Switching the Regioselectivity Access to Pyrroles and Isoquinolines from Ketoxime Acetates and Ynals.

A novel formal [3+2] and [4+2] annulation of ketoxime acetates and ynals for the synthesis of pyrroles and isoquinolines has been developed. By simply switching the catalyst and solvent, the reaction proceeds via two pathways. The reactions are achieved under mild conditions with broad substrate scope and excellent regioselectivity.

Introduction

Nitrogen-containing heterocycles have always attracted considerable attention in natural products, pharmaceutical chemistry, and materials science.[1] Hence, the establishment of efficient approaches for their preparation is the hot spot in organic synthesis. Divergent synthesis allows the rapid entry to structurally diverse products from the same substrates and therefore has been a powerful tool to forge a variety of bioactive molecules.[2] The realization of diversity synthesis requires control of the reaction conditions to regulate the selectivity according to the reactivity of the substrates and the intermediates.[3] Among them, transition-metal-catalyzed annulation has been the most effective strategies in the divergent synthesis of N-containing heterocycles.[4]

Recently, oxime esters have drawn extensive interest as the readily available chemicals and internal oxidants.[5] Due to the relatively low bond energy of the N–O bond, they have been widely used as versatile starting materials for N-containing heterocycle construction through N–O bond cleavage.[6] Specifically, oxime acetates provide structurally feasible C2N1 synthons in the assembly of the framework of N-heterocycles,[7] including pyridines,[8] pyrroles,[9] azoles,[10] fused nitrogen heterocycles, etc.[11] Despite many recent advances in this field, continuing to explore practical and regioselective routes for the synthesis of significant N-heterocycles is still highly desirable.

Pyrroles and isoquinolines represent prevalent heterocyclic skeletons with a broad array of biological and pharmacological activities.[12] Therefore, numbers of classical protocols[13] and alternative methods[14,15] have been well documented over the past decades. Despite the significance of these procedures, the novel and complementary methodologies for pyrrole and isoquinoline synthesis is of high interest, especially using divergent synthesis strategy from available raw materials. Ynals, as readily accessible precursors and valuable building blocks, have been extensively applied in many cyclization reactions for the construction of heterocyclic compounds.[16] Originating from our continuous studies on ynals,[17] herein we present the first divergent synthesis of pyrroles and isoquinolines from ketoxime acetates and ynals via formal [3+2] and [4+2] annulations under different catalytic systems (Scheme ). It is important to note that these carbonyl-containing heterocycle products have potential applications in synthetic and pharmaceutical chemistry. Moreover, the annulation of ketoxime acetates and enals generally furnished the pyridine products.[18]

Scheme 1

Formal [3+2] and [4+2] Annulations of Ketoxime Acetates and Ynals

Results and Discussion

Initially, the reaction of acetophenone oxime acetate 1a and phenylpropiolaldehyde 2a under argon was explored to obtain the optimal conditions. As illustrated in Table , the reaction failed to produce the desired product in the absence of a catalyst (entry 1). Various common copper catalysts were tried (entries 2–6). All of the copper salts had positive effects on the reaction, and CuBr was found to deliver the best result in 65% yield (entry 4). Then, CuBr was chosen as the catalyst, some solvents were tested (entries 7–9). The results revealed that acetonitrile was beneficial to the transformation. After further investigation of the reaction, it was found that the main byproduct was acetylated pyrrole. Therefore, the reaction can furnish the 3a product in 82% yield through the N-deacetylation step (entry 10).[19] Interestingly, a mixture of 3a and 4a was observed when adding a catalytic amount of [Cp*RhCl2]2 to the system (entry 11). It showed that the Cu(OAc)2 catalyst proved effective for yield improvement (entries 12–14). When the solvent was switched from acetonitrile to DMF, 4a was exclusively generated in good yield (entry 15). As a solvent, MeOH was deleterious to this transformation (entries 16–18). Finally, it was disadvantageous when the reaction was performed at higher or lower temperatures (entries 19 and 20).

Table 1

Optimization of the Reaction Parameters for the Switchable Formation of Productsa

entry	catalyst	solvent	temperature	yield (%) 3a/4a
1		MeCN	60	-/-
2	CuI	MeCN	60	50/-
3	CuCl	MeCN	60	42/-
4	CuBr	MeCN	60	65/-
5	CuBr2	MeCN	60	31/-
6	Cu(OAc)2	MeCN	60	26/-
7	CuBr	DMF	60	48/-
8	CuBr	toluene	60	33/-
9	CuBr	DCE	60	30/-
10b	CuBr	MeCN	60	82/-
11c	CuBr	MeCN	60	29/41
12c	CuBr2	MeCN	60	13/28
13c	Cu(OTf)2	MeCN	60	16/53
14c	Cu(OAc)2	MeCN	60	17/68
15c	Cu(OAc)2	DMF	60	-/84
16c	Cu(OAc)2	DMSO	60	-/36
17c	Cu(OAc)2	toluene	60	-/32
18c	Cu(OAc)2	MeOH	60	-/-
19c	Cu(OAc)2	DMF	80	-/55
20c	Cu(OAc)2	DMF	40	-/20

Reaction conditions: 1a (0.2 mmol), 2a (0.2 mmol) with catalyst (30 mol %) in a solvent (1.0 mL) for 8 h under argon. Isolated yield.

BuOK (0.4 mmol) was added to the reaction mixture after the reaction, and the reaction continued at room temperature for 1 h.

[Cp*RhCl2]2 (2.5 mol %) was used.

With the optimal reaction conditions in hand, the substrate scope of the copper-catalyzed formal [3+2] annulation reactions for pyrrole formation was screened, and the results are summarized in Scheme . Initially, a set of aryl propargyl aldehydes worked well with acetophenone oxime acetate 1a to generate pyrroles in moderate to good yields (3b–3k). The substrate bearing either an electron-rich or an electron-deficient group on the benzene ring was tolerated and furnished the pyrrole derivatives in 60%–81% yields. A bulky tert-butyl group substituted ynal could transfer into the desired products in good yield (3d). The yield was not affected obviously with the methoxy group at the ortho-position of the benzene ring (3f). The heterocycle ynal reacted smoothly and achieved the desired product in satisfactory yield (3j). To our delight, aliphatic ynal was also applicable and transfer into the corresponding product in 56% yield (3k). In continuous evaluation of the generality of this annulation reaction, a wide range of substituted acetophenone oxime acetates were examined (3l–3u). The steric effects of the methyl group were not apparent (3l–3n). Naphthyl oxime led to the corresponding product 3p in good yield. Heterocyclic 2-furyl and 2-thienyl substituted ketoxime acetates also proceeded well to deliver the products in 66% and 63% yields, respectively (3s and 3t). Finally, substituted oxime reacted successfully with substituted ynal, which implied that this annulation reaction can be effective for the pyrrole library (3v). Notably, the reaction could be employed on large-scale synthesis and produced 3a in 70% yield. The structure of 3a was further confirmed by X-ray crystallographic analysis.[20] Interestingly, N-acetylated pyrroles can be obtained in moderate yields without the N-deacetylation step (3w–3y).

Scheme 2

Synthesis of Pyrrole Derivatives

Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), and CuBr (30 mol %) in MeCN (1 mL) were stirred at 60 °C for 8 h under argon, then BuOK (0.4 mmol) was added to the reaction mixture after the reaction, and the reaction continued at room temperature for 1 h.

2 mmol scale of the reaction.

Without the deacetylation step.

Subsequently, the Rh/Cu co-catalyzed reaction toward isoquinolines was evaluated under the optimal conditions (Scheme ). In general, the formal [4+2] annulation reaction has good functional group tolerance. Initially, both electron-donating and electron-withdrawing groups on the aromatic ring of ynals were compatible under the standard conditions. A variety of substituents were perfectly tolerated in this catalytic reaction, such as alkyl, aryl, methoxy, fluoro, chloro, bromo, acetyl, and ester groups (4b–4l). The disubstituted ynal afforded the products in good yields (4e). It is noteworthy that the products containing bromo, acetyl, or ester groups could be further functionalized and have potential applications in synthetic and pharmaceutical chemistry (4j–4l). The scope with respect to the oximes was then screened under the standard conditions (4n–4w). A set of aromatic ketoxime acetates were successfully coupled with phenylpropiolaldehyde 2a to achieve the respective isoquinoline-4-carbaldehydes in moderate to good yields. Significantly, the straight-chain, cyclic, and diaryl oximes were all reactive in this annulation reaction and converted to the isoquinolines in satisfactory yields (4n–4q). A para-substituted oxime was beneficial for the reaction compared to the ortho-substituted substrate (4s and 4t). The challenging substrate, heteroaromatic oxime, was suitable in this reaction, albeit in relatively low yield (4w). Ynals bearing the substituents of opposite properties participated efficiently with substituted oximes (4x–4z). Unluckily, alkyl-substituted progargyl aldehyde was investigated, and only the trace product could be tested (4aa). The structure and regioselectivity of 4a was further proved by X-ray crystal diffraction measurement.[20] A large-scale synthesis using 2 mmol of 1a and 2a was conducted, and 4a was formed in 73% yield.

Scheme 3

Synthesis of Isoquinoline Derivatives

Reaction conditions: 1 (0.2 mmol), 2 (0.2 mmol), [Cp*RhCl2]2 (2.5 mol %), and Cu(OAc)2 (30 mol %) in DMF (1 mL) were stirred at 60 °C for 8 h under argon.

2 mmol scale of the reaction.

To probe the possible reaction pathway, some control experiments were carried out, and the results are shown in Scheme . When the radical inhibitors TEMPO and BHT were added to the reaction of 1a with 2a under the standard conditions, the formation of 3a and 4a was largely suppressed (Scheme a). Oxygen was disadvantageous for the formation of 3a (Scheme b). Product 3a′ with 18O in the carbonyl group was not detected by using H218O as the additive (Scheme c). These results may suggest that electron-transfer processes were involved in the transformations, and the oxygen atom of the pyrrole products originated from the OAc group other than O2 or H2O.

Scheme 4

Control Experiments

On the basis of previous reports on copper-catalyzed transformation of oxime acetates and our experiment results,[21] a plausible mechanism toward pyrroles was proposed (Scheme a). First, the intermediate copper(II) enamide C was produced via the sequential single-electron reduction and tautomerization process from oxime acetate 1a.[8b,18a] Next, nucleophilic addition of C to ynal 2a generated intermediate D, and elimination of D achieved intermediate E.[22] Subsequently, N-acetylated pyrrole G was afforded via a tandem nucleophilic attack and annulation followed by a rearrangement process. Finally, the 3a product was formed through the N-deacetylation step.

Scheme 5

Possible Mechanism toward Pyrroles and Isoquinolines

On the other hand, a possible mechanism for isoquinoline formation was simply presented according to the related literature (Scheme b).[23] Iminylcopper(II) species B reacted with Rh(III) to afford rhodacyclic intermediate G via an iminyl rhodium intermediate I. Insertion of ynal 2a furnished intermediate K, which was converted into the product 4a and Rh(I) species via reductive elimination. A redox reaction between Rh(I) and Cu(II) regenerated Rh(III) and Cu(I).

Conclusions

In conclusion, we have developed an efficient divergent strategy to construct pyrroles as well as isoquinolines from ketoxime acetates and ynals with excellent regioselectivity. The reaction involves N–O bond cleavages and new C–C/C–N bond formations. The merit of this protocol includes commercial or readily available substrates, ligand and additive-free, good functional group tolerance, high atom economy, etc. Further studies regarding the mechanism and synthetic applications are currently underway in our laboratory.

Experimental Section

General Information

1H and 13C{1H} NMR spectra were obtained on a 400 and 100 MHz NMR spectrometer. The chemical shifts are referenced to signals at 7.26 and 77.0 ppm, respectively, and chloroform was used as the solvent with TMS as the internal standard unless otherwise noted. Melting points (mp) were determined using a melting point instrument (uncorrected). Mass spectra were recorded on a GC-MS spectrometer at an ionization voltage of 70 eV equipped with a DB-WAX capillary column (internal diameter: 0.25 mm, length: 30 m). High-resolution mass spectra (HRMS) (TOF) were measured using an electrospray ionization (ESI) mass spectrometry. Silica gel (300–400 mesh) was used for flash column chromatography, eluting (unless otherwise stated) with ethyl acetate/petroleum ether (PE) (60–90 °C) mixture.

The propargyl aldehydes 2a and 2k were commercially available from Sigma-Aldrich China. Substituted ketoxime acetates and other propargyl aldehydes were synthesized according to the literature,[17,23b] and data of known compounds were compared with the reported data.[8]

General Procedure for the Synthesis of Pyrroles (3a–3v)

A mixture of ketoxime acetate (0.2 mmol), ynal (0.2 mmol), CuBr (8.6 mg, 30 mol %) in MeCN (1.0 mL) was stirred in a preheated oil bath at 60 °C for 8 h in a sealed tube under an argon atmosphere, then BuOK (44.8 mg, 0.4 mmol) was added to the reaction mixture after the reaction, and the reaction continued at room temperature for 1 h. After the reaction was finished, water (5 mL) was added and the solution was extracted with ethyl acetate (3 × 5 mL), and the combined extract was dried with anhydrous MgSO4. The solvent was removed, and the residue was separated by column chromatography to give the pure sample.

Large-Scale Synthesis

An oven-dried 25 mL screw cap test tube was charged with a magnetic stir bar, 1a (354 mg, 2 mmol), 2a (260 mg, 2 mmol), CuBr (85 mg, 30 mol %), and MeCN (6.0 mL). Then, the tube was placed in a preheated oil bath at 60 °C for 8 h. After the solution cooled to room temperature, water (10 mL) was added and the solution was extracted with ethyl acetate (3 × 10 mL); the combined extract was dried with anhydrous MgSO4. The solvent was removed, and the residue was separated by column chromatography (ethyl acetate/petroleum ether = 1:7) to give 3a (346 mg, 70%).

Phenyl(5-phenyl-1H-pyrrol-2-yl)methanone (3a)[24]

Yellow solid (41 mg, 82%); mp 162–164 °C; R = 0.30 (ethyl acetate/petroleum ether = 1:7); 1H NMR (400 MHz, CDCl3): δ = 10.52 (s, 1H), 7.97–7.91 (m, 2H), 7.76–7.71 (m, 2H), 7.62–7.57 (m, 1H), 7.53–7.48 (m, 2H), 7.41–7.36 (m, 2H), 7.33 (dt, J = 9.6, 4.3 Hz, 1H), 6.96 (dd, J = 4.0, 2.4 Hz, 1H), 6.65 (dd, J = 4.0, 2.7 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.62, 139.42, 138.54, 131.75, 131.73, 130.97, 129.01, 128.99, 128.29, 128.19, 125.29, 121.45, 108.76. MS (EI) m/z: 247, 219, 191, 170, 140, 115, 77, 51. HRMS (ESI): calcd for C17H13NNaO [M + Na]+ 270.0889; found 270.0904.

(5-Phenyl-1H-pyrrol-2-yl)(p-tolyl)methanone (3b)

White solid (42 mg, 81%); mp 183–185 °C; R = 0.48 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 10.29 (s, 1H), 7.85 (d, J = 8.1 Hz, 2H), 7.72–7.68 (m, 2H), 7.41 (dd, J = 10.3, 4.7 Hz, 2H), 7.35–7.32 (m, 1H), 7.30 (d, J = 7.9 Hz, 2H), 6.95 (dd, J = 3.9, 2.4 Hz, 1H), 6.64 (dd, J = 3.9, 2.8 Hz, 1H), 2.45 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.41, 142.39, 139.06, 135.78, 135.76, 131.76, 131.00, 129.13, 128.98, 128.11, 125.20, 121.08, 108.61, 21.58. MS (EI) m/z: 261, 246, 207, 170, 141, 115, 91, 65, 39. HRMS (ESI): calcd for C18H16NO [M + H] + 262.1226; found 262.1239.

(3,5-Dimethylphenyl)(5-phenyl-1H-pyrrol-2-yl)methanone (3c)

Yellow solid (39 mg, 74%); mp 144–146 °C; R = 0.35 (ethyl acetate/petroleum ether = 1:10); 1H NMR (400 MHz, CDCl3): δ = 10.54 (s, 1H), 7.75–7.71 (m, 2H), 7.54 (s, 2H), 7.38 (t, J = 7.3 Hz, 2H), 7.34–7.31 (m, 1H), 7.22 (s, 1H), 6.96 (dd, J = 3.9, 2.4 Hz, 1H), 6.64 (dd, J = 3.8, 2.8 Hz, 1H), 2.41 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ = 185.07, 139.28, 138.55, 137.88, 133.42, 131.87, 131.01, 128.93, 128.07, 126.80, 125.30, 121.43, 108.58, 21.27. MS (EI) m/z: 275, 260, 246, 170, 141, 115, 77, 63, 39. HRMS (ESI): calcd for C19H18NO [M + H]+ 276.1383; found 276.1394.

(4-(tert-Butyl)phenyl)(5-phenyl-1H-pyrrol-2-yl)methanone (3d)

Yellow solid (44 mg, 72%); mp 158–160 °C; R = 0.34 (ethyl acetate/petroleum ether = 1:7); 1H NMR (400 MHz, CDCl3): δ = 10.37 (s, 1H), 7.89 (d, J = 8.3 Hz, 2H), 7.71 (d, J = 7.4 Hz, 2H), 7.52 (d, J = 8.4 Hz, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.34–7.30 (m, 1H), 6.98 (dd, J = 3.9, 2.4 Hz, 1H), 6.65 (dd, J = 3.8, 2.8 Hz, 1H), 1.39 (s, 9H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.41, 155.39, 139.08, 135.72, 131.81, 131.00, 128.98, 128.96, 128.07, 125.26, 125.21, 121.14, 108.62, 35.01, 31.18. MS (EI) m/z: 303, 288, 260, 246, 207, 170, 130, 115, 91, 65. HRMS (ESI): calcd for C21H22NO [M + H]+ 304.1696; found 304.1711.

(4-Methoxyphenyl)(5-phenyl-1H-pyrrol-2-yl)methanone (3e)

Yellow solid (43 mg, 78%); mp 162–164 °C; R = 0.44 (ethyl acetate/petroleum ether = 1:4); 1H NMR (400 MHz, CDCl3): δ = 10.47 (s, 1H), 7.99–7.92 (m, 2H), 7.74–7.67 (m, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.32 (dd, J = 8.3, 6.4 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 6.95 (dd, J = 3.9, 2.3 Hz, 1H), 6.64 (dd, J = 3.8, 2.7 Hz, 1H), 3.90 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 162.72, 138.75, 131.78, 131.23, 131.17, 131.12, 131.10, 128.97, 128.03, 125.19, 120.50, 113.61, 108.55, 55.43. MS (EI) m/z: 277, 260, 246, 206, 169, 125, 115, 77, 63, 40. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 278.1176; found 278.1185.

(2-Methoxyphenyl)(5-phenyl-1H-pyrrol-2-yl)methanone (3f)

Yellow solid (39 mg, 70%); mp 162–164 °C; R = 0.33 (ethyl acetate/petroleum ether = 1:4); 1H NMR (400 MHz, CDCl3): δ = 10.09 (s, 1H), 7.66 (d, J = 7.5 Hz, 2H), 7.49–7.43 (m, 2H), 7.39 (t, J = 7.4 Hz, 2H), 7.34–7.29 (m, 1H), 7.02 (dd, J = 12.1, 4.7 Hz, 2H), 6.69 (dd, J = 3.9, 2.4 Hz, 1H), 6.57 (dd, J = 3.9, 2.7 Hz, 1H), 3.82 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.24, 157.21, 139.17, 132.93, 131.49, 130.93, 129.56, 128.99, 128.47, 128.15, 125.10, 121.58, 119.99, 111.48, 108.56, 55.70. MS (EI) m/z: 277, 259, 230, 217, 178, 156, 143, 115, 77, 63, 39. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 278.1176; found 278.1189.

Benzo[d][1,3]dioxol-5-yl(5-phenyl-1H-pyrrol-2-yl)methanone (3g)

Yellow solid (42 mg, 73%); mp 170–172 °C; R = 0.35 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 10.16 (s, 1H), 7.74–7.64 (m, 2H), 7.56 (dd, J = 8.1, 1.6 Hz, 1H), 7.45–7.39 (m, 3H), 7.33 (t, J = 7.4 Hz, 1H), 6.94 (dd, J = 3.9, 2.4 Hz, 1H), 6.90 (d, J = 8.1 Hz, 1H), 6.63 (dd, J = 3.8, 2.8 Hz, 1H), 6.07 (s, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 182.91, 150.90, 147.81, 138.76, 132.66, 131.46, 130.95, 129.07, 128.19, 125.09, 124.74, 120.54, 109.19, 108.62, 107.92, 101.69. MS (EI) m/z: 291, 262, 233, 204, 170, 131, 115, 91, 65, 39. HRMS (ESI): calcd for C18H14NO3 [M + H]+ 292.0968; found 292.0975.

1-(4-(5-Phenyl-1H-pyrrole-2-carbonyl)phenyl)ethan-1-one (3h)

Yellow solid (37 mg, 64%); mp 188–190 °C; R = 0.44 (ethyl acetate/petroleum ether = 1:3); 1H NMR (400 MHz, CDCl3): δ = 10.42 (s, 1H), 8.07 (d, J = 8.4 Hz, 2H), 7.98 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 7.2 Hz, 2H), 7.43–7.38 (m, 2H), 7.37–7.32 (m, 1H), 6.93 (dd, J = 4.0, 2.3 Hz, 1H), 6.66 (dd, J = 4.0, 2.7 Hz, 1H), 2.67 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 197.61, 183.45, 142.23, 139.97, 139.19, 132.50, 131.41, 130.64, 129.10, 129.07, 128.25, 125.28, 121.81, 109.10, 26.85. MS (EI) m/z: 289, 272, 246, 218, 189, 170, 137, 115, 77, 65, 43. HRMS (ESI): calcd for C19H16NO2 [M + H]+ 290.1176; found 290.1178.

(5-Phenyl-1H-pyrrol-2-yl)(3-(trifluoromethyl)phenyl)methanone (3i)

Red solid (38 mg, 60%); mp 141–143 °C; R = 0.36 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.11 (s, 1H), 8.08 (s, 1H), 7.99 (d, J = 7.7 Hz, 1H), 7.73 (d, J = 7.8 Hz, 1H), 7.62–7.57 (m, 2H), 7.54 (t, J = 7.8 Hz, 1H), 7.36–7.30 (m, 2H), 7.28–7.23 (m, 1H), 6.82 (dd, J = 4.0, 2.4 Hz, 1H), 6.57 (dd, J = 4.0, 2.7 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 182.80, 140.13, 139.08, 132.09, 131.13, 130.78, 130.62, 129.09, 128.94, 128.58, 128.24 (q, J = 4 Hz), 125.78 (q, J = 4 Hz), 125.33, 123.78 (q, J = 271 Hz), 121.78, 109.19. MS (EI) m/z: 315, 287, 266, 246, 217, 170, 145, 115, 89, 63, 39. HRMS (ESI): calcd for C18H13F3NO [M + H]+ 316.0944; found 316.0954.

(5-Phenyl-1H-pyrrol-2-yl)(thiophen-2-yl)methanone (3j)

Yellow solid (37 mg, 74%); mp 141–143 °C; R = 0.37 (ethyl acetate/petroleum ether = 1:6); 1H NMR (400 MHz, CDCl3): δ = 10.41 (s, 1H), 7.93 (dd, J = 3.8, 1.1 Hz, 1H), 7.71 (dd, J = 5.2, 3.3 Hz, 2H), 7.65 (dd, J = 5.0, 1.1 Hz, 1H), 7.44–7.39 (m, 2H), 7.33 (ddd, J = 7.3, 3.8, 1.1 Hz, 1H), 7.24 (dd, J = 4.0, 2.4 Hz, 1H), 7.19 (dd, J = 4.9, 3.8 Hz, 1H), 6.66 (dd, J = 4.0, 2.8 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 175.34, 142.82, 139.29, 132.13, 131.97, 131.26, 130.88, 129.02, 128.17, 127.79, 125.23, 119.56, 108.87. MS (EI) m/z: 253, 169, 141, 115, 89, 63, 39. HRMS (ESI): calcd for C15H12NOS [M + H]+ 254.0634; found 254.0638.

1-(5-Phenyl-1H-pyrrol-2-yl)hexan-1-one (3k)

Yellow oil (27 mg, 56%); R = 0.37 (ethyl acetate/petroleum ether = 1:3); 1H NMR (400 MHz, CDCl3): δ = 9.83 (s, 1H), 7.62 (dd, J = 5.2, 3.3 Hz, 2H), 7.41 (dd, J = 10.4, 4.8 Hz, 2H), 7.32 (ddd, J = 7.4, 3.9, 1.1 Hz, 1H), 6.96 (dd, J = 3.9, 2.4 Hz, 1H), 6.57 (dd, J = 3.9, 2.7 Hz, 1H), 2.82–2.73 (m, 2H), 1.78–1.70 (m, 2H), 1.40–1.32 (m, 4H), 0.94–0.88 (m, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 191.00, 138.19, 132.44, 131.06, 129.02, 128.06, 125.00, 117.68, 108.15, 37.90, 31.66, 25.22, 22.49, 13.94. MS (EI) m/z: 241, 198, 185, 170, 143, 115, 89, 55, 43. HRMS (ESI): calcd for C16H20NO [M + H]+ 242.1539; found 242.1549.

Phenyl(5-(p-tolyl)-1H-pyrrol-2-yl)methanone (3l)

Yellow solid (44 mg, 85%); mp 171–173 °C; R = 0.30 (ethyl acetate/petroleum ether = 1:7); 1H NMR (400 MHz, CDCl3): δ = 10.07 (s, 1H), 7.92 (d, J = 7.4 Hz, 2H), 7.57 (dd, J = 7.6, 2.2 Hz, 3H), 7.50 (t, J = 7.5 Hz, 2H), 7.23 (d, J = 7.9 Hz, 2H), 6.97–6.90 (m, 1H), 6.65–6.56 (m, 1H), 2.39 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.40, 139.40, 138.51, 138.34, 131.70, 131.34, 129.77, 128.92, 128.30, 128.09, 125.07, 121.38, 108.37, 21.28. MS (EI) m/z: 261, 244, 217, 184, 156, 129, 105, 77, 51, 39. HRMS (ESI): calcd for C18H16NO [M + H]+ 262.1226; found 262.1241.

Phenyl(5-(m-tolyl)-1H-pyrrol-2-yl)methanone (3m)

Yellow solid (43 mg, 82%); mp 151–153 °C; R = 0.42 (ethyl acetate/petroleum ether = 1:6); 1H NMR (400 MHz, CDCl3): δ = 10.22 (s, 1H), 7.98–7.91 (m, 2H), 7.64–7.56 (m, 1H), 7.55–7.48 (m, 4H), 7.32 (t, J = 7.8 Hz, 1H), 7.18 (d, J = 7.4 Hz, 1H), 6.97 (dd, J = 4.0, 2.4 Hz, 1H), 6.65 (dd, J = 3.9, 2.7 Hz, 1H), 2.41 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.51, 139.45, 138.72, 138.48, 131.72, 131.52, 130.81, 129.07, 128.94, 128.75, 128.28, 125.87, 122.36, 121.37, 108.70, 21.42. MS (EI) m/z: 261, 244, 217, 184, 156, 129, 105, 77, 51, 39. HRMS (ESI): calcd for C18H16NO [M + H]+ 262.1226; found 262.1240.

Phenyl(5-(o-tolyl)-1H-pyrrol-2-yl)methanone (3n)

Yellow solid (41 mg, 78%); mp 95–97 °C; R = 0.32 (ethyl acetate/petroleum ether = 1:7); 1H NMR (400 MHz, CDCl3): δ = 10.04 (s, 1H), 7.89 (d, J = 7.5 Hz, 2H), 7.57 (t, J = 7.3 Hz, 1H), 7.48 (t, J = 7.3 Hz, 3H), 7.32–7.24 (m, 3H), 7.01–6.92 (m, 1H), 6.51–6.41 (m, 1H), 2.50 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.45, 138.97, 138.39, 135.83, 131.70, 131.20, 131.12, 130.96, 128.95, 128.72, 128.34, 128.25, 126.19, 120.34, 111.65, 21.04. MS (EI) m/z: 261, 244, 215, 184, 156, 129, 105, 77, 51, 39. HRMS (ESI): calcd for C18H16NO [M + H]+ 262.1226; found 262.1241.

(5-(4-Isobutylphenyl)-1H-pyrrol-2-yl)(phenyl)methanone (3o)

Yellow solid (42 mg, 69%); mp 171–173 °C; R = 0.30 (ethyl acetate/petroleum ether = 1:7); R = 0.32 (ethyl acetate/petroleum ether = 1:7); 1H NMR (400 MHz, CDCl3): δ = 10.86 (s, 1H), 7.96 (d, J = 7.3 Hz, 2H), 7.69 (d, J = 7.5 Hz, 2H), 7.59 (t, J = 7.1 Hz, 1H), 7.51 (t, J = 7.3 Hz, 2H), 7.14 (d, J = 7.8 Hz, 2H), 6.97 (s, 1H), 6.63 (s, 1H), 2.50 (d, J = 7.0 Hz, 2H), 1.90 (dt, J = 13.3, 6.6 Hz, 1H), 0.95 (s, 3H), 0.94 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.51, 141.97, 140.00, 138.67, 131.61, 131.51, 129.65, 129.06, 128.42, 128.21, 125.18, 121.79, 108.41, 45.13, 30.13, 22.33. MS (EI) m/z: 303, 260, 182, 154, 128, 105, 77, 51, 43. HRMS (ESI): calcd for C21H22NO [M + H]+ 304.1696; found 304.1704.

(5-(Naphthalen-2-yl)-1H-pyrrol-2-yl)(phenyl)methanone (3p)

Yellow solid (45 mg, 75%); mp 170–172 °C; R = 0.47 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 10.20 (s, 1H), 8.32–8.24 (m, 1H), 7.94–7.87 (m, 4H), 7.65 (d, J = 7.1 Hz, 1H), 7.54 (ddd, J = 16.5, 12.7, 7.7 Hz, 6H), 7.04 (s, 1H), 6.63 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.53, 138.36, 138.13, 133.91, 131.76, 131.44, 131.10, 129.67, 129.01, 128.97, 128.54, 128.28, 127.02, 126.85, 126.23, 125.33, 125.27, 120.45, 112.40. MS (EI) m/z: 297, 268, 220, 190, 165, 139, 105, 77, 51, 39. HRMS (ESI): calcd for C21H16NO [M + H]+ 298.1226; found 298.1237.

(5-(4-Methoxyphenyl)-1H-pyrrol-2-yl)(phenyl)methanone (3q)

Yellow solid (40 mg, 73%); mp 180–182 °C; R = 0.43 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 10.20 (s, 1H), 8.32–8.24 (m, 1H), 7.94–7.87 (m, 4H), 7.65 (d, J = 7.1 Hz, 1H), 7.54 (ddd, J = 16.5, 12.7, 7.7 Hz, 6H), 7.04 (s, 1H), 6.63 (s, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.24, 159.80, 139.32, 138.56, 131.66, 131.17, 128.89, 128.30, 126.55, 123.65, 121.52, 114.54, 107.97, 55.37. MS (EI) m/z: 277, 262, 234, 200, 184, 156, 145, 105, 77, 51, 39. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 278.1176; found 278.1184.

(5-(2-Bromophenyl)-1H-pyrrol-2-yl)(phenyl)methanone (3r)

Yellow oil (44 mg, 68%); R = 0.32 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.16 (s, 1H), 7.92 (dd, J = 5.2, 3.3 Hz, 2H), 7.69 (dd, J = 8.0, 1.1 Hz, 1H), 7.57 (ddt, J = 5.7, 4.0, 1.9 Hz, 2H), 7.49 (dd, J = 10.3, 4.6 Hz, 2H), 7.37 (td, J = 7.6, 1.2 Hz, 1H), 7.21 (td, J = 7.8, 1.7 Hz, 1H), 6.94 (dd, J = 3.9, 2.5 Hz, 1H), 6.68 (dd, J = 3.9, 2.8 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.53, 138.21, 136.88, 134.19, 131.88, 131.37, 130.64, 129.50, 129.07, 128.94, 128.33, 127.76, 121.01, 119.59, 112.20. MS (EI) m/z: 325, 308, 297, 248, 217, 193, 170, 140, 114, 77, 51. HRMS (ESI): calcd for C17H13BrNO2 [M + H]+ 326.0170; found 326.0181.

(5-(Furan-2-yl)-1H-pyrrol-2-yl)(phenyl)methanone (3s)

Yellow solid (31 mg, 66%); mp 123–125 °C; R = 0.45 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 9.84 (s, 1H), 7.84–7.80 (m, 2H), 7.49 (ddd, J = 6.5, 3.9, 1.4 Hz, 1H), 7.44–7.37 (m, 3H), 6.82 (dd, J = 4.0, 2.5 Hz, 1H), 6.58 (dd, J = 3.4, 0.5 Hz, 1H), 6.45 (dd, J = 4.0, 2.6 Hz, 1H), 6.41 (dd, J = 3.4, 1.8 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.22, 146.47, 142.41, 138.38, 131.79, 130.89, 130.34, 128.87, 128.33, 120.86, 111.87, 107.77, 106.63. MS (EI) m/z: 237, 220, 180, 160, 132, 105, 77, 51, 39. HRMS (ESI): calcd for C15H12NO2 [M + H]+ 238.0863; found 238.0872.

Phenyl(5-(thiophen-2-yl)-1H-pyrrol-2-yl)methanone (3t)

Yellow solid (32 mg, 63%); mp 136–138 °C; R = 0.37 (ethyl acetate/petroleum ether = 1:6); 1H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1H), 7.95–7.88 (m, 2H), 7.60–7.55 (m, 1H), 7.52–7.47 (m, 2H), 7.39 (dd, J = 3.6, 1.1 Hz, 1H), 7.29 (dd, J = 5.1, 1.0 Hz, 1H), 7.05 (dd, J = 5.1, 3.7 Hz, 1H), 6.90 (dd, J = 4.0, 2.4 Hz, 1H), 6.52 (dd, J = 3.9, 2.7 Hz, 1H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.40, 138.38, 134.03, 133.90, 131.80, 131.23, 128.95, 128.31, 128.04, 125.31, 124.12, 121.37, 109.22. MS (EI) m/z: 253, 236, 207, 176, 147, 121, 77, 51, 45. HRMS (ESI): calcd for C15H12NOS [M + H]+ 254.0634; found 254.0643.

(4,5-Dihydro-1H-benzo[g]indol-2-yl)(phenyl)methanone (3u)

Yellow solid (31 mg, 57%); mp 198–200 °C; R = 0.38 (ethyl acetate/petroleum ether = 1:6); 1H NMR (400 MHz, CDCl3): δ = 10.66 (s, 1H), 7.97–7.93 (m, 2H), 7.71 (dd, J = 5.6, 3.3 Hz, 1H), 7.58 (ddd, J = 6.4, 3.8, 1.4 Hz, 1H), 7.53–7.48 (m, 2H), 7.25–7.22 (m, 1H), 7.21–7.16 (m, 2H), 6.77 (d, J = 2.2 Hz, 1H), 2.97 (t, J = 7.5 Hz, 2H), 2.78 (t, J = 7.5 Hz, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.39, 138.90, 136.90, 135.60, 131.54, 130.87, 128.99, 128.47, 128.24, 127.65, 126.85, 122.58, 121.52, 119.05, 29.70, 21.42. MS (EI) m/z: 273, 244, 207, 196, 168, 141, 105, 77, 51, 39. HRMS (ESI): calcd for C19H16NO [M + H]+ 274.1226; found 274.1239.

(5-(4-Bromophenyl)-1H-pyrrol-2-yl)(4-methoxyphenyl)methanone (3v)

Yellow solid (36 mg, 50%); mp 195–197 °C; R = 0.41 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 10.25 (s, 1H), 7.96–7.91 (m, 2H), 7.57–7.50 (m, 4H), 7.00 (dd, J = 9.2, 2.3 Hz, 2H), 6.93 (dd, J = 3.9, 2.4 Hz, 1H), 6.62 (dd, J = 3.9, 2.8 Hz, 1H), 3.90 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 183.47, 162.86, 137.36, 132.18, 131.98, 131.17, 130.86, 130.01, 126.58, 121.99, 120.39, 113.69, 108.86, 55.48. MS (EI) m/z: 355, 326, 312, 284, 249, 221, 195, 163, 135, 108, 77. HRMS (ESI): calcd for C18H15BrNO2 [M + H]+ 356.0281; found 356.0286.

General Procedure for the Synthesis of N-Acetylated Pyrroles (3w–3y)

A mixture of ketoxime acetate (0.2 mmol), ynal (0.2 mmol), and CuBr (8.6 mg, 30 mol %) in MeCN (1.0 mL) was stirred in a preheated oil bath at 60 °C for 8 h in a sealed tube under an argon atmosphere. After the reaction was finished, water (5 mL) was added and the solution was extracted with ethyl acetate (3 × 5 mL), and the combined extract was dried with anhydrous MgSO4. The solvent was removed, and the residue was separated by column chromatography to give the pure sample.

1-(2-Benzoyl-5-(4-fluorophenyl)-1H-pyrrol-1-yl)ethan-1-one (3w)

Yellow solid (41 mg, 67%); mp 124–126 °C; R = 0.43 (ethyl acetate/petroleum ether = 1:10); 1H NMR (400 MHz, CDCl3): δ = 7.99–7.91 (m, 2H), 7.60 (t, J = 7.4 Hz, 1H), 7.50 (t, J = 7.5 Hz, 2H), 7.45–7.40 (m, 2H), 7.15–7.08 (m, 2H), 6.84 (d, J = 3.8 Hz, 1H), 6.30 (d, J = 3.8 Hz, 1H), 2.45 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.50, 173.90, 162.97 (d, J = 248 Hz), 139.96, 137.46, 133.27, 132.52, 130.69 (d, J = 8 Hz), 129.36, 128.42, 127.23 (d, J = 4 Hz), 122.56, 115.69 (d, J = 22 Hz), 111.69, 28.79. MS (EI) m/z: 307, 296, 265, 237, 209, 188, 159, 133, 105, 77, 51, 39. HRMS (ESI): calcd for C19H15FNO2 [M + H]+ 308.1081; found 308.1086.

1-(2-([1,1′-Biphenyl]-4-carbonyl)-5-phenyl-1H-pyrrol-1-yl)ethan-1-one (3x)

Viscous liquid (41 mg, 56%); R = 0.43 (ethyl acetate/petroleum ether = 1:10); 1H NMR (400 MHz, CDCl3): δ = 8.07–8.03 (m, 2H), 7.75–7.72 (m, 2H), 7.67 (dd, J = 5.2, 3.2 Hz, 2H), 7.53–7.46 (m, 3H), 7.45–7.42 (m, 5H), 6.90 (d, J = 3.8 Hz, 1H), 6.35 (d, J = 3.8 Hz, 1H), 2.47 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 184.06, 174.12, 145.30, 140.84, 139.98, 136.24, 133.44, 131.24, 130.06, 128.95, 128.76, 128.68, 128.59, 128.15, 127.28, 127.09, 122.31, 111.56, 28.80. MS (EI) m/z: 365, 354, 323, 295, 265, 246, 207, 181, 170, 141, 115, 77. HRMS (ESI): calcd for C25H20NO2 [M + H]+ 366.1489; found 366.1494.

1-(2-(4-Fluorophenyl)-5-(4-methoxybenzoyl)-1H-pyrrol-1-yl)ethan-1-one (3y)

Yellow solid (36 mg, 54%); mp 155–157 °C; R = 0.46 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 8.03–7.93 (m, 2H), 7.45–7.36 (m, 2H), 7.11 (t, J = 8.6 Hz, 2H), 7.01–6.97 (m, 2H), 6.81 (d, J = 3.8 Hz, 1H), 6.28 (d, J = 3.8 Hz, 1H), 3.90 (s, 3H), 2.42 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 183.47, 173.86, 163.33, 162.92 (d, J = 248 Hz), 139.39, 133.55, 131.69, 130.64 (d, J = 8 Hz), 130.13, 127.45, 121.65, 115.67 (d, J = 21 Hz), 113.73, 111.55, 55.50, 28.77. MS (EI) m/z: 337, 295, 264, 224, 187, 159, 133, 108, 77, 64, 39. HRMS (ESI): calcd for C20H17FNO3 [M + H]+ 338.1187; found 338.1199.

General Procedure for the Synthesis of Isoquinolines (4a–4v)

A mixture of ketoxime acetate (0.2 mmol), ynal (0.2 mmol), [Cp*RhCl2]2 (3.1 mg, 2.5 mol %), and Cu(OAc)2 (10.9 mg, 30 mol %) in DMF (1.0 mL) was stirred in a preheated oil bath at 60 °C for 8 h in a sealed tube under an argon atmosphere. After the reaction was finished, water (5 mL) was added and the solution was extracted with ethyl acetate (3 × 5 mL), and the combined extract was dried with anhydrous MgSO4. The solvent was removed, and the residue was separated by column chromatography to give the pure sample.

Large-Scale Synthesis

An oven-dried 25 mL screw cap test tube was charged with a magnetic stir bar, 1a (354 mg, 2 mmol), 2a (260 mg, 2 mmol), [Cp*RhCl2]2 (31 mg, 2.5 mol %), Cu(OAc)2 (109 mg, 30 mol %), and DMF (6.0 mL). Then, the tube was placed in a preheated oil bath at 60 °C for 8 h. After the solution cooled to room temperature, water (10 mL) was added and the solution was extracted with ethyl acetate (3 × 10 mL); the combined extract was dried with anhydrous MgSO4. The solvent was removed, and the residue was separated by column chromatography (ethyl acetate/petroleum ether = 1:8) to give 4a (361 mg, 73%).

1-Methyl-3-phenylisoquinoline-4-carbaldehyde (4a)

Yellow solid (42 mg, 84%); mp 61–63 °C; R = 0.48 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1H), 9.28 (d, J = 8.6 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.88–7.84 (m, 1H), 7.69 (t, J = 4.2 Hz, 1H), 7.66 (dd, J = 5.4, 2.1 Hz, 2H), 7.52 (dt, J = 3.9, 2.2 Hz, 3H), 3.09 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.32, 163.79, 159.47, 138.16, 133.15, 132.64, 131.25, 129.32, 128.38, 127.67, 126.31, 125.87, 125.43, 121.46, 23.51. MS (EI) m/z: 247, 219, 176, 151, 123, 109, 88, 63, 39. HRMS (ESI): calcd for C17H14NO [M + H]+ 248.1070; found 248.1078.

1-Methyl-3-(p-tolyl)isoquinoline-4-carbaldehyde (4b)

Yellow solid (45 mg, 86%); mp 71–73 °C; R = 0.30 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1H), 9.27 (d, J = 8.6 Hz, 1H), 8.21 (d, J = 8.4 Hz, 1H), 7.86–7.82 (m, 1H), 7.67 (dd, J = 11.3, 4.0 Hz, 1H), 7.56 (d, J = 8.0 Hz, 2H), 7.33 (d, J = 7.9 Hz, 2H), 3.07 (s, 3H), 2.45 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.38, 163.66, 159.48, 139.51, 135.28, 133.20, 132.52, 131.27, 129.10, 127.49, 126.15, 125.82, 125.34, 121.24, 23.50, 21.30. MS (EI) m/z: 261, 233, 217, 189, 165, 130, 115, 94, 63, 39. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 262.1226; found 262.1221.

1-Methyl-3-(m-tolyl)isoquinoline-4-carbaldehyde (4c)

Yellow solid (44 mg, 85%); mp 87–89 °C; R = 0.30 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1H), 9.28 (d, J = 8.6 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.85 (ddd, J = 8.5, 6.9, 1.3 Hz, 1H), 7.68 (ddd, J = 8.2, 6.9, 1.1 Hz, 1H), 7.50 (s, 1H), 7.41 (dd, J = 3.9, 1.5 Hz, 2H), 7.34–7.30 (m, 1H), 3.08 (s, 3H), 2.46 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.39, 163.71, 159.73, 138.17, 138.10, 133.15, 132.58, 131.65, 130.10, 128.61, 128.21, 127.58, 126.26, 125.84, 125.41, 121.39, 23.51, 21.42. MS (EI) m/z: 261, 233, 217, 189, 165, 130, 115, 94, 63, 39. HRMS (ESI): calcd for C18H16NO [M + H]+ 262.1226; found 262.1226.

1-Methyl-3-(o-tolyl)isoquinoline-4-carbaldehyde (4d)

Yellow solid (32 mg, 62%); mp 107–109 °C; R = 0.40 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.05 (s, 1H), 9.34 (d, J = 8.6 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.88 (t, J = 7.7 Hz, 1H), 7.71 (t, J = 7.6 Hz, 1H), 7.36–7.32 (m, 2H), 7.30 (d, J = 3.5 Hz, 2H), 3.08 (s, 3H), 2.21 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.31, 164.25, 160.85, 137.70, 136.69, 133.01, 132.85, 130.73, 130.51, 129.02, 127.78, 126.63, 125.95, 125.76, 125.69, 121.62, 23.42, 20.10. MS (EI) m/z: 261, 232, 217, 189, 165, 130, 115, 89, 63, 39. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 262.1226; found 262.1221.

3-(3,5-Dimethylphenyl)-1-methylisoquinoline-4-carbaldehyde (4e)

Yellow solid (46 mg, 83%); mp 118–120 °C; R = 0.34 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.16 (s, 1H), 9.29 (d, J = 8.6 Hz, 1H), 8.22 (d, J = 8.3 Hz, 1H), 7.87–7.83 (m, 1H), 7.69–7.65 (m, 1H), 7.25 (s, 2H), 7.14 (s, 1H), 3.08 (s, 3H), 2.41 (s, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.50, 163.68, 160.04, 138.08, 137.98, 133.18, 132.56, 130.99, 129.07, 127.52, 127.15, 126.25, 125.85, 125.42, 121.34, 23.51, 21.29. MS (EI) m/z: 275, 247, 217, 189, 165, 137, 115, 77, 63, 39. HRMS (ESI): calcd for C19H18NO [M + H]+ 276.1383; found 276.1380.

3-([1,1′-Biphenyl]-4-yl)-1-methylisoquinoline-4-carbaldehyde (4f)

Yellow solid (50 mg, 78%); mp 125–127 °C; R = 0.44 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.27 (s, 1H), 9.30 (d, J = 8.6 Hz, 1H), 8.24 (d, J = 8.1 Hz, 1H), 7.89–7.85 (m, 1H), 7.76 (s, 4H), 7.68 (ddd, J = 7.1, 3.7, 2.3 Hz, 3H), 7.50 (dd, J = 10.3, 4.7 Hz, 2H), 7.42–7.38 (m, 1H), 3.10 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.22, 163.80, 159.03, 142.24, 140.33, 137.02, 133.18, 132.63, 131.77, 128.87, 127.72, 127.66, 127.20, 127.14, 126.29, 125.87, 125.41, 121.47, 23.53. MS (EI) m/z: 323, 295, 246, 218, 176, 161, 126, 115, 77, 51, 39. HRMS (ESI): calcd for C23H18NO [M + H]+ 324.1383; found 324.1397.

3-(4-Methoxyphenyl)-1-methylisoquinoline-4-carbaldehyde (4g)

Yellow solid (44 mg, 80%); mp 89–91 °C; R = 0.36 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.14 (s, 1H), 9.25 (d, J = 8.6 Hz, 1H), 8.19 (d, J = 8.3 Hz, 1H), 7.85–7.81 (m, 1H), 7.66 (d, J = 8.0 Hz, 1H), 7.62 (d, J = 8.6 Hz, 2H), 7.05 (d, J = 8.6 Hz, 2H), 3.88 (s, 3H), 3.06 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.31, 163.57, 160.85, 158.96, 133.29, 132.87, 132.49, 130.94, 130.55, 127.38, 125.83, 125.24, 120.99, 113.94, 55.43, 23.49. MS (EI) m/z: 277, 249, 234, 206, 190, 165, 140, 118, 88, 63, 39. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 278.1176; found 278.1175.

3-(4-Fluorophenyl)-1-methylisoquinoline-4-carbaldehyde (4h)

Yellow solid (43 mg, 82%); mp 124–126 °C; R = 0.58 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.19 (s, 1H), 9.29 (d, J = 8.6 Hz, 1H), 8.26 (d, J = 8.4 Hz, 1H), 7.89 (dd, J = 11.4, 4.1 Hz, 1H), 7.71 (dt, J = 6.6, 5.4 Hz, 3H), 7.29 (d, J = 6.1 Hz, 1H), 7.24 (s, 1H), 3.11 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.94, 163.88, 163.64 (d, J = 249 Hz), 158.18, 134.26 (d, J = 4 Hz), 133.13, 133.12 (d, J = 9 Hz), 132.75, 127.79, 126.32, 125.90, 125.38, 121.51, 115.51(d, J = 22 Hz), 23.49. MS (EI) m/z: 265, 237, 221, 194, 169, 141, 115, 75, 63, 39. HRMS (ESI): calcd for C17H13FNO [M + H]+ 266.0976; found 266.0976.

3-(4-Chlorophenyl)-1-methylisoquinoline-4-carbaldehyde (4i)

Yellow solid (41 mg, 73%); mp 109–111 °C; R = 0.52 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1H), 9.25 (d, J = 8.6 Hz, 1H), 8.24 (d, J = 8.3 Hz, 1H), 7.89–7.85 (m, 1H), 7.71 (d, J = 7.1 Hz, 1H), 7.62–7.59 (m, 2H), 7.53–7.50 (m, 2H), 3.08 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.76, 163.95, 158.04, 136.69, 135.85, 133.15, 132.78, 132.52, 128.66, 127.90, 126.45, 125.91, 125.48, 121.67, 23.49. MS (EI) m/z: 281, 253, 246, 217, 176, 150, 141, 109, 88, 63, 39. HRMS (ESI): calcd for C17H13ClNO [M + H]+ 282.0680; found 282.0676.

3-(4-Bromophenyl)-1-methylisoquinoline-4-carbaldehyde (4j)

Yellow solid (46 mg, 71%); mp 138–140 °C; R = 0.39 (ethyl acetate/petroleum ether = 1:12); 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1H), 9.25 (d, J = 8.6 Hz, 1H), 8.23 (d, J = 8.4 Hz, 1H), 7.87 (ddd, J = 8.5, 6.9, 1.3 Hz, 1H), 7.72–7.69 (m, 1H), 7.68–7.65 (m, 2H), 7.55–7.52 (m, 2H), 3.08 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.74, 163.98, 158.06, 137.11, 133.12, 132.79, 132.76, 131.61, 127.91, 126.43, 125.91, 125.45, 124.14, 121.62, 23.49. MS (EI) m/z: 325, 297, 246, 217, 191, 150, 123, 108, 88, 63, 39. HRMS (ESI): calcd for C17H13BrNO [M + H]+ 326.0175; found 326.0175.

3-(4-Acetylphenyl)-1-methylisoquinoline-4-carbaldehyde (4k)

Yellow solid (38 mg, 65%); mp 116–118 °C; R = 0.28 (ethyl acetate/petroleum ether = 1:5); 1H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1H), 9.26 (d, J = 8.6 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.11 (d, J = 8.3 Hz, 2H), 7.89 (dd, J = 7.9, 6.6 Hz, 1H), 7.76 (d, J = 8.3 Hz, 2H), 7.74–7.71 (m, 1H), 3.09 (s, 3H), 2.68 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 197.61, 193.61, 164.07, 158.08, 142.73, 137.42, 133.06, 132.89, 131.48, 128.26, 128.12, 126.63, 125.95, 125.57, 122.01, 26.75, 23.47. MS (EI) m/z: 289, 261, 246, 218, 189, 150, 123, 103, 88, 57, 43. HRMS (ESI): calcd for C19H16NO2 [M + H]+ 290.1176; found 290.1185.

Methyl 4-(4-Formyl-1-methylisoquinolin-3-yl)benzoate (4l)

Yellow solid (38 mg, 62%); mp 95–97 °C; R = 0.24 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.17 (s, 1H), 9.26 (d, J = 8.6 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 8.19 (d, J = 8.0 Hz, 2H), 7.90–7.86 (m, 1H), 7.73 (d, J = 8.1 Hz, 3H), 3.97 (s, 3H), 3.09 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.68, 166.63, 164.04, 158.20, 142.59, 133.04, 132.86, 131.24, 130.78, 129.55, 128.07, 126.59, 125.93, 125.56, 121.93, 52.31, 23.52. MS (EI) m/z: 305, 277, 246, 218, 189, 151, 123, 109, 88, 63, 39. HRMS (ESI): calcd for C19H16NO3 [M + H]+ 306.1125; found 306.1130.

1-Methyl-3-(thiophen-2-yl)isoquinoline-4-carbaldehyde (4m)

Yellow solid (34 mg, 67%); mp 94–96 °C; R = 0.40 (ethyl acetate/petroleum ether = 1:12); 1H NMR (400 MHz, CDCl3): δ = 10.35 (s, 1H), 9.17 (d, J = 8.6 Hz, 1H), 8.19 (d, J = 8.4 Hz, 1H), 7.85–7.81 (m, 1H), 7.65 (dd, J = 14.7, 6.5 Hz, 2H), 7.25 (s, 1H), 7.21–7.18 (m, 1H), 3.05 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.40, 163.64, 151.58, 141.71, 133.09, 132.62, 132.60, 130.39, 127.96, 127.64, 126.04, 125.93, 125.20, 121.04, 23.39. MS (EI) m/z: 253, 226, 209, 180, 152, 139, 115, 92, 63, 40. HRMS (ESI): calcd for C15H12NOS [M + H]+ 254.0634; found 254.0633.

1-Ethyl-3-phenylisoquinoline-4-carbaldehyde (4n)

Yellow solid (40 mg, 76%); mp 107–109 °C; R = 0.60 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1H), 9.29 (d, J = 8.6 Hz, 1H), 8.28 (d, J = 8.4 Hz, 1H), 7.86 (dd, J = 11.4, 4.2 Hz, 1H), 7.68 (dd, J = 5.7, 3.8 Hz, 3H), 7.53 (dd, J = 5.1, 1.9 Hz, 3H), 3.48–3.42 (m, 2H), 1.51 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.44, 168.12, 159.43, 138.36, 133.53, 132.44, 131.40, 129.32, 128.35, 127.59, 125.57, 125.51, 125.46, 121.28, 29.35, 13.49. MS (EI) m/z: 261, 232, 204, 176, 154, 127, 102, 77, 51, 39. HRMS (ESI): calcd for C18H16NO [M + H]+ 262.1226; found 262.1230.

1-Ethyl-3-(p-tolyl)isoquinoline-4-carbaldehyde (4o)

Yellow solid (43 mg, 78%); mp 127–129 °C; R = 0.50 (ethyl acetate/petroleum ether = 1:12); 1H NMR (400 MHz, CDCl3): δ = 10.18 (s, 1H), 9.28 (d, J = 8.5 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.83 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.68–7.64 (m, 1H), 7.59 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 7.8 Hz, 2H), 3.43 (d, J = 7.5 Hz, 2H), 2.46 (s, 3H), 1.50 (t, J = 7.5 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.45, 167.91, 159.38, 139.50, 135.47, 133.54, 132.29, 131.40, 129.05, 127.39, 125.44, 125.38, 125.33, 121.02, 29.26, 21.31, 13.37. MS (EI) m/z: 275, 260, 246, 218, 189, 154, 127, 115, 91, 65, 39. HRMS (ESI): calcd for C19H18NO2 [M + H]+ 276.1383; found 276.1382.

2-Phenyl-8,9-dihydro-7H-benzo[de]quinoline-3-carbaldehyde (4p)

Yellow solid (33 mg, 60%); mp 98–100 °C; R = 0.24 (ethyl acetate/petroleum ether = 1:3); 1H NMR (400 MHz, CDCl3): δ = 10.16 (s, 1H), 9.10 (d, J = 8.6 Hz, 1H), 7.76 (dd, J = 8.6, 7.2 Hz, 1H), 7.64 (dt, J = 4.7, 2.7 Hz, 2H), 7.53–7.49 (m, 3H), 7.46–7.43 (m, 1H), 3.38–3.34 (m, 2H), 3.19 (t, J = 6.1 Hz, 2H), 2.27–2.22 (m, 2H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.31, 165.43, 159.77, 139.01, 138.33, 133.48, 132.83, 131.17, 129.22, 128.36, 126.11, 124.16, 122.85, 121.38, 35.54, 30.66, 23.20. MS (EI) m/z: 273, 245, 202, 189, 166, 129, 121, 77, 51, 40. HRMS (ESI): calcd for C19H16NO2 [M + H]+ 274.1226; found 274.1223.

1,3-Diphenylisoquinoline-4-carbaldehyde (4q)

Yellow solid (32 mg, 51%); mp 204–206 °C; R = 0.46 (ethyl acetate/petroleum ether = 1:12); 1H NMR (400 MHz, CDCl3): δ = 10.26 (s, 1H), 9.35 (d, J = 8.6 Hz, 1H), 8.20 (d, J = 8.4 Hz, 1H), 7.89 (ddd, J = 8.4, 6.9, 1.3 Hz, 1H), 7.80–7.77 (m, 2H), 7.75–7.72 (m, 2H), 7.65–7.61 (m, 1H), 7.54 (ddd, J = 10.5, 5.2, 2.0 Hz, 6H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.35, 164.64, 159.35, 139.06, 138.22, 134.48, 132.66, 131.55, 130.30, 129.43, 129.38, 128.39, 128.38, 128.22, 127.60, 125.55, 125.10, 121.43. MS (EI) m/z: 309, 280, 252, 226, 202, 176, 155, 139, 113, 77, 51, 40. HRMS (ESI): calcd for C22H16NO [M + H]+ 310.1226; found 310.1221.

1,6-Dimethyl-3-phenylisoquinoline-4-carbaldehyde (4r)

Yellow solid (42 mg, 80%); mp 157–159 °C; R = 0.46 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.15 (s, 1H), 9.08 (s, 1H), 8.12 (d, J = 8.6 Hz, 1H), 7.64 (dd, J = 5.3, 1.8 Hz, 2H), 7.52 (s, 2H), 7.51 (d, J = 1.7 Hz, 2H), 3.05 (s, 3H), 2.61 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.50, 163.41, 159.82, 143.55, 138.36, 133.45, 131.22, 129.71, 129.23, 128.35, 125.76, 124.71, 124.47, 121.12, 23.42, 22.44. MS (EI) m/z: 261, 233, 217, 189, 154, 130, 109, 77, 51, 39. HRMS (ESI): calcd for C18H16NO [M + H]+ 262.1226; found 262.1232.

6-Methoxy-1-methyl-3-phenylisoquinoline-4-carbaldehyde (4s)

Yellow solid (40 mg, 72%); mp 155–157 °C; R = 0.33 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.16 (s, 1H), 8.78 (d, J = 2.6 Hz, 1H), 8.11 (d, J = 9.2 Hz, 1H), 7.66–7.62 (m, 2H), 7.53–7.49 (m, 3H), 7.29–7.26 (m, 1H), 4.02 (s, 3H), 3.02 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.62, 163.22, 162.89, 161.18, 138.41, 135.76, 131.17, 129.22, 128.33, 127.70, 121.91, 120.58, 120.14, 103.51, 55.66, 23.38. MS (EI) m/z: 277, 249, 233, 206, 190, 163, 139, 102, 77, 63, 39. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 278.1176; found 278.1167.

8-Methoxy-1-methyl-3-phenylisoquinoline-4-carbaldehyde (4t)

Yellow solid (29 mg, 53%); mp 106–108 °C; R = 0.43 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.15 (s, 1H), 8.88 (dd, J = 8.6, 0.7 Hz, 1H), 7.73 (t, J = 8.3 Hz, 1H), 7.68–7.64 (m, 2H), 7.51 (dd, J = 5.1, 2.0 Hz, 3H), 7.01 (d, J = 7.9 Hz, 1H), 4.02 (s, 3H), 3.20 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.31, 163.62, 159.65, 158.39, 138.11, 135.89, 133.17, 131.23, 129.32, 128.32, 120.42, 119.02, 116.86, 107.25, 55.49, 30.14. MS (EI) m/z: 277, 249, 234, 219, 190, 164, 128, 102, 77, 51, 40. HRMS (ESI): calcd for C18H16NO2 [M + H]+ 278.1176; found 278.1171.

6-Fluoro-1-methyl-3-phenylisoquinoline-4-carbaldehyde (4u)

Yellow solid (40 mg, 75%); mp 112–114 °C; R = 0.20 (ethyl acetate/petroleum ether = 1:12); 1H NMR (400 MHz, CDCl3): δ = 10.14 (s, 1H), 9.02 (dd, J = 11.5, 2.6 Hz, 1H), 8.25 (dd, J = 9.2, 5.8 Hz, 1H), 7.65 (dd, J = 6.6, 3.0 Hz, 2H), 7.53 (dd, J = 5.0, 1.6 Hz, 3H), 7.45–7.41 (m, 1H), 3.07 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.92, 165.21 (d, J = 252 Hz), 163.55, 160.80, 137.80, 135.28 (d, J = 12 Hz), 131.25, 129.57, 128.89 (d, J = 10 Hz), 128.45, 123.62, 120.98 (d, J = 5 Hz), 117.75 (d, J = 25 Hz), 109.93 (d, J = 24 Hz), 23.61. MS (EI) m/z: 265, 237, 221, 194, 158, 133, 118, 77, 51, 39. HRMS (ESI): calcd for C17H13FNO [M + H]+ 266.0976; found 266.0979.

6-Chloro-1-methyl-3-phenylisoquinoline-4-carbaldehyde (4v)

Yellow solid (35 mg, 63%); mp 110–112 °C; R = 0.21 (ethyl acetate/petroleum ether = 1:12); 1H NMR (400 MHz, CDCl3): δ = 10.12 (s, 1H), 9.34 (d, J = 2.0 Hz, 1H), 8.15 (d, J = 8.9 Hz, 1H), 7.64 (d, J = 2.0 Hz, 2H), 7.53 (dd, J = 6.8, 2.8 Hz, 4H), 3.06 (s, 3H). 13C{1H} NMR (101 MHz, CDCl3) δ 193.81, 163.71, 160.55, 139.59, 137.73, 134.07, 131.26, 129.61, 128.64, 128.47, 127.43, 124.67, 124.56, 120.40, 23.52. MS (EI) m/z: 281, 253, 237, 217, 176, 150, 140, 109, 95, 51, 39. HRMS (ESI): calcd for C17H13ClNO [M + H]+ 282.0680; found 282.0680.

7-Methyl-5-phenylthieno[2,3-c]pyridine-4-carbaldehyde (4w)

Yellow solid (24 mg, 48%); mp 97–99 °C; R = 0.43 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.12 (s, 1H), 8.49 (d, J = 5.4 Hz, 1H), 7.92 (d, J = 5.4 Hz, 1H), 7.62 (dd, J = 5.2, 1.9 Hz, 2H), 7.52 (dd, J = 5.3, 1.8 Hz, 3H), 2.95 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 192.63, 159.78, 157.26, 143.22, 137.81, 136.04, 134.93, 131.00, 129.13, 128.43, 124.68, 121.81, 24.29. MS (EI) m/z: 253, 225, 209, 197, 152, 139, 112, 77, 51, 45. HRMS (ESI): calcd for C15H12NOS [M + H]+ 254.0634; found 254.0634.

3-(2-Ethylphenyl)-1,6-dimethylisoquinoline-4-carbaldehyde (4x)

Yellow solid (48 mg, 83%); mp 120–122 °C; R = 0.46 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.06 (s, 1H), 9.15 (s, 1H), 8.14 (d, J = 8.6 Hz, 1H), 7.53 (dd, J = 8.6, 1.6 Hz, 1H), 7.42–7.36 (m, 2H), 7.31–7.27 (m, 1H), 7.25 (dd, J = 7.3, 1.5 Hz, 1H), 3.04 (s, 3H), 2.62 (s, 3H), 2.54 (dd, J = 14.4, 7.2 Hz, 2H), 1.08 (t, J = 7.6 Hz, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.49, 163.62, 161.25, 143.74, 142.62, 137.42, 133.25, 130.78, 129.72, 129.10, 128.81, 125.81, 125.59, 124.96, 124.67, 121.30, 26.35, 23.30, 22.42, 14.92. MS (EI) m/z: 289, 260, 245, 202, 189, 165, 122, 115, 77, 63, 39. HRMS (ESI): calcd for C20H20NO [M + H]+ 290.1539; found 290.1543.

Methyl 4-(4-Formyl-1,6-dimethylisoquinolin-3-yl)benzoate (4y)

Yellow solid (38 mg, 60%); mp 138–140 °C; R = 0.28 (ethyl acetate/petroleum ether = 1:8); 1H NMR (400 MHz, CDCl3): δ = 10.15 (s, 1H), 9.06 (s, 1H), 8.19 (d, J = 8.3 Hz, 2H), 8.16–8.10 (m, 2H), 7.72 (d, J = 8.3 Hz, 2H), 7.54 (dd, J = 8.6, 1.3 Hz, 1H), 3.97 (s, 4H), 3.05 (s, 3H), 2.62 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 193.83, 166.67, 163.64, 158.54, 143.85, 142.80, 133.36, 131.20, 130.72, 130.11, 129.52, 125.82, 125.00, 124.60, 121.59, 52.28, 23.37, 22.45. MS (EI) m/z: 319, 291, 260, 232, 217, 189, 155, 115, 94, 59, 43. HRMS (ESI): calcd for C20H18NO3 [M + H]+ 320.1281; found 320.1283.

6-Methoxy-3-(4-methoxyphenyl)-1-methylisoquinoline-4-carbaldehyde (4z)

Yellow solid (37 mg, 61%); mp 164–166 °C; R = 0.30 (ethyl acetate/petroleum ether = 1:4); 1H NMR (400 MHz, CDCl3): δ = 10.14 (s, 1H), 8.77 (d, J = 2.6 Hz, 1H), 8.09 (d, J = 9.2 Hz, 1H), 7.62–7.59 (m, 2H), 7.24 (d, J = 2.6 Hz, 1H), 7.06–7.03 (m, 2H), 4.02 (s, 3H), 3.89 (s, 3H), 3.01 (s, 3H). 13C{1H} NMR (100 MHz, CDCl3): δ = 194.65, 163.13, 162.74, 160.78, 160.66, 135.90, 132.80, 130.79, 127.69, 121.62, 120.23, 119.85, 113.90, 103.40, 55.65, 55.44, 23.38. MS (EI) m/z: 307, 279, 264, 236, 221, 193, 153, 132, 102, 77, 63, 40. HRMS (ESI): calcd for C19H18NO3 [M + H]+ 308.1281; found 308.1279.