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. 2022 Oct 14;7(42):37050–37060. doi: 10.1021/acsomega.2c01941

Acid-Promoted Redox-Annulation toward 1,2-Disubstituted-5,6-dihydropyrrolo[2,1-α]isoquinolines: Synthesis of the Lamellarin Core

Guo-Quan Hou 1, Wenyan Zhao 1, Changjiang Deng 1, Chunping Dong 1, Cheli Wang 1, Li Liu 1,*, Jian Li 1,*
PMCID: PMC9608416  PMID: 36312359

Abstract

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An efficient synthesis of a variety of 1,2-disubstituted-5,6-dihydropyrrolo[2,1-α]isoquinoline derivatives via an acid-promoted cyclization reaction between 1,2,3,4-tetrahydroisoquinoline (THIQ) and substituted α,β-unsaturated aldehyde derivatives is reported. This cycloaddition allows access to structurally diverse multisubstituted dihydropyrrolo[2,1-α]isoquinolines in moderate to good yields, which was the core scaffold of marine natural alkaloid lamellarins.

Introduction

Pyrroles are prominent structural motifs in numerous biologically active substances,1,2 especially pyrrolo[2,1-α]isoquinoline and its derivatives, which have a variety of pharmacological properties.3−5 For example, pyrroloisoquinoline alkaloid crispine A, which has emerged as natural products’ target of interest isolated in 2002 from the antitumor active extract of Carduus crispus (Figure 1), due to reports of its cytotoxic activity and similarity to known congeners, has been shown to exhibit antidepressant-like activity.6−13 The marine natural alkaloid lamellarins, bearing a pyrrolo[2,1-α]isoquinoline core, were found to have a wide spectrum of pharmacological activities.14−19 For example, lamellarin I exhibited direct inhibition of P-glycoprotein-mediated drug efflux at noncytotoxic doses to reverse multidrug resistance;20,21 lamellarin D showed potent antitumor activity to be an inhibitor of human topoisomerase I.22−25 Also, lamellarin K and L have been investigated for their immunomodulatory effects in the micromolar range,26,27 and lamellarin α-20-sulfate was expected to be a drug candidate for the inhibition of HIV integrase at noncytotoxic concentrations.28,29

Figure 1.

Figure 1

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Representative examples of pyrroloisoquinoline.

The novel structure of the lamellarin as well as their pharmacological potential led to a tremendous interest in these compounds. The lamellarin alkaloids were first isolated by Faulkner and co-workers from the prosobranch mollusc Lamellaria sp.30 To better understand these attractive compounds, various efficient synthetic methods have been developed.31−39 These processes mostly entail 1,3-dipolar cycloaddition to construct the core scaffold pyrrolo[2,1-α]isoquinoline (Scheme 1). In 2007, Porco’s group developed an efficient synthesis of lamellarin products involving Ag(I)-catalyzed domino cycloisomerization/dipolar cycloaddition of readily available alkynyl N-benzylidene glycinates via azomethine ylides as a key intermediate (Scheme 1, eq. 1).40 Zhen and Wang reported an azodicarboxylate (DEAD)-promoted oxidative [3+2] cycloaddition/aromatization tandem reaction for the construction of pyrrolo[2,1-α]isoquinolines (eq. 21).41 Wu and co-workers demonstrated an intermolecular [3+2] cycloaddition for the directed synthesis of pyrrolo[2,1-α]isoquinolines core from 1,2,3,4-tetrahydroisoquinoline (THIQ), phenylglyoxal monohydrate, and (E)-(2-nitrovinyl)benzene (eq. 31).42

Scheme 1. Synthetic Strategies of Pyrroloisoquinoline.

Scheme 1

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However, efficient approaches for synthesizing pyrrolo[2,1-α]isoquinoline are still rare in the literature. Thus, exploiting more new synthetic strategies is still a pressing task to realize the potential applications of biologically active lamellarin alkaloids. Recently, Seidel developed a strategy for the rapid formation of fused tricyclic ring systems via redox-neutral annulations of cyclic amines (e.g., pyrrolidine and THIQ) with aldehydes and ketones (eq. 41).43−47 Previously, we developed a concise and general strategy for the construction of quinazolinones by a direct cyclization reaction between anthranils and cyclic amines in the absence of a transition-metal catalyst without the use of an additional initiator/oxidant.48 To continue the synthesis of heterocycle-fused quinazolinones, we herein develop an efficient one-pot acid-promoted redox-annulation of cascade C–C and C–N coupling for the synthesis of 1,2-disubstituted-5,6-dihydropyrrolo[2,1-α]isoquinoline using THIQ and α, β-unsaturated aldehydes as the starting materials (Scheme 1, eq. 5). A similar reaction was reported by the Seidel group in 2015,45 different from our covering work; the substrates and reaction conditions used were different and the products they obtained were dihydropyrrole derivatives, and further oxidation (TEMPO, air) was required to obtain aromatized products (eq. 41).

Results and Discussion

Initially, (E)-2,3-diphenylacrylaldehyde 1a (0.5 mmol) was reacted with 1,2,3,4-tetrahydroisoquinoline (THIQ) 2a (1 mmol, 2 equiv) in the presence of TFA (trifluoroacetic acid, 2 equiv) at 80 °C under air in PhMe (2 mL), and the desired product 1,2-diphenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline 3a was obtained in 8% yield in 5 h (Table 1, entry 1). Then, the screening of reaction temperature was carried out (entries 2–4). To our delight, an increase in the temperature to 130 °C resulted in a high yield of 81%. Higher temperatures could result in solvent loss and product decomposition. A variety of acid additives and Lewis acids, such as PhCOOH, AcOH, TfOH (trifluoromethanesulfonic acid), CuCl2, and AuBr3, were examined to investigate their effects on the reaction. Among the various additives tested, we were pleased to find that TfOH was the most effective one for the reaction with a best yield of up to 90%, and the reaction gave the target compound in 74% yield in the absence of an acid additive (entries 5–10). Encouraged by this result, various solvents, including DCE, MeOH, DMSO, 1,4-dioxane, DMF, and MeCN, were screened for the reaction, but toluene was indicated from the results to be the best choice for this reaction; other solvents gave lower yields (entries 11–16). Extending the reaction time and increasing the reaction temperature did not improve the reaction yield either (entries 17–18, Table 1). Therefore, 2 equiv of TfOH in toluene at 130 °C for 5 h were found to be the optimal conditions for the synthesis of 1,2-diphenyl-5,6-dihydropyrrolo[2,1-a]isoquinoline (Scheme 2).

Table 1. Optimization of the Reaction Conditionsa.

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entry additive time (h) solvent temperature (°C) yield (%)b
1 TFA 5 PhMe 80 8
2 TFA 5 PhMe 100 65
3 TFA 5 PhMe 130 81
4 TFA 5 PhMe 150 76
5 PhCOOH 5 PhMe 130 83
6 AcOH 5 PhMe 130 89
7 TfOH 5 PhMe 130 90
8 CuCl2 5 PhMe 130 7
9 AuBr3 5 PhMe 130 68
10   5 PhMe 130 74
11 TfOH 5 DCE 130 88
12 TfOH 5 MeOH 130  
13 TfOH 5 DMSO 130 3
14 TfOH 5 1,4-dioxane 130 trace
15 TfOH 5 DMF 130 trace
16 TfOH 5 MeCN 130 10
17 TfOH 12 PhMe 130 81
18 TfOH 5 PhMe 150 67
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a

Reaction condition: 1a (0.5 mmol), 2a (1 mmol), and additive (2 equiv) in solvent (2 mL) were stirred at a temperature under air for 5–12 h.

b

Isolated yield.

Scheme 2. Substrate Scope of Unsaturated Aldehydes,

Scheme 2

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Reaction condition: 1 (0.5 mmol), 2a (1 mmol), and TfOH (2 equiv) in toluene (2 mL) were stirred at 130 °C under air for 5 h.

Isolated yield.

With the optimized reaction conditions in hand, we proceeded to investigate the substrate scope of the reaction using a variety of substituted (E)-2,3-diphenylacrylaldehyde derivatives 1. Notably, the (E)-2,3-diphenylacrylaldehyde derivatives 1 with both electron-withdrawing and electron-donating substituents on the R2 aromatic moiety were tolerated under the optimized reaction conditions to furnish the desired products 3b–3k in moderate to good yields. Halogen-substituted substrates (4-Br, 3-Br) reacted smoothly to afford the corresponding products in 55–80% yields. The phenyl ring R2 bearing electron-donating (−CH3, −OMe) and electron-withdrawing groups (−Br, −CF3) reacted smoothly to afford the desired products 3b–3g in 55–88% yields. As expected, substitution at the meta position of arenes R2 gives products 3f and 3g smoothly in 55 and 57% yields, respectively. Moreover, the arene ring was not limited to benzene; the polycyclic-substituted derivatives also worked well and afforded products 3i and 3j in 72 and 76% yields, respectively. Remarkably, the pyrene-substituted substrate reacted as anticipated to give the corresponding product 3k in 53% yield. Satisfactory yields were observed with electron-donating (−CH3, −OMe) groups attached to the benzene ring R1 (92%, 94%; 3l, 3m). Prompted by the results achieved above, the scope of cinnamic aldehyde derivatives 1 was further investigated. As expected, derivatives 1 with electron-donating (−CH3) and electron-withdrawing (−Br) groups at the aryl para position both reacted well to provide the corresponding products 3n–3p in 45–58% yields. The molecular structure of 3o was unambiguously confirmed using X-ray crystallography (CCDC 2078071, for detail, see the Supporting Information). Moreover, (E)-2-methyl-3-phenylacrylaldehyde also worked well and afforded products 3q in 43% yield.

Next, we turned our attention to investigating the scope and limitations of the reaction with various THIQs. The results are summarized in Scheme 3. Notably, the THIQ derivatives 2 with both electron-withdrawing and electron-donating substituents on the aromatic moiety were tolerated under the optimized reaction conditions to furnish the desired products 4a–4e in moderate to good yields. Halogen-substituted substrates (6-Br, 7-Br) reacted smoothly to afford the corresponding products in 70 and 72% yields, respectively. Furthermore, to demonstrate the synthetic utility of this protocol developed, the product 3i was treated with N-bromosuccinimide (NBS) in THF at 25 °C for 30 min to give the brominated compound 5 in 90% yield. Suzuki coupling of the brominated product 5 with phenylboronic acid afforded the lamellarin-like compound 6 in good yield (Scheme 4).49 The formyl group was introduced by the Vilsmeier–Haack reaction with DMF/POCl3 to give the derivative 7 in 62% yield, which could transform to lamellarin in few steps.50 Finally, the pyrrolo[2,1-α]isoquinoline derivative 3a was modified with methyl acrylate with the Pd(OAc)2/AgOAc system through oxidative Heck coupling to give the corresponding product 8 in 76% yield.51

Scheme 3. Substrate Scope of THIQs,

Scheme 3

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Reaction condition: 1 (0.5 mmol), 2 (1 mmol), and TfOH (2 equiv) in toluene (2 mL) were stirred at 130 °C under air for 5 h.

Isolated yield.

Scheme 4. Product Application.

Scheme 4

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To study the mechanism of this strategy, some control experiments were carried out (Scheme 5). When Ar was employed as the reaction atmosphere, the yield of the desired product was reduced to 5%, which indicates that air is essential for the formation of the final product. The unoxidized product 3a′ was found using GCMS in the blank reaction (without TfOH) in 1 h and was converted into the oxidized target product 3a with the passage of time. However, when the acid was added into the reaction, the unoxidized product 3a′ was not detected in 1 h, indicating that the acid promoted the formation of the target product (GCMS and NMR spectra attached to the Supporting Information).

Scheme 5. Control Experiment.

Scheme 5

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On the basis of the above control experimental results, a reasonable mechanism of the reaction was proposed (Figure 2). The reaction is most likely initiated by addition of THIQ 2 to α,β-unsaturated aldehydes 1; subsequent elimination of water could occur with the assistance of TfOH, yielding iminium B, which resonated from intermediate A. Electrocyclization of intermediate B leads to the formation of compound C. Finally, air oxidative aromatization as key step for this process, affords the final product 3.

Figure 2.

Figure 2

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Proposed reaction mechanism.

In conclusion, we have developed a facile and efficient approach for the synthesis of the 1,2-disubstituted-5,6-dihydropyrrolo[2,1-α]isoquinoline derivative by a direct cyclization reaction between THIQ and substituted α,β-unsaturated aldehydes. Applying this electrocyclization reaction, an easy synthesis of lamellarin core, which is an important class of marine natural alkaloids, has been accomplished without a multistep process under simple reaction conditions. Further synthetic applications and mechanism of this strategy are currently underway in our laboratory.

Experimental Section

General Information

Unless otherwise noted, all commercially available reagents were used without further purification. Solvents and reagents were purchased from commercial sources and used without further purification. Flash column chromatography was performed using silica gel (200–300 mesh). Analytical thin-layer chromatography was performed using glass plates precoated with 200–300 mesh silica gel impregnated with a fluorescent indicator (254 nm). NMR spectra were recorded in CDCl3 or DMSO-d6 on Bruker NMR-300 (300 MHz) and NMR-400 (400 MHz) spectrometers with TMS as an internal reference. HRMS was performed on an Agilent 6540 Q-TOF mass spectrometer (ESI). IR spectra were recorded on a Thermo Fisher IS50 FT-IR spectrometer. X-ray crystallographic data were collected using a SMART APEX II X-ray diffractometer. THIQ derivatives were prepared according to the previously reported literature procedures.16

General Procedure for the Preparation of 1

Starting materials 1 were prepared according to the previously reported literature procedures.191b, 1f, 1g, and 1i–1k are unknown compounds.

General Procedure for the Target Products 3 and 4

In a 25 mL Shrek tube were added compound 1 (0.5 mmol), 1,2,3,4-tetrahydroisoquinoline derivatives 2 (1.0 mmol), TfOH (1.0 mmol), and 2.0 mL of toluene. The mixture was stirred under air at 130 °C for 5 h. After the complete conversion of the substrates (monitored by TLC), the reaction mixture was concentrated, and the residue was purified using silica gel column chromatography to give the desired product. The obtained product was analyzed by 1H NMR, 13C NMR, and HRMS.

(E)-2-(4-Bromophenyl)-3-phenylacrylaldehyde (1b)

Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 1b as a yellow solid (1.07 g, 78% yield). 1H NMR (400 MHz, CDCl3) δ 9.73 (s, 1H), 7.53 (d, J = 8.4 Hz, 2H), 7.40 (s, 1H), 7.32 (t, J = 7.1 Hz, 1H), 7.28–7.18 (m, 4H), 7.08 (d, J = 8.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 193.3, 150.6, 140.4, 133.5, 132.0, 131.9, 131.1, 130.6, 130.4, 128.5, 122.5, 99.8. MS (m/z): 285.9.

(E)-2-(3-Bromophenyl)-3-phenylacrylaldehyde (1f)

Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 1f as a yellow solid (1.09 g, 76% yield). 1H NMR (300 MHz, CDCl3) δ 9.73 (s, 1H), 7.51 (ddd, J = 8.0, 2.0, 1.1 Hz, 1H), 7.40 (s, 1H), 7.36 (t, J = 1.8 Hz, 1H), 7.33–7.17 (m, 6H), 7.12 (dt, J = 7.6, 1.3 Hz, 1H). 13C NMR (75 MHz, CDCl3) δ 193.1, 150.8, 140.1, 135.3, 133.4, 132.1, 131.3, 130.6, 130.5, 130.3, 128.6, 128.0, 122.7. MS (m/z): 285.9.

(E)-3-Phenyl-2-(m-tolyl)acrylaldehyde (1g)

Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 1g as a white solid (0.81 g, 73% yield). 1H NMR (400 MHz, CDCl3) δ 9.73 (s, 1H), 7.34 (s, 1H), 7.31–7.15 (m, 7H), 7.04–6.92 (m, 2H), 2.33 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 193.9, 149.9, 141.7, 138.3, 133.9, 133.1, 130.6, 130.0, 129.6, 128.9, 128.6, 128.3, 126.1, 21.3. MS (m/z): 222.1.

(E)-2-(Benzo[d][1,3]dioxol-5-yl)-3-phenylacrylaldehyde (1i)

Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 1i as a white solid (0.97 g, 77% yield). 1H NMR (400 MHz, CDCl3) δ 9.70 (s, 1H), 7.32 (s, 1H), 7.26 (q, J = 7.4, 6.2 Hz, 5H), 6.83 (d, J = 7.7 Hz, 1H), 6.65 (d, J = 8.1 Hz, 2H), 5.95 (s, 2H). 13C NMR (100 MHz, CDCl3) δ 193.8, 150.1, 147.8, 147.4, 141.0, 133.8, 130.5, 130.0, 128.3, 126.4, 122.8, 109.5, 108.7, 101.0. MS (m/z): 252.1.

(E)-2-(Dibenzo[b,d]furan-4-yl)-3-phenylacrylaldehyde (1j)

Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 1j as a yellow solid (1.07 g, 72% yield). 1H NMR (400 MHz, CDCl3) δ 9.89 (s, 1H), 8.05–7.89 (m, 2H), 7.65 (s, 1H), 7.39 (d, J = 7.5 Hz, 3H), 7.33–7.24 (m, 2H), 7.23–7.15 (m, 3H), 7.11 (t, J = 7.5 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 193.0, 155.9, 153.5, 151.4, 136.4, 133.9, 130.4, 130.3, 128.4, 128.0, 127.2, 124.7, 123.9, 123.1, 122.7, 120.9, 120.5, 117.9, 111.7. MS (m/z): 298.1.

(E)-3-Phenyl-2-(pyren-4-yl)acrylaldehyde (1k)

Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 1k as a yellow solid (1.10 g, 66% yield). 1H NMR (400 MHz, CDCl3) δ 9.99 (s, 1H), 8.17 (dd, J = 17.2, 7.7 Hz, 2H), 8.11–8.03 (m, 3H), 7.94 (dd, J = 8.4, 5.0 Hz, 2H), 7.81 (d, J = 9.2 Hz, 1H), 7.74 (d, J = 5.7 Hz, 2H), 7.13–7.05 (m, 1H), 6.95 (d, J = 5.1 Hz, 4H). 13C NMR (100 MHz, CDCl3) δ 194.1, 151.4, 140.7, 133.7, 131.4, 131.1, 130.9, 130.7, 130.4, 128.8, 128.8, 128.4, 128.0, 127.7, 127.3, 127.0, 126.0, 125.3, 125.2, 124.9, 124.7, 124.2. MS (m/z): 334.1.

3a: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3a as a yellow solid (144 mg, 90%). mp: 52–53 °C. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 4.7 Hz, 5H), 7.14 (d, J = 7.4 Hz, 3H), 7.10 (d, J = 7.1 Hz, 3H), 7.01 (td, J = 7.3, 1.6 Hz, 1H), 6.98–6.88 (m, 2H), 6.84 (s, 1H), 4.07 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 157.4, 136.5, 131.7, 130.9, 129.5, 129.0, 128.4, 127.9, 127.8, 126.5, 126.4, 125.8, 125.3, 124.1, 123.8, 120.0, 118.4, 113.4, 55.0, 44.4, 30.0. IR (KBr): v = 3054, 2922, 1601, 1534, 1467, 1395, 1330, 1165, 766, 751, 700. HRMS (ESI) m/z: [M + H]+ calcd for C24H20N 322.1590; found 322.1587.

3b: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3b as a yellow solid (160 mg, 80%). mp: 168–169 °C. 1H NMR (400 MHz, CDCl3) δ 7.41–7.23 (m, 7H), 7.16 (d, J = 7.4 Hz, 1H), 7.03 (td, J = 7.0, 2.1 Hz, 1H), 6.95 (d, J = 8.7 Hz, 4H), 6.84 (s, 1H), 4.09 (t, J = 6.4 Hz, 2H), 3.10 (t, J = 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 136.1, 134.4, 131.7, 131.0, 130.8, 129.4, 129.3, 128.6, 127.9, 126.6, 126.6, 126.3, 125.6, 123.9, 123.3, 120.0, 119.1, 118.9, 44.5, 30.0. IR (KBr): v = 3045, 2916, 1604, 1529, 1469, 1405, 1167, 1020, 828, 768, 700. HRMS (ESI) m/z: [M + H]+ calcd for C24H19BrN 400.0695; found 400.0692.

3c: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3c as a light green solid (155 mg, 78%). mp: 128–129 °C. 1H NMR (400 MHz, CDCl3) δ 7.44–7.27 (m, 7H), 7.18 (d, J = 7.8 Hz, 3H), 7.08–7.01 (m, 1H), 6.93 (d, J = 8.6 Hz, 3H), 4.12 (t, J = 6.4 Hz, 2H), 3.12 (t, J = 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 139.2, 136.1, 131.8, 130.8, 129.2, 128.7, 127.9, 127.7, 126.8, 126.7, 126.5, 125.7, 124.9, 124.9, 124.0, 123.1, 120.2, 119.4, 44.6, 29.9. 19F NMR (282 MHz, CDCl3) δ −62.18. IR (KBr): v = 3058, 2940, 1615, 1605, 1459, 1324, 1160, 1119, 1064, 845, 773, 748, 697. HRMS (ESI) m/z: [M + H]+ calcd for C25H19F3N 390.1464; found 390.1462.

3d: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3d as a yellow solid (127 mg, 76%). mp: 140–141 °C. 1H NMR (400 MHz, CDCl3) δ 7.32 (d, J = 4.6 Hz, 5H), 7.15 (d, J = 7.4 Hz, 1H), 7.03–6.88 (m, 7H), 6.83 (s, 1H), 4.07 (t, J = 6.4 Hz, 2H), 3.09 (t, J = 6.4 Hz, 2H), 2.26 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 136.6, 134.7, 132.4, 131.7, 130.9, 129.5, 128.7, 128.4, 127.8, 126.5, 126.4, 126.0, 125.3, 124.4, 123.9, 120.1, 118.7, 44.5, 30.0, 21.0. IR (KBr): v = 3022, 2891, 1603, 1540, 1396, 1329, 1157, 822, 771, 764, 754. HRMS (ESI) m/z: [M + H]+ calcd for C25H22N 336.1747; found 336.1746.

3e: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3e as a white solid (154 mg, 88%). mp: 133–134 °C. 1H NMR (400 MHz, CDCl3) δ 7.31 (d, J = 4.3 Hz, 5H), 7.13 (d, J = 7.4 Hz, 1H), 7.05–6.87 (m, 5H), 6.77 (s, 1H), 6.70 (d, J = 8.7 Hz, 2H), 4.04 (t, J = 6.4 Hz, 2H), 3.71 (s, 3H), 3.06 (t, J = 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 157.6, 136.7, 131.9, 131.0, 129.7, 129.2, 128.6, 128.1, 128.0, 126.7, 126.5, 126.0, 125.5, 124.3, 124.0, 120.2, 118.6, 113.6, 55.2, 44.6, 30.2. IR (KBr): v = 3001, 2956, 1602, 1556, 1501, 1468, 1398, 1242, 1032, 833, 763. HRMS (ESI) m/z: [M + H]+ calcd for C25H22NO 352.1696; found 352.1693.

3f: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3f as a white solid (110 mg, 55%). mp: 116–117 °C. 1H NMR (400 MHz, CDCl3) δ 7.38–7.27 (m, 6H), 7.19 (dd, J = 13.4, 7.6 Hz, 2H), 7.04 (td, J = 7.1, 2.1 Hz, 1H), 7.00–6.90 (m, 4H), 6.88 (s, 1H), 4.11 (t, J = 6.5 Hz, 2H), 3.11 (t, J = 6.4 Hz, 2H).13C NMR (101 MHz, CDCl3) δ 137.7, 136.0, 131.7, 130.8, 130.6, 129.4, 129.3, 128.6, 128.1, 127.9, 126.7, 126.6, 126.4, 126.3, 125.6, 124.0, 123.0, 122.0, 120.2, 119.1, 44.6, 30.0. IR (KBr): v = 3038, 2923, 1602, 1592, 1467, 1328, 1163, 1017, 782, 771, 703, 656. HRMS (ESI) m/z: [M + H]+ calcd for C24H19BrN 400.0695; found 400.0692.

3g: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3g as a yellow solid (95 mg, 57%). mp: 52–53 °C. 1H NMR (400 MHz, CDCl3) δ 7.35–7.25 (m, 5H), 7.15 (d, J = 8.1 Hz, 1H), 7.06–6.95 (m, 4H), 6.92 (dd, J = 7.4, 5.0 Hz, 2H), 6.86 (d, J = 5.1 Hz, 2H), 4.08 (t, J = 6.4 Hz, 2H), 3.09 (t, J = 6.4 Hz, 2H), 2.21 (s, 3H). 13C NMR (100 MHz, CDCl3) δ 137.3, 136.5, 135.3, 131.7, 130.9, 129.5, 128.7, 128.4, 127.8, 127.8, 126.6, 126.4, 126.0, 126.0, 125.4, 125.1, 124.5, 123.9, 120.2, 118.9, 44.5, 30.0, 21.4. IR (KBr): v = 3022, 2919, 1603, 1466, 765, 742. HRMS (ESI) m/z: [M + H]+ calcd for C25H22N 336.1747; found 336.1745.

3h: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3h as a white solid (106 mg, 61%). mp: 59–60 °C. 1H NMR (400 MHz, CDCl3) δ 7.40–7.23 (m, 5H), 7.14 (d, J = 7.4 Hz, 1H), 6.99 (d, J = 9.3 Hz, 2H), 6.92 (d, J = 8.0 Hz, 1H), 6.84 (s, 1H), 6.73 (d, J = 9.9 Hz, 3H), 4.07 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 6.4 Hz, 2H), 2.15 (s, 6H). 13C NMR (101 MHz, CDCl3) δ 137.1, 136.6, 135.1, 131.7, 130.9, 129.5, 128.3, 127.8, 126.9, 126.5, 126.3, 125.9, 125.9, 125.3, 124.6, 123.9, 120.3, 118.9, 44.4, 30.0, 21.2. IR (KBr): v = 3022, 2915, 1601, 1466, 1371, 1160, 848, 763, 702, 639. HRMS (ESI) m/z: [M + H]+ calcd for C26H24N 350.1903; found 350.1902.

3i: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3i as a white solid (131 mg, 72%). mp: 61–62 °C. 1H NMR (400 MHz, CDCl3) δ 7.30 (s, 5H), 7.14 (d, J = 7.4 Hz, 1H), 7.00 (t, J = 8.0 Hz, 1H), 6.91 (dd, J = 14.2, 6.9 Hz, 2H), 6.76 (s, 1H), 6.59 (d, J = 12.0 Hz, 3H), 5.83 (s, 2H), 4.04 (t, J = 6.4 Hz, 2H), 3.06 (t, J = 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 147.1, 145.3, 136.3, 131.7, 130.8, 129.5, 129.4, 128.5, 127.8, 126.5, 126.5, 125.9, 125.4, 124.2, 123.8, 121.2, 120.0, 118.6, 108.6, 107.9, 100.5, 44.4, 29.9. IR (KBr): v = 2882, 1603, 1534, 1483, 1038, 811, 766, 701. HRMS (ESI) m/z: [M + H]+ calcd for C25H20NO2 366.1489; found 366.1486.

3j: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3j as a white solid (156 mg, 76%). mp: 93–94 °C. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J = 1.2 Hz, 1H), 7.68 (dd, J = 7.6, 1.3 Hz, 1H), 7.54 (d, J = 8.2 Hz, 1H), 7.44–7.34 (m, 4H), 7.33–7.22 (m, 4H), 7.16 (d, J = 7.5 Hz, 1H), 7.08–6.89 (m, 5H), 4.18 (t, J = 6.4 Hz, 2H), 3.12 (t, J = 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 155.5, 153.2, 136.3, 131.5, 130.4, 129.1, 128.1, 127.5, 127.1, 126.4, 126.3, 126.2, 125.7, 125.1, 124.2, 123.7, 123.7, 122.1, 122.0, 121.1, 120.5, 120.1, 119.8, 117.3, 117.1, 111.2, 44.4, 29.7. IR (KBr): v = 3055, 1603, 1532, 1167, 764, 752, 701. HRMS (ESI) m/z: [M + H]+ calcd for C30H22NO 412.1696; found 412.1693.

3k: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3k as a light green solid (118 mg, 53%). mp: 125–126 °C. 1H NMR (400 MHz, CDCl3) δ 8.38 (d, J = 9.2 Hz, 1H), 8.05 (t, J = 7.2 Hz, 2H), 7.98–7.85 (m, 5H), 7.66 (d, J = 7.9 Hz, 1H), 7.23–7.11 (m, 4H), 7.05 (d, J = 5.9 Hz, 4H), 7.00–6.93 (m, 1H), 6.86 (s, 1H), 4.06 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 6.4 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ 136.1, 131.8, 131.3, 131.3, 131.0, 130.5, 129.7, 129.6, 129.5, 129.2, 128.1, 127.9, 127.4, 126.7, 126.6, 126.6, 126.1, 126.0, 125.6, 125.5, 125.5, 124.8, 124.5, 124.3, 124.2, 124.1, 123.0, 122.3, 121.3, 44.6, 30.0. IR (KBr): v = 3038, 1602, 1458, 1166, 847, 765, 754, 700. HRMS (ESI) m/z: [M + H]+ calcd for C34H24N 446.1903; found 446.1905.

3l: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3l as a white solid (154 mg, 92%). mp: 59–60 °C. 1H NMR (300 MHz, CDCl3) δ 7.24–7.07 (m, 10H), 7.04–6.97 (m, 2H), 6.96–6.88 (m, 1H), 6.83 (s, 1H), 4.06 (t, J = 6.5 Hz, 2H), 3.07 (t, J = 6.4 Hz, 2H), 2.37 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 135.9, 135.6, 133.3, 131.7, 130.7, 129.6, 129.3, 128.0, 127.9, 127.8, 126.6, 126.1, 125.4, 125.2, 124.5, 124.0, 120.2, 118.9, 44.5, 30.1, 21.3. IR (KBr): v = 3051, 2921, 1601, 1534, 1469, 1108, 1031, 766, 697, 593. HRMS (ESI) m/z: [M + H]+ calcd for C25H22N 336.1747; found 336.1748.

3m: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3m as a white solid (164 mg, 94%). mp: 61–62 °C. 1H NMR (300 MHz, CDCl3) δ 7.26–7.07 (m, 8H), 7.05–6.92 (m, 3H), 6.87 (d, J = 8.7 Hz, 2H), 6.84 (s, 1H), 4.07 (dd, J = 7.0, 5.9 Hz, 2H), 3.82 (s, 3H), 3.08 (t, J = 6.4 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 158.3, 135.6, 131.9, 131.7, 129.7, 128.7, 128.0, 127.9, 127.9, 126.6, 126.1, 125.4, 125.2, 124.6, 123.9, 119.8, 118.9, 114.0, 55.1, 44.5, 30.0. IR (KBr): v = 3059, 2931, 1601, 1534, 1173, 1032, 835, 765, 740, 698. HRMS (ESI) m/z: [M + H]+ calcd for C25H22NO 352.1696; found 352.1693.

3n: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3n as a yellow oil (71 mg, 58%). 1H NMR (400 MHz, CDCl3) δ 7.42 (d, J = 6.9 Hz, 2H), 7.28 (t, J = 7.8 Hz, 3H), 7.18 (t, J = 7.3 Hz, 1H), 7.12–7.07 (m, 1H), 6.94 (dtd, J = 22.9, 7.5, 1.4 Hz, 2H), 6.63 (d, J = 2.7 Hz, 1H), 6.16 (d, J = 1.9 Hz, 1H), 3.97 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 6.4 Hz, 2H). 13C NMR (101 MHz, CDCl3) δ 137.7, 131.9, 129.0, 128.4, 127.9, 126.6, 126.1, 125.6, 124.0, 122.5, 120.3, 110.5, 44.7, 30.2. HRMS (ESI) m/z: [M + H]+ calcd for C18H16N 246.1277; found 246.1276.

3o: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3o as a red solid (73 mg, 45%). mp: 111–112 °C. 1H NMR (400 MHz, CDCl3) δ 7.47 (d, J = 8.4 Hz, 2H), 7.36 (d, J = 8.5 Hz, 2H), 7.31 (d, J = 7.6 Hz, 1H), 7.19 (d, J = 7.4 Hz, 1H), 7.04 (dtd, J = 20.4, 7.4, 1.5 Hz, 2H), 6.71 (d, J = 2.7 Hz, 1H), 6.20 (d, J = 2.7 Hz, 1H), 4.05 (t, J = 6.4 Hz, 2H), 3.08 (t, J = 6.4 Hz, 2H). 13C NMR (126 MHz, CDCl3) δ 136.6, 131.9, 131.4, 130.5, 129.4, 128.0, 126.6, 125.8, 123.8, 121.0, 120.4, 119.8, 110.2, 44.6, 30.1. IR (KBr): ν = 3043, 2944, 1653, 1493, 1069, 1010, 836, 825, 764, 742. HRMS (ESI) m/z: [M + H]+ calcd for C18H15BrN 324.0382; found 324.0380.

3p: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3p as a yellow solid (63 mg, 49%). mp: 144–145 °C. 1H NMR (400 MHz, CDCl3) δ 7.35–7.27 (m, 3H), 7.09 (d, J = 7.8 Hz, 3H), 6.94 (dtd, J = 19.0, 7.4, 1.5 Hz, 2H), 6.63 (s, 1H), 6.14 (s, 1H), 3.97 (t, J = 6.4 Hz, 2H), 3.00 (t, J = 6.4 Hz, 2H), 2.31 (s, 3H). 13C NMR (101 MHz, CDCl3) δ 135.3, 134.3, 131.5, 129.5, 128.8, 128.5, 127.6, 126.2, 125.1, 123.6, 122.1, 119.8, 110.1, 44.3, 29.9, 20.9. IR (KBr): ν = 3019, 2938, 2914, 2360, 2341, 1510, 1491, 1330, 825, 763, 738, 699, 668. HRMS (ESI) m/z: [M + H]+ calcd for C19H18N 260.1434; found 260.1434.

3q: Column chromatography on silica gel (EA/PE = 1:50) afforded the title product 3q as a colorless oil (55 mg, 43%). 1H NMR (300 MHz, CDCl3) δ 7.39 (d, J = 6.5 Hz, 5H), 7.16–7.12 (m, 1H), 7.04–6.87 (m, 3H), 6.54 (d, J = 1.0 Hz, 1H), 4.01 (t, J = 6.5 Hz, 2H), 3.06 (t, J = 6.5 Hz, 2H), 2.00 (d, J = 0.9 Hz, 3H). 13C NMR (75 MHz, CDCl3) δ 136.9, 131.6, 130.4, 129.7, 128.4, 127.9, 126.5, 126.2, 125.2, 125.1, 123.6, 121.9, 118.7, 118.4, 44.2, 30.1, 10.5. IR (KBr): v = 3011, 2928, 1513, 1481, 1340, 834, 767, 738, 697. HRMS (ESI) m/z: [M + H]+ calcd for C19H18N 260.1434; found 260.1431.

4a: Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 4a as a green solid (119 mg, 71% yield). mp: 70–71 °C. 1H NMR (300 MHz, CDCl3) δ 7.37–7.26 (m, 5H), 7.17–7.07 (m, 5H), 7.03 (d, J = 7.7 Hz, 1H), 6.82 (d, J = 4.3 Hz, 2H), 6.74 (s, 1H), 4.04 (dd, J = 7.0, 5.9 Hz, 2H), 3.03 (t, J = 6.4 Hz, 2H), 2.01 (s, 3H). 13C NMR (75 MHz, CDCl3) δ 136.5, 135.9, 135.5, 130.9, 129.3, 128.8, 128.4, 128.0, 127.9, 127.7, 126.4, 126.2, 126.2, 125.2, 124.7, 124.3, 120.1, 118.9, 44.6, 29.6, 21.2. IR (KBr): v = 3022, 2921, 2868, 1598, 1497, 1449, 1330, 1262, 813, 766, 741, 719, 699. HRMS (ESI) m/z: [M + H]+ calcd for C25H22N 336.1747; found 336.1747.

4b: Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 4b as a yellow solid (128 mg, 73% yield). mp: 63–64 °C. 1H NMR (300 MHz, CDCl3) δ 7.38–7.27 (m, 5H), 7.20–7.08 (m, 5H), 7.05 (d, J = 8.3 Hz, 1H), 6.88 (s, 1H), 6.58 (dd, J = 8.3, 2.7 Hz, 1H), 6.51 (d, J = 2.7 Hz, 1H), 4.08 (t, J = 6.5 Hz, 2H), 3.33 (s, 3H), 3.04 (t, J = 6.5 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 158.1, 136.6, 135.4, 131.1, 130.3, 128.7, 128.5, 128.0, 127.9, 126.6, 126.3, 125.3, 124.3, 123.8, 120.3, 119.0, 112.6, 108.0, 54.6, 44.8, 29.1. IR (KBr): v = 3000, 2957, 1604, 1555, 1508, 1394, 1031, 830, 766, 701. HRMS (ESI) m/z: [M + H]+ calcd for C25H22NO 352.1696; found 352.1696.

4c: Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 4c as a white solid (139 mg, 70% yield). mp: 146–147 °C. 1H NMR (300 MHz, CDCl3) δ 7.40–7.27 (m, 5H), 7.21–7.07 (m, 6H), 7.02 (dd, J = 5.0, 3.0 Hz, 2H), 6.88 (s, 1H), 4.09 (t, J = 6.5 Hz, 2H), 3.05 (t, J = 6.4 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 135.8, 135.1, 131.4, 130.7, 130.4, 129.4, 128.7, 128.1, 128.0, 128.0, 126.9, 126.6, 125.5, 124.8, 124.7, 121.2, 120.4, 119.5, 44.3, 29.5. IR (KBr): ν = 3050, 2951, 2873, 1728, 1598, 1549, 1497, 1480, 789, 728. HRMS (ESI) m/z: [M + H]+ calcd for C24H19BrN 400.0695; found 400.0693.

4d: Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 4d as a white solid (133 mg, 67% yield). mp: 110–111 °C. 1H NMR (300 MHz, CDCl3) δ 7.30 (m, 6H), 7.21–7.07 (m, 5H), 7.04 (dd, J = 8.5, 2.1 Hz, 1H), 6.88 (s, 1H), 6.79 (d, J = 8.5 Hz, 1H), 4.10 (t, J = 6.5 Hz, 2H), 3.09 (t, J = 6.4 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 136.1, 135.2, 133.8, 130.8, 130.7, 129.7, 128.6, 128.5, 128.0, 128.0, 126.7, 125.5, 125.4, 125.3, 124.8, 120.7, 119.3, 118.7, 44.3, 29.8. IR (KBr): ν = 3056, 2954, 2868, 1726, 1592, 1544, 1456, 782, 726, 685. HRMS (ESI) m/z: [M + H]+ calcd for C24H19BrN 400.0695; found 400.0696.

4e: Column chromatography on silica gel (EA/PE = 1:20) afforded the title product 4e as a yellow solid (119 mg, 67% yield). mp: 65–66 °C. 1H NMR (300 MHz, CDCl3) δ 7.24–7.03 (m, 8H), 7.02–6.93 (m, 2H), 6.95–6.84 (m, 3H), 4.08 (t, J = 6.5 Hz, 2H), 3.84 (s, 3H), 3.06 (t, J = 6.4 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 158.6, 135.3, 132.3, 131.7, 131.2, 129.9, 129.0, 128.0, 127.9, 127.9, 125.4, 125.1, 125.0, 124.8, 123.6, 120.7, 119.4, 114.1, 55.2, 44.4, 29.5. IR (KBr): v = 3063, 2918, 1593, 1559, 1176, 1150, 1061, 1018, 839, 794, 772, 729. HRMS (ESI) m/z: [M + H]+ calcd for C25H21ClNO 386.1306; found 386.1306.

5: To a 10 mL round-bottomed flask were added dry THF (2 mL) and NBS (2 equiv), 3i (0.09 mmol) was added at 25 °C, and the mixture was stirred overnight. Then, the solvent was evaporated under a vacuum. The crude product was purified using flash column chromatography on silica gel (EA/PE = 1:20) to afford the title product 5 as a white solid (0.09 mmol scale, 36 mg, 90% yield). mp: 57–58 °C. 1H NMR (300 MHz, CDCl3) δ 7.19–7.08 (m, 6H), 6.99–6.92 (m, 1H), 6.85 (t, J = 6.6 Hz, 2H), 6.58 (s, 2H), 6.55–6.49 (m, 1H), 5.80 (s, 2H), 4.05 (dd, J = 7.1, 5.9 Hz, 2H), 3.02 (t, J = 6.5 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 145.9, 144.9, 134.5, 130.8, 129.7, 128.0, 127.4, 126.8, 126.7, 125.7, 125.6, 124.9, 123.1, 122.9, 122.9, 120.9, 109.8, 106.8, 101.7, 99.7, 42.2, 28.6. IR (KBr): v = 2888, 1601, 1481, 1388, 1034, 934, 811, 773, 707. HRMS (ESI) m/z: [M + H]+ calcd for C25H19BrNO2 444.0594; found 444.0597.

6: A solution of 5 (0.08 mmol), K2CO3 (2 equiv), Pd(PPh3)4 (20 mol %), and phenylboronic acid (1.5 equiv) were added to a 10 mL Schlenk tube under a N2 atmosphere. Anhydrous THF (15 mL) was added, and the mixture was heated to 70 °C for 12 h. After the mixture was cooled down to room temperature, it was filtered through a short plug of silica (EA/PE = 1:20), and the volatiles were removed in vacuo and afforded the title product 6 as a white solid (0.081 mmol scale, 28 mg, 80% yield). mp: 57–58 °C. 1H NMR (300 MHz, CDCl3) δ 7.22–7.15 (m, 3H), 7.11 (ddd, J = 7.7, 2.9, 1.8 Hz, 3H), 7.00–6.93 (m, 1H), 6.89–6.82 (m, 2H), 6.63–6.50 (m, 3H), 5.82 (s, 2H), 4.14–4.01 (m, 2H), 3.04 (t, J = 6.5 Hz, 2H).13C NMR (75 MHz, CDCl3) δ 145.9, 144.9, 134.5, 130.8, 129.7, 128.0, 127.4, 126.8, 126.7, 125.7, 125.6, 124.9, 123.1, 122.9, 122.9, 120.9, 109.8, 106.8, 101.7, 99.7, 42.2, 28.6. IR (KBr): v = 2879, 1602, 1478, 1383, 1319, 1234, 1213, 1037, 935, 760, 698. HRMS (ESI) m/z: [M + H]+ calcd for C31H24NO2 442.1802; found 442.1804.

7: Under a N2 atmosphere, to a 25 mL round-bottomed flask were added dry DMF (1 mL) and POCl3 (2 equiv), 3e (0.19 mmol) dissolved in dry DMF (1 mL) was added slowly below 35 °C, and the mixture was stirred for 35 min. Then, the solvent was evaporated under a vacuum. The crude product was purified using flash column chromatography on silica gel (EA/PE= 1:50) to afford the desired product 7 as a white solid (44 mg, 62% yield). mp: 193–194 °C. 1H NMR (300 MHz, CDCl3) δ 9.50 (s, 1H), 7.26 (dd, J = 9.1, 3.4 Hz, 4H), 7.20–7.13 (m, 3H), 7.07 (d, J = 8.7 Hz, 2H), 7.02–6.93 (m, 2H), 6.78 (d, J = 8.7 Hz, 2H), 4.81–4.69 (m, 2H), 3.77 (s, 3H), 3.12 (t, J = 6.6 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 181.0, 158.8, 138.5, 134.5, 134.2, 133.1, 132.0, 130.8, 128.4, 127.9, 127.9, 127.5, 126.9, 126.7, 126.6, 126.1, 124.4, 122.7, 113.3, 55.1, 42.0, 29.3. IR (KBr): v = 2836, 1640, 1531, 1416, 1402, 1208, 1031, 847, 762, 745. HRMS (ESI) m/z: [M + H]+ calcd for C26H22NO2 380.1645; found 380.1642.

8: To a 25 mL round-bottomed flask were added 3a (0.12 mmol), AgOAc (2 equiv), Pd(OAc)2 (10 mol %), methyl acrylate (3 equiv), and DMF (2 mL). The resulting mixture was stirred at 100 °C for 4 h. Then, the solvent was evaporated under a vacuum. The crude product was purified using flash column chromatography on silica gel (EA/PE = 1:20) and afforded the title product 8 as a yellow solid (37 mg, 76% yield). mp: 200–201 °C. 1H NMR (300 MHz, CDCl3) δ 7.67 (d, J = 16.1 Hz, 1H), 7.26–7.20 (m, 7H), 7.18–7.06 (m, 5H), 6.95 (d, J = 3.8 Hz, 2H), 5.79 (d, J = 16.1 Hz, 1H), 4.28 (t, J = 6.5 Hz, 2H), 3.72 (s, 3H), 3.16 (t, J = 6.5 Hz, 2H). 13C NMR (75 MHz, CDCl3) δ 145.9, 144.9, 134.5, 130.8, 129.7, 128.0, 127.4, 126.8, 126.7, 125.7, 125.6, 124.9, 123.1, 122.9, 122.9, 120.9, 109.8, 106.8, 101.7, 99.7, 42.2, 28.6. IR (KBr): v = 2945, 1702, 1615, 1133, 761, 696. HRMS (ESI) m/z: [M + H]+ calcd for C28H24NO2 406.1802; found 406.1800.

Acknowledgments

The authors are grateful to the National Natural Science Foundation of China (21402013), Jiangsu Key Laboratory of Advanced Catalytic Materials and Technology (BM2012110), Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX22_3099), and Advanced Catalysis and Green Manufacturing Collaborative Innovation Center in Changzhou University.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsomega.2c01941.

  • Experimental procedures and spectral data for all new compounds (PDF)

  • Crystallographic data (CIF)

Accession Codes

CCDC 2078071 contains the supplementary crystallographic data for this article. These data can be obtained free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk, or by contacting the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax: +44 1223 336033.

The authors declare no competing financial interest.

Supplementary Material

ao2c01941_si_001.pdf (3.9MB, pdf)
ao2c01941_si_002.cif (590KB, cif)

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