole (1p, 16.7 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3pa was obtained (31.0 mg, 0.077 mmol, 77% yield) after 14 h as a brown solid. 1H NMR (300 MHz, Acetone) δ 11.25 (bs, 1H), 8.27 (d, J = 8.2 Hz, 1H), 7.94 (d, J = 8.0 Hz, 1H), 7.69 (d, J = 8.8 Hz, 1H), 7.58–7.29 (m, 8H), 7.18–7.02 (m, 2H), 6.99–6.87 (m, 3H), 5.68 (d, J = 0.6 Hz, 1H), 4.68 (d, J = 15.1 Hz, 1H), 4.40 (d, J = 15.1 Hz, 1H); 13C NMR (75 MHz, Acetone) δ 165.05 (C), 143.02 (C), 138.04 (C), 135.22 (C), 131.87 (C), 131.47 (C), 129.52 (CH), 129.40 (CH), 128.60 (CH), 128.32 (CH), 126.48 (CH), 126.08 (CH), 125.02 (CH), 123.09 (C), 123.00 (C), 122.23 (CH), 121.56 (CH), 121.12 (CH), 120.64 (CH), 119.68 (CH), 116.95 (CH), 115.37 (CH), 110.99 (C), 57.46 (CH), 52.53 (CH2); HRMS (ESI) m/z: 405,1592 [M + H]+, C27H21N2O2 required 405,1598.
3-(1H-indol-3-yl)-4-(4-methoxybenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ab)
Catalysts 08 00653 i019
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-(4-methoxybenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2b, 40.4 mg, 0.15 mmol), in accordance with General Procedure, the product 3ab was obtained (21.5 mg, 0.056 mmol, 56% yield) after 10 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.09 (bs, 1H), 7.50 (d, J = 7.9 Hz, 1H), 7.35–7.30 (m, 1H), 7.24–7.16 (m, 3H), 7.16–7.04 (m, 3H), 6.92 (dd, J = 7.7, 1.4 Hz, 1H), 6.90–6.83 (m, 3H), 6.71 (d, J = 2.4 Hz, 1H), 5.37 (d, J = 0.4 Hz, 1H), 4.57 (d, J = 14.4 Hz, 1H), 4.07 (d, J = 14.3 Hz, 1H), 3.82 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.54 (C), 159.22 (C), 141.93 (C), 135.76 (C), 134.29 (C), 129.22 (CH), 127.80 (C), 126.10 (C), 125.34 (CH), 122.79 (CH), 122.76 (CH), 120.40 (CH), 119.81 (CH), 119.20 (CH), 116.50 (CH), 114.21 (CH), 113.86 (CH), 111.21 (CH), 108.75 (C), 55.30 (CH), 50.90 (CH2). The spectroscopic data match with those reported in the literature [70].
4-(4-cyanobenzyl)-(3-(1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ac)
Catalysts 08 00653 i020
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-(4-cyanobenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2c, 39.6 mg, 0.15 mmol), in accordance with General Procedure, the product 3ac was obtained (33.4 mg, 0.088 mmol, 88% yield) after 13 h as a white solid. 1H NMR (300 MHz, CDCl3) δ 8.15 (bs, 1H), 7.66–7.59 (m, 2H), 7.52 (d, J = 7.9 Hz, 1H), 7.41 (d, J = 8.5 Hz, 2H), 7.35 (d, J = 8.1 Hz, 1H), 7.26–7.19 (m, 1H), 7.18–7.11 (m, 2H), 7.04 (td, J = 7.7, 1.6 Hz, 1H), 6.94 (td, J = 7.7, 1.5 Hz, 1H), 6.76 (d, J = 2.5 Hz, 1H), 6.65 (dd, J = 8.0, 1.4 Hz, 1H), 5.39 (s, 1H), 4.60 (d, J = 16.0 Hz, 1H), 4.27 (d, J = 16.0 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.1 (C), 142.1 (C), 141.9 (C), 135.8 (C), 133.4 (C), 132.7 (CH), 128.1 (CH), 126.0 (C), 125.4 (CH), 123.1 (CH), 122.9 (CH), 120.7 (CH), 120.6 (CH), 118.9 (CH), 118.6 (C), 116.8 (CH), 113.9 (CH), 111.6 (C), 111.4 (CH), 108.5 (C), 57.0 (CH), 51.7 (CH2); HRMS (ESI) m/z: 380,1398 [M + H]+, C24H18N3O2 required 380,1394.
4-(3-bromobenzyl)-3-(1H-indol-3-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ad)
Catalysts 08 00653 i021
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-(3-bromobenzyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2d, 47.7 mg, 0.15 mmol), in accordance with General Procedure, the product 3ad was obtained (25.5 mg, 0.059 mmol, 59% yield) after 13 h as a brown oil. 1H NMR (300 MHz, CDCl3) δ 8.13 (s, 1H), 7.54–7.49 (m, 1H), 7.46–7.41 (m, 2H), 7.35–7.31 (m, 1H), 7.25–7.18 (m, 3H), 7.17–7.11 (m, 2H), 7.05 (dd, J = 7.9, 1.6 Hz, 1H), 6.93 (td, J = 7.7, 1.4 Hz, 1H), 6.81–6.69 (m, 2H), 5.39 (d, J = 0.5 Hz, 1H), 4.54 (d, J = 15.2 Hz, 1H), 4.12 (d, J = 15.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.4 (C), 141.9 (C), 138.7 (C), 135.8 (C), 133.7 (C), 130.9 (CH), 130.7 (CH), 130.4 (CH), 126.2 (CH), 126.0 (C), 125.4 (CH), 122.9 (C), 122.9 (CH), 122.9 (CH), 120.6 (CH), 120.2 (CH), 119.0 (CH), 116.7 (CH), 113.9 (CH), 111.3 (CH), 108.6 (C), 56.3 (CH), 51.2 (CH2); HRMS (ESI) m/z: 433,0539 [ M + H]+, C23H18BrN2O2 required 433,0546.
3-(1H-indol-3-yl)-4-(thiophen-2-ylmethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ae)
Catalysts 08 00653 i022
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-(thiophen-2-ylmethyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2e, 36.8 mg, 0.15 mmol), in accordance with General Procedure, the product 3ad was obtained (27.8 mg, 0.077 mmol, 77% yield) after 24 h as a brown solid. 1H NMR (300 MHz, CDCl3) δ 8.13 (bs, 1H), 7.56 (d, J = 7.9 Hz, 1H), 7.32 (d, J = 8.0 Hz, 1H), 7.27 (dd, J = 5.0, 1.0 Hz, 1H), 7.25–7.17 (m, 1H), 7.17–7.06 (m, 3H), 6.99–6.90 (m, 4H), 6.74 (d, J = 2.4 Hz, 1H), 5.45 (s, 1H), 4.77 (d, J = 15.1 Hz, 1H), 4.35 (d, J = 15.4 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.6 (C), 142.0 (C), 139.3 (C), 135.8 (C), 133.7 (C), 126.9 (CH), 126.6 (CH), 126.0 (C), 125.7 (CH), 125.4 (CH), 123.2 (CH), 122.8 (CH), 120.4 (CH), 120.3 (CH), 119.1 (CH), 116.7 (CH), 114.0 (CH), 111.3 (CH), 108.5 (C), 55.5 (CH), 46.7 (CH2); HRMS (ESI) m/z: 361,1008 [M + H]+, C21H17N2O2S required 361,1005.
3-(1H-indol-3-yl)-4-(3-phenylpropyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3af)
Catalysts 08 00653 i023
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-(3-phenylpropyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2f, 40.1 mg, 0.15 mmol), in accordance with General Procedure, the product 3af was obtained (28.3 mg, 0.074 mmol, 74% yield) after 24 h as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 8.07 (bs, 1H), 7.66 (dd, J = 7.7, 0.5 Hz, 1H), 7.33–7.25 (m, 3H), 7.25–7.11 (m, 5H), 7.11–7.04 (m, 2H), 6.86 (ddd, J = 8.1, 7.4, 1.4 Hz, 1H), 6.75 (dd, J = 8.0, 1.3 Hz, 1H), 6.69 (d, J = 2.2 Hz, 1H), 5.40 (d, J = 0.7 Hz, 1H), 3.50–3.36 (m, 1H), 3.16–3.00 (m, 1H), 2.68 (t, J = 7.4 Hz, 2H), 2.09–1.94 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 164.3 (C), 141.6 (C), 141.1 (C), 135.9 (C), 133.8 (C), 128.5 (CH), 128.4 (CH), 126.1 (CH), 125.9 (C), 125.3 (CH), 122.8 (CH), 122.8 (CH), 120.5 (CH), 119.1 (CH), 119.1 (CH), 116.6 (CH), 112.9 (CH), 111.3 (CH), 109.4 (C), 56.8 (CH), 47.3 (CH2), 32.9 (CH2), 28.3 (CH2); HRMS (ESI) m/z: 383,1759 [M + H]+, C25H23N2O2 required 383,1754.
4-Benzyl-3-(1H-indol-3-yl)-7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ag)
Catalysts 08 00653 i024
Using indole (1a, 11.7 mg, 0.1 mmol) and 4-benzyl-7-methyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2g, 38.0 mg, 0.15 mmol), in accordance with General Procedure, the product 3ag was obtained (25.4 mg, 0.069 mmol, 69% yield) after 16 h as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 8.11 (bs, 1H), 7.52 (d, J = 7.9 Hz, 1H), 7.38–7.26 (m, 6H), 7.24–7.17 (m, 1H), 7.16–7.10 (m, 1H), 6.93 (d, J = 1.4 Hz, 1H), 6.86 (ddd, J = 8.1, 1.9, 0.6 Hz, 1H), 6.73 (d, J = 2.5 Hz, 1H), 6.70 (d, J = 8.2 Hz, 1H), 5.37 (d, J = 0.4 Hz, 1H), 4.56 (d, J = 14.8 Hz, 1H), 4.12 (d, J = 14.8 Hz, 1H), 2.31 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 164.8 (C), 141.9 (C), 136.3 (C), 135.8 (C), 131.7 (C), 129.9 (C), 128.8 (CH), 127.8 (CH), 127.7 (CH), 126.2 (C), 125.7 (CH), 122.8 (CH), 122.8 (CH), 120.4 (CH), 119.2 (CH), 117.1 (CH), 114.0 (CH), 111.2 (CH), 108.8 (C), 56.0 (CH), 51.8 (CH2), 20.5 (CH3). The spectroscopic data match with those reported in the literature [70].
3-(1H-indol-3-yl)-6-methyl-4-(3-phenylpropyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (3ah)
Catalysts 08 00653 i025
Using indole (1a, 11.7 mg, 0.1 mmol) and 6-methyl-4-(3-phenylpropyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2h, 38.0 mg, 0.15 mmol), in accordance with General Procedure, the product 3ah was obtained (23.8 mg, 0.060 mmol, 60% yield) after 16 h as a colourless oil. 1H NMR (300 MHz, CDCl3) δ 8.08 (bs, 1H), 7.71–7.61 (m, 1H), 7.39–7.25 (m, 3H), 7.24–7.09 (m, 5H), 6.93 (d, J = 8.1 Hz, 1H), 6.72 (d, J = 2.3 Hz, 1H), 6.64 (ddd, J = 8.1, 1.8, 0.6 Hz, 1H), 6.50 (d, J = 1.5 Hz, 1H), 5.37 (d, J = 0.6 Hz, 1H), 3.41 (ddd, J = 13.9, 8.0, 5.8 Hz, 1H), 3.13–2.98 (m, 1H), 2.68 (td, J = 7.4, 3.1 Hz, 2H), 2.30 (s, 3H), 2.10–1.88 (m, 2H); 13C NMR (75 MHz, CDCl3) δ 164.4 (C), 141.1 (C), 139.6 (C), 135.9 (C), 135.0 (C), 133.4 (C), 128.5 (CH), 128.4 (CH), 126.1 (CH), 126.0 (C), 122.9 (CH), 122.7 (CH), 120.4 (CH), 119.6 (CH), 119.1 (CH), 116.2 (CH), 113.5 (CH), 111.3 (CH), 109.5 (C), 56.9 (CH), 47.2 (CH2), 32.9 (CH2), 28.3 (CH2), 21.4 (CH3); HRMS (ESI) m/z: 397,1918 [M + H]+, C26H25N2O2 required 397,1911.
4-Benzyl-3-(1H-pyrrol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (6a)
Catalysts 08 00653 i026
Using pyrrole (4a, 7 μL, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 6a was obtained (16.7 mg, 0.055 mmol, 55% yield) after 12 h as a brown oil. 1H NMR (300 MHz, CDCl3) δ 7.95 (bs, 1H), 7.45–7.27 (m, 5H), 7.15–7.07 (m, 2H), 6.97–6.87 (m, 2H), 6.67 (td, J = 2.7, 1.5 Hz, 1H), 6.06 (dd, J = 6.1, 2.7 Hz, 1H), 5.92–5.83 (m, 1H), 5.03 (s, 1H), 4.65 (d, J = 14.3 Hz, 1H), 4.08 (d, J = 14.3 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 164.15 (C), 141.39 (C), 135.58 (C), 133.73 (C), 128.96 (CH), 128.12 (CH), 128.04 (CH), 127.73 (CH), 125.67 (CH), 123.09 (C), 120.34 (CH), 119.12 (CH), 116.79 (CH), 113.85 (CH), 108.87 (CH), 56.86 (CH), 51.60 (CH2). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(1-methyl-1H-pyrrol-2-yl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (6b)
Catalysts 08 00653 i027
Using N-methylpyrrole (4b, 9 μL, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 6b was obtained (18.4 mg, 0.058 mmol, 58% yield) after 11 h as a yellow oil. 1H NMR (300 MHz, CDCl3) δ 7.37–7.30 (m, 5H), 7.10 (dd, J = 7.9, 1.5 Hz, 1H), 7.06–7.00 (m, 1H), 6.89 (dd, J = 7.7, 1.5 Hz, 1H), 6.76 (dd, J = 8.0, 1.3 Hz, 1H), 6.42 (t, J = 2.5 Hz, 1H), 6.31 (t, J = 2.0 Hz, 1H), 5.75 (dd, J = 2.6, 1.9 Hz, 1H), 4.93 (s, 1H), 4.55 (d, J = 14.5 Hz, 1H), 4.07 (d, J = 14.5 Hz, 1H), 3.53 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 165.64 (C), 141.93 (C), 136.25 (C), 134.19 (C), 128.80 (CH), 127.96 (CH), 127.70 (CH), 125.17 (CH), 122.33 (CH), 120.54 (CH), 119.68 (CH), 116.36 (CH), 115.67 (C), 113.82 (CH), 107.83 (CH), 56.93 (CH), 51.18 (CH2), 36.24 (CH3). The spectroscopic data match with those reported in the literature [70].
4-Benzyl-3-(2,4,6-trimethoxyphenyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (7)
Catalysts 08 00653 i028
Using 1,3,5-trimethoxybenzene (5, 16.8 mg, 0.1 mmol) and 4-benzyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-one (2a, 35.8 mg, 0.15 mmol), in accordance with General Procedure, the product 7 was obtained (33.6 mg, 0.083 mmol, 83% yield) after 19 h as a yellowish solid. 1H NMR (400 MHz, CDCl3) δ 7.25–7.21 (m, 2H), 7.21–7.15 (m, 3H), 7.04 (dd, J = 7.9, 1.5 Hz, 1H), 6.88 (ddd, J = 8.0, 7.6, 1.5 Hz, 1H), 6.70 (td, J = 7.7, 1.4 Hz, 1H), 6.50 (dd, J = 8.1, 1.3 Hz, 1H), 6.04 (s, 2H), 5.87 (s, 1H), 4.37 (d, J = 16.6 Hz, 1H), 4.22 (d, J = 16.6 Hz, 1H), 3.77 (s, 3H), 3.59 (s, 6H);13C NMR (75 MHz, CDCl3) δ 167.51 (C), 161.76 (C), 159.31 (C), 140.98 (C), 137.86 (C), 133.86 (C), 128.35 (CH), 126.80 (CH), 126.53 (CH), 124.63 (CH), 117.37 (CH), 115.70 (CH), 111.83 (CH), 106.70 (C), 90.68 (CH), 55.51 (CH3), 55.33 (CH), 53.89 (CH3), 50.71 (CH2). The spectroscopic data match with those reported in the literature [70].

3.4. Synthesis and Characterization of Cephalandole A (8)

In a 25 mL round bottomed flask were placed compound 3aa (30 mg, 0.085 mmol) and Pd/C 10% w/w (18.1 mg, 0.017 mmol, 20 mol%). Subsequently, THF (2 mL) and EtOH (1 mL) were added and the resulting suspension was bubbled with H2. After this, the reaction mixture was stirred at room temperature for 16 h with a H2 balloon. The reaction was monitored by TLC, and, when compound 3aa was consumed, DDQ (19.3 mg, 0.085 mmol) was added directly to the reaction mixture. After 1 h, the reaction mixture was filtered through a pad of Celite, the solvents were removed by reduced pressure and the resulting residue was purified by column chromatography using a hexane:EtOAc 95:5 mixture as eluent to afford Cephalandole A, 8 (20.3 mg, 0.077 mmol, 92% yield) as a bright yellow solid.
3-(1H-indol-3-yl)-2H-benzo[b][1,4]oxazin-2-one (Cephalandole A, 8)
Catalysts 08 00653 i029
Bright yellow solid; 1H NMR (300 MHz, Acetone) δ 11.04 (s, 1H), 8.88–8.82 (m, 1H), 8.78 (t, J = 1.5 Hz, 1H), 7.87–7.83 (m, 1H), 7.57–7.49 (m, 1H), 7.49–7.35 (m, 2H), 7.35–7.28 (m, 1H), 7.28–7.21 (m, 2H); 13C NMR (75 MHz, Acetone) δ 153.00 (C), 149.05 (C), 146.22 (C), 137.86 (C), 134.58 (CH), 133.20 (C), 129.58 (CH), 128.88 (CH), 127.36 (C), 126.12 (CH), 124.18 (CH), 124.10 (CH), 122.47 (CH), 116.75 (CH), 112.77 (CH), 112.37 (C). The spectroscopic data match with those reported in the literature [70].

3.5. Synthesis and Characterization of Compound 9

In a 10 mL round bottomed flask was placed compound 3aa (15.5 mg, 0.044 mmol) and it was purgued with N2. Afterwards, dry THF (1 mL) was added via syringe and the resulted solution was cooled down to 0 °C. After 5 min, LiAlH4 (0.08 mL 1 M in THF, 0.087 mmol, two equivalents) was added via syringe and the mixture was stirred for 1.5 h at 0 °C. Subsequently, the reaction was stopped with the addition of saturated aqueous NH4Cl solution (1 mL) and saturated aqueous Rochelle Salt solution (5 mL). The resulting mixture was extracted with EtOAc (three times), washed with brine, and dried over anhydrous MgSO4. The solvent was removed by reduced pressure and the resulting residue was purified by column chromatography using hexane: EtOAc mixtures as eluent (from 90:10 to 60:40) to afford compound 9 (9.0 mg, 0.025 mmol, 57% yield) as a colourless oil.
2-(Benzyl(2-hydroxy-1-(1H-indol-3-yl)ethyl)amino)phenol (9)
Catalysts 08 00653 i030
Brown oil; 1H NMR (300 MHz, CDCl3:CD3OD) δ 8.59 (bs, 1H), 7.42 (d, J = 8.0 Hz, 1H), 7.36–7.27 (m, 5H), 7.25–7.20 (m, 1H), 7.11 (t, J = 7.6 Hz, 2H), 7.03–6.95 (m, 2H), 6.70 (d, J = 7.8 Hz, 2H), 6.55 (d, J = 7.9 Hz, 1H), 4.29–4.21 (m, 3H), 4.12 (dd, J = 10.8, 6.1 Hz, 1H), 4.01 (dd, J = 10.8, 7.7 Hz, 1H); 13C NMR (75 MHz, CDCl3) δ 144.42 (C), 138.92 (C), 136.28 (C), 128.45 (CH), 127.68 (CH), 127.16 (CH), 126.90 (C), 121.85 (CH), 121.77 (CH), 120.18 (CH), 119.32 (CH), 119.08 (CH), 116.17 (C), 116.10 (C), 114.15 (CH), 112.24 (CH), 111.08 (CH), 111.03 (CH), 66.23 (CH2), 48.79 (CH2), 44.63 (CH); HRMS (ESI) m/z: 359,1757 [M + H]+, C23H23N2O2 required 359,1754.

4. Conclusions

In summary, we have described a visible-light functionalization of 3,4-dihydro-1,4-benzoxazin-2-ones with indoles and other electron-rich arenes using a dual catalytic system that was formed by a Lewis acid (Zn(OTf)2) and 9,10-phenanthrenedione as photocatalyst. Under our reaction conditions, the corresponding products are obtained with good yields. Unlike the photoredox catalytic system described earlier [76], the results that were obtained with our method are not affected by the steric hindrance around the reactive carbon atom. Thus, 2- and 4-substituted indoles and 1,3,5-trimethoxybenzene give the corresponding reaction products with good yields. Besides our method uses one of the cheapest, simple, and commercially available organophotocatalyst (9,10-phenanthrenedione) and oxygen from air as oxidant, providing a valuable contribution for the development of more “green” chemical synthesis. Moreover, several transformations have been carried out with the reaction products. Studies to further extend the scope of this reaction are currently underway in our laboratory.

Supplementary Materials

The following materials are available online at https://www.mdpi.com/2073-4344/8/12/653/s1, Complete experimental procedures and characterization of new products, 1H and 13C NMR spectra for all compounds.

Author Contributions

C.V. and J.R.-B. conceived and designed the experiments; J.R.-B. performed the experiments; J.R.-B. and C.V. analyzed the data; G.B. contributed reagents/materials/analysis tools; C.V. and J.R.P. wrote the paper. All authors read, revised and approved the final manuscript.

Funding

Agencia Estatal de Investigación (AEI, Spanish Government) and Fondo Europeo de Desarrollo Regional (FEDER, European Union) (CTQ2017-84900-P).

Acknowledgments

Financial support from the Agencia Estatal de Investigación (AEI, Spanish Government) and Fondo Europeo de Desarrollo Regional (FEDER, European Union) (CTQ2017-84900-P) is acknowledged. J.R-B thanks the Ministerio de Ciencia, Innovación y Universidades for a predoctoral grant and C.V. thanks the Spanish Government for RyC contract (RYC-2016-20187). Access to NMR, MS and X-ray facilities from the Servei Central de Suport a la Investigació Experimental (SCSIE)-UV is also acknowledged.

Conflicts of Interest

The authors declare no conflict of interest.

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Catalysts 08 00653 g001 550
Figure 1. Comparison of commercially available common visible-light photoredox catalysts and 9,10-phenanthrenedione (source: Sigma-Aldrich (2018)).
Figure 1. Comparison of commercially available common visible-light photoredox catalysts and 9,10-phenanthrenedione (source: Sigma-Aldrich (2018)).
Catalysts 08 00653 g001
Catalysts 08 00653 sch001 550
Scheme 1. Scope of the Friedel-Crafts reaction with different indoles 1 and 2a. Reaction conditions: 1 (0.1 mmol), 2a (0.15 mmol), F (5 mol%) and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under white LEDs irradiation. Isolated yields after column chromatography.
Scheme 1. Scope of the Friedel-Crafts reaction with different indoles 1 and 2a. Reaction conditions: 1 (0.1 mmol), 2a (0.15 mmol), F (5 mol%) and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under white LEDs irradiation. Isolated yields after column chromatography.
Catalysts 08 00653 sch001
Catalysts 08 00653 sch002 550
Scheme 2. Scope of the Friedel-Crafts reaction with indole 1a and different benzoxazinones 2. Reaction conditions: 1a (0.1 mmol), 2 (0.15 mmol), F (5 mol%), and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under white LEDs irradiation. Isolated yields after column chromatography.
Scheme 2. Scope of the Friedel-Crafts reaction with indole 1a and different benzoxazinones 2. Reaction conditions: 1a (0.1 mmol), 2 (0.15 mmol), F (5 mol%), and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under white LEDs irradiation. Isolated yields after column chromatography.
Catalysts 08 00653 sch002
Catalysts 08 00653 sch003 550
Scheme 3. Scope of the Friedel-Crafts reaction with other electron-rich arenes and benzoxazinone 2a. Reaction conditions: arene (0.1 mmol), 2a (0.15 mmol), F (5 mol%), and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under white LEDs irradiation. Isolated yields after column chromatography.
Scheme 3. Scope of the Friedel-Crafts reaction with other electron-rich arenes and benzoxazinone 2a. Reaction conditions: arene (0.1 mmol), 2a (0.15 mmol), F (5 mol%), and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under white LEDs irradiation. Isolated yields after column chromatography.
Catalysts 08 00653 sch003
Catalysts 08 00653 sch004 550
Scheme 4. Friedel-Crafts alkylation of indole 1a with benzoxazinone 2a using sun-light irradiation. Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), F (5 mol%) and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under sun-light irradiation. Isolated yield after column chromatography.
Scheme 4. Friedel-Crafts alkylation of indole 1a with benzoxazinone 2a using sun-light irradiation. Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), F (5 mol%) and Zn(OTf)2 (2.5 mol%) in 1 mL of CH3CN at rt under sun-light irradiation. Isolated yield after column chromatography.
Catalysts 08 00653 sch004
Catalysts 08 00653 sch005 550
Scheme 5. Pausible mechanism for the visible-light photoredox Friedel-Crafts alkylation of 1a with 2a.
Scheme 5. Pausible mechanism for the visible-light photoredox Friedel-Crafts alkylation of 1a with 2a.
Catalysts 08 00653 sch005
Catalysts 08 00653 sch006 550
Scheme 6. Synthetic transformations. Isolated yields after column chromatography.
Scheme 6. Synthetic transformations. Isolated yields after column chromatography.
Catalysts 08 00653 sch006
Table
Table 1. Preliminary optimization of the reaction conditions a.
Table 1. Preliminary optimization of the reaction conditions a.
Catalysts 08 00653 i001
EntryPhotocatalyst (mol%)1a (mmol)2a (mmol)t (h)Yield of 3aa (%) b
1A (1%)0.150.12428
2B (5%)0.150.12738
3C (5%)0.150.14627
4D (5%)0.150.14813
5E (5%)0.150.14835
6F (10%)0.150.12533
7A (1%)0.10.152448
8B (5%)0.10.152453
9E (5%)0.10.154827
10F (10%)0.10.152453
11G (10%)0.10.152415
a Reaction conditions: 1a, 2a, x mol% of photocatalyst in 1 mL of CH3CN at rt under white LEDs 5W irradiation and air atmosphere. b Isolated yield of 3aa.
Table
Table 2. Optimization of the reaction conditions a.
Table 2. Optimization of the reaction conditions a.
Catalysts 08 00653 i002
EntryPhotocat. (mol%)Additive (mol%)Solventt (h)Yield of 3aa (%) b
1F (10%)-CH3CN2453
2F (10%)PhCO2H (10 mol%)CH3CN2436
3F (10%)AcOH (10 mol%)CH3CN2426
4F (10%)Zn(OAc)2 (10 mol%)CH3CN2437
5F (10%)Zn(OTf)2 (10 mol%)CH3CN976
6F (10%)Fe(OTf)2 (10 mol%)CH3CN2022
7F (10%)Cu(OTf)2 (10 mol%)CH3CN1719
8F (10%)Sc(OTf)3 (10 mol%)CH3CN1916
9F (10%)Zn(OTf)2 (5 mol%)CH3CN974
10F (10%)Zn(OTf)2 (5 mol%)Toluene840
11F (10%)Zn(OTf)2 (5 mol%)CH2Cl22030
12F (10%)Zn(OTf)2 (5 mol%)DMF7212
13F (10%)Zn(OTf)2 (5 mol%)THF934
14F (10%)Zn(OTf)2 (5 mol%)MeOH1722
15F (5%)Zn(OTf)2 (5 mol%)CH3CN1074
16F (5%)Zn(OTf)2 (2.5 mol%)CH3CN1075
17B (5%)Zn(OTf)2 (2.5 mol%)CH3CN1738
18 cF (5%)Zn(OTf)2 (2.5 mol%)CH3CN1545
19 dF (5%)Zn(OTf)2 (2.5 mol%)CH3CN72n.d. e
20-Zn(OTf)2 (2.5 mol%)CH3CN72<5 e
a Reaction conditions: 1a (0.1 mmol), 2a (0.15 mmol), x mol% of photocatalyst, x mol% of additive in 1 mL of solvent at rt under white LEDs 5W irradiation and air atmosphere; b Isolated yield of 3aa; c 0.12 mmol of 2a was used; d Reaction performed under darkness; e Conversion to product 3aa by 1H NMR of the crude reaction mixture. N.d. = not detected.

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MDPI and ACS Style

Rostoll-Berenguer, J.; Blay, G.; Pedro, J.R.; Vila, C. 9,10-Phenanthrenedione as Visible-Light Photoredox Catalyst: A Green Methodology for the Functionalization of 3,4-Dihydro-1,4-Benzoxazin-2-Ones through a Friedel-Crafts Reaction. Catalysts 2018, 8, 653. https://doi.org/10.3390/catal8120653

AMA Style

Rostoll-Berenguer J, Blay G, Pedro JR, Vila C. 9,10-Phenanthrenedione as Visible-Light Photoredox Catalyst: A Green Methodology for the Functionalization of 3,4-Dihydro-1,4-Benzoxazin-2-Ones through a Friedel-Crafts Reaction. Catalysts. 2018; 8(12):653. https://doi.org/10.3390/catal8120653

Chicago/Turabian Style

Rostoll-Berenguer, Jaume, Gonzalo Blay, José R. Pedro, and Carlos Vila. 2018. "9,10-Phenanthrenedione as Visible-Light Photoredox Catalyst: A Green Methodology for the Functionalization of 3,4-Dihydro-1,4-Benzoxazin-2-Ones through a Friedel-Crafts Reaction" Catalysts 8, no. 12: 653. https://doi.org/10.3390/catal8120653

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