Metal-Catalyzed Domino Synthesis of Benzophenanthridines and 6H

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Metal-catalyzed Domino Synthesis of Benzophenanthridines and 6H-Naphtho[2,3-c]-chromenes Baitan Chakraborty, Swapnadeep Jalal, Kartick Paul, Sandip Kundal, and Umasish Jana J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b00924 • Publication Date (Web): 11 Jun 2018 Downloaded from http://pubs.acs.org on June 11, 2018

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The Journal of Organic Chemistry

Metal-catalyzed Domino Synthesis of Benzophenanthridines and 6H-Naphtho[2,3-c]-chromenes Baitan Chakraborty, Swapnadeep Jalal, Kartick Paul, Sandip Kundal, Umasish Jana* Department of Chemistry, Jadavpur University, Kolkata 700 032, West Bengal, India * E-mail: [email protected], [email protected].

R1

OHC Iron

Palladium

R1 X Isomerisation/ Cycloaromatisation X = NTs,O

R1

I/Br X

X Domino Heck-Suzuki

ABSTRACT: A new and efficient synthesis of tetracyclic phenanthridines and benzo[c]chromenes has been described involving metal-mediated two-step domino strategy. The first step involved efficient palladium-catalyzed domino carbopalladation/cross coupling, and second step involved iron-catalyzed domino isomerisation/cyclodehydration. The important features of this strategy include high yields, generality, wide substrate scope and broad functional group tolerance. A plausible mechanism has been proposed to explain the formation of the product.

Introduction Natural as well as synthetically produced polycyclic heterocycles are important synthetic targets, owing to their wide abundance in natural products and widespread applications in medicinal chemistry and material sciences. Therefore, the development of quick, efficient, and versatile methods for the syntheses of new classes of benzo-fused heterocycles is in high demand in the area of medicinal chemistry and material sciences. For examples, phenanthridine ring systems are significant structural motifs found in a wide variety of naturally occurring phenanthridines and benzophenanthridine alkaloids with extensive pharmacological activities, and are of great interest in the field of material sciences.1 Important compounds in this class include ethidium salts as DNA intercalators, fagaronine, nitidine and trispheridine as promising antitumor agents, which were subjected to clinical trials (Figure 1).2 Looking at such potential therapeutic and material

Figure 1. Some important natural products containing fused phenanthridines and fused benzo[c]chromenes

applications, extensive efforts have been devoted toward the development of new strategies and methods to access large varieties of phenanthridines, benzo[b]phenanthridines and other annulated forms.3,4 In comparison, the isomeric benzo[j]phenanthridine has been reported for good pharmacological activity, but the synthesis has been less explored. 5

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Similarly, tricyclic benzo[c]chromene and tetracyclic 6H-naphtho[2,3-c]chromene skeletons are important structural motifs embedded in numerous natural products, and show remarkable biological activities.6 Consequently, numerous synthetic methods have been developed for the synthesis of tricyclic 6H-benzo[c]chromene derivatives,7 whereas, the synthesis of tetracyclic 6H-naphtho[2,3-c]chromene skeletons is scarcely reported.8 In addition, most of these synthetic methods can only be applied to furnish the products only with a narrow scope of structural diversity. Therefore, a novel strategy that provides a general and efficient synthetic route to many different benzo[j]phenanthridines and 6Hnaphtho[2,3-c]chromenes is still highly desirable. In recent years, the construction of polycyclic heterocycles involving metal-mediated domino reactions has been a powerful tool, and has received tremendous attention,9 as it provides step-economic access to furnish structural complexity with great diversity from simple starting materials. In this regard, our group has recently reported a novel twostep strategy involving palladium-catalyzed domino carbon-carbon bond formation and, subsequently, iron mediated domino isomerisation/cyclodehydration for easy access to varieties of benzofused indoles and benzofuran derivatives, under extremely mild conditions.10 In light of this precedence, we envisioned that this strategy could also be useful for the Scheme 1. Our synthetic strategy for the tetracyclic heterocycle

synthesis of very important benzofused quinoline and chromene derivatives from substrate B. We, herein, report a general strategy for the efficient synthesis of both benzo[j]phenanthridine and 6H-naphtho[2,3-c]chromene derivatives C under modified reaction conditions. Our strategy for the synthesis of tetracyclic phenanthridine and benzo[c]chromene derivatives is delineated in the Scheme 1. The compound B can be constructed from compound A via a domino HeckSuzuki coupling reaction of homopropargylated 2-bromoanilide or 2-bromophenolic ether with 2-formylphenylboronic acid. To the best of our knowledge, this would be the first report for the syntheses of benzophenanthridine and benzo[c]chromene derivatives via a single and efficient strategy. Results and Discussion The required dihydroquinoline derivatives 2, were prepared using our modified domino carbopalladation/Suzuki coupling of 1 (1 equiv) with 2-formylphenylboronic acid (1.5 equiv) in the presence of Pd(PPh 3)4 (5 mol %), 2.5 M K2CO3, and toluene/ethanol at 80 ˚C. A number of substrates were prepared under these conditions; the results are summarized in Scheme 2. This reaction was found to be general for the preparation of varieties of dihydroquinoline derivatives in good yields in a stereoselective manner via 6-exo-dig cyclisation onto the carbon–carbon triple bond. For example, 2-haloaniline derivatives possessing strong electron-donating groups, such as –Me, –OMe and weakly electron-withdrawing groups such as –F and –Cl (Scheme 2, entries 2b–2e and 2g–2h) underwent smooth Heck-Suzuki coupling under normal reaction conditions in high yields (56–78%). Similarly, different groups on the aryl ring at the alkyne terminus such as –Me, –OMe and –Cl (Scheme 2, entries 2f–2j) were also compatible and gave the desired products in good yields (60–77%). After preparing the series of substrates, we focused on optimizing the reaction condition of domino isomerisation/cyclodehydration for the construction of benzo[j]phenanthridine derivative 3a using dihydroquinoline derivative 2a in the presence of various catalysts. The results are summarized in Table 1. We began our probe with anhydrous FeCl3 (10 mol %) as catalyst in 1,2-dichloroethane at room temperature, according to our previous work. Unfortunately, the reaction did not proceed in the presence of FeCl3 (10 mol %) at room temperature; however, heating under reflux for 6 h resulted formation of desired 3a in trace amounts. We understood that the driving force for our previous isomerization/cyclodehydration for the preparation of benzofused indole and benzofused benzofuran was complete aromatization, while the expected product in the present study would be partially aromatized 5,6dihydrobenzo[j]phenanthridine 3a, and, hence, less likely to form. Further investigations showed that the said


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Scheme 2. Preparation of the substrates 2a R2 CHO R1

X HO B +

N Ts X = Br/I 1

OH CHO

Pd(PPh3)4, ( 5 mol %) R 1 2.5 M K2CO3 toluene, EtOH 80 oC

CHO

CHO

CH3 N Ts 2a, 4 h, 75% CHO

CHO

N Ts 2b, 3 h, 78% CHO OCH3

N Ts 2f, 7 h, 60% CHO

CHO

N Ts 2c, 6 h, 58% CHO

CH3

N Ts 2d, 5 h, 56%b CHO

OCH3

CH3 N Ts 2g, 3 h, 77%

Cl

N Ts

F

CH3 N Ts 2e, 5 h, 63%

2

H3CO

Cl

R2

CHO

N Ts 2h, 5 h, 60% OCH3

CH3 N Ts 2i, 3.5 h, 67%

N Ms 2j, 4 h, 62%

aReaction

conditions: 0.5 mmol of 1, 0.75 mmol of 2-formylphenylboronic acid, 0.01 mmol of Pd(PPh 3)4 in 3 mL of aq 2.5 M K2CO3 solution, 3 mL of ethanol and 3 mL of toluene at 80 oC under Ar atmosphere. bYield of the reaction performed at 95 oC.

isomerisation/cycloaromatization is quite sensitive to catalyst and the reaction temperature. When the reaction was carried out in the presence of more reactive Fe(OTf)3 (10 mol %) as catalyst in 1,2-dichloroethane at room temperature, a trace amount of product was obtained, and the yield dramatically improved to 86% when the reaction mixture was heated to reflux for 3 h (Table 1, entries 2 and 3). Catalyst loading of 5 mol % provided a lower yield of 68% (Table 1, entry 14), and 15 mol % did not improve the results. Solvents such as MeNO 2, CH3CN and chlorobenzene were screened in the presence of Fe(OTf)3 only to find inferior results (Table 1, entries 4–6). We also examined the reaction with different catalysts under similar conditions. Among the metal salts, Cu(OTf) 2 (60%), AgOTf (55%) and In(OTf)3 (42%) gave lower yields; whereas, FeBr3, SC(OTf)3 and Yb(OTf)3 did not initiate the reaction (Table 1, entries 7–12). These results demonstrated that Fe(OTf)3 exhibited remarkably higher catalytic activity for this particular transformation compared to other Lewis acids. On the other hand, strong Brønsted acid such as TfOH (10 mol %) gave a good yield of the desired product in 80% yield (Table 1, entry 13). Hence, the optimum condition that stood out for the isomerization/cycloaromatization reaction is the catalysis of Fe(OTf) 3 (10 mol %) in refluxing 1,2-DCE for 3 h.



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Table 1. Optimization of the reaction conditionsa

entry

catalyst

solvent

temperture

time (h)

yield (%)

1

FeCl3

DCE

reflux

6

trace

2

Fe(OTf)3

DCE

rt

6

trace

3

Fe(OTf)3

DCE

reflux

3

86

4

Fe(OTf)3

CH3NO2

85 ºC

6

40

5

Fe(OTf)3

CH3CN

reflux

6

33

6

Fe(OTf)3

C6H5Cl

85 ºC

4

65

7

FeBr3

DCE

reflux

3

0

8

Cu(OTf)2

DCE

reflux

6

60

9

In(OTf)3

DCE

reflux

6

42

10

AgOTf

DCE

reflux

6

55

11

Sc(OTf)3

DCE

reflux

6

NR

12

Yb(OTf)3

DCE

reflux

6

NR

13

TfOH

DCE

reflux

2

80

14

Fe(OTf)3b

DCE

reflux

3

68

aReaction

conditions: 0.15 mmol of 2a and 0.015 mmol of catalyst in 1.5 mL of solvent under Ar atmosphere. bCatalyst load: 0.0075 mmol.

We moved forward with the aforementioned optimal conditions to find the robustness of the synthesis in terms of variation in the substrate. At first, the substrates with substituent R 1 at the 2-haloaniline nucleus were tested. Under the optimized reaction conditions, the 2-haloaniline nucleus bearing electron-donating groups such as p-Me and p-OMe reacted smoothly and offered excellent yields of 90% and 85%, respectively (Scheme 3, 3b and 3c). The reaction seemed to be a little less expressive toward electron-withdrawing R1 groups. However, on heating at 120 oC in chlorobenzene for a little longer, substrates with p-F and p-Cl groups yielded 67% and 60% of desired products (Scheme 3, 3d and 3e). Next, we investigated the influence of different substitutions at the olefinic centre, which is directly involved in the isomerization process. Strongly electron-donating 4-methoxyphenyl substitution was quite efficient in this position with yields of 80%, 72% and 75% (Scheme 3, 3j, 3f, 3h), respectively. In case of aryl groups with a weakly electron-donating group such as pMe and a weakly electron-withdrawing group such as p-Cl, the reactions were sluggish under the optimized conditions. But the reactions smoothly proceeded in chlorobenzene at 120 oC and gave the desired products in 70% and 58% yields, respectively (Scheme 3, 3g and 3i). Along this line, it is worth mentioning that instead of a tosyl protecting group on nitrogen, mesyl group also gave impressive result as well (Scheme 3, 3j). All the structures of dihydrophenanthridine derivatives were charaterised by NMR spectroscopy and HRMS. The structure of 3b was also confirmed by X-ray diffraction of the single crystal (see Supporting Information for the ORTEP diagram and other X-ray crystallography details).


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Scheme 3. Substrate scopes for the synthesis of 5,6-dihydrobenzo[j]phenanthridinesa

CHO

R2 R2

R1

Fe(OTf)3 (10 mol %) N R3 2b-2j

DCE, reflux 3b-3j

N 3c; 3 h, 85% Ts

N 3b; 3 h, 90% Ts

N R3

F

MeO

Me

R1

MeO

N 3d; 5 h, 67%b Ts Me

Cl

Me N

N 3f; 2.5 h, 72% Ts

3e; 6 h, 60%b Ts

Cl

MeO

N 3g; 8 h, 70%b Ts MeO

Me

Me N 3h; 3 h, 75% Ts

N 3i; 8 h, 58%b Ts

N 3j; 4.5 h, 80% Ms

aReaction

conditions: 0.15 mmol of 2 and 0.015 mmol of Fe(OTf)3 in 1.5 mL of 1,2-DCE at reflux under Ar atmosphere. bYields of the reactions performed in 1.5 mL of chlorobenzene at 120 oC under Ar atmosphere.

Moreover, this synthetic route can further be extended by one facile step to fabricate the complete aromatic framework of benzo[j]phenanthridine. The detosylation reaction of the 5,6-dihydrobenzo[j]phenanthridine 3a was carried out in a sealed tube using K2CO3 in ethanol at 100 oC for 6 hours to obtain benzo[j]phenanthridine 4a in 80% yield (Scheme 4). Scheme 4. Detosylation of dihydrobenzo[j]phenanthridine

Encouraged by the versatility of the Fe(OTf)3 catalyzed isomerization/cycloaromatization strategy, we attempted a new route toward the synthesis of 6H-naphtho[2,3-c]chromene derivatives. Necessary starting materials 6a–6d were prepared following a similar strategy. However, it was observed that better results of Heck-Suzuki coupling of 5 with 2formylphenylboronic acid was obtained in the presence of K3PO4 in 1,4-dioxane with Pd(dppf)2Cl2 (5 mol %) at 65 oC–80 o C to avail a variety of substrates such as 6a–6d in good yields (Scheme 5, 54-78%).



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Scheme 5. Preparation of the Substrate 6

Thereafter, the standardized reaction conditions for the earlier synthesis were successfully employed for the isomerization/cyclodehydration of 6a–6d to scrutinize the generality of this motivated synthesis. It was noticed that, with no substitutions at the phenolic part, or at the olefinic aryl variant, the reaction produced the expected product with 80% yield (Scheme 6, 7a). Like in the earlier synthesis, electron-rich substrate 6b with a p-methoxyphenyl group at the olefinic centre proved to suit well in this case (82%, Scheme 6, 7b). However, the substrate 6c, having both Br and Me group in the phenol part, required heating for 6 h at 115 oC in chlorobenzene to provide a yield of 75% (Scheme 6, 7c). Furthermore, it was observed that the two mutually opposing substituents in the same ring, i. e., –OMe and –CHO were well tolerated to furnish the product in 73% yield, although a higher temperature was needed (Scheme 6, 7d). Therefore, it is evident that stereoelectronic factors of the substituents are not that impactful in our synthesis of 6H-naphtho[2,3c]chromene derivatives. Scheme 6. Synthesis of Some 6H-Naphtho[2,3-c]chromene derivativesa CHO

R4

R5

R5

Fe(OTf)3 (10 mol %)

R4

1,2-DCE

O

O

6a-6d

7a-7d

Me

MeO

Me

O 7a; 3 h, 80%

O 7b; 2 h, 82%

OMe

Br

O OHC 7c; 6 h, 75%b

O

7d; 5 h, 73%b

aReaction

conditions: 0.15 mmol of 6, 0.015 mmol of Fe(OTf)3 in 1.5 mL of 1,2-DCE at 70 ºC under Ar atmosphere. bYields of the reactions in 1.5 mL of chlorobenzene at 115 ºC.

Finally, a plausible mechanism that is similar to our previous work is, hereby, proposed for this reaction as shown in Scheme 7.10 b,c In the first step, the palladium(0) complex would react with substrate 1 via oxidative addition, followed by syn-carbopalladation, leading to a σ-alkylpalladium(II) intermediate 1a′ via a 6-exo-dig cyclization process. Next, the intermediate 1a′ would undergo smooth transmetallation with 2-formylphenylboronic acid to furnish intermediate 1b′, with subsequent reductive elimination furnishing the product 2. In most of the cases, only syn-product was isolated as a sole product; however, in a few cases, concomitant formation of minor anti-isomers resulted due to the isomerisation of intermediate 1b′.10c In the second step, the isomerisation of product 2 to 2b′ presumably took place through the complexation of the carbonyl group with the Fe(OTf)3. As Fe(OTf)3 has better polarizing power compared to FeCl3, Fe(OTf)3 worked efficiently for this process. Then, protonation of 2b′ would produce the intermediate 2c′, which on intramolecular Friedel−Crafts alkylation and subsequent aromatization by dehydration of water, affords the desired tetracyclic phenanthridine or benzo[c]chromene derivatives 3.


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Scheme 7. Proposed mechanism for two step domino synthesis of tetracyclic benzofused heterocycles

Conclusion In summary, we have developed a unique approach for the synthesis of 5,6-dihydrobenzo[j]phenanthridine and 6Hnaphtho[2,3-c]chromene derivatives via a palladium catalyzed domino Heck-Suzuki reaction and a subsequent ironcatalyzed isomeriztion/cyclodehydration reaction. Apart from being general and atom-economical, mild reaction conditions, high yields, broad substrate scope and the use of easily available starting materials promote this as a promising cyclization strategy that may be exploited in the formation of larger rings and other polycyclic heterocycles in future.

Experimental section General: 1H NMR spectra were recorded with a Bruker (300, 400 or 500 MHz) spectrometer as solutions in CDCl3. Chemical shifts are expressed in parts per million (ppm, δ) and are referenced to CDCl3 (δ 7.26 ppm for all of the compounds) as an internal standard. All coupling constants are absolute values and are expressed in Hz. The description of the signals include: s = singlet, bs = broad singlet d = doublet, dd = double doublet, t = triplet, m = multiplet, dt = doublet of triplets and td = triplet of doublets. 13C NMR spectra were recorded with Bruker 300 (75 MHz), 500 (125 MHz) spectrometers as solutions in CDCl3 with complete proton decoupling. Chemical shifts are expressed in parts per million (ppm, δ) and are referenced to CHCl3 (δ = 77.0 ppm) as an internal standard. Electrospray ionization technique and TOF mass analyzer were used for HRMS. The routine monitoring of reaction was performed with silica gel coated glass slides (Merck, silica gel G for TLC), which were analyzed with iodine. Solvents, reagents and chemicals were purchased from Aldrich, Alfa aeser, Merck, SRL, Spectrochem and Process Chemicals. All reactions involving moisture-sensitive reactants were executed with oven-dried glassware. Representative experimental procedure for the synthesis and characterization data of (Z)-2-(phenyl(1-tosyl-2,3dihydroquinolin-4(1H)-ylidene)methyl)benzaldehyde (2a): In a round-bottom flask filled with Ar gas, N-(2bromophenyl)-4-methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide (1a) (227 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol) were taken in a mixed solvent of toluene (3 mL) and ethanol (3 mL). The reaction mixture was stirred at 80 ˚C for 4 hours. After the reaction was complete (monitored by TLC), the reaction mixture was extracted with ethyl acetate (15 mL, twice); the combined organic layer was washed with water (15 mL, thrice) and dried over anhydrous Na 2SO4 and concentrated under reduced pressure. The crude was purified by silica gel (100-200 mesh) column chromatography, eluted by petroleum ether/ ethyl acetate (90:10 v/v), to afford 179 mg of product 2a (75%) as a pale yellow solid, m.p. 130-132 ˚C. 1H NMR (CDCl3, 300 MHz): δ 9.97 (s, 1H), 7.81-7.75 (m, 2H), 7.63 (d, J = 7.8 Hz, 2H), 7.30-7.22 (m, 7H), 7.09 (t, J = 7.8 Hz, 1H), 6.97 (d,



J = 6.9 Hz, 2H), 6.69-6.64 (m, 1H), 6.56 (d, J = 6.6 Hz, 1H), 6.24 (d, J = 6.9 Hz, 1H), 3.83 (t, J = 6.0 Hz, 2H), 2.87 (bs, 1H), 2.77 (bs, 1H), 2.45 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.4, 145.8, 143.8, 141.8, 137.8, 136.5, 134.4, 133.6, 132.8, 132.1, 130.2, 129.8, 129.5, 128.9, 128.5, 128.2, 127.6, 127.5, 127.5, 124.3, 124.3, 46.9, 31.4, 21.6. HRMS: Calcd for C30H25NO3SNa [M+Na]+ 502.1452; found 502.1450. (Z)-2-((6-methyl-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)(phenyl)methyl)benzaldehyde (2b): N-(2-iodo-4methylphenyl)-4-methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide (1b) (259 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 3 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (90:10 v/v), the desired product 2b (193 mg, 78%) was obtained as white solid, m.p. 132-134 ˚C. 1H NMR (CDCl3, 300 MHz): δ 9.94 (s, 1H), 7.77 (d, J = 7.2 Hz, 1H), 7.63 (t, J = 8.1 Hz, 3H), 7.30-7.23 (m, 7H), 6.98-6.88 (m, 3H), 6.30 (d, J = 11.1 Hz, 2H), 3.81 (d, J = 6.6 Hz, 2H), 2.81-2.70 (m, 2H), 2.45 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.5, 146.0, 143.7, 141.9, 136.6, 135.4, 135.3, 134.2, 133.9, 133.6, 132.8, 132.0, 130.8, 130.4, 129.8, 129.7, 129.6, 129.4, 129.0, 128.6, 128.5, 127.5, 127.4, 127.3, 124.4, 122.5, 46.8, 31.4, 21.6, 20.6. HRMS: Calcd for C31H27NO3SNa [M+Na]+ 516.1609; found 516.1610. (Z)-2-((6-methoxy-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)(phenyl)methyl)benzaldehyde (2c): N-(2-iodo-4methoxyphenyl)-4-methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide (1c) (265 mg, 0.5 mmol), 2formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K 2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 6 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (88:12 v/v), the desired product 2c (147 mg, 58%) was obtained as yellow solid, m.p. 151-153 ˚C. 1H NMR (CDCl3, 300 MHz): δ 9.94 (s, 1H), 7.78-7.75 (m, 1H), 7.64 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 2.7 Hz, 1H), 7.35-7.18 (m, 7H), 6.96 (d, J = 7.8 Hz, 2H), 6.46 (d, J = 8.7 Hz, 1H), 6.38-6.36 (m, 1H), 6.23 (dd, J = 8.7, 2.7 Hz, 1H), 3.87-3.79 (m, 2H), 3,75 (s, 3H), 2.80-2.71 (m, 2H), 2.45 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.6, 159.3, 146.4, 144.0, 142.2, 138.9, 136.5, 134.3, 133.8, 133.7, 132.6, 132.3, 131.2, 129.9, 129.6, 128.8, 128.6, 127.6, 127.4, 122.7, 111.4, 108.8, 55.4, 47.0, 31.2, 21.8. HRMS: Calcd for C31H27NO4SNa [M+Na]+ 532.1559; found 532.1555. (Z)-2-((6-fluoro-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)(phenyl)methyl)benzaldehyde (2d): N-(2-bromo-4fluorophenyl)-4-methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide (1d) (236 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were heated at 95 oC similarly to the procedure for the synthesis of 2a for 5 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (90:10 v/v), the desired product 2d (139 mg, 56%) was obtained as off-white flaky solid. 1H NMR (CDCl3, 300 MHz): δ 9.91 (s, 1H), 7.80-7.72 (m, 2H), 7.61 (d, J = 7.8 Hz, 3H), 7.367.21 (m, 6H), 6.95 (d, J = 7.2 Hz, 2H), 6.84-6.81 (m, 1H), 6.24-6.19 (m, 2H), 3.85-3.79 (m, 2H), 2.85-2.72 (m, 2H), 2.47 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.2, 144.8, 144.0, 141.3, 137.3, 136.4, 134.3, 133.8, 131.7, 131.3, 130.5, 129.8, 129.7, 129.3, 128.5, 128.0, 127.7, 127.6, 126.6, 126.5, 116.4, 116.1, 115.3, 115.0, 46.7, 31.3, 21.7. HRMS: Calcd for C30H24FNO3SNa [M+Na]+ 520.1358; found 520.1359. (Z)-2-((6-chloro-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)(phenyl)methyl)benzaldehyde (2e): N-(4-chloro-2iodophenyl)-4-methyl-N-(4-phenylbut-3-yn-1-yl)benzenesulfonamide (1e) (268 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 5 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (90:10 v/v), the desired product 2e (161 mg, 63%) was obtained as a pale yellow solid, m.p. 180-182 ˚C. 1H NMR (CDCl3, 300 MHz): δ 9.88 (s, 1H), 7.78-7.70 (m, 2H), 7.60 (d, J = 8.4 Hz, 2H), 7.377.19 (m, 7H), 7.03-6.94 (m, 3H), 6.45 (d, J = 2.4 Hz, 1H), 6.29 (dd, J = 7.8, 1.2 Hz, 1H), 3.84-3.77 (m, 2H), 2.81-2.70 (m, 2H), 2.44 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.0, 144.7, 144.1, 141.2, 137.0, 136.2, 134.3, 133.7, 132.0, 131.4, 129.8, 129.8, 129.4, 128.4, 128.0, 127.5, 125.4, 46.9, 30.9, 21.6. HRMS: Calcd for C30H24ClNO3SNa [M+Na]+ 536.1063; found 536.1066. (Z)-2-((4-methoxyphenyl)(1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)methyl)benzaldehyde (2f): N-(2-bromophenyl)N-(4-(4-methoxyphenyl)but-3-yn-1-yl)-4-methylbenzenesulfonamide (1f) (243 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 7 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography.


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Eluted by petroleum ether/ ethyl acetate (85:15 v/v), the desired product 2f (154 mg, 60%) was obtained as a pale yellow solid. 1H NMR (CDCl3, 300 MHz): δ 9.97 (s, 1H), 7.77 (t, J = 8.4 Hz, 2H), 7.60 (d, J = 4.5 Hz, 2H), 7.28 (d, J = 8.7 Hz, 3H), 7.20 (td, J = 7.2, 1.5 Hz, 1H), 7.07 (t, J = 7.8 Hz, 1H), 6.90 (dd, J = 6.6, 2.1 Hz, 2H), 6.81 (d, J = 8.1 Hz, 2H), 6.65 (t, J = 7.5 Hz, 1H),6.55 (dd, J = 7.8, 1.5 Hz, 1H), 6.18 (dd, J = 7.5, 0.9 Hz, 1H), 3.87-3.73 (m, 5H), 2.93-2.89 (m, 1H), 2.802.74 (m, 1H), 2.44 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.6, 158.9, 146.2, 143.9, 137.7, 136.5, 135.5, 134.6, 134.4, 133.6, 132.2, 131.2, 130.9, 130.3, 129.8, 128.9, 128.0, 127.6, 124.4, 113.9, 55.4, 47.1, 31.6, 21.7. HRMS: Calcd for C31H27NO4SNa [M+Na]+ 532.1559; found 532.1559. (Z)-2-((6-methyl-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)(p-tolyl)methyl)benzaldehyde (2g): N-(2-iodo-4methylphenyl)-4-methyl-N-(4-(p-tolyl)but-3-yn-1-yl)benzenesulfonamide (1g) (264 mg, 0.5 mmol), 2formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K 2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 3 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (85:15 v/v), the desired product 2g (196 mg, 77%) was obtained as a greenish white solid. 1H NMR (CDCl3, 300 MHz): δ 9.98 (s, 1H), 7.76 (dd, J = 7.5, 1.8 Hz, 1H), 7.67-7.60 (m, 3H), 7.32-7.21 (m, 4H), 7.09 (d, J = 7.8 Hz, 2H), 6.90-6.84 (m, 3H), 6.31-6.25 (m, 2H), 3.85-3.75 (m, 2H), 2.79 (dt, J = 22.8, 6.6 Hz, 2H), 2.44 (s, 3H), 2.32 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.6, 146.4, 143.8, 139.2, 137.4, 136.7, 135.5, 135.3, 134.4, 133.9, 133.6, 132.5, 132.1, 130.9, 130.7, 129.8, 129.4, 129.3, 128.9, 128.5, 127.6, 127.5, 124.4, 46.9, 31.6, 21.7, 21.3, 20.7. HRMS: Calcd for C32H29NO3SNa [M+Na]+ 530.1765; found 530.1766. (Z)-2-((4-methoxyphenyl)(6-methyl-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)methyl)benzaldehyde (2h): N-(2iodo-4-methylphenyl)-N-(4-(4-methoxyphenyl)but-3-yn-1-yl)-4-methylbenzenesulfonamide (1h) (273 mg, 0.5 mmol), 2formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K 2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 5 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (85:15 v/v), the desired product 2h (157 mg, 60%) was obtained as a greenish semi-solid. 1H NMR (CDCl3, 300 MHz): δ 9.95 (s, 1H), 7.76 (d, J = 7.5 Hz, 1H), 7.63 (t, J = 7.5 Hz, 3H), 7.32-7.20 (m, 4H), 6.88 (d, J = 6.9 Hz, 3H), 6.81 (d, J = 8.7 Hz, 2H), 6.30 (s, 1H), 6.22 (d, J = 7.2 Hz, 1H), 3.843.79 (m, 5H), 2.85-2.77 (m, 2H), 2.44 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.5, 158.8, 146.4, 143.7, 136.6, 135.2, 135.1, 134.4, 133.8, 133.5, 132.2, 132.0, 130.8, 130.7, 129.7, 128.8, 128.5, 127.6, 127.4, 124.3, 113.8, 55.3, 46.9, 31.5, 21.6, 20.6. HRMS: Calcd for C32H29NO4SNa [M+Na]+ 546.1715; found 546.1714. (Z)-2-((4-chlorophenyl)(6-methyl-1-tosyl-2,3-dihydroquinolin-4(1H)-ylidene)methyl)benzaldehyde (2i): N-(4-(4chlorophenyl)but-3-yn-1-yl)-N-(2-iodo-4-methylphenyl)-4-methylbenzenesulfonamide (1i) (274 mg, 0.5 mmol), 2formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K 2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 3.5 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (90:10 v/v), the desired product 2i (175 mg, 67%) was obtained as a brown semi-solid. 1H NMR (CDCl3, 400 MHz): δ 9.92 (s, 1H), 7.78 (d, J = 7.2 Hz, 1H), 7.66-7.61 (m, 3H), 7.37-7.27 (m, 6H), 6.97-6.91 (m, 3H), 6.30 (t, J = 7.2 Hz, 2H), 3.87-3.77 (m, 2H), 2.85-2.72 (m, 2H), 2.46 (s, 3H), 1.87 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.2, 145.3, 143.7, 140.1, 136.6, 135.3, 134.5, 134.3, 134.0, 133.7, 133.3, 133.0, 132.0, 130.9, 130.8, 130.3, 129.7, 129.5, 129.1, 128.7, 127.7, 127.6, 124.4, 46.6, 31.5, 21.6, 20.6. HRMS: Calcd for C31H26ClNO3SNa [M+Na]+ 550.1220; found 550.1224. (Z)-2-((4-methoxyphenyl)(1-(methylsulfonyl)-2,3-dihydroquinolin-4(1H)-ylidene)methyl)benzaldehyde (2j): N-(2bromophenyl)-N-(4-(4-methoxyphenyl)but-3-yn-1-yl)methanesulfonamide (1j) (202 mg, 0.5 mmol), 2formylphenylboronic acid (113 mg, 0.75 mmol), 2.5 M aqueous K 2CO3 solution (3 mL) and Pd(PPh3)4 (11.5 mg, 0.01 mmol), in a mixed solvent of toluene (3 mL) and ethanol (3 mL) were treated similarly to the procedure for the synthesis of 2a for 4 hours. After the completion of reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (80:20 v/v), the desired product 2j (135 mg, 62%) was obtained as a brown semi-solid. 1H NMR (CDCl3, 500 MHz): δ 10.16 (s, 1H), 7.77-7.73 (m, 2H), 7.48 (t, J = 7.5 Hz, 1H), 7.37 (t, J = 7.5 Hz, 1H), 7.16 (d, J = 7.5 Hz, 1H), 7.12-7.06 (m, 3H), 6.88 (d, J = 8.5 Hz, 2H), 6.66 (t, J = 7.5 Hz, 1H), 6.60 (dd, J = 7.5, 1.5 Hz, 1H), 3.95-3.91 (m, 1H), 3.82 (s, 3H), 3.66-3.65 (m, 1H), 3.09-3.07 (m, 1H), 3.00 (s, 3H), 2.85 (m, 1H). 13C{1H} NMR (CDCl3, 125 MHz): δ 191.3, 159.3, 146.1, 138.1, 134.5, 134.4, 134.2, 134.0, 133.8, 132.3, 131.2, 130.6, 129.4, 128.9, 128.7, 127.9, 123.7, 121.6, 114.2, 55.4, 47.3, 37.8, 31.3. HRMS: Calcd for C25H23NO4SNa [M+Na]+ 456.1246; found 456.1248.



Representative experimental procedure for the synthesis and characterization data of 12-phenyl-5-tosyl-5,6dihydrobenzo[j]phenanthridine (3a): In an oven-dried round-bottom flask, (Z)-2-(phenyl(1-tosyl-2,3-dihydroquinolin4(1H)-ylidene)methyl)benzal-dehyde (2a) (72 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were added to 1,2dichloroethane (1.5 mL) under Ar atmosphere and stirred for 3 hours at refluxing condition. The solvent was evaporated after the completion of reaction (monitored by TLC). The crude reaction mixture was purified by column chromatography on silica gel (100-200 mesh), eluted by petroleum ether/ ethyl acetate (90:10 v/v), to afford the desired product 3a (59 mg, 86%) as a white solid, m.p. 195-197 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.83-7.75 (m, 2H), 7.66 (s, 1H), 7.51-7.29 (m, 6H), 7.22-7.13 (m, 3H), 6.78 (bs, 3H),6.64-6.55 (m, 3H), 4.99 (s, 2H), 1.86 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 143.2, 139.4, 138.1, 135.6, 132.5, 131.9, 130.6, 130.4, 129.8, 128.7, 128.4, 127.9, 127.8, 127.5, 127.3, 126.7, 126.4, 125.9 125.7, 124.9, 51.8, 20.9. HRMS: Calcd for C30H23NO2SNa [M+Na]+ 484.1347; found 484.1348. 2-Methyl-12-phenyl-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3b): Substrate 2b (74 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in 1,2-DCE (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3a for 3 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3b (64 mg, 90%) as yellow crystals, m.p. 213-215 ˚C . 1H NMR (CDCl3, 300 MHz): δ 7.81 (d, J = 8.1 Hz, 1H), 7.64-7.58 (m, 3H), 7.50-7.31 (m, 5H), 7.12 (d, J = 6.6 Hz, 2H), 7.00 (d, J = 8.1 Hz, 1H), 6.78 (bs, 2H), 6.54 (d, J = 6.9 Hz, 2H), 6.33 (s, 1H), 4.97 (s, 2H), 1.89 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 143.1, 139.5, 136.3, 135.6, 135.5, 135.2, 132.8, 132.5, 131.9, 130.6, 130.4, 130.1, 128.6, 128.6, 128.4, 127.5, 127.3, 127.2, 126.7, 126.3, 125.9, 124.9, 51.9, 21.1, 20.9. HRMS: Calcd for C31H25NO2SNa [M+Na]+ 498.1504; found 498.1501. 2-Methoxy-12-phenyl-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3c): Substrate 2c (76 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in 1,2-DCE (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3a for 3 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3c (63 mg, 85%) as a yellow crystalline solid, m.p. 221-223 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.80 (d, J = 7.8 Hz, 1H), 7.64 (s, 1H), 7.48-7.35 (m, 4H), 7.30 (s, 2H), 7.16 (d, J = 7.8 Hz, 2H), 6.78 (s, 2H), 6.57 (d, J = 7.8 Hz, 2H), 6.50 (d, J = 9.0 Hz, 1H), 6.35 (d, J = 7.8 Hz, 1H), 4.97 (s, 2H), 3.83 (s, 3H), 1.87 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 158.8, 143.2, 139.6, 139.3, 135.5, 135.3, 132.9, 132.1, 131.3, 130.6, 130.4, 128.7, 128.4, 127.5, 127.3, 127.3, 126.5, 126.0, 125.8, 124.8, 12 3.2, 113.0, 111.9, 55.5, 51.9, 20.9. HRMS: Calcd for C31H25NO3SNa [M+Na]+ 514.1453; found 514.1453. 12-(4-methoxyphenyl)-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3f): Substrate 2f (76 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in 1,2-DCE (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3a for 2.5 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3f (53 mg, 72%) as a dark brown solid, m.p. 167-169 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.82-7.74 (m, 2H), 7.64 (s, 1H), 7.48-7.42 (m, 2H), 7.32 (d, J = 6.9 Hz, 1H), 7.20 (t, J = 7.8 Hz, 1H), 7.12 (d, J = 7.8 Hz, 2H), 6.93 (d, J = 8.0 Hz, 2H), 6.82 (t, J = 7.5 Hz, 1H), 6.68 (d, J = 7.8 Hz, 3H), 6.54 (d, J = 7.8 Hz, 2H), 4.98 (s, 2H), 3.90 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 159.0, 143.1, 138.0, 136.2, 135.6, 133.3, 132.5, 132.0, 131.5, 131.4, 130.8, 129.8, 128.4, 128.0, 127.7, 127.4, 127.3, 126.8, 126.3, 125.8, 125.8, 124.7, 114.1, 55.3, 51.9, 20.9. HRMS: Calcd for C31H25NO3SNa [M+Na]+ 514.1453; found 514.1454. 12-(4-methoxyphenyl)-2-methyl-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3h): Substrate 2h (79 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in 1,2-DCE (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3a for 3 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3h (57 mg, 75%) as a moss green solid, m.p. 198-200 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.81 (d, J = 8.1 Hz, 1H), 7.63 (s, 2H), 7.49 (d, J = 7.2 Hz, 2H), 7.38-7.30 (m, 1H), 7.12 (d, J = 7.5 Hz, 2H), 7.01 (d, J = 7.8 Hz, 1H), 6.95 (d, J = 7.8 Hz, 2H), 6.68 (bs, 2H), 6.53 (d, J = 7.5 Hz, 2H), 6.39 (s, 1H), 4.96 (s, 2H), 3.90 (s, 3H), 1.94 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 159.1, 143.0, 136.1, 135.5, 135.4, 135.2, 133.1, 132.5, 131.9, 131.5, 131.2, 130.6, 130.3, 128.5, 128.3, 127.5, 127.3, 126.7, 126.3, 125.8, 124.7, 114.1, 55.5, 52.0, 21.2, 20.9. HRMS: Calcd for C32H27NO3SNa [M+Na]+ 528.1610; found 528.1611. 12-(4-methoxyphenyl)-5-(methylsulfonyl)-5,6-dihydrobenzo[j]phenanthridine (3j): Substrate 2j (65 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in 1,2-DCE (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3a for 4.5 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (85:15 v/v), to obtain the desired product 3j (50 mg, 80%) as a white crystalline solid, m.p. 193-195 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.89-7.84 (m, 2H), 7.65 (t, J = 8.4 Hz, 2H), 7.54-7.50 (m, 1H), 7.42 (d, J = 8.1 Hz, 1H), 7.23-7.18 (m, 1H), 7.12 (d, J = 7.2 Hz, 2H), 7.03 (d, J = 7.5 Hz, 2H), 6.986.92 (m, 2H), 4.93 (s, 2H), 3.92 (s, 3H), 2.32 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 159.4, 138.1, 137.6, 133.8,


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132.8, 132.6, 131.9, 131.4, 130.7, 130.2, 128.3, 128.1, 127.9, 127.8, 127.3, 127.0, 126.6, 126.5, 124.8, 114.7, 55.5, 51.6, 38.4. HRMS: Calcd for C25H21NO3SNa [M+Na]+ 438.1140; found 438.1140. Representative experimental procedure for the synthesis and characterization data of 2-Fluoro-12-phenyl-5-tosyl5,6-dihydrobenzo[j]phenanthridine (3d): In an oven-dried round-bottom flask, (Z)-2-((6-fluoro-1-tosyl-2,3dihydroquinolin-4(1H)-ylidene)(phenyl)methyl)-benzaldehyde (2d) (74 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were added to chlorobenzene (1.5 mL) under Ar atmosphere and stirred for 5 hours at 120 oC. The solvent was evaporated after the completion of reaction (monitored by TLC). The crude reaction mixture was purified by column chromatography on silica gel (100-200 mesh), eluted by petroleum ether/ ethyl acetate (90:10 v/v), to afford the desired product 3d (49 mg, 67%) as a greenish yellow solid, m.p. 185-187 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.83 (d, J = 7.8 Hz, 1H), 7.74-7.68 (m, 2H), 7.53-7.30 (m, 6H), 7.11 (d, J = 7.8 Hz, 2H), 6.93-6.88 (m, 1H), 6.77 (bs, 2H), 6.57 (d, J = 7.8 Hz, 2H), 6.26 (d, J = 11.1 Hz, 1H), 4.99 (s, 2H), 1.88 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 143.3, 138.7, 137.0, 135.3, 133.9, 132.8, 132.7, 131.5, 130.1, 129.6, 129.4, 129.0, 128.5, 127.8, 127.5, 127.3, 126.8, 126.7, 126.1, 125.0, 116.3, 116.0, 115.0, 114.7, 51.8, 20.9. HRMS: Calcd for C30H22FNO2SNa [M+Na]+ 502.1253; found 502.1255. 2-chloro-12-phenyl-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3e): Substrate 2e (77 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in chlorobenzene (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3d for 6 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (92:8 v/v), to obtain the desired product 3e (44 mg, 60%) as a brownish solid, m.p. 190-192 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.82 (d, J = 7.8 Hz, 1H), 7.68 (d, J = 8.7 Hz, 2H), 7.53-7.41 (m, 5H), 7.35 (d, J = 7.8 Hz, 1H), 7.17-7.11 (m, 3H), 6.77 (s, 2H), 6.57 (d, J = 7.8 Hz, 2H), 6.50 (s, 1H), 4.97 (s, 2H), 1.86 (s, 3H). 13C{1H} NMR (CDCl3, 125 MHz): δ 143.5, 139.0, 137.2, 136.7, 135.7, 133.0, 132.2, 131.7, 130.3, 129.9, 129.1, 128.7, 128.0, 127.9, 127.6, 127.5, 127.0, 126.9, 126.3, 125.2, 51.9, 21.0. HRMS: Calcd for C30H22ClNO2SNa [M+Na]+ 518.0958; found 518.0957. 2-methyl-12-(p-tolyl)-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3g): Substrate 2g (76 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in chlorobenzene (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3d for 8 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3g (52 mg, 70%) as off-white crystals, m.p. 194-196 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.81 (d, J = 7.8 Hz, 1H), 7.64 (d, J = 3.9 Hz, 2H), 7.50-7.43 (m, 3H), 7.31 (t, J = 7.5 Hz, 1H), 7.22 (d, J = 7.8 Hz, 1H), 7.12 (d, J = 8.1 Hz, 2H), 7.00 (d, J = 7.8 Hz, 1H), 6.66 (bs, 2H), 6.54 (d, J = 7.8 Hz, 2H), 6.38 (s, 1H), 4.96 (s, 2H), 2.46 (s, 3H), 1.91 (s, 3H), 1.85 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 143.0, 137.0, 136.4, 136.4, 135.6, 135.4, 135.2, 132.9, 132.6, 132.5, 131.9, 130.7, 130.5, 130.3, 129.3, 128. 5, 128.4, 127.7, 127.5, 127.4, 127.3, 126.8, 126.3, 125.8, 124.7, 52.0, 21.2, 21.1, 20.9. HRMS: Calcd for C32H27NO2SNa [M+Na]+ 512.1660; found 512.1660. 12-(4-chlorophenyl)-2-methyl-5-tosyl-5,6-dihydrobenzo[j]phenanthridine (3i): Substrate 2i (79 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were taken in chlorobenzene (1.5 mL) and treated similarly to the procedure for the synthesis of compound 3d for 8 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3i (44 mg, 58%) as greenish white crystals. 1H NMR (CDCl3, 400 MHz): δ 7.83 (d, J = 8.4 Hz, 1H), 7.68-7.63 (m, 2H), 7.52-7.48 (m, 1H), 7.40-7.32 (m, 4H), 7.10 (d, J = 8.0 Hz, 2H), 7.03 (d, J = 8.0 Hz, 1H), 6.69 (s, 2H), 6.53 (d, J = 8.0 Hz, 2H), 6.35 (s, 1H), 4.96 (s, 2H), 1.96 (s, 3H), 1.86 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 143.1, 138.0, 135.6, 135.5, 135.4, 134.9, 133.4, 132.6, 132.4, 132.0, 131.9, 130.5, 129.9, 128.8, 128.3, 127.6, 127.5, 126.5, 126.2, 126.1, 125.2, 51.9, 21.1, 20.9. HRMS: Calcd for C31H24ClNO2SNa [M+Na]+ 532.1114; found 532.1117. 1 mmol scale synthesis of the compound 3i: Substrate 2i (528 mg, 1 mmol) and Fe(OTf)3 (50.3 mg, 0.1 mmol) were taken in chlorobenzene (10 mL) and treated similarly to the procedure for the synthesis of compound 3d for 10 hours. Likewise, the purification of the crude product was done by column chromatography, the eluent being petroleum ether/ ethyl acetate (90:10 v/v), to obtain the desired product 3i (285 mg, 56%) as greenish white crystals. Experimental procedure for the synthesis and characterization data of 12-phenylbenzo[j]phenanthridine (4a): In an oven-dried sealed tube, substrate 3a (46 mg, 0.1 mmol) and K2CO3 (42 mg, 0.3 mmol) were taken in 2 mL of ethanol and heated at 100 ˚C for 6 hours. After the completion of the reaction, the reaction mixture was extracted with dichloromethane (20 mL) and washed with water (20 mL). The combined organic layer was separated and dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (100-200 mesh), eluted by petroleum ether / ethyl acetate (85:15 v/v), to obtain the desired product 4a (24 mg, 80%) as a fluorescent green solid, m.p. 137-139 ˚C. 1H NMR (CDCl3, 300 MHz): δ 9.38 (s, 1H), 8.64 (s, 1H), 8.18 (d, J = 8.4 Hz, 1H), 8.10 (d, J = 8.1 Hz, 1H), 7.66-7.50 (m, 7H), 7.42-7.33 (m, 3H), 7.16-7.11 (m, 1H). 13C{1H} NMR



(CDCl3, 75 MHz): δ 155.9, 145.3, 141.2, 137.0, 134.8, 131.7, 130.4, 130.1, 129.9, 128.7, 128.3, 128.2, 127.8, 127.6, 127.3, 126.8, 126.4, 126.3, 125.8, 125.0. HRMS: Calcd for C23H15NNa [M+Na]+ 328.1102; found 328.1101. Representative experimental procedure for the synthesis and characterization data of (Z)-2-(chroman-4ylidene(phenyl)-methyl)benzaldehyde (6a): In an oven-dried round-bottom flask filled with Ar gas, 1-iodo-2-((4phenylbut-3-yn-1-yl)oxy)benzene (5a, 174 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), K3PO4 (318 mg, 1.5 mmol) and Pd(dppf)2Cl2 (8.2 mg, 0.01 mmol) were taken in 1,4-dioxane (5.5 mL). The reaction mixture was stirred at 70 ˚C for 4 hours. After the reaction was complete (monitored by TLC), the reaction mixture was extracted with ethyl acetate (20 mL, twice); the combined organic layer was washed with water (15 mL, thrice) and dried over anhydrous Na2SO4 and concentrated under reduced pressure. The crude was purified by silica gel (100-200 mesh) column chromatography, eluted by petroleum ether/ ethyl acetate (98:2 v/v), to afford the desired product 6a (116 mg, 72%) as a brown semi-solid, along with the inseparable isomer from the Suzuki reaction only (almost 10% of 6a, yield is calculated using the NMR data). 1H NMR (CDCl3, 300 MHz): δ 10.26 (s, 1H), 7.88 (d, J = 8.1 Hz, 1H), 7.54 (s, 2H), 7.44-7.24 (m, 4H), 7.16 (d, J = 6.9 Hz, 2H), 7.00 (s, 1H), 6.77 (d, J = 8.1 Hz, 1H), 6.50-6.42 (m, 2H), 4.28 (t, J = 5.4 Hz, 2H), 2.85 (s, 2H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.5, 155.4, 146.4, 142.2, 134.2, 134.1, 132.7, 132.5, 132.1, 130.2, 129.9, 129.4, 128.5, 128.4, 127.9, 127.4, 121.3, 119.5, 117.1, 66.9, 29.3. HRMS: Calcd for C23H18O2Na [M+Na]+ 349.1205; found 349.1205. (Z)-2-(chroman-4-ylidene(4-methoxyphenyl)methyl)benzaldehyde (6b): 1-iodo-2-((4-(4-methoxyphenyl)but-3-yn-1yl)oxy)benzene (5b, 189 mg, 0.5mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), K3PO4 (318 mg, 1.5 mmol) and Pd(dppf)2Cl2 (8.2 mg, 0.01 mmol) were taken in 1,4-dioxane (5.5 mL). The reaction mixture was stirred at 65 ˚C for 3 hours. After the completion of the reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. The crude was purified by silica gel (100-200 mesh) column chromatography, eluted by petroleum ether/ ethyl acetate (95:5 v/v), to afford the desired product 6b (139 mg, 78%) as a pale yellow solid, m.p. 141-143 ˚C. 1H NMR (CDCl3, 300 MHz): δ10.24 (s, 1H), 7.88 (dd, J = 7.5, 1.5 Hz, 1H), 7.53 (td, J = 7.5, 1.5 Hz, 1H), 7.41 (t, J = 7.52 Hz, 1H), 7.27 (dd, J = 7.5, 1.5 Hz), 7.07 (dd, J = 6.6, 2.1 Hz, 2H), 7.01-6.96 (m, 1H), 6.86 (dd, J = 6.6, 2.4 Hz, 2H), 6.76 (dd, J = 8.1, 1.2 Hz, 1H), 6.50-6.38 (m, 2H), 4.28 (t, J = 5.7 Hz, 2H), 3.80 (s, 3H), 2.91-2.79 (m, 2H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.7, 158.7, 155.4, 146.9, 134.8, 134.4, 134.3, 133.1, 132.7, 132.0, 131.9, 131.8, 131.5, 130.0, 129.2, 128.5, 127.9, 121.6, 119.6, 117.2, 113.9, 67.0, 55.4, 29.5. HRMS: Calcd for C24H20O3Na [M+Na]+ 379.1310; found 379.1312. (Z)-2-((8-bromo-6-methylchroman-4-ylidene)(phenyl)methyl)benzaldehyde (6c): 1,3-dibromo-5-methyl-2-((4phenylbut-3-yn-1-yl)oxy)benzene (5c, 160 mg, 0.41 mmol), 2-formylphenylboronic acid (92 mg, 0.61 mmol), K3PO4 (261 mg, 1.23 mmol) and Pd(dppf)2Cl2 (6.5 mg, 0.008 mmol) in 1,4-dioxane (4.5 mL) were treated similarly to the procedure for the synthesis of 6a for 5 hours at 75 ˚C. After the completion of the reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (97:3 v/v), the desired product 6c (92 mg, 54%) was obtained as a white solid. 1H NMR (CDCl3, 300 MHz): δ 10.24 (s, 1H), 7.90 (d, J = 7.5 Hz, 1H), 7.55 (td, J = 7.5, 1.2 Hz, 1H ), 7.44 (t, J = 7.5 Hz, 1H), 7.37-7.26 (m, 4H), 7.17 (d, J = 7.5 Hz, 2H), 7.10 (s, 1H), 6.21 (s, 1H), 4.39-4.35 (m, 2H), 2.88-2.83 (m, 2H), 1.81 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.3, 149.5, 146.0, 141.8, 134.1, 133.4, 133.3, 132.5, 132.0, 130.1, 129.8, 129.2, 128.6, 128.4, 128.0, 127.6, 122.5, 110.5, 67.7, 29.1, 20.1. HRMS: Calcd for C24H19BrO2Na [M+Na]+ 441.0466; found 441.0465. (Z)-4-((2-formylphenyl)(p-tolyl)methylene)-5-methoxychroman-7-carbaldehyde (6d): 4-iodo-3-methoxy-5-((4-(ptolyl)but-3-yn-1-yl)oxy)benzaldehyde (5d) (210 mg, 0.5 mmol), 2-formylphenylboronic acid (113 mg, 0.75 mmol), K3PO4 (318 mg, 1.5 mmol) and Pd(dppf)2Cl2 (8.2 mg, 0.01 mmol) in 1,4-dioxane (5.5 mL) were treated similarly to the procedure for the synthesis of 6a for 3 hours at 75 ˚C. After the completion of the reaction, the reaction mixture was also treated likewise up to the purification by column chromatography. Eluted by petroleum ether/ ethyl acetate (85:15 v/v), the desired product 6d (138 mg, 69%) was obtained as an off-white solid. 1H NMR (CDCl3, 300 MHz): δ 10.13 (s, 1H), 9.06 (s, 1H), 7.79 (d, J = 7.5 Hz, 1H), 7.50-7.46 (m, 1H), 7.39-7.34 (m, 1H), 7.22-7.18 (m, 2H), 7.09-6.97 (m, 5H), 6.42 (d, J = 1.5 Hz, 1H), 4.44-4,30 (m, 2H), 3.81 (s, 3H), 2.91-2.74 (m, 2H), 2.27 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.2, 190.7, 150.4, 149.4, 145.7, 138.5, 137.9, 134.5, 134.4, 134.4, 132.6, 130.4, 130.1, 129.3, 129.1, 128.8, 128.5, 128.3, 122.0, 107.0, 68.2, 56.2, 28.7, 21.3. HRMS: Calcd for C26H22O4Na [M+Na]+ 421.1416; found 421.1412. Representative experimental procedure for the synthesis and characterization data of 12-phenyl-6H-naphtho[2,3c]chromene (7a): In an oven-dried round-bottom flask, (Z)-2-(chroman-4-ylidene(phenyl)methyl)benzaldehyde (6a) (49 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were added to 1,2-dichloroethane (1.5 mL) under Ar atmosphere and stirred for 3 hours at 70 ˚C. The solvent was evaporated after the completion of reaction (monitored by TLC). The crude reaction mixture was purified by column chromatography on silica gel (100-200 mesh), eluted by petroleum ether/ ethyl acetate (98:2 v/v), to afford the desired product 7a (37 mg, 80%) as a pale yellow solid, m.p. 138-140 ˚C. 1H NMR


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(CDCl3, 300 MHz): δ 7.84 (d, J = 7.8 Hz, 1H), 7.71 (s, 1H), 7.55-7.44 (m, 5H), 7.37-7.32 (m, 3H), 7.09 (t, J = 7.2 Hz, 1H), 7.01 (d, J = 7.8 Hz, 1H), 6.71 (d, J = 7.8 Hz, 1H), 6.58 (t, J = 7.2 Hz, 1H), 5.19 (s, 2H). 13C{1H} NMR (CDCl3, 75 MHz): δ 157.2, 139.8, 135.8, 133.6, 132.7, 132.4, 130.7, 129.2, 129.0, 128.7, 127.5, 127.5, 126.9, 126.1, 126.0, 123.8, 123.3, 121.2, 117.5, 70.3. HRMS: Calcd for C23H16ONa [M+Na]+ 331.1099; found 331.1096. 12-(4-methoxyphenyl)-6H-naphtho[2,3-c]chromene (7b): (Z)-2-(chroman-4-ylidene(4-methoxyphenyl)methyl)benzaldehyde (6b) (54 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were added to 1,2-dichloroethane (1.5 mL) under Ar atmosphere and stirred for 2 hours at 70 ˚C. The solvent was evaporated after the completion of reaction. The crude reaction mixture was purified by column chromatography on silica gel (100-200 mesh), eluted by petroleum ether/ ethyl acetate (95:5 v/v), to afford the desired product 7b (42 mg, 82%) as a pale yellow solid, m.p. 131-133 ˚C. 1H NMR (CDCl3, 300 MHz): δ 7.83 (d, J = 7.8 Hz, 1H), 7.69 (s, 1H), 7.58 (d, J = 8.4 Hz, 1H), 7.48-7.44 (m, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.21 (d, J = 8.4 Hz, 2H), 7.12-7.00 (m, 4H), 6.80 (d, J = 7.8 Hz, 1H), 6.63 (t, J = 7.2 Hz, 1H). 13C{1H} NMR (CDCl3, 75 MHz): δ 159.1, 157.2, 134.0, 132.7, 132.5, 131.9, 131.7, 129.5, 129.2, 128.6, 128.4, 127.5, 126.9, 126.5, 126.0, 125.9, 124.0, 123.3, 123.1, 121.3, 117.5, 114.5, 70.3, 55.4. HRMS: Calcd for C24H18O2Na [M+Na]+ 361.1205; found 361.1207. Representative experimental procedure for the synthesis and characterization data of 4-bromo-2-methyl-12phenyl-6H-naphtho[2,3-c]chromene (7c): In an oven-dried round-bottom flask, (Z)-2-((8-bromo-6-methylchroman-4ylidene)(phenyl)methyl)benzaldehyde (6c) (63 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol) were added to chlorobenzene (1.5 mL) under Ar atmosphere and stirred for 6 hours at 115 ˚C. The solvent was evaporated after the completion of reaction (monitored by TLC). The crude reaction mixture was purified by column chromatography on silica gel (100-200 mesh), eluted by petroleum ether/ ethyl acetate (97:3 v/v), to afford the desired product 7c (45 mg, 75%) as an off-white solid, m.p. 155-157 ˚C. 1H NMR (CDCl3, 400 MHz): δ 7.86 (d, J = 8.4 Hz, 1H), 7.72 (s, 1H), 7.61 (d, J = 8.4 Hz, 1H), 7.51-7.47 (m, 4H), 7.40-7.36 (m, 1H), 7.29 (t, J = 3.6 Hz, 2H), 7.16 (s, 1H), 6.39 (s, 1H), 5.24 (s, 2H), 1.88 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 151.6, 139.6, 136.3, 133.5, 132.6, 132.5, 132.2, 131.1, 130.6, 129.4, 129.0, 127.6, 127.0, 126.3, 126.2, 125.9, 124.9, 123.4, 110.9, 70.8, 20.5. HRMS: Calcd for C24H17BrONa [M+Na]+ 423.0361; found 423.0360. 1-methoxy-12-(p-tolyl)-6H-naphtho[2,3-c]chromene-3-carbaldehyde (7d): Substrate 6d (60 mg, 0.15 mmol) and Fe(OTf)3 (7.5 mg, 0.015 mmol), in 1.5 mL of chlorobenzene, were treated similarly to the procedure for the synthesis of 7c for 5h. Employing the similar mode of purification, eluent being petroleum ether/ ethyl acetate (88:12 v/v), we obtained the desired product 7d (41 mg, 73%) as a white solid, m.p. 143-145 ˚C. 1H NMR (CDCl3, 300 MHz): δ 9.21 (s, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.74 (s, 1H), 7.63 (d, J = 8.7 Hz, 1H), 7.52-7.48 (m, 1H), 7.40 (d, J = 8.1 Hz, 1H), 7.34 (d, J = 7.8 Hz, 3H), 7.18 (d, J = 7.8 hz, 2H), 6.78 (s, 1H), 5.34 (s, 2H), 3.95 (s, 3H), 2.49 (s, 3H). 13C{1H} NMR (CDCl3, 75 MHz): δ 191.4, 152.0, 150.1, 138.0, 136.7, 136.4, 133.8, 132.9, 131.1, 130.5, 130.1, 129.6, 128.4, 127.7, 127.3, 126.7, 126.5, 125.0, 124.5, 123.6, 107.2, 71.0, 56.3, 21.5. HRMS: Calcd for C26H20O3Na [M+Na]+ 403.1310; found 403.1310.

Supporting Information available: 1

H and 13C NMR (scanned copies) of the compounds 2a-2j, 3a-3j, 4a, 6a-6d, 7a-7d, X-ray crystallographic data of the compound 3b. This material is available free of charge via the internet at http://pubs.acs.org.

Author Information: Corresponding author * E-mail: [email protected], [email protected]. Orcid Umasish Jana: 0000-0002-1583-5129

Acknowledgement B.C. and S.K. are thankful to the UGC, New Delhi, India, and S.J. and K.P. are thankful to the CSIR, New Delhi, India, for their fellowships.



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L.; Knyukshto, V. N.; Tikhomirov, S. A.; Pyrko, A. N. Picosecond Dynamics of Singlet Excited States of Oxotetrahydrobenzo[c]phenanthridine in Protic and Aprotic Solvents. Opt. Spectrosc. 2006, 100, 386-393. 2. (a) Sripada, L.; Teske, J. A.; Deiters, A. Phenanthridine Synthesis via [2+2+2] Cyclotrimerization Reactions. Org. Biomol. Chem. 2008, 6, 263-265. (b) Clement, B.; Weide, M.; Wolschendorf, U.; Kock, I. A Two-Step Synthesis of Cytostatically Active Benzo[c]phenanthridine Derivatives. Angew. Chem. Int. Ed. 2005, 44, 635-638. (c) Zupko, I.; Rethy, B.; Hohmann, J.; Molnar, J.; Ocsovszki, I.; Falkay, G. Antitumor Activity of Alkaloids Derived from Amaryllidaceae Species. In Vivo 2009, 23, 41-48. 3. Selected recent literatures on phenanthridine and annulated phenathridines: (a) Rafiee, F. Synthesis of Phenanthridine and Phenanthridinone Derivatives Based on Pd-Catalyzed C-H Activation. Appl.Organomet. Chem. 2017, 31, e3820. (b) Zhang, B.; Studer, A. Recent Advances in the Synthesis of Nitrogen Heterocycles via Radical Cascade Reactions Using Isonitriles as Radical Acceptors. Chem. Soc. Rev. 2015, 44, 3505-3521. (c) Peng, J.; Chen, T.; Chen, C.; Li, B. Palladium-Catalyzed Intramolecular C–H Activation/C–C Bond Formation: A Straightforward Synthesis of Phenanthridines. J. Org. Chem. 2011, 76, 9507-9513. (d) An, X.-D.; Yu, S. Visible-Light-Promoted and One-Pot Synthesis of Phenanthridines and Quinolines from Aldehydes and O-Acyl Hydroxylamine. Org. Lett. 2015, 17, 2692-2695. (e) Chen, W. -L.; Chen, C.-Y. Chen, Y. -F.; Hsieh, J. -C. Hydride-Induced Anionic Cyclization: An Efficient Method for the Synthesis of 6-H-Phenanthridines via a Transition-Metal-Free Process. Org. Lett. 2015, 17, 1613-1616. (f) Gupta, P. K.; Yadav, N.; Jaiswal, S.; Asad, M.; Kant, R.; Hajela, K. PalladiumCatalyzed Synthesis of Phenanthridine/Benzoxazine-Fused Quinazolinones by Intramolecular C-H Bond Activation. Chem. Eur. J. 2015, 21, 13210-13215. 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(a) Sun, C. -L.; Gu, Y.-F.; Huang, W. -P.; Shi, Z. -J. Neocuproine–KOtBu Promoted Intramolecular Cross Coupling to Approach Fused Rings. Chem. Commun. 2011, 47, 9813-9815. (b) Guo, D.-D.; Li, B.; Wang, D. -Y.; Gao, Y. -R.; Guo, S. -H.; Pan, G.-F.; Wang, Y.-Q. Synthesis of 6H-Benzo[c]chromenes via Palladium-Catalyzed Intramolecular Dehydrogenative


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Coupling of Two Aryl C–H Bonds. Org. Lett. 2017, 19, 798-801. (c) He, Y.; Zhang, X.; Cui, L.; Wang, J.; Fan, X. Catalystfree Synthesis of Diversely Substituted 6H-Benzo[c]chromenes and 6H-benzo[c]chromen-6-ones in Aqueous Media under MWI. Green Chem. 2012, 14, 3429-3435. (d) Majumdar, N.; Paul, N. D.; Mandal, S.; de-Bruin, B.; Wulff, W. D. Catalytic Synthesis of 2H-Chromenes. ACS Catalysis 2015, 5, 2329-2366. 8. Pan, X.; Chen, M.; Yao, L.; Wu, J. Access to 6H-Naphtho[2,3-c]chromenes by a Palladium-Catalyzed Reaction of 2-Haloaryl Allene with 2-Alkynylphenol. Chem. Commun. 2014, 50, 5891-5894. 9. For metal-catalyzed domino reaction, see: (a) Ohno, H. Recent Advances in the Construction of Polycyclic Compounds by Palladium-Catalyzed Atom-Economical Cascade Reactions. Asian J. Org. Chem. 2013, 2, 18-28. (b) de Meijere, A.; Zezschwitz, P.; Bráse, S. The Virtue of Palladium-Catalyzed Domino Reactions−Diverse Oligocyclizations of Acyclic 2-Bromoenynes and 2Bromoenediynes. Acc. Chem. Res. 2005, 38, 413-422. (c) Düfert, A.; Werz, D. B. Carbopalladation Cascades Using Carbon– Carbon Triple Bonds: Recent Advances to Access Complex Scaffolds. Chem. Eur. J. 2016, 22, 16718-16732. (d) Ardkhean, R.; Caputo, D. F. J.; Morrow, S. M.; Shi, H.; Xiong, Y.; Anderson, E. A. Cascade Polycyclizations in Natural Product Synthesis. Chem. Soc. Rev. 2016, 45, 1557-1569. (e) Padwa, A. Domino Reactions of Rhodium(II) Carbenoids for Alkaloid Synthesis. Chem. Soc. Rev. 2009, 38, 3072-3081. 10. (a) Kundal, S.; Jalal, S.; Paul, K.; Jana, U. Fe(OTf)3-Catalyzed Aromatization of Substituted 3-Methyleneindoline and Benzo-furan Derivatives: A Selective Route to C-3-Alkylated Indoles and Benzofurans. Eur. J. Org. Chem. 2015, 5513-5517. (b) Paul, K.; Bera, K.; Jalal,S.; Sarkar, S.; Jana, U. Fe-Catalyzed Novel Domino Isomerization/Cyclodehydration of Substituted 2[(Indoline-3-ylidene)(methyl)]benzaldehyde Derivatives: An Efficient Approach toward Benzo[b]carbazole Derivatives. Org. Lett. 2014, 16, 2166-2169. (c) Paul, K.; Jalal, S.; Kundal, S.; Jana, U. Synthesis of Fused Dibenzofuran Derivatives via Palladium-Catalyzed Domino C–C Bond Formation and Iron-Catalyzed Cycloisomerization/Aromatization. J. Org. Chem. 2016, 81, 1164-1174. (d) Jalal, S.; Paul, K.; Jana, U. Iron-Catalyzed 1,5-Enyne Cycloisomerization via 5-Endo-Dig Cyclization for the Synthesis of 3-(Inden-1-yl)indole Derivatives. Org. Lett. 2016, 18, 6512-6515.


Metal-Catalyzed Domino Synthesis of Benzophenanthridines and 6H

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