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Article

Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes Using Molecular Oxygen as the Sole Oxidant Enabled by Quaternary Ammonium Salt

by
Weihui Zhuang
1,
Jiaqi Zhang
1,
Yanping Zheng
1 and
Qiufeng Huang
1,2,*
1
Fujian Key Laboratory of Polymer Materials, College of Chemistry & Materials Science, Fujian Normal University, Fuzhou 350007, China
2
Fujian Provincial Key Laboratory of Advanced Materials Oriented Chemical Engineering, Fuzhou 350007, China
*
Author to whom correspondence should be addressed.
Molecules 2021, 26(17), 5329; https://doi.org/10.3390/molecules26175329
Submission received: 10 August 2021 / Revised: 29 August 2021 / Accepted: 29 August 2021 / Published: 2 September 2021
(This article belongs to the Special Issue Advances in Alkyne Chemistry)
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Abstract

Developing an efficient catalytic system using molecular oxygen as the oxidant for rhodium-catalyzed cross-dehydrogenative coupling remains highly desirable. Herein, rhodium-catalyzed oxidative annulation of 2- or 7-phenyl-1H-indoles with alkenes or alkynes to assemble valuable 6H-isoindolo[2,1-a]indoles, pyrrolo[3,2,1-de]phenanthridines, or indolo[2,1-a]isoquinolines using the atmospheric pressure of air as the sole oxidant enabled by quaternary ammonium salt has been accomplished. Mechanistic studies provided evidence for the fast intramolecular aza-Michael reaction and aerobic reoxidation of Rh(I)/Rh(III), facilitated by the addition of quaternary ammonium salt.

Graphical Abstract

1. Introduction

C-H functionalization, including the reaction of a C-H bond with a (pseudo)halide, the reaction of a C-H bond with an organometallic reagent, and cross-coupling between two C-H bonds (CDC reaction), has gained tremendous popularity in recent years as a methodology for the construction of C-C bonds or C-heteroatom bonds [1,2,3,4,5,6,7,8,9,10,11,12]. Among these reactions, the CDC reaction is especially noteworthy because this reaction precludes both coupling partners from pre-functionalization, and as a result has high step economy and atom economy [13,14,15,16,17,18,19,20,21]. In 2007, Miura and Satoh reported on [RhCp*Cl2]2-catalyzed oxidative coupling of benzoic acids with alkynes [22]. Since then, rhodium-catalyzed oxidative C-H coupling has drawn increasing attention, and many important organic building blocks have been produced [23,24,25,26,27,28,29,30]. However, despite indisputable advances, all rhodium-catalyzed C-H oxidative coupling reactions are extremely limited to hazardous and stoichiometric oxidants such as AgOAc [31,32,33,34,35,36,37] and Cu(OAc)2 [38,39,40,41,42,43,44,45,46,47]. The use of molecular oxygen is advantageous over other oxidants because only water is generated as a by-product [48,49,50,51,52,53,54]. So far, in sharp contrast to aerobic palladium-catalyzed CDC reactions [55,56,57,58,59,60,61,62,63,64,65], only very limited examples of rhodium-catalyzed CDC reaction utilizing molecular oxygen as the sole oxidant have been reported to date [66,67,68,69,70]. Therefore, the development of protocols using molecular oxygen as the oxidant is highly desirable. In continuation of our research on transition metal-catalyzed aerobic CDC reactions [71,72,73], herein we report on the rhodium-catalyzed oxidative annulation of 2-arylindoles or 7-arylindoles with alkenes or alkynes using molecular oxygen as the sole oxidant enabled by quaternary ammonium salt (Scheme 1).

2. Results and Discussion

Our investigation on the aerobic rhodium-catalyzed CDC reaction began with the NH-indole-directed ortho-C-H alkenylation of 2-phenyl-1H-indole (1a) with n-butyl acrylate. The catalytic system consisting of [Cp*RhCl2]2 (2.5 mol%) and n-Bu4NOAc (1 equiv.) promoted the reaction at 140 °C under air atmosphere in xylenes to afford 6H-isoindolo[2,1-a]indole (4a) in 93% yield (Table 1, entry 2), derived from ortho-C-H olefination and the subsequent intramolecular aza-Michael addition. The addition of n-Bu4NOAc was indispensable as the reaction became very sluggish in its absence in various solvents such as xylenes, DMF, THF, EtOAc, and 1,4-dioxane (entry 1). A similar yield was obtained when Me4NOAc (1 equiv.) was added (entry 3), while other quaternary ammonium salts gave inferior results (entries 4–11). Control experiments have shown that no reaction occurred in the absence of rhodium catalyst or molecular oxygen (entry 12).
To gain further insights into the impact of quaternary ammonium salts in the present transformation, we conducted several kinetic studies via 1H NMR spectroscopy. The time study shown in Figure 1 revealed that the one-pot C-H olefination/aza-Michael reaction under air atmosphere afforded 50% yield of 4a after 30 min and was completed within 2 h by adding n-Bu4NOAc. It must be pointed out that the C-H olefinated product was not detected during monitoring period. Without n-Bu4NOAc, 4a was not obtained at all, and nor was the C-H olefinated product (3a) formed. Quaternary ammonium salts have always been considered to be an effective catalyst for Michael reactions [74,75,76,77,78,79]. As one can see from Figure 2, the intramolecular aza-Michael reaction of ortho-alkenylated-2-phenyl-1H-indole could indeed be improved by the addition of n-Bu4NOAc. 1 equiv. of n-Bu4NOAc, and provided complete conversion and quantitative yield of 4a after just 3 min. In the absence of n-Bu4NOAc, no reaction occurred, and the ortho-alkenylated-2-phenyl-1H-indole was totally recovered. The further kinetic experiments were carried out using Cu(OAc)2 instead of O2 as the terminal oxidant. As seen in Figure 3, the C-H olefination of 2-phenylindole with with n-butyl acrylate completed within 2 h in the absence of n-Bu4NOAc, affording 90% yield of 3a. By adding n-Bu4NOAc, the C-H olefinated product (3a) was totally transformed into aza-Michael product 4a within 2 h (Figure 4). In order to illustrate the impact of n-Bu4NOAc in the C-H olefination step, styrene was chosen as the coupling partner because it is not a Michael acceptor, and the reaction can stop after C-H olefination. As shown in Figure 5, no significant differences were observed between experiments performed with or without n-Bu4NOAc. These observations suggest that quaternary ammonium salt plays at least two roles in the oxidative annuation of 2-phenyl-1H-indole with with alkenes: (a) It promotes the intramolecular aza-Michael reaction of the C-H olefinated product; and (b) It promotes aerobic reoxidation of Rh(I) to Rh(III). The second role was partly validated by the fact that the current catalytic system ([Cp*RhCl2]2/n-Bu4NOAc/O2) was also effective for the oxidative annulation of 2-phenylindoles with alkynes to assemble indolo[2,1-a]isoquinoline skeletons. One reason why quaternary ammonium salt can speed up aerobic reoxidation is probably due to the increased dissolved quantity of O2 from adding quaternary ammonium salt [80,81,82].
Reaction condition: Figure 1. A solution of 1a (0.2 mmol), 2a (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and n-Bu4NOAc (1.0 equiv.) in xylenes (4 mL) at 140 °C under air. Figure 2. A solution of 3a (0.2 mmol) and n-Bu4NOAc (1.0 equiv.) in xylenes (4 mL) at 140 °C under air. Figure 3. A solution of 1a (0.2 mmol), 2a (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and Cu(OAc)2 (2.0 equiv.) in xylenes (4 mL) at 140 °C under N2. Figure 4. A solution of 1a (0.2 mmol), 2a (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), n-Bu4NOAc (1.0 equiv.), and Cu(OAc)2 (2.0 equiv.) in xylenes (4 mL) at 140 °C under N2. Figure 5. A solution of 1a (0.2 mmol), 2e (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), n-Bu4NOAc (1.0 equiv.), and Cu(OAc)2 (2.0 equiv.) in xylenes (4 mL) at 140 °C under N2. The yields were determined by the 1H NMR yield using CH2Br2 (0.3 M, 0.2 mmol, 14 mg) as an internal standard.
With the optimized conditions in hand, the generality of the rhodium-catalyzed aerobic C-H olefination/aza-Michael reaction was then explored (Scheme 2). The reaction of 2-phenyl-1H-indole, which contains two ortho-C-H bonds with n-butyl acrylate, provided the desired annulated product 4b in low yield (30%) with recovered starting material (65%). Therefore, blocking one of the ortho-C-H bonds with methyl or chloro is essential for full conversion. 2-phenyl-1H-indole derivatives with substituents at the benzene ring or indole ring were delivered the corresponding products in good to excellent yields, showing very limited effect on the reaction efficiency (4c–4f). As expected, other acrylates bearing methyl, ethyl, or tert-butyl all well reacted with 1a to afford the desired product 4g–4i in good yields. The C-H olefination/aza-Michael reaction of 7-phenyl-1H-indoles with ethyl acrylate afforded the corresponding pyrrolo[3,2,1-de]phenanthridine derivatives under the reaction conditions by changing n-Bu4NOAc with Me4NOAc. By contrast, only one ortho-C-H bond was cleaved, showing good chemoselectivity (4j–4q). 7-phenylindoles and acrylates bearing various substituents, such as chloro (4l), ketone (4m), CN (4n), NO2 (4o), naphthyl (4p), and n-butyl (4q) coupled well with ethyl acrylate or ethyl acrylate, showing good functional group tolerance. The experiment results also showed no electronic effect on the reaction efficiency.
Next, the scope of oxidative annulation of 2-phenyl-1H-indoles with alkynes was briefly investigated. As shown in Scheme 3, the reaction of 2-phenyl-1H-indoles 1 bearing an electron-rich or electron-deficient group at the phenyl ring or indole ring proceeded smoothly to give the corresponding products 6a–6c, 6f–6g in 39–81% yields. For 2-(2-chlorophenyl)-1H-indole or 2-(2-bromophenyl)-1H-indole, both C-H and C-Cl (or C-Br) cleavage occurred. The corresponding C-H oxidative annulation product is difficult to separate from the mixture (6d + 6a or 6e + 6a). In the present [4 + 2] oxidative annulation, when an unsymmetrical diarylalkyne was employed, the formation of two possible regioisomers was observed as expected (6h). Again, valuable functional groups were well accommodated.
Based on the experimental results obtained above and precedent reports [31,32,34,44], a plausible mechanism for the aerobic rhodium-catalyzed oxidative annulation of 2-phenylindole with alkene or alkyne is postulated in Scheme 4. Coordination of N atom of phenylindole to Rh(III) and the subsequent ortho-C-H activation produced the five-membered rhodacycle B. B inserted into the alkene or alkyne affording the intermediate C1 or C2, and the subsequent β-H elimination/reductive elimination provided Rh(I) sandwich complex D1 or D2. Then D1 or D2 was oxidized by oxygen to regenerate the active Rh(III) species and released the corresponding product 3 or 5. The C-H olefinated product (3) can be transformed into aza-Michael product 4 efficiently, and the oxidation step by molecular oxygen will be sped up substantially by adding quaternary ammonium salts.

3. Materials and Methods

3.1. General Information

Unless otherwise noted, the reagents (chemicals) were purchased from commercial sources and were used without further purification. 2-phenyl-1H-indole is commercially available. The other 2-arylindoles were synthesized from phenylhydrazine hydrochlorides via Fisher indole synthesis [44]. 7-phenyl-1H-indoles were synthesized from 7-bromo-1H-indoles and phenylboronic acid via Suzuki coupling [34,35]. Quaternary ammonium salts were purchased from commercial sources. Their purity was more than 99.0% and they were stored in a glovebox. 1H NMR spectra were recorded at 400 MHz and 13C NMR spectra at 100 MHz, respectively (Supplementary material). 1H chemical shifts (δ) were referenced to TMS, and 13C NMR chemical shifts (δ) were referenced to internal solvent resonance. ESI-HRMS spectra were recorded by using a Q-TOF mass spectrometer.

3.2. General Procedure for Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes

Under air atmosphere, 2- or 7-arylindoles (0.2 mmol), alkenes or alkynes (0.4 mmol), [Cp*RhCl2]2 (3.2 mg, 0.005 mmol, 2.5 mol%), n-Bu4NOAc or Me4NOAc (0.2 mmol, 1 equiv.), and xylenes (4 mL) were placed in a 25 mL tube. The mixture was heated in oil bath at 140 °C for 2 h or 80 °C for 20 h. After the reaction mixture cooled to room temperature, the crude reaction mixture was diluted with EtOAc to 5 mL, filtered through a celite pad, and then washed with 10 mL EtOAc. The combined mixture was washed with saturated aqueous Na2CO3 and dried over anhydrous MgSO4. After filtration, the volatiles were removed under reduced pressure, and the residue was subjected to silica gel column chromatography (eluting with petroleum ether/dichloromethane = 1/1 or petroleum ether/ethyl acetate = 100/1) to afford the corresponding product.

3.3. Analytical Characterization Data of Products

Butyl 3-(2-(1H-indol-2-yl)-3-methylphenyl)acrylate (3a), 57.3 mg, 85% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 7.68 (d, J = 7.6 Hz, 1H), 7.60–7.55 (m, 2H), 7.39–7.32 (m, 3H), 7.24–7.15 (m, 2H), 6.48 (dd, J = 2.0, 1.2 Hz, 1H), 6.33 (d, J = 16.0 Hz, 1H), 4.06 (t, J = 6.4 Hz, 2H), 2.23 (s, 3H), 1.59–1.51 (m, 2H), 1.31–1.25 (m, 2H), 0.86 (t, J = 7.2 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [44].
2-(2-Methyl-6-styrylphenyl)-1H-indole (3b), 25.3 mg, 41% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.73–7.71 (m, 1H), 7.67 (d, J = 8.0 Hz, 1H), 7.42–7.36 (m, 2H), 7.32–7.25 (m, 4H), 7.24–7.18 (m, 4H), 7.03 (d, J = 8.4 Hz, 2H), 6.54 (dd, J = 2.0, 0.8 Hz, 1H), 2.26 (s, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [44].
Butyl 2-(10-methyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4a), 61.4 mg, 93% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (d, J = 8.0 Hz, 1H), 7.40 (dd, J = 8.4, 0.8 Hz, 1H), 7.30 (t, J = 4.4 Hz, 1H), 7.23–7.19 (m, 3H), 7.13 (td, J = 8.0, 0.8 Hz, 1H), 6.61 (s, 1H), 5.75 (dd, J = 8.0, 4.4 Hz, 1H), 4.21–4.14 (m, 2H), 3.30 (dd, J = 16.4, 4.8 Hz, 1H), 2.76 (dd, J = 16.4, 8.0 Hz, 1H), 2.63 (s, 3H), 1.62–1.55 (m, 2H), 1.35–1.30 (m, 2H), 0.92 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 171.1, 145.8, 143.1, 133.5, 133.2, 132.5, 131.3, 129.9, 127.5, 121.9, 120.7, 119.8, 109.6, 94.2, 65.2, 56.8, 39.9, 30.6, 19.5, 19.2, 13.8. HRMS (ESI) calcd for C22H24NO2 [M + H]+: 334.1807, found: 334.1808.
Butyl 3-(6-(2-butoxy-2-oxoethyl)-6H-isoindolo[2,1-a]indol-10-yl)acrylate (4b), 29.7 mg, 30% yield, red solid. 1H NMR (400 MHz, CDCl3) δ 8.32 (d, J = 16.0 Hz, 1H), 7.70 (dt, J = 8.0, 0.8 Hz, 1H), 7.64 (d, J = 7.6 Hz, 1H), 7.46 (dt, J = 7.2, 1.2 Hz, 1H), 7.39 (dd, J = 8.0, 0.8 Hz, 1H), 7.30 (t, J = 7.6 Hz, 1H), 7.23 (td, J = 7.2, 1.2 Hz, 1H), 7.16–7.12 (m, 1H), 6.79 (s, 1H), 6.56 (d, J = 15.6 Hz, 1H), 5.74 (dd, J = 8.0, 4.4 Hz, 1H), 4.29 (t, J = 6.8 Hz, 2H), 4.19–4.12 (m, 2H), 3.31 (dd, J = 16.4, 4.4 Hz, 1H), 2.77 (dd, J = 16.0, 8.0 Hz, 1H), 1.80–1.73 (m, 2H), 1.56–1.48 (m, 4H), 1.33–1.26 (m, 2H), 1.02 (t, J = 7.6 Hz, 3H), 0.90 (t, J = 7.6 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [44].
Butyl 2-(10-chloro-6H-isoindolo[2,1-a]indol-6-yl)acetate (4c), 50.6 mg, 72% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.71 (dt, J = 8.0, 0.8 Hz, 1H), 7.40–7.36 (m, 3H), 7.23 (td, J = 8.0, 1.2 Hz, 2H), 7.16–7.12 (m, 1H), 6.91 (s, 1H), 5.77 (dd, J = 8.0, 4.4 Hz, 1H), 4.19–4.13 (m, 2H), 3.31 (dd, J = 16.4, 4.4 Hz, 1H), 2.77 (dd, J = 16.4, 8.4 Hz, 1H), 1.59–1.55 (m, 2H), 1.34–1.28 (m, 2H), 0.91 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.7, 147.4, 140.6, 133.3, 133.2, 131.0, 129.4, 128.3, 128.0, 122.5, 121.8, 120.1, 109.6, 96.0, 65.3, 57.0, 39.6, 30.6, 19.2, 13.8. HRMS (ESI) calcd for C21H21NO2Cl [M + H]+: 354.1261, found: 354.1257.
Butyl 2-(8,10-dimethyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4d), 56.2 mg, 81% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (dt, J = 7.6, 1.2 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.23–7.19 (m, 1H), 7.15–7.11 (m, 2H), 7.05 (s, 1H), 6.56 (s, 1H), 5.70 (dd, J = 8.0, 4.4 Hz, 1H), 4.25–4.16 (m, 2H), 3.29 (dd, J = 16.0, 4.4 Hz, 1H), 2.76 (dd, J = 16.0, 8.0 Hz, 1H), 2.59 (s, 3H), 2.40 (s, 3H), 1.63–1.59 (m, 2H), 1.38–1.33 (m, 2H), 0.94 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 171.1, 146.1, 143.2, 137.6, 133.6, 133.1, 132.2, 130.8, 128.6, 121.7, 121.6, 121.4, 119.6, 109.4, 93.4, 65.1, 56.7, 39.9, 30.7, 21.7, 19.4, 19.2, 13.8. HRMS (ESI) calcd for C23H26NO2 [M + H]+: 348.1964, found: 348.1960.
Butyl 2-(2,10-dimethyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4e), 60.7 mg, 88% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.47 (s, 1H), 7.30–7.27 (m, 2H), 7.22–7.20 (m, 2H), 7.04 (dd, J = 8.4, 1.2 Hz, 1H), 6.52 (s, 1H), 5.72 (dd, J = 8.0, 4.8 Hz, 1H), 4.21–4.14 (m, 2H), 3.27 (dd, J = 16.4, 4.8 Hz, 1H), 2.74 (dd, J = 16.0, 8.0 Hz, 1H), 2.62 (s, 3H), 2.47 (s, 3H), 1.61–1.57 (m, 2H), 1.36–1.30 (m, 2H), 0.92 (t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 171.1, 145.8, 143.1, 133.8, 132.4, 131.6, 131.5, 129.9, 129.0, 127.3, 123.5, 121.6, 120.7, 109.2, 93.7, 65.1, 56.8, 39.9, 30.7, 21.6, 19.5, 19.2, 13.8. HRMS (ESI) calcd for C23H26NO2 [M + H]+: 348.1964, found: 348.1964.
Butyl 2-(2-chloro-10-methyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4f), 57.2 mg, 77% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.63 (dd, J = 2.0, 0.4 Hz, 1H), 7.31–7.28 (m, 2H), 7.23–7.22 (m, 2H), 7.14 (dd, J = 8.4, 2.0 Hz, 1H), 6.53 (s, 1H), 5.71 (dd, J = 7.6, 4.8 Hz, 1H), 4.18–4.12 (m, 2H), 3.19 (dd, J = 16.4, 4.8 Hz, 1H), 2.79 (dd, J = 16.0, 7.6 Hz, 1H), 2.61 (s, 3H), 1.58–1.54 (m, 2H), 1.33–1.27 (m, 2H), 0.91 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 170.8, 145.7, 144.4, 134.5, 132.7, 131.6, 130.9, 130.1, 127.9, 125.4, 122.0, 121.1, 120.7, 110.4, 93.8, 65.2, 57.1, 39.9, 30.6, 19.5, 19.2, 13.8. HRMS (ESI) calcd for C22H23NO2Cl [M + H]+: 368.1417, found: 368.1412.
Methyl 2-(10-methyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4g), 49.4 mg, 85% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.74 (dd, J = 7.6, 0.8 Hz, 1H), 7.41 (d, J = 8.0 Hz, 1H), 7.33–7.30 (m, 1H), 7.28–7.24 (m, 3H), 7.19–7.15 (m, 1H), 6.64 (s, 1H), 5.74 (dd, J = 8.4, 4.8 Hz, 1H), 3.82 (s, 3H), 3.32 (dd, J = 16.4, 4.8 Hz, 1H), 2.73 (dd, J = 16.0, 8.0 Hz, 1H), 2.64 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 171.4, 145.7, 142.9, 133.5, 133.1, 132.5, 131.1, 129.9, 127.4, 121.8, 120.7, 119.7, 109.5, 94.2, 56.7, 52.2, 39.6, 19.5. HRMS (ESI) calcd for C19H18NO2 [M + H]+: 292.1338, found: 292.1340.
Ethyl 2-(10-methyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4h), 51.9 mg, 86% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (dt, J = 7.6, 1.2 Hz, 1H), 7.40 (dq, J = 8.0, 0.8 Hz, 1H), 7.32–7.29 (m, 1H), 7.23–7.19 (m, 3H), 7.14–7.10 (m, 1H), 6.61 (s, 1H), 5.75 (dd, J = 8.0, 4.4 Hz, 1H), 4.24 (qd, J = 7.2, 2.4 Hz, 2H), 3.29 (dd, J = 16.4, 4.8 Hz, 1H), 2.74 (dd, J = 16.0, 8.0 Hz, 1H), 2.62 (s, 3H), 1.25 (t, J = 6.8 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 171.0, 145.8, 143.1, 133.5, 133.2, 132.5, 131.3, 129.9, 127.5, 121.9, 120.8, 119.8, 109.6, 94.2, 61.2, 56.8, 39.9, 19.5, 14.2. HRMS (ESI) calcd for C20H20NO2 [M + H]+: 306.1494, found: 306.1493.
Tert-butyl 2-(10-methyl-6H-isoindolo[2,1-a]indol-6-yl)acetate (4i), 53.6 mg, 81% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.69 (dt, J = 8.0, 0.8 Hz, 1H), 7.44 (dq, J = 8.0, 0.8 Hz, 1H), 7.35–7.32 (m, 1H), 7.24–7.19 (m, 3H), 7.15–7.10 (m, 1H), 6.61 (s, 1H), 5.71 (dd, J = 7.6, 4.4 Hz, 1H), 3.21 (dd, J = 16.0, 4.4 Hz, 1H), 2.77 (dd, J = 16.0, 7.6 Hz, 1H), 2.63 (s, 3H), 1.39 (s, 9H). 13C NMR (100 MHz, CDCl3) δ 170.0, 145.9, 143.2, 133.5, 133.2, 132.4, 131.4, 129.8, 127.4, 121.8, 120.8, 119.7, 109.7, 105.1, 94.0, 81.6, 57.0, 40.8, 28.0, 19.5. HRMS (ESI) calcd for C22H24NO2 [M + H]+: 334.1807, found: 334.1804.
Ethyl 2-(7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4j), 43.5 mg, 74% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 7.6 Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.55 (dd, J = 7.6, 0.4 Hz, 1H), 7.41–7.37 (m, 1H), 7.32–7.30 (m, 2H), 7.25 (d, J = 3.2 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 6.56 (d, J = 3.2 Hz, 1H), 6.14 (dd, J = 7.2, 5.2 Hz, 1H), 4.19–4.03 (m, 2H), 2.77 (dd, J = 7.2, 4.8 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
Ethyl 2-(9-methyl-7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4k), 39.1 mg, 63% yield, yellow soild. 1H NMR (400 MHz, CDCl3) δ 7.85 (d, J = 7.6 Hz, 1H), 7.54 (d, J = 7.2 Hz, 1H), 7.51 (dd, J = 8.0, 0.8 Hz, 1H), 7.23 (d, J = 3.2 Hz, 1H), 7.21–7.11 (m, 3H), 6.54 (d, J = 3.2 Hz, 1H), 6.08 (dd, J = 6.8, 5.6 Hz, 1H), 4.15–4.07 (m, 2H), 2.76 (d, J = 1.6 Hz, 1H), 2.75 (s, 1H), 2.38 (s, 3H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
Ethyl 2-(9-chloro-7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4l), 48.4 mg, 71% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 8.4 Hz, 1H), 7.55–7.52 (m, 2H), 7.35 (dd, J = 8.4, 2.0 Hz, 1H), 7.30 (d, J = 2.0 Hz, 1H), 7.23 (d, J = 3.2 Hz, 1H), 7.14 (t, J = 7.6 Hz, 1H), 6.56 (d, J = 3.2 Hz, 1H), 6.08 (dd, J = 6.8, 5.2 Hz, 1H), 4.11 (q, J = 7.2 Hz, 2H), 2.76 (dd, J = 7.2, 4.8 Hz, 2H), 1.17 (t, J = 6.8 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
Ethyl 2-(9-acetyl-7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4m), 40.9 mg, 61% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.00–7.91 (m, 3H), 7.60 (t, J = 6.4 Hz, 2H), 7.25 (s, 1H), 7.16 (t, J = 8.0 Hz, 1H), 6.57 (d, J = 3.2 Hz, 1H), 6.15 (dd, J = 7.6, 5.2 Hz, 1H), 4.14–4.05 (m, 2H), 2.82–2.74 (m, 2H), 2.62 (s, 3H), 1.15 (t, J = 7.2 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 197.1, 170.4, 136.2, 134.9, 134.0, 133.3, 128.6, 127.7, 127.1, 126.4, 122.9, 122.4, 120.9, 117.0, 115.1, 103.8, 61.2, 55.4, 46.4, 26.7, 14.1. HRMS (ESI) calcd for C21H20NO3 [M + H]+: 334.1443, found: 334.1446.
Ethyl 2-(9-cyano-7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4n), 44.7 mg, 71% yield, yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.0 Hz, 1H), 7.66 (dd, J = 8.0, 1.6 Hz, 1H), 7.63–7.58 (m, 3H), 7.25 (d, J = 3.2 Hz, 1H), 7.18 (t, J = 7.6 Hz, 1H), 6.59 (d, J = 3.2 Hz, 1H), 6.13 (dd, J = 7.6, 5.2 Hz, 1H), 4.10 (q, J = 7.2 Hz, 2H), 2.77 (qd, J = 16.0, 7.6 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
Ethyl 2-(9-nitro-7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4o), 41.3 mg, 61% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 8.24 (dd, J = 8.8, 2.4 Hz, 1H), 8.20 (d, J = 2.0 Hz, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.64 (d, J = 3.2 Hz, 1H), 7.62 (d, J = 2.4 Hz, 1H), 7.27 (d, J = 3.2 Hz, 1H), 7.19 (t, J = 7.6 Hz, 1H), 6.60 (d, J = 3.2 Hz, 1H), 6.20 (dd, J = 7.2, 4.8 Hz, 1H), 4.10 (qd, J = 7.2, 2.0 Hz, 2H), 2.82 (qd, J = 16.0, 7.2 Hz, 2H), 1.16 (t, J = 7.2 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
Ethyl 2-(7H-benzo[j]pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4p), 44.5 mg, 65% yield, yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.40 (s, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.80 (s, 1H), 7.78 (d, J = 2.8 Hz, 2H), 7.59 (dd, J = 8.0, 0.8 Hz, 1H), 7.55–7.44 (m, 2H), 7.30 (d, J = 3.2 Hz, 1H), 7.23 (t, J = 7.6 Hz, 1H), 6.60 (d, J = 3.2 Hz, 1H), 6.26 (t, J = 6.4 Hz, 1H), 4.14–4.06 (m, 2H), 2.82 (qd, J = 15.6, 7.2 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
Butyl 2-(7H-pyrrolo[3,2,1-de]phenanthridin-7-yl)acetate (4q), 47.5 mg, 72% yield, yellow oil. 1H NMR (400 MHz, CDCl3) δ 7.97 (d, J = 7.6 Hz, 1H), 7.58 (d, J = 7.6 Hz, 1H), 7.54 (dd, J = 8.0, 0.8 Hz, 1H), 7.41–7.37 (m, 1H), 7.32–7.30 (m, 2H), 7.24 (d, J = 3.2 Hz, 1H), 7.16 (t, J = 7.6 Hz, 1H), 6.55 (d, J = 3.2 Hz, 1H), 6.14 (dd, J = 7.2, 5.2 Hz, 1H), 4.11–4.00 (m, 2H), 2.78 (qd, J = 16.0, 7.6 Hz, 2H), 1.54–1.47 (m, 2H), 1.30–1.24 (m, 2H), 0.89 (t, J = 7.6 Hz, 3H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [35].
5,6-Diphenylindolo[2,1-a]isoquinoline (6a), 55.8 mg, 75% yield, yellow solid. 1H NMR (400 MHz, CDCl3) δ 8.31 (d, J = 8.0 Hz, 1H), 7.81 (d, J = 8.0 Hz, 1H), 7.52 (t, J = 7.6 Hz, 1H), 7.43 (s, 1H), 7.41–7.25 (m, 7H), 7.26–7.13 (m, 6H), 6.83 (t, J = 8.0 Hz, 1H), 6.01 (d, J = 8.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 136.9, 136.1, 135.5, 132.9, 132.0, 131.0, 130.4, 129.8, 128.8, 128.7, 128.0, 127.5, 127.2, 126.9, 126.3, 125.5, 123.4, 121.8, 120.3, 120.2, 114.7, 94.3. HRMS data for the desired product were in agreement with the previously reported literature data [40].
10-Nitro-5,6-diphenylindolo[2,1-a]isoquinoline (6b), 64.8 mg, 79% yield, orange solid. 1H NMR (400 MHz, CDCl3) δ 8.70 (d, J = 2.4 Hz, 1H), 8.32 (d, J = 8.0 Hz, 1H), 7.66 (dd, J = 9.6, 2.4 Hz, 1H), 7.59–7.54 (m, 2H), 7.44–7.36 (m, 4H), 7.31–7.27 (m, 3H), 7.25–7.17 (m, 5H), 5.99 (d, J = 9.6 Hz, 1H). 13C NMR and HRMS data for the desired product were in agreement with the previously reported literature data [40].
1-Methyl-5,6-diphenylindolo[2,1-a]isoquinoline (6c), 55.3 mg, 73% yield, yellow solid, m.p. 173.7–174.0 °C. 1H NMR (400 MHz, CDCl3) δ 7.84 (d, J = 8.0 Hz, 1H), 7.56 (s, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.36–7.26 (m, 6H), 7.25–7.16 (m, 6H), 7.04 (d, J = 8.0 Hz, 1H), 6.86–6.81 (m, 1H), 6.00 (d, J = 8.4 Hz, 1H), 3.03 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 137.6, 135.9, 135.2, 132.0, 131.9, 131.0, 130.3, 129.6, 128.7, 128.0, 126.8, 126.6, 125.1, 124.5, 121.6, 120.6, 120.5, 114.8, 100.7, 25.4. HRMS (ESI) calcd for C29H22N [M + H]+: 384.1752, found: 384.1751.
1-Chloro-5,6-diphenylindolo[2,1-a]isoquinoline (6d) and 5,6-diphenylindolo[2,1-a]isoquinoline (6a), 37.5 mg, 47% yield, yellow solid, m.p. 201.1–201.6 °C. 1H NMR (400 MHz, CDCl3) δ 8.40 (6d, d, J = 0.8 Hz, 1H), 8.30 (6a, dt, J = 8.0, 0.8 Hz, 1H), 7.85 (6d, dt, J = 8.0, 1.2 Hz, 1H), 7.79 (6a, dt, J = 8.0, 1.2 Hz, 1H), 7.57 (6d, dd, J = 8.0, 1.2 Hz, 1H), 7.53–7.49 (6a, m, 1H), 7.42 (6a, d, J = 0.4 Hz, 1H), 7.36–7.28 (6d + 6a, m, 11H), 7,24–7.13 (6d + 6a, m, 14H), 7.05 (6d, dd, J = 8.0, 1.2 Hz, 1H), 6.87–6.79 (6d + 6a, m, 2H), 6.00–5.95 (6d + 6a, m, 2H). 13C NMR (100 MHz, CDCl3) δ 137.0, 135.4, 132.9, 132.0, 131.0, 130.8, 129.7, 128.9, 128.8, 128.7, 128.1, 128.0, 127.5, 127.2, 127.1, 126.9, 126.3, 125.1, 123.6, 123.4, 121.8, 121.8, 121.3, 121.1, 120.2, 114.7, 102.5, 94.3. HRMS (ESI) calcd for 6d C29H19NCl [M + H]+: 404.1206, found: 404.1209.
1-Bromo-5,6-diphenylindolo[2,1-a]isoquinoline (6e) and 5,6-diphenylindolo[2,1-a]isoquinoline (6a), 34.9 mg, 39% yield, yellow solid, m.p. 188.5–188.9 °C. 1H NMR (400 MHz, CDCl3) δ 8.67 (6e, s, 1H), 8.31 (6a, d, J = 8.0 Hz, 1H), 7.85 (6e, d, J = 8.0 Hz, 1H), 7.82–7.79 (6e + 6a, m, 2H), 7.53–7.49 (6a, m, 1H), 7.43–7.27 (6e + 6a, m, 13H), 7.25–7.10 (6e + 6a, m, 14H), 6.87–6.79 (6e + 6a, m, 2H), 6.00 (6a, d, J = 8.8 Hz, 1H), 5.97 (6e, d, J = 8.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ 133.7, 132.0, 132.0, 131.0, 130.8, 128.9, 128.9, 128.8, 128.8, 128.2, 128.0, 127.5, 127.3, 127.2, 127.1, 127.1, 126.9, 126.3, 125.9, 121.3, 121.1, 120.3, 120.2, 119.7, 114.7, 102.2, 94.3. HRMS (ESI) calcd for 6e C29H19NBr [M + H]+: 448.0701, found: 448.0705.
1,3-Dimethyl-5,6-diphenylindolo[2,1-a]isoquinoline (6f), 64.4 mg, 81% yield, orange solid, m.p. 183.2–183.7 °C. 1H NMR (400 MHz, CDCl3) δ 7.82 (dt, J = 8.0, 1.2 Hz, 1H), 7.50 (s, 1H), 7.35–7.27 (m, 5H), 7.25–7.15 (m, 7H), 6.84–6.79 (m, 2H), 5.98 (d, J = 8.4 Hz, 1H), 2.99 (s, 3H), 2.31 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 137.7, 136.5, 136.0, 135.9, 135.7, 135.1, 132.1, 131.9, 131.7, 131.0, 129.7, 128.7, 128.7, 128.0, 126.7, 124.5, 122.7, 122.0, 121.5, 120.3, 120.3, 114.7, 99.9, 25.3, 21.5. HRMS (ESI) calcd for C30H24N [M + H]+: 398.1909, found: 398.1905.
1,10-Dimethyl-5,6-diphenylindolo[2,1-a]isoquinoline (6g), 64.2 mg, 81% yield, orange solid, m.p. 212.6–213.0 °C. 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1H), 7.38 (d, J = 7.2 Hz, 1H), 7.36–7.26 (m, 6H), 7.25–7.16 (m, 6H), 7.05 (dd, J = 8.0, 1.2 Hz, 1H), 6.68 (dd, J = 8.8, 2.0 Hz, 1H), 5.87 (d, J = 8.8 Hz, 1H), 3.02 (s, 3H), 2.44 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 137.7, 136.0, 135.9, 135.6, 135.1, 132.1, 131.9, 131.0, 130.3, 130.2, 130.0, 128.7, 128.0, 126.8, 126.5, 125.1, 124. 5, 122.4, 121.8, 120.0, 114.4, 100.3, 25.4, 21.5. HRMS (ESI) calcd for C30H24N [M + H]+: 398.1909, found: 398.1912.
5-(4-Ethylphenyl)-1-methyl-6-(p-tolyl)indolo[2,1-a]isoquinoline and 6-(4-ethylphenyl)-1-methyl-5-(p-tolyl)indolo[2,1-a]isoquinoline (6h), 68.6 mg, 82% yield, yellow solid, m.p. 151.6–151.9 °C. 1H NMR (400 MHz, CDCl3) δ 7.82 (dq, J = 8.0, 1.2 Hz, 1H), 7.54 (s, 1H), 7.37 (d, J = 6.8 Hz, 1H), 7.25–7.12 (m, 6H), 7.07 and 7.05 (a pair of s, 5H), 6.87–6.81 (m, 1H), 6.04 and 5.98 (a pair of dd, J = 8.8, 0.8 Hz, 1H), 3.02 (s, 3H), 2.69 and 2.62 (a pair of q, J = 7.6 Hz, 2H), 2.39 and 2.32 (a pair of s, 3H), 1.27 and 1.22 (a pair of t, J = 7.6 Hz, 3H). 13C NMR (100 MHz, CDCl3) δ 144.8, 142.5, 138.3, 136.1, 135.6, 135.1, 134.8, 134.6, 133.2, 132.0, 131.8, 130.8, 130.8, 130.1, 129.6, 129.4, 128.7, 128.2, 127.4, 126.5, 125.0, 124.6, 124.5, 122.1, 122.0, 121.4, 120.4, 120.4, 115.0, 100.6, 28.8, 28.6, 25.4, 21.6, 21.4, 15.6, 15.5. HRMS (ESI) calcd for C32H28N [M + H]+: 426.2222, found: 426.2224.

4. Conclusions

In conclusion, we have reported on the rhodium-catalyzed oxidative annulation of 2- or 7-phenyl-1H-indoles with alkenes or alkynes to assemble valuable 6H-isoindolo[2,1-a]indoles, pyrrolo[3,2,1-de]phenanthridines, or indolo[2,1-a]isoquinolines using molecular oxygen as the sole oxidant enable by quaternary ammonium salt. Salient features of present catalytic system comprise (a) the atmospheric pressure of air as the sole oxidant, (b) one catalytic system for three discrete reactions, and (c) mechanistic insights. Mechanistic studies provided support for fast intramolecular aza-Michael reaction and aerobic reoxidation of Rh(I) to Rh(III) by adding quaternary ammonium salt. Additional mechanistic/computational studies will be needed to fully elucidate the unique influence of quaternary ammonium salt on the catalytic cycle, and are in progress in our laboratory.

Supplementary Materials

The following are available online. Figure S1: Copies of the 1H NMR, 13C NMR charts for compounds.

Author Contributions

Conceptualization, W.Z. and Q.H.; experiments and analyses, W.Z., Y.Z., and J.Z.; writing—original draft preparation, W.Z.; writing—review and editing, Q.H. All authors have read and agreed to the published version of the manuscript.

Funding

This research was funded by the National Science Foundation of China (Grant No. 21872028), the Natural Science Foundation of Fujian Province (Grant No. 2020J01149), the Fujian Province University Fund for New Century Excellent Talents, and the National College Students’ innovation and entrepreneurship training program (Y.Z.).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

The data presented in this study are available in Supplementary Materials.

Conflicts of Interest

The authors declare no conflict of interest.

Sample Availability

Samples of the compounds are available from the authors.

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Molecules 26 05329 sch001
Scheme 1. Rhodium-catalyzed oxidative annulation of 2- or 7-phenyl-1H-indoles with alkenes or alkynes using molecular oxygen as the sole oxidant enabled by quaternary ammonium salt.
Scheme 1. Rhodium-catalyzed oxidative annulation of 2- or 7-phenyl-1H-indoles with alkenes or alkynes using molecular oxygen as the sole oxidant enabled by quaternary ammonium salt.
Molecules 26 05329 sch001
Molecules 26 05329 g001
Figure 1. The one-pot C-H olefination/aza-Michael reaction of 1a with 2a under air.
Figure 1. The one-pot C-H olefination/aza-Michael reaction of 1a with 2a under air.
Molecules 26 05329 g001
Molecules 26 05329 g002
Figure 2. The intramolecular aza-Michael reaction of 3a under air.
Figure 2. The intramolecular aza-Michael reaction of 3a under air.
Molecules 26 05329 g002
Molecules 26 05329 g003
Figure 3. The C-H olefination of 1a with 2a using Cu(OAc)2 instead of O2 as the terminal oxidant.
Figure 3. The C-H olefination of 1a with 2a using Cu(OAc)2 instead of O2 as the terminal oxidant.
Molecules 26 05329 g003
Molecules 26 05329 g004
Figure 4. The C-H olefination/aza-Michael reaction of 1a with 2a using Cu(OAc)2 as the terminal oxidant.
Figure 4. The C-H olefination/aza-Michael reaction of 1a with 2a using Cu(OAc)2 as the terminal oxidant.
Molecules 26 05329 g004
Molecules 26 05329 g005
Figure 5. The C-H olefination of 1a with 2e using Cu(OAc)2 as the terminal oxidant.
Figure 5. The C-H olefination of 1a with 2e using Cu(OAc)2 as the terminal oxidant.
Molecules 26 05329 g005
Molecules 26 05329 sch002
Scheme 2. Substrate scope of oxidative annulation of 2- or 7-phenyl-1H-indoles with alkenes. a: Reaction condition: 1a (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and n-Bu4NOAc (1 equiv.) in xylenes (4 mL) at 140 °C under air atmosphere for 2 h. Isolated yield. b: Me4NOAc was used.
Scheme 2. Substrate scope of oxidative annulation of 2- or 7-phenyl-1H-indoles with alkenes. a: Reaction condition: 1a (0.2 mmol), 2 (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and n-Bu4NOAc (1 equiv.) in xylenes (4 mL) at 140 °C under air atmosphere for 2 h. Isolated yield. b: Me4NOAc was used.
Molecules 26 05329 sch002
Molecules 26 05329 sch003
Scheme 3. Substrate scope of oxidative annulation of 2-phenyl-1H-indoles with alkynes a. a: Reaction condition: 1a (0.2 mmol), 5 (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and n-Bu4NOAc (1 equiv.) in xylenes (4 mL) at 80 °C under air atmosphere for 20 h. Isolated yield.
Scheme 3. Substrate scope of oxidative annulation of 2-phenyl-1H-indoles with alkynes a. a: Reaction condition: 1a (0.2 mmol), 5 (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and n-Bu4NOAc (1 equiv.) in xylenes (4 mL) at 80 °C under air atmosphere for 20 h. Isolated yield.
Molecules 26 05329 sch003
Molecules 26 05329 sch004
Scheme 4. Plausible mechanism for the aerobic rhodium-catalyzed oxidative annulation of 2-phenylindole with alkene or alkyne.
Scheme 4. Plausible mechanism for the aerobic rhodium-catalyzed oxidative annulation of 2-phenylindole with alkene or alkyne.
Molecules 26 05329 sch004
Table 1. Optimization of the reaction conditions a.
Table 1. Optimization of the reaction conditions a.
Molecules 26 05329 i001
EntryAdditiveYield (%) (3a) b
1 c-0
2 n-Bu4NOAc93 (91 d)
3 Me4NOAc88
4 n-Bu4NPF6trace
5 n-Bu4NBF40
6 n-Bu4NHSO40
7 n-Bu4NCltrace
8 n-Bu4NI0
9 NH4Cl 0
10 NH4PF6trace
11 Et4NBr0
12 en-Bu4NOActrace
a: Reaction condition: 1a (0.2 mmol), 2a (0.4 mmol), [Cp*RhCl2]2 (2.5 mol%), and additive (1 equiv.) in xylenes (4 mL) at 140 °C under air for 8 h. b: Determined by 1H NMR yield using CH2Br2 as an internal standard. c: Xylenes, DMF, THF, EtOAc, or 1,4-dioxane. d: Isolated yield. e: In the absence of [Cp*RhCl2]2 or under N2 atmosphere.
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Zhuang, W.; Zhang, J.; Zheng, Y.; Huang, Q. Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes Using Molecular Oxygen as the Sole Oxidant Enabled by Quaternary Ammonium Salt. Molecules 2021, 26, 5329. https://doi.org/10.3390/molecules26175329

AMA Style

Zhuang W, Zhang J, Zheng Y, Huang Q. Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes Using Molecular Oxygen as the Sole Oxidant Enabled by Quaternary Ammonium Salt. Molecules. 2021; 26(17):5329. https://doi.org/10.3390/molecules26175329

Chicago/Turabian Style

Zhuang, Weihui, Jiaqi Zhang, Yanping Zheng, and Qiufeng Huang. 2021. "Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes Using Molecular Oxygen as the Sole Oxidant Enabled by Quaternary Ammonium Salt" Molecules 26, no. 17: 5329. https://doi.org/10.3390/molecules26175329

APA Style

Zhuang, W., Zhang, J., Zheng, Y., & Huang, Q. (2021). Rhodium-Catalyzed Oxidative Annulation of 2- or 7-Arylindoles with Alkenes/Alkynes Using Molecular Oxygen as the Sole Oxidant Enabled by Quaternary Ammonium Salt. Molecules, 26(17), 5329. https://doi.org/10.3390/molecules26175329

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