Br?nsted/Lewis Acid-Promoted Site-Selective Intramolecular Cycloisomerizations of Aryl-Fused 1,6-Diyn-3-ones for Diversity-Oriented Synthesis of Benzo-Fused Fluorenes and Fluorenones and Naphthyl Ketones

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Brønsted/Lewis Acid-Promoted Site-Selective Intramolecular

Cycloisomerizations of Aryl-Fused 1,6-Diyn-3-ones for Diversity-

Oriented Synthesis of Benzo-Fused Fluorenes and Fluorenones and

Naphthyl Ketones

Mou Mandal, Shanmugam Sakthivel, and Rengarajan Balamurugan*

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ABSTRACT: Herein, a facile diversity-oriented approach to

access functionalized benzo[a]ﬂuorenes, benzo[b]ﬂuorenones,

and naphthyl ketones has been demonstrated via site-selective

intramolecular cyclization of aryl-fused 1,6-diyn-3-ones. Synthesis

of benzo[a]ﬂuorenes and naphthyl ketones has been achieved

selectively using TfOH and AgBF₄, respectively, via in situ-formed

acetals. Aryl-fused 1,6-diyn-3-ones undergo triﬂic acid-mediated

intramolecular cyclization, leading to benzo[b]ﬂuorenone deriva-

tives via a radical intermediate as supported by EPR studies.

Kinetic studies of these transformations have also been performed

by UV−visible spectroscopic analysis to shed light on the reaction

proﬁle.

past decades, interest toward these scaﬀolds evoked diﬀerent

groups to come up with alternate protocols to the existing

methodologies for the preparation of benzo[a]ﬂuorene,⁷

benzo[b]ﬂuorenone,⁸and naphthalene cores.⁹

Easily accessible aryl fused 1,6-diyn-3-ones oﬀer unique

opportunities to synthesize diﬀerent polyaromatic hydro-

INTRODUCTION

■

Polyaromatic hydrocarbons have engrossed extensive interest

due to their electrochemical and photochemical properties and

utility as π-conjugated functional materials such as organic

semiconductors and luminescent materials.¹Polyarylated

derivatives of aromatic cores are of particular interest because

of their stability, immense ability to transport charge, and

ﬂuorescence properties due to the presence of the fused ring

structures.²Among the polyaromatic hydrocarbons, naphtha-

lene, ﬂuorene, and their analogues such as benzoﬂuorene and

benzoﬂuorenone are signiﬁcant scaﬀolds and are often

employed in developing organic materials.³This include

electrogenerated chemiluminescence (ECL) devices,^3asemi-

conductors,^3borganic light-emitting diodes,^3c,horganic ﬁeld

eﬀect transistors,^3dsolar cells,³ⁱliquid crystals,^3j,ketc. Benzo-

[a]ﬂuorenes have widely been employed in organic light-

emitting diodes (OLEDs),^3cpotent photosensitizers in photo-

conductor devices,^3eoptoelectronic materials,^3fchemo/bio-

sensors,^3getc. On the other hand, benzoﬂuorenone moieties

have been applied in a range of organic electronics.^3f−hThese

structural motifs are even frequently found in many natural

products and also constitute the core of many pharmaceutical

agents.⁴The tetracyclic core of benzo[b]ﬂuorenones is found

in several natural products such as stealthin C, kinoscurinone,

cysﬂuoretin, and kinamycins,⁵which exhibits a range of vital

biological activities. They have also been employed as synthetic

intermediates in the development of bowl-shaped PAHs having

carbon skeletons represented on the exterior of C₆₀.⁶Over the

́

carbons. In 2000, Saa and co-workers synthesized benzo[b]-

ﬂuorenones from 1,6-diyn-3-ones via thermal [4 + 2]

cycloaromatization by heating them at 150 °C in toluene

solvent (Scheme 1II).^8hLiu and co-workers developed a gold-

catalyzed hydrative carbocyclization of 1,5- and 1,6-diyn-3-

ones via an oxygen transfer process for the preparation of

naphthyl ketones (Scheme 1III).^9hIn the recent years, use of

aryl-fused 1,6-enynones in ﬁnding new transformations has

gained much interest.¹⁰Indeno[1,2-c]pyrroles have been

accessed from the enaminones derived from aryl-fused 1,6-

enynones by Baire and co-workers.^10aDithiane derivatives of

aryl-fused 1,6-enynones, under gold-catalyzed cyclization

conditions, resulted in benzo[a]ﬂuorenes.^7dZhao and co-

workers have also utilized the enaminone derived from aryl-

fused 1,6-enynones for the synthesis of dihydroisobenzofur-

Received: September 3, 2020

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A

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Scheme 1. Strategies for the Access of Polyaromatic Hydrocarbons from Aryl-Fused 1,6-Diynones

an,^10bα-naphthylamines, and indeno[1,2-c]pyrrolones.^10cVery

recently, Chen and co-workers have disclosed the synthesis of

5-brominated benzo[b]ﬂuorenones via an iron-catalyzed cyclo-

aromatization of aryl-fused 1,6-enynones (Scheme 1I).^8a

we had used alkenones,^7b,gwhich upon acetal formation

facilitated nucleophilic attack at the β-carbon or at the formed

oxocarbenium carbon for cyclization. With alkynones present

in the molecule, we were curious about the reactivity of the

aryl-fused 1,6-diynones as it is expected to generate an allenyl

cation via in situ-formed acetal as shown in Scheme 1B. Strong

Brønsted acid, TfOH-promoted intramolecular cyclization of

aryl-fused 1,6-diynones to aﬀord benzo[b]ﬂuorenones and a

diﬀerent scaﬀold of benzo[a]ﬂuorenes in the presence of

trimethyl orthoformate. Interestingly, the same starting ma-

terial resulted in substituted naphthyl ketone when the reaction

was catalyzed by AgBF₄in the presence of trimethyl

orthoformate.

RESULTS AND DISCUSSION

■

In our endeavor to develop methodologies involving in situ-

formed acetals,¹¹we have reported alternate methods for the

synthesis of benzo[a]ﬂuorenes^7b,gand substituted napththa-

lenes.^9eHerein, we present a diversity-oriented approach using

aryl-fused 1,6-diynones as the starting material to access

benzo[a]ﬂuorenes and naphthyl ketones by choosing diﬀerent

acid promoters for the cyclization involving in situ-formed

acetal and benzo[b]ﬂuorenones directly. In our earlier works,

B

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Table 1. Optimization of Conditions for the Selective Synthesis of Benzo[a]ﬂuorene, Benzo[b]ﬂuorenone, and Naphthyl

a

Ketone

yield (%)

entry

solvent

promotor (equiv)

HC(OR)₃(equiv)

time (h)

2a

3a

4a/4b

1

2

3

4

5

6

7

8

DCM

HFIP

CH₃CN

CH₃NO₂

DCE

dioxane

DCM

TMOF

DCM

TfOH (1)

-

TfOH (1)

TfOH (0.5)

TfOH (1)

Tf₂NH (0.5)

TfOH (1)

TMOF (2)

TMOF (4)

-

TMOF (4)

TMOF (6)

-

TMOF (4)

TMOF (6)

TMOF (4)

TMOF (6)

-

3

2

24

4

3

4

5

3

2

4

31

79

-

14

26

-

55

17

37

30

11

85

-

77

17

34

9

-

19

89

-

51

31

-

60

-

90

17

-

57

-

93

76

-

48

-

9

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

36

37

38

39

40

41

42

43

44

DCM

CH₃CN

b

DCM/CH₃CN (1:1)

DCM/HFIP (6:1)

toluene

CHCl₃

DCM

dioxane

CH₃NO₂

DCE

-

TfOH (1)

1

4

TfOH (0.5)

AgBF₄(0.05)

AgOTf (0.05)

AgNTf₂(0.05)

AgClO₄(0.05)

AgSbF₆(0.05)

Cu(OTf)₂(0.05)

In(OTf)₃(0.05)

Sn(OTf)₂(0.05)

Sc(OTf)₃(0.05)

BiBr₃(0.05)

FeCl₃(0.05)

I₂(0.05)

-

TMOF (1)

TEOF (1)

TEOF (2)

TEOF (3)

TEOF (0.5)

-

24

16

24

26

24

12

11

19

11

24

70

79

69

22

75

-

56

68

72

68

34

-

TEOF (1)

-

87

88

87

79

74

85

88

86

78

87

22

79

-

AuCl₃(0.05)

PPh₃AuCl (0.05)

IprAuCl (0.05)

c

CSA (0.05)

-

15

-

63

-

AgBF₄(0.05)

-

CH₃CN

75

a

Reaction conditions: 1a (0.1 mmol), LA/BA, HC(OR)₃, and solvent (1 mL) with continuous stirring at R.T. under a N₂atmosphere. ‘-’: No

b

c

Reaction. Reaction conducted at 60 °C. 10-(+) Camphor sulfonic acid.

A number of reactions were performed to ﬁnd out the

optimum condition for the selective formation of benzo[a]-

ﬂuorene, benzo[b]ﬂuorenone, and naphthyl ketone from the

aryl fused 1,6-diyn-3-one 1a. The details of the optimization

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Table 2. Substrate Scope for Benzo[a]Fluorene Synthesis

experiments are collected in Table 1. When the aryl fused 1,6-

diyn-3-one derivative 1a was treated with 1 equiv of triﬂic acid

in presence of 2 equiv of trimethyl orthoformate (TMOF), it

led to the formation of benzo[a]ﬂuorene derivative 2a in 31%

isolated yield (Table 1, entry 1). Then, the reaction was

attempted with varying amounts of TMOF and triﬂic acid and

diﬀerent solvents. The highest yield of benzo[a]ﬂuorene (2a)

(85%) was achieved when the reaction was carried out in the

presence of 6 equiv of TMOF and 1 equiv of TfOH in DCM

solvent at room temperature under a nitrogen atmosphere

(Table 1, entry 12). Remarkably, the same reaction in the

absence of trimethyl orthoformate resulted in the formation of

benzo[b]ﬂuorenone 3a exclusively with 93% isolated yield

(Table 1, entry 18). Decreasing the amount of TfOH to 0.5

equiv decreased the yield of 3a considerably (Table 1, entry

19). Further, catalyst screening was done with various Lewis

and Brønsted acids. To our delight, we have achieved a

diﬀerent PAH, namely, naphthyl ketone 4a, in 70% isolated

yield from the reaction of the same aryl-fused 1,6-diyn-3-one

derivative 1a with trimethyl orthoformate in the presence of 5

mol % AgBF₄catalyst (Table 1, entry 20). Using triethyl

orthoformate (TEOF) in place of trimethyl orthoformate

increased the yield of the product 4b (Table 1, entry 21).

Increasing or decreasing the amount of TEOF reduced the

yield of the product (Table 1, entries 22−24). In the absence

of TEOF, the reaction resulted in the benzoﬂuorenone

derivative 3a only (Table 1, entry 25). Reaction parameters

such as catalyst, solvent, amount of TEOF, etc. were changed

and were found to be less eﬃcient for the formation of

naphthyl ketone derivative 4b. Therefore, the condition

described in reactions 12, 18, and 21 were used to evaluate

the substrate scope for the synthesis of benzo[a]ﬂuorene,

benzo[b]ﬂuorenone, and napthyl ketone derivatives, respec-

tively.

In the case of benzo[a]ﬂuorene synthesis, substrates with

diverse substituents were well tolerated and provided the

corresponding benzo[a]ﬂuorene derivatives with moderate to

excellent yields (42−85%) in a short time period (Table 2). It

is important to mention that electronic and steric eﬀects of

substituents did not show an appreciable inﬂuence on the

reaction outcome except for the substrates having R²

substituents and ﬂuorine on the aryl ring attached to the β-

carbon of the alkynone. The ﬂuoro substituent is a para-donor

and reactions at the para-position of ﬂuorobenzene are usually

high yielding than the corresponding reaction at any other

single position of benzene.¹²However, here the carbon meta to

ﬂuoro substitution is involved in the second cyclization. Thus,

a decreased yield was observed in the case of 2e and 2i.

However, a ﬂuoro substitution on the aryl bridging the

alkynone and arylalkyne did not decrease the yield of 2g (76%)

and 2j (74%). Substrates having 4-Me, 4-F, and 2-Me-5-NO₂

as R²did not result in the desired products and instead

resulted in complex product mixtures. This reaction failed to

give the desired product when an aliphatic substituent is

present at the β-carbon of the alkynone. Instead, naphthyl

ketone derivatives 4k and 4l were obtained from substrates 1p

and 1q, respectively, as there is no aryl for further

benzannulation (Scheme 2). From this observation we were

curious to know whether the benzo[a]ﬂuorene 2a formation is

happening through the naphthyl ketone (4a) intermediate. For

this purpose, the naphthyl ketone (4a) was treated with 6

equiv of TMOF and 1 equiv of TfOH. However, even after 24

h, no benzo[a]ﬂuorene formation was observed; only the

starting material 4a remained. Thus, it can be concluded that

D

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́

(Table 1, entry 18). It is worth mentioning that Saa and co-

workers reported the synthesis of benzo[b]ﬂuorenone from

aryl-fused 1,6-diynone by reﬂuxing it in toluene at 150 °C.

However, they ended up with a mixture of two regioisomeric

benzo[b]ﬂuorenones in an almost quantitative combined yield

(72 and 24%) in 11 h.^8hHowever, in our methodology using

TfOH, solely one isomer of benzo[b]ﬂuorenone is obtained in

excellent yield.

Scheme 2. Reaction of Aryl-Fused 1,6-Diyn-3-one Having

an Aliphatic Substituent

The scope of this reaction has been demonstrated by

successful cyclization of a diverse 1,6-diyn-3-one derivatives

containing diﬀerent substituents on diﬀerent aryl groups in the

presence of triﬂic acid (Table 3). Exceptional yields were

obtained for all the substrates studied, and there were

essentially not much substituent eﬀects on the yield of the

products. When any of the benzene ring is replaced by an

aliphatic group, this reaction resulted in a complex product

mixture.

To understand the mechanism of the reaction, an EPR

experiment was done on the reaction mixture at diﬀerent

times. In all the cases the outcomes of the experiments were

the same. They gave a positive response with a signal having a

G value of 2.0129 (Figure 1). Also, upon addition of triﬂic acid

to the substrates, the color of the reaction mixture immediately

changed to greenish yellow from pale yellow and ﬁnally to dark

yellow. In the presence of TEMPO, the yield of the reaction

decreased to 62%. Therefore, the reaction might be happening

via Schmittel cyclization involving a diradical intermediate [H]

as depicted in Scheme 4. The role of a Brønsted acid in making

this reaction to happen at room temperature may be the

protonation of the carbonyl facilitated the cycloisomerization

to form the intermediate [H].¹³This undergoes an intra-

molecular radical cyclization to furnish a strained cyclic allene

[I]. The strained allene [I] might lead to the formation of

aromatic product 3a. The role of acid in this reaction was

evaluated by carrying out the reaction of 1a in the presence of

2 equiv of H₂¹⁸O. Signiﬁcant ¹⁸O labeling of carbonyl oxygen

in the product was noticed from the HRMS spectra of the

product (Scheme 6). The reaction took the same 1 h time for

its completion without an appreciable drop in the yield. In

another experiment, product 3a was treated with TfOH (1

equiv) and 2 equiv of H₂¹⁸O in dichloromethane. Surprisingly,

very little ¹⁸O labeling was observed in the product. Acid-

benzo[a]ﬂuorene formation is not happening via the formation

of the naphthyl ketone intermediate.

On the basis of these results and our previous reports,^7b,gwe

propose a plausible reaction mechanism for the formation of

benzo[a]ﬂuorene 2a as shown in Scheme 3. First, in the

presence of trimethyl orthoformate and TfOH, acetal [A] is

formed from 1a. Then, in the presence of strong acid, one of

the −OMe groups is protonated and departed as MeOH

leading to the formation of oxocarbenium ion intermediate [C]

from intermediate [B]. At this stage, an intramolecular

cyclization of the alkyne occurs on the proton-activated alkyne

as shown in intermediate [C]. This may be facilitated by the

electron-withdrawing nature of the oxocarbenium ion. Thus,

generated intermediate [D] will undergo aromatic electrophilic

substitution on the vinyl carbocation to form [E]. Finally,

benzo[a]ﬂuorene derivative (2a) is formed by isomerization of

intermediate [E] followed by quenching with methanol. When

an aliphatic group is present at the β-carbon of the enynone,

second cyclization is not possible due to the absence of aryl

moiety and the reaction ended up with the formation of

naphthyl ketone (Scheme 2).

As stated in Table 1, in the absence of trimethyl

orthoformate, the same reaction ended up with the formation

of the benzo[b]ﬂuorenone derivative in 93% isolated yield

Scheme 3. Plausible Reaction Mechanism for the Formation of Benzo[a]ﬂuorenes

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Table 3. Substrate Scope for Benzo[b]ﬂuorenone Synthesis

promoted hydration of the carbonyl in 1a might be the reason

for the ¹⁸O incorporation. This supports the role of acid in

promoting the cyclization by activation of the carbonyl.

Having achieved the intramolecular cyclization of aryl-fused

1,6-diyn-3-one 1 to form benzo[a]ﬂuorene 2 and benzo[b]-

ﬂuorenone 3, we explored the scope of naphthyl ketone

formation using various aryl-fused 1,6-diyn-3-ones 1 under the

optimized reaction condition depicted in Table 1, entry 21.

Substrates with donor and acceptor groups in all the three aryl

rings were evaluated. Although the reaction conditions were

not optimized for each of the substrates studied, the reaction

showed good functional group tolerance for all types of

substituents (62−80%), indicating the generality and robust-

ness of this transformation (Table 4). In this methodology,

Figure 1. EPR spectra of the reaction mixture of reaction 1a with

TfOH.

Scheme 4. Plausible Reaction Mechanism for the Formation of Benzo[a]ﬂuorenones

F

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Table 4. Substrate Scope for Naphthyl Ketone Synthesis

Scheme 5. Tentative Reaction Mechanism for the Formation of Naphthyl Ketones

when any of the benzene ring is replaced with an aliphatic

group, the desired product was not formed.

acetal (Scheme 3). Therefore, the vinyl carbocation

intermediate undergoes intramolecular benzannulation to

form the benzo[a]ﬂuorene. The possibility of intramolecular

transfer of OEt in the acetal to the tethered alkyne as proposed

by Liu and co-workers in the synthesis of 4-hydroxy-1-naphthyl

ketones^9hfollowed by cyclization cannot be excluded. It has to

be mentioned that Yamamoto and co-workers favored the

formation of 1-allenylisochromes in the silver-catalyzed

reaction of the same title compounds with alcohols through

a diﬀerent mechanism.¹⁴However, the spectral characteristics

of the napthyl ketone derivative 4a matched with that of the

compound obtained by them in the reaction of the same

substrate involving MeOH, suggesting the possibility of

naphthyl ketone formation in their study as well, at least

with this particular substrate.

A tentative mechanism for the formation of naphthyl ketone

(4a) can be proposed as shown in Scheme 5. In the presence

of triethyl orthoformate and AgBF₄, acetal [J] will from.

Coordination of the silver catalyst to both alkyne and acetal

oxygen as in intermediate [K] might facilitate the removal of

OEt⁻to form the oxocarbenium ion intermediate [L]. Now, a

tandem attack of OEt⁻on the alkyne followed by cyclization

on the silver-activated alkyne will generate intermediate [M].

This will undergo protodemetallation to form intermediate

[N]. Now, aromatization will result in the formation of the

naphthyl ketone product. In the TfOH-promoted formation of

benzo[a]ﬂuorene, TfOH was used in a stoichiometric amount

and less nucleophilic MeOH is formed during the generation

of the oxocarbenium ion intermediate from the in situ-formed

G

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To prove the proposed mechanisms for the formation of

benzo[a]ﬂuorene and naphthyl ketone moieties, we did some

control experiments. First, fully deuterated trimethyl ortho-

formate (DC(OCD₃)₃) was prepared following the literature-

reported method.¹⁵Then, the reactions for the formation of

benzo[a]ﬂuorene 2a and naphthyl ketone 4a were carried out

using DC(OCD₃)₃under standard reaction conditions

(Scheme 6A). Incorporation of -OCD₃in both the products

present in the reaction mixture involved in the reaction. We

did not observe any ¹⁸O labeling in the products benzo[a]-

ﬂuorene 2a and naphthyl ketone 4a from HRMS analysis.

Thus, it can be concluded that the oxocarbenium ion involved

in the formation of products 2 and 4 is formed through the in

situ-formed acetal and not the possible hemiacetal.

Then, to prove whether the formation of the naphthyl

ketone moiety is through the formation of acetal or not, we

performed a competition experiment. First, we performed a

reaction under the standard condition using 2 equiv of MeOH

instead of TMOF. However, we got the naphthyl ketone in

62% yield only (Scheme 6B). Another reaction was performed

in the presence of 1 equiv of TMOF and 1 equiv of EtOH,

keeping other reaction conditions unchanged. Both the OMe

and OEt incorporated naphthyl ketone derivatives (4a and 4b)

involving TMOF and EtOH, respectively, were obtained.

Interestingly, the ratio of OMe and OEt incorporated naphthyl

ketones was found to be 85:15 (Scheme 6B), as indicated by

the ¹H NMR spectrum of the product mixture (Figure 2). This

reveals clearly that the reaction takes place via the formation of

acetal as a ketone would form acetal readily with trimethyl

orthoformate than with an alcohol. From these results we can

conclude that the reaction happens via in situ-formed acetal

only.

Scheme 6. Control Experiments

We then attempted some interesting transformations of the

synthesized compounds. When benzo[a]ﬂuorene 2a was

treated with BBr₃, it resulted in the corresponding benzo[a]-

ﬂuorenol derivative 5a with the benzylic OMe group intact

(Scheme 7A). Remarkably, the naphthyl ketone 4a, upon

treatment with BBr₃, produced a new class of benzo[a]-

ﬂuorenone 6a instead of stopping at the OMe deprotection

alone. We have also examined the scope of this transformation

with a couple of more substrates, and the structures of the

products are presented in Scheme 7C. A probable mechanism

for its formation is also presented in Scheme 7B. This

conversion requires two equivalents of BBr₃. The ﬁrst

equivalent of BBr₃reacts with the OMe group, leading to

intermediate [O]. The generated Br⁻will attack methyl,

thereby forming intermediate [P]. Activation of the carbonyl

by another molecule of BBr₃eﬀects electrophilic cyclization.

Finally, aqueous workup will generate the benzo[a]ﬂuorenone

with the extrusion of two molecules of boronic acid. The

structures of all the synthesized compounds were conﬁrmed by

NMR, IR, and high-resolution mass spectroscopic analysis.

The structures of 2f, 3b, 4b, and 4k were further conﬁrmed by

X-ray crystallographic analysis with the CCDC numbers,

1998442, 1998443, 1998444, and 1998445, respectively.

Since the starting material and the products are aromatic,

having speciﬁc absorption maxima, all the three trans-

formations have been followed by UV−visible spectroscopy

to get more insight into the reactions. For each transformation,

the UV spectra were recorded at regular intervals of time. An

absorbance versus wavelength plot clearly revealed the smooth

decrease in the intensity of starting material’s absorbance with

a gradual increase in the intensity of the product’s absorbance.

A plot of ln [A]_t/[A]_ofor the starting material versus time

resulted in a linear ﬁt in each case, suggesting ﬁrst-order

reaction kinetics (Figure 3).

2a-d₆and 4a-d₃was conﬁrmed from the ¹H NMR spectrum of

the respective products. The singlets at 4.14 and 2.90 ppm

corresponding to the two -OCH₃protons of 2a disappeared in

2a-d₆and the singlet at 4.02 ppm corresponding to the -OCH₃

protons of 4a disappeared in 4a-d₃in their respective ¹H NMR

spectra.

In addition, we have performed the reactions leading to

benzo[a]ﬂuorene 2a and naphthyl ketone 4a formation in the

presence of H₂¹⁸O to check whether the adventitious water

Reaction Kinetics by UV−Vis Experiments for the

Formation of Benzo[a]Fluorene, Benzo[b]Fluorenone,

and Naphthyl Ketone. In conclusion, we have developed

facile protocols for the construction of diverse molecular

scaﬀolds such as benzo[a]ﬂuorenes, benzo[b]ﬂuorenones, and

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1

Figure 2. HRMS and H NMR spectra of the crude product obtained in the Ag-catalyzed reaction of 1a with TMOF and EtOH.

Scheme 7. Transformations of the Synthesized Benzo[a]ﬂuorene and Naphthyl ketone

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Figure 3. (a) UV proﬁle and (b) reaction kinetics for the formation of (A) benzo[a]ﬂuorene, (B) benzo[b]ﬂuorenone, and (C) naphthyl ketone.

4-ethoxy arylnaphthalenes from aryl-fused 1,6-diyn-3-ones.

Formation of acetal under the reaction condition using

trimethyl orthoformate changes the reactivity of the title

substrate under diﬀerent Lewis or Brønsted acid conditions.

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Scheme 8. Preparation of 1,6-Diyn-3-ones (1)

literature, and the analytical data of the synthesized compounds are in

good accordance with the literature data.^8a,9h,16

Further, it has been shown that the 4-methoxy napthyl ketones

can be converted into a diﬀerent benzo[a]ﬂuorenone

derivative.

3-(4-Ethylphenyl)-1-(2-(phenylethynyl)phenyl)prop-2-yn-1-one

(1b, Scheme 8). Yellow gummy (yield = 380 mg, 81%); R_f= 0.44 in

5% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 8.23 (d, J = 6.9

Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.64−7.60 (m, 2H), 7.56 (d, J =

8.2 Hz, 3H), 7.48 (t, J = 7.6 Hz, 1H), 7.35−7.32 (m, 3H), 7.19 (d, J =

8.0 Hz, 2H), 2.67 (q, J = 7.6 Hz, 2H), 1.25 (t, J = 7.6 Hz, 3H);

¹³C{¹H}NMR (100 MHz, CDCl₃): δ 177.5, 147.6, 138.4, 134.2,

133.2, 132.3, 131.9, 131.5, 128.5, 128.2, 128.1, 127.9, 123.1, 122.9,

117.2, 95.4, 94.0, 88.3, 88.0, 28.9, 15.1; IR (KBr, cm⁻¹): υ 2929, 1697,

1598, 1307, 1188, 760, 726, 598; HRMS (ESI-TOF) m/z: [M + H]⁺

Calcd for C₂₅H₁₉O 335.1430; found 335.1430.

3-(3-Methoxyphenyl)-1-(2-(phenylethynyl)phenyl)prop-2-yn-1-

one (1c, Scheme 8). Yellow gummy (yield = 402 mg, 72%); R_f= 0.31

in 10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 8.17 (d, J =

7.7 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.59−7.51 (m, 3H), 7.47−7.42

(m, 1H), 7.30 (s, 3H), 7.26−7.20 (m, 2H), 7.10 (s, 1H), 6.96 (d, J =

7.7 Hz, 1H), 3.71 (s, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ

177.5, 159.3, 138.2, 134.3, 132.5, 131.9, 131.5, 129.6, 128.6, 128.2,

128.0, 125.6, 123.1, 123.0, 121.0, 117.6, 117.3, 95.5, 93.3, 88.2, 87.8,

55.2; IR (KBr, cm⁻¹): υ 2995, 1703, 1580, 1463, 1245, 1032, 756,

698, 529; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₄H₁₇O₂

337.1223; found 337.1229.

1-(5-Methoxy-2-(phenylethynyl)phenyl)-3-phenylprop-2-yn-1-

one (1f, Scheme 8). Yellow gummy (yield = 350 mg, 83%); R_f= 0.28

in 10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 7.69 (d, J =

2.7 Hz, 1H), 7.63 (d, J = 8.2 Hz, 2H), 7.61 (s, 1H), 7.56−7.53 (m,

2H), 7.45 (t, J = 7.4 Hz, 1H), 7.36 (t, J = 7.6 Hz, 2H), 7.31−7.28 (m,

3H), 7.12 (dd, J = 8.6, 2.8 Hz, 1H), 3.94 (s, 3H); ¹³C{¹H}NMR (100

MHz, CDCl₃): δ 177.6, 159.2, 139.7, 135.7, 133.2, 131.7, 130.8,

128.6, 128.3, 128.2, 123.4, 120.2, 118.9, 115.9, 115.4, 94.0, 93.8, 88.2,

88.0, 55.7; IR (KBr, cm⁻¹): υ 2995, 1699, 1607, 1484, 1275, 1029,

747, 700, 549; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₄H₁₇O₂337.1223; found 337.1226.

EXPERIMENTAL SECTION

■

General Information. Except otherwise mentioned, all the

chemicals and solvents were obtained commercially and used without

puriﬁcation. Starting materials were prepared by following known

literature procedures. THF and toluene were dried over sodium and

freshly distilled before use. Dichloromethane and dichloroethane were

dried over CaH₂and freshly distilled before use. H and ¹³C NMR

1

spectra were recorded at room temperature on 400 and 500 MHz

spectrometers using CDCl₃solutions containing tetramethylsilane

(TMS) as an internal standard. IR spectra were recorded using an FT-

IR spectrometer and are reported in cm⁻¹. High-resolution mass

spectra (HRMS) were recorded using ESI-Q-TOF and ESI-Orbitrap

techniques. Melting points were determined using a melting range

apparatus and are uncorrected. For TLC, silica gel plates 60F₂₅₄were

used and the spots were visualized by UV light and/or by treatment

with Seebach solution (phosphomolybdic acid (2.5 g), Ce(SO₄)₂(1

g), conc. H₂SO₄(6 mL), and H₂O (94 mL)) followed by heating.

Column chromatography was performed on silica gel (100−200

mesh) using an ethyl acetate and hexanes mixture as the eluent.

Preparation of Aryl-Fused 1,6-Diyn-3-ones (1). 2′-Bromo-

benzaldehyde derivative 7 (1.0 equiv), Pd(PPh₃)₂Cl₂(2 mol %), and

CuI (4 mol %) were dissolved in dry THF/Et₃N (1:1) in a round-

bottom ﬂask under a nitrogen atmosphere at room temperature. After

5 min of stirring, the corresponding terminal alkyne 8 (1.2 equiv) was

added and the reaction mixture was reﬂuxed at 60 °C using an oil

bath. After the completion of the reaction as indicated by TLC, the

reaction mixture was ﬁltered through Celite and the solvents were

evaporated under reduced pressure. Finally, the crude product was

puriﬁed by column chromatography (silica gel, hexanes/EtOAc) to

get pure 2-(arylethynyl)benzaldehyde derivatives 9.

To a solution of alkyne 10 (1.2 equiv) in dry THF at −78 °C, n-

BuLi (2.5 M in hexanes, 1.2 equiv) was added slowly and stirred for

45 min at −78 °C and then a solution of o-alkynylaldehyde 9 (1

equiv) in THF was added slowly. The resulting mixture was allowed

to stir for 2 h at room temperature. After completion of the reaction

as mentioned by TLC, the reaction mixture was quenched by aqueous

NH₄Cl solution and the organic layer was extracted with EtOAc and

dried over anhydrous Na₂SO₄. The organic layer was concentrated

under reduced pressure, and it was directly used for further reaction.

MnO₂(15 equiv) was added in portions to a solution of the alcohol

derivative 11 in DCM and stirred at room temperature. After

completion of the reaction as indicated by TLC, the reaction mixture

was ﬁltered through Celite and concentrated under reduced pressure.

The residue was puriﬁed by column chromatography to yield the

corresponding 1,6-diyn-3-ones 1.

1-(5-Methoxy-2-(phenylethynyl)phenyl)-3-(p-tolyl)prop-2-yn-1-

one (1h, Scheme 8). Yellow gummy (yield = 376 mg, 85%); R_f= 0.47

1

in 5% EtOAc/hexanes; H NMR (400 MHz, CDCl₃): δ 7.70−7.48

(m, 6H), 7.31 (s, 3H), 7.18−7.10 (m, 3H), 3.94 (s, 3H), 2.40 (s,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 177.5, 159.2, 141.5, 139.9,

135.7, 133.2, 131.7, 129.4, 128.2, 123.5, 118.7, 117.1, 115.9, 115.3,

94.5, 93.9, 88.2, 88.1, 85.6; IR (KBr, cm⁻¹): υ 3006, 1632, 1554, 1292,

1163, 1003, 756, 692; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₅H₁₉O₂351.1380; found 351.1379.

3-(4-Fluorophenyl)-1-(5-methoxy-2-(phenylethynyl)phenyl)-

prop-2-yn-1-one (1i, Scheme 8). Yellow gummy (yield = 365 mg,

81%); R_f= 0.50 in 10% EtOAc/hexanes; ¹H NMR (500 MHz,

CDCl₃): δ 7.63 (d, J = 2.7 Hz, 1H), 7.62−7.55 (m, 3H), 7.54−7.51

(m, 2H), 7.30−7.26 (m, 3H), 7.09 (d, J = 8.6 Hz, 1H), 7.01 (t, J = 8.5

Hz, 2H), 3.89 (s, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ 177.3,

163.9 (d, J = 253.7 Hz), 159.2, 139.7, 135.7, 135.4 (d, J = 8.9 Hz),

131.6, 128.2 (d, J = 6.9 Hz), 123.4, 118.8, 116.3 (d, J = 3.5 Hz),

116.1, 115.9, 115.7, 115.4, 94.1, 92.7, 88.2, 88.0, 55.6; IR (KBr,

cm⁻¹): υ 2835, 1649, 1594, 1500, 1191, 1005, 831, 745, 522; HRMS

The above procedure was used for the preparation of all the 1,6-

diyn-3-one derivatives 1 employed in this study by using

corresponding o-alkynylaldehydes and terminal alkynes (Scheme 8).

Analytical Data of Aryl-Fused 1,6-Diyn-3-ones (1). The aryl-

fused 1,6-diyn-3-ones 1a, 1d, 1e, 1g, 1l, and 1p are reported in the

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(ESI-TOF) m/z: [M + H]⁺Calcd for C₂₄H₁₆O₂F 355.1129; found

355.1130.

To a solution of compound 1a (100 mg, 0.326 mmol, 1.0 equiv) in

dichloromethane solvent (1.5 mL), trimethyl orthoformate (214.2 μL,

1.958 mmol, 6 equiv) and triﬂic acid (28.8 μL, 0.326 mmol, 1 equiv)

were charged sequentially at room temperature (25 °C) under a

nitrogen atmosphere. The reaction mixture was allowed to stir at

room temperature under a nitrogen atmosphere until the completion

of the reaction. The progress of the reaction was monitored by TLC.

After that, it was quenched with a saturated NaHCO₃solution. Then,

it was extracted using ethyl acetate. The combined organic layers were

washed with saturated brine solution and dried over anhydrous

Na₂SO₄. The solvents were evaporated under reduced pressure. The

crude product was puriﬁed by column chromatography (using silica

gel, EtOAc/hexanes eluent) to get pure 5,11-dimethoxy-11-phenyl-

11H-benzo[a]ﬂuorene 2a as a red solid with 85% isolated yield (97.4

mg).

1-(5-Fluoro-2-(phenylethynyl)phenyl)-3-(p-tolyl)prop-2-yn-1-one

(1j, Scheme 8). Yellow gummy (yield = 302 mg, 77%); R_f= 0.58 in

10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 7.86 (d, J = 8.8

Hz, 1H), 7.67−7.57 (m, 3H), 7.49 (d, J = 7.8 Hz, 2H), 7.32 (s, 3H),

7.26−7.21 (m, 1H), 7.13 (d, J = 7.7 Hz, 2H), 2.34 (s, 3H);

¹³C{¹H}NMR (100 MHz, CDCl₃): δ 175.9, 161.5 (d, J = 251.7 Hz),

141.8, 140.1 (d, J = 6.4 Hz), 136.2 (d, J = 7.5 Hz), 133.2, 131.8,

129.4, 128.6, 128.3, 123.0, 119.8 (d, J = 22.0 Hz), 119.1, 118.0 (d, J =

23.7 Hz), 116.7, 95.2, 94.8, 87.7, 87.3, 21.7; IR (KBr, cm⁻¹): υ 2919,

1706, 1604, 1478, 1262, 828, 753, 585; HRMS (ESI-TOF) m/z: [M +

H]⁺Calcd for C₂₄H₁₆OF 339.1180; found 339.1185.

1-(2-((4-Ethylphenyl)ethynyl)phenyl)-3-phenylprop-2-yn-1-one

(1k, Scheme 8). Yellow gummy (yield = 354 mg, 82%); R_f= 0.47 in

10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 7.88−7.78 (m,

1H), 7.73 (d, J = 6.8 Hz, 1H), 7.67−7.54 (m, 5H), 7.53−7.40 (m,

4H), 7.38−7.17 (m, 2H), 2.69 (q, J = 4.1 Hz, 2H), 1.26 (t, J = 6.5 Hz,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 177.6, 147.6, 138.3, 134.3,

133.2, 132.4, 131.9, 131.5, 128.5, 128.2, 128.15, 127.9, 123.1, 122.9,

117.2, 95.3, 94.1, 88.3, 88.0, 29.0, 15.1; IR (KBr, cm⁻¹): υ 2961, 1701,

1600, 1468, 1075, 759, 724, 601; HRMS (ESI-TOF) m/z: [M + H]⁺

Calcd for C₂₅H₁₉O 335.1430; found 335.1436.

3-Phenyl-1-(6-(phenylethynyl)benzo[d][1,3]dioxol-5-yl)prop-2-

yn-1-one (1m, Scheme 8). Yellow gummy (yield = 336 mg, 72%); R_f

= 0.31 in 10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 8.12

(s, 1H), 7.91 (d, J = 7.0 Hz, 1H), 7.64−7.60 (m, 2H), 7.54 (s, 1H),

7.45−7.38 (m, 4H), 7.16 (s, 1H), 6.10 (d, J = 12.2 Hz, 1H), 5.97 (s,

2H), 5.71 (s, 1H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 177.6, 164.0,

161.5, 138.3, 134.2, 133.9, 133.1, 132.6, 131.7, 130.8, 128.6, 128.1,

122.9, 120.2, 119.3, 115.7, 115.5, 94.4, 93.4, 88.1, 88.0; IR (KBr,

cm⁻¹): υ 2920, 1699, 1500, 1421, 1264, 1029, 699; HRMS (ESI-

TOF) m/z: [M + H]⁺Calcd for C₂₄H₁₅O₃351.1016; found 351.1021.

1-(2-((4-Ethylphenyl)ethynyl)phenyl)-3-(4-ﬂuorophenyl)prop-2-

yn-1-one (1n, Scheme 8). Yellow gummy (yield = 304 mg, 79%); R_f

= 0.73 in 10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 7.83

(s, 1H), 7.75 (d, J = 8.3 Hz, 1H), 7.68 (d, J = 7.4 Hz, 1H), 7.58 (d, J =

7.4 Hz, 1H), 7.5 (t, J = 7.4 Hz, 1H), 7.43−7.35 (m, 2H), 7.34−7.28

(m, 2H), 7.28−7.20 (m, 3H), 2.66 (q, J = 7.6 Hz, 2H), 1.20 (t, J = 7.6

Hz, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ 177.1, 147.2 (d, J =

300.9 Hz), 138.1, 134.8, 133.1, 132.7, 132.2, 130.9, 130.3, 128.72,

128.7, 127.2, 124.6, 123.2, 121.1(d, J = 263.7 Hz), 94.1, 93.5, 91.6,

87.8, 29.7, 21.2; IR (KBr, cm⁻¹): υ 2959, 1699, 1600, 1507, 1220,

874, 759, 556; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₅H₁₈OF 353.1336; found 353.1345.

The reaction was carried out using 1g of 1a to furnish 2a (911 mg;

79% yield); thus, the scalability of the reaction has been checked. m.p.

1

= 152−153 °C; R_f= 0.63 in 10% EtOAc/hexanes; H NMR (400

MHz, CDCl₃): δ 8.29 (d, J = 7.7 Hz, 1H), 7.81 (d, J = 7.4 Hz, 1H),

7.71 (d, J = 7.5 Hz, 1H), 7.42−7.33 (m, 5H), 7.28 (d, J = 7.0 Hz,

1H), 7.25−7.14 (m, 5H), 4.14 (s, 3H), 2.90 (s, 3H); ¹³C{¹H}NMR

(125 MHz, CDCl₃): δ 157.7, 149.4, 143.6, 141.0, 139.8, 132.6, 130.7,

128.6, 128.2, 127.8, 127.4, 126.9, 125.9, 125.4, 124.9, 124.4, 124.39,

123.0, 119.4, 96.3, 89.9, 55.8, 51.2; IR (KBr, cm⁻¹): υ 2927, 1620,

1584, 1449, 1215, 1156, 757; HRMS (ESI-TOF) m/z: [M + H]⁺

Calcd for C₂₅H₂₁O₂353.1536; found 353.1536.

9-Ethyl-5,11-dimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2b,

Table 2). The reaction was carried out using 105 mg of corresponding

aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 93.2 mg, 78%); m.p. =

178−179 °C; R_f= 0.64 in 10% EtOAc/hexanes; ¹H NMR (400 MHz,

CDCl₃): δ 8.30−8.27 (m, 1H), 7.81−7.77 (m, 1H), 7.62 (d, J = 7.6

Hz, 1H), 7.39−7.32 (m, 4H), 7.23−7.15 (m, 5H), 7.11 (s, 1H), 4.15

(s, 3H), 2.90 (s, 3H), 2.64 (q, J = 7.6 Hz, 2H), 1.22 (t, J = 7.6 Hz,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 157.6, 149.5, 144.2, 143.7,

139.9, 138.6, 132.4, 130.7, 128.2, 128.1, 127.3, 126.8, 125.6, 125.4,

124.7, 124.2, 124.0, 123.0, 119.2, 96.3, 89.8, 55.8, 51.2, 29.0, 15.6; IR

(KBr, cm⁻¹): υ 2927, 1618, 1581, 1456, 1215, 1098, 863, 691; HRMS

(ESI-TOF) m/z: [M + H]⁺Calcd for C₂₇H₂₅O₂381.1849; found

381.1849.

5,11-Diethoxy-9-ethyl-11-phenyl-11H-benzo[a]ﬂuorene (2c,

Table 2). The reaction was carried out using 150 mg of corresponding

aryl-fused 1,6-diyn-3-one. Oﬀ-white solid (yield = 143.3 mg, 78%);

1

m.p. = 169−170 °C; R_f= 0.77 in 10% EtOAc/hexanes; H NMR

(500 MHz, CDCl₃): δ 8.31 (d, J = 7.7 Hz, 1H), 7.84 (d, J = 7.5 Hz,

1H), 7.58 (d, J = 7.7 Hz, 1H), 7.38 (d, J = 7.0 Hz, 2H), 7.36−7.30

(m, 2H), 7.20−7.13 (m, 5H), 7.11 (s, 1H), 4.36 (q, J = 7.0 Hz, 2H),

3.06−2.99 (m, 1H), 2.97−2.90 (m, 1H), 2.62 (q, J = 7.6 Hz, 2H),

1.62 (t, J = 7.0 Hz, 3H), 1.21 (t, J = 7.6 Hz, 3H), 1.08 (t, J = 7.0 Hz,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 156.8, 150.4, 144.1, 139.6,

138.4, 133.1, 130.8, 128.1, 127.9, 127.1, 126.7, 125.7, 125.5, 124.5,

124.3, 123.9, 123.0, 121.9, 119.1, 96.9, 89.2, 64.0, 58.7, 29.0, 15.7,

15.6, 14.9; IR (KBr, cm⁻¹): υ 2923, 1582, 1446, 1209, 1069, 863, 761;

HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₉H₂₉O₂409.2162;

found 409.2163.

1-(2-((2-Methyl-5-nitrophenyl)ethynyl)phenyl)-3-phenylprop-2-

yn-1-one (1o, Scheme 8). Reddish yellow solid (yield = 328 mg,

1

78%); m.p. = 159−160 °C; R_f= 0.47 in 10% EtOAc/hexanes; H

NMR (500 MHz, CDCl₃): δ 8.34 (d, J = 2.3 Hz, 1H), 8.28 (d, J = 7.8

Hz, 1H), 8.04 (dd, J = 8.4, 2.3 Hz, 1H), 7.71 (d, J = 7.4 Hz, 1H), 7.63

(d, J = 7.1 Hz, 2H), 7.60 (t, J = 7.6 Hz, 1H), 7.53 (t, J = 7.6 Hz, 1H),

7.45 (t, J = 7.5 Hz, 1H), 7.37 (t, J = 8.5 Hz, 3H), 2.70 (s, 3H);

¹³C{¹H}NMR (125 MHz, CDCl₃): δ 177.0, 148.4, 146.0, 138.0,

134.8, 133.1, 132.7, 132.2, 130.9, 130.3, 128.7, 128.67, 127.1, 124.5,

123.2, 122.1, 120.0, 94.1, 93.5, 91.7, 87.7, 21.2; IR (KBr, cm⁻¹): υ

3103, 1646, 1512, 1350, 1270, 1009, 751, 677; HRMS (ESI-TOF) m/

z: [M + H]⁺Calcd for C₂₄H₁₆O₃N 366.1125; found 366.1125.

1-(2-(Phenylethynyl)phenyl)non-2-yn-1-one (1q, Scheme 8,

Table 2). Yellow gummy (yield = 406 mg, 83%); R_f= 0.63 in 5%

5,10,11-Trimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2d, Table

2). The reaction was carried out using 149 mg of corresponding aryl-

fused 1,6-diyn-3-one. Brown solid (yield = 127.2 mg, 75%); m.p. =

169−170 °C; R_f= 0.65 in 10% EtOAc/hexanes; ¹H NMR (500 MHz,

CDCl₃): δ 8.26 (d, J = 7.6 Hz, 1H), 7.87 (d, J = 7.7 Hz, 1H), 7.40−

7.31 (m, 6H), 7.18 (s, 1H), 7.16−7.08 (m, 3H), 6.76 (d, J = 6.9 Hz,

1H), 4.14 (s, 3H), 3.68 (s, 3H), 2.97 (s, 3H); ¹³C{¹H}NMR (125

MHz, CDCl₃): δ 157.5, 156.5, 143.0, 142.4, 139.0, 134.8, 133.9,

130.8, 130.4, 127.5, 127.3, 126.4, 126.1, 126.0, 124.9, 124.2, 122.9,

112.3, 111.4, 96.3, 90.6, 55.8, 51.3; IR (KBr, cm⁻¹): υ 2923, 1583,

1458, 1262, 1041, 765; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₆H₂₃O₃383.1642; found 383.1642.

1

EtOAc/hexanes; H NMR (500 MHz, CDCl₃): δ 8.12 (dd, J = 7.9,

1.0 Hz, 1H), 7.64−7.60 (m, 3H), 7.50 (t, J = 7.6 Hz, 1H), 7.41 (t, J =

7.7 Hz, 1H), 7.36−7.33 (m, 3H), 2.42 (t, J = 7.2 Hz, 2H), 1.62−1.55

(m, 2H), 1.43−1.36 (m, 2H), 1.32−1.22 (m, 4H), 0.88 (t, J = 7.0 Hz,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 177.6, 138.3, 134.2, 132.2,

131.9, 131.7, 128.6, 128.3, 127.8, 123.3, 122.8, 97.1, 95.1, 88.3, 80.7,

31.2, 28.6, 27.7, 22.4, 19.3, 14.0; IR (KBr, cm⁻¹): υ 2927, 1707, 1646,

1492, 1242, 1069, 754, 690; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd

for C₂₃H₂₃O 315.1743; found 315.1745.

9-Fluoro-5,11-dimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2e,

Table 2). The reaction was carried out using 112 mg of corresponding

aryl-fused 1,6-diyn-3-one. Brown solid (yield = 53.9 mg, 42%); m.p. =

Representative Procedure for the Synthesis of 5,11-

Dimethoxy-11-phenyl-11H-benzo[a]ﬂuorene 2a Is as Follows.

1

152−153 °C; R_f= 0.85% in 10% EtOAc/hexanes; H NMR (400

L

https://dx.doi.org/10.1021/acs.joc.0c02131

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

MHz, CDCl₃): δ 8.29 (d, J = 7.6 Hz, 1H), 7.76 (d, J = 7.9 Hz, 1H),

7.63 (s, 1H), 7.39−7.32 (m, 5H), 7.91 (d, J = 6.4 Hz, 2H), 7.16 (s,

1H), 7.04 (t, J = 8.1 Hz, 1H), 6.98 (d, J = 8.2 Hz, 1H), 4.15 (s, 3H),

2.91 (s, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 169.1, 157.9,

151.9, 142.9, 139.0, 136.7, 132.4, 130.7, 129.7, 128.3, 127.5, 127.2,

125.5, 125.3, 125.0, 124.2, 123.0, 120.4 (d, J = 8.6 Hz), 115.4 (d, J =

22.7 Hz), 112.2 (d, J = 23.3 Hz), 96.1, 55.8, 51.4; IR (KBr, cm⁻¹): υ

2926, 1707, 1582, 1397, 1219, 1072, 738, 696; HRMS (ESI-TOF) m/

z: [M + H]⁺Calcd for C₂₅H₂₀FO₂371.1442; found 371.1442.

3,5,11-Trimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2f, Table

2). The reaction was carried out using 110 mg of corresponding

aryl-fused 1,6-diyn-3-one. Pale yellow solid (yield = 91.4 mg, 73%);

126.9, 126.8, 126.5 (d, J = 8.1 Hz), 125.3, 125.2, 119.2, 117.4 (d, J =

25.1 Hz), 107.3, 97.2, 89.7, 58.8, 55.8, 51.2, 21.7, 15.7; IR (KBr,

cm⁻¹): υ 2924, 1591, 1457, 1202, 1072, 989, 808, 697; HRMS (ESI-

TOF) m/z: [M + H]⁺Calcd for C₂₆H₂₂FO₂385.1598; found

385.1597.

(4-Methoxy-2-propylnaphthalen-1-yl)(phenyl)methanone (4k,

Scheme 2). The reaction was carried out using 118 mg of

corresponding aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 95.3

mg, 76%); m.p. = 133−134 °C; R_f= 0.72 in 10% EtOAc/hexanes; ¹H

NMR (400 MHz, CDCl₃): δ 8.27 (d, J = 7.8 Hz, 1H), 7.82 (d, J = 7.1

Hz, 2H), 7.59−7.53 (m, 1H), 7.44−7.32 (m, 5H), 6.73 (s, 1H), 4.06

(s, 3H), 2.54 (t, J = 7.8 Hz, 2H), 1.68−1.59 (m, 2H), 0.86 (t, J = 7.3

Hz, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 200.4, 156.0, 138.5,

138.2, 133.6, 131.9, 129.8, 128.7, 128.3, 127.2, 125.0, 124.8, 124.0,

122.1, 105.2, 55.6, 36.4, 24.6, 14.2; IR (KBr, cm⁻¹): υ 2952, 1657,

1619, 1591, 1448, 1250, 1115, 903, 769, 613; HRMS (ESI-TOF) m/

z: [M + Na]⁺Calcd for C₂₁H₂₀O₂Na 327.1356; found 327.1355.

(2-Hexyl-4-methoxynaphthalen-1-yl)(phenyl)methanone (4l,

Scheme 2). The reaction was carried out using 100 mg of

corresponding aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 98.5

mg, 89.3%); m.p. = 156−157 °C; R_f= 0.66 in 5% EtOAc/hexanes; ¹H

NMR (500 MHz, CDCl₃): δ 8.27 (d, J = 8.6 Hz, 1H), 7.82 (d, J = 7.2

Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H), 7.44−7.39 (m, 4H), 7.37−7.33 (m,

1H), 6.73 (s, 1H), 4.06 (s, 3H), 2.55 (t, J = 8.0 Hz, 2H), 1.61−1.54

(m, 3H), 1.26−1.16 (m, 5H), 0.82 (t, J = 7.0 Hz, 3H); ¹³C{¹H}NMR

(100 MHz, CDCl₃): δ 200.4, 156.0, 138.5, 138.4, 133.5, 131.9, 129.8,

128.7, 128.2, 127.2, 124.9, 124.8, 123.9, 122.1, 105.1, 55.6, 34.4, 31.5,

31.3, 29.2, 22.5, 14.1; IR (KBr, cm⁻¹): υ 2924, 1663, 1582, 1376,

1242, 1107, 718, 688; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₄H₂₇O₂347.2006; found 347.2006.

Representative Procedure for the Synthesis of 10-Phenyl-

11H-benzo[b]ﬂuoren-11-one 3a Is as Follows. To a solution of

compound 1a (100 mg, 0.326 mmol, 1.0 equiv) in dichloromethane

solvent (1.5 mL), triﬂic acid (28.8 μL, 0.326 mmol, 1 equiv) was

charged at room temperature (25 °C) under a nitrogen atmosphere.

The reaction mixture was allowed to stir at room temperature under a

nitrogen atmosphere until the completion of the reaction. The

progress of the reaction was monitored by TLC. After that, it was

quenched with a saturated NaHCO₃solution. Then, it was extracted

using ethyl acetate and water. The combined organic layers were

washed with saturated brine solution and dried over anhydrous

Na₂SO₄. The solvent was evaporated under reduced pressure. The

crude product was puriﬁed by column chromatography (using silica

gel, EtOAc/hexanes eluent) to get pure 10-phenyl-11H-benzo[b]-

ﬂuoren-11-one (3a) as a yellow solid with 93% isolated yield (92.9

mg).

1

m.p. = 204−205 °C; R_f= 0.68 in 10% EtOAc/hexanes; H NMR

(500 MHz, CDCl₃): δ 7.72 (d, J = 9.1 Hz, 1H), 7.66 (d, J = 7.5 Hz,

1H), 7.60 (d, J = 2.6 Hz, 1H), 7.36−7.31 (m, 3H), 7.25 (d, J = 6.2

Hz, 1H), 7.21 (s, 1H), 7.21−7.13 (m, 4H), 7.02 (dd, J = 9.2, 2.7 Hz,

1H), 4.15 (s, 3H), 3.91 (s, 3H), 2.88 (s, 3H); ¹³C{¹H}NMR (125

MHz, CDCl₃): δ 157.3, 156.6, 148.9, 143.7, 141.2, 137.5, 133.0,

128.6, 128.2, 127.3, 127.0, 126.9, 126.1, 126.0, 125.4, 124.4, 119.8,

119.1, 101.7, 96.9, 89.8, 55.8, 55.3, 51.2; IR (KBr, cm⁻¹): υ 2929,

1586, 1478, 1211, 1081, 829, 752, 696; HRMS (ESI-TOF) m/z: [M +

H]⁺Calcd for C₂₆H₂₃O₃383.1642; found 383.1642.

3-Fuoro-5,11-dimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2g,

Table 2). The reaction was carried out using 85 mg of corresponding

aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 74.2 mg, 76%); m.p. =

1

206−207 °C; R_f= 0.75 in 5% EtOAc/hexanes; H NMR (500 MHz,

CDCl₃): δ 7.70 (d, J = 9.2 Hz, 1H), 7.59 (d, J = 2.6 Hz, 1H), , 7.55

(d, J = 7.6 Hz, 1H), 7.40−7.33 (m, 3H), 7.22 (d, J = 7.0 Hz, 2H),

7.20−7.10 (m, 5H), 4.14 (s, 3H), 2.90 (s, 3H); ¹³C{¹H}NMR (125

MHz, CDCl₃): δ 157.7, 149.4, 143.6, 141.0, 139.8, 132.6, 130.7,

128.6, 128.2, 127.8, 127.4, 126.9, 125.9, 125.4, 124.9, 124.4, 124.39,

123.0, 119.4, 96.3, 89.9, 55.8, 51.2; IR (KBr, cm⁻¹): υ 2911, 1589,

1452, 1170, 1069, 920, 745, 693; HRMS (ESI-TOF) m/z: [M + H]⁺

Calcd for C₂₅H₂₀FO₂371.1442; found 371.1441.

3,5,11-Trimethoxy-9-methyl-11-phenyl-11H-benzo[a]ﬂuorene

(2h, Table 2). The reaction was carried out using 100 mg of

corresponding aryl-fused 1,6-diyn-3-one. Brown solid (yield = 92.6

1

mg, 82%); m.p. = 255−256 °C; R_f= 0.61 in 5% EtOAc/hexanes; H

NMR (500 MHz, CDCl₃): δ 7.70 (d, J = 9.2 Hz, 1H), 7.59 (d, J = 2.6

Hz, 1H), 7.55 (d, J = 7.6 Hz, 1H), 7.35 (d, J = 7.0 Hz, 2H), 7.21−

7.13 (m, 5H), 7.07 (s, 1H), 7.01 (dd, J = 9.1, 2.6 Hz, 1H), 4.15 (s,

3H), 3.91 (s, 3H), 2.89 (s, 3H), 2.33 (s, 3H); ¹³C{¹H}NMR (125

MHz, CDCl₃): δ 157.1, 156.6, 149.1, 143.9, 138.6, 137.6, 137.2,

132.6, 129.3, 128.2, 126.8, 126.7, 126.2, 125.9, 125.4, 125.1, 119.7,

118.8, 101.7, 96.9, 89.7, 55.8, 55.3, 51.2, 21.6; IR (KBr, cm⁻¹): υ

2921, 1581, 1461, 1207, 1079, 816, 695, 556; HRMS (ESI-TOF) m/

z: [M + H]⁺Calcd for C₂₇H₂₅O₃397.1798; found 397.1799.

The reaction was carried out using 1g of 1a to obtain 3a (904 mg;

90% yield). m.p. = 216−217 °C; R_f= 0.60 in 10% EtOAc/hexanes;

¹H NMR (500 MHz, CDCl₃): δ 7.93 (s, 1H), 7.87 (d, J = 8.1 Hz,

9-Fluoro-3,5,11-trimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2i,

Table 2). The reaction was carried out using 70 mg of corresponding

aryl-fused 1,6-diyn-3-one. Oﬀ-white solid (yield = 35.9 mg, 45%);

m.p. = 254−255 °C; R_f= 0.50 in 5% EtOAc/hexanes; ¹H NMR (400

MHz, CDCl₃): 7.66 (d, J = 9.1 Hz, 1H), 7.56 (dd, J = 8, 4.8 Hz, 2H),

7.33−7.28 (m, 2H), 7.20−7.14 (m, 3H), 7.12 (s, 1H), 7.00 (d, J = 9.2

Hz, 2H), 6.94 (d, J = 8.2 Hz, 1H), 4.11 (s, 3H), 3.87 (s, 3H), 2.88 (s,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 164.0, 161.6, 157.3, 156.8,

151.4 (d, J = 27.6 Hz), 143.1, 137.0, 136.7, 132.7, 128.3, 127.2, 126.7,

126.1, 125.8, 125.3, 119.9 (d, J = 21.2 Hz), 115.4 (d, J = 90.7 Hz),

112.1 (d, J = 93.1 Hz), 101.7, 96.7, 89.5, 55.8, 55.3, 51.3; IR (KBr,

cm⁻¹): υ 2930, 1583, 1481, 1217, 1074, 815, 695; HRMS (ESI-TOF)

m/z: [M + H]⁺Calcd for C₂₅H₂₀FO₂401.1547; found 401.1532.

3-Fluoro-5,11-dimethoxy-9-methyl-11-phenyl-11H-benzo[a]-

ﬂuorene (2j, Table 2). The reaction was carried out using 120 mg of

corresponding aryl-fused 1,6-diyn-3-one. Brown solid (yield = 100.8

1H), 7.76 (d, J = 7.5 Hz, 1H), 7.64 (d, J = 4.4 Hz, 1H), 7.62 (d, J =

3.4 Hz, 1H), 7.58−7.52 (m, 5H), 7.39−7.35 (m, 3H), 7.32 (td, J =

7.4, 0.8 Hz, 1H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ 192.2, 144.1,

141.3, 138.5, 136.7, 136.4, 135.6, 134.7, 133.9, 129.7, 129.3, 129.25,

129.1, 128.8, 128.7, 128.1, 128.05, 126.9, 124.2, 120.7, 118.8; IR

(KBr, cm⁻¹): υ 2920, 1697, 1620, 1599, 1443, 1187, 1158, 951, 757,

719, 699; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₃H₁₅O

307.1117; found 307.1117.

10-(p-Tolyl)-11H-benzo[b]ﬂuoren-11-one (3b, Table 3). The

reaction was carried out using 100 mg of corresponding aryl-fused

1,6-diyn-3-one. Yellow solid (yield = 94.8 mg, 95%); m.p. = 286−287

°C; R_f= 0.56 in 10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃):

δ 7.92 (s, 1H), 7.87 (d, J = 8.1 Hz, 1H), 7.76 (d, J = 7.6 Hz, 1H), 7.68

(d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.55 (q, J = 7.4 Hz, 2H),

7.40−7.30 (m, 4H), 7.29 (s, 1H), 7.26 (d, J = 1.8 Hz, 1H), 2.50 (s,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 192.3, 144.0, 141.5, 138.5,

137.7, 136.7, 136.4, 134.7, 134.0, 132.4, 129.7, 129.5, 129.3, 129.2,

129.1, 128.9, 128.8, 128.7, 128.6, 126.7, 124.1, 120.7, 118.6, 21.5; IR

(KBr, cm⁻¹): υ 2915, 1797, 1621, 1601, 1468, 1108, 884, 866, 756,

718, 597; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₄H₁₇O

321.1274; found 321.1275.

1

mg, 74%); m.p. = 203−204 °C; R_f= 0.64 in 5% EtOAc/hexanes; H

NMR (500 MHz, CDCl₃): δ 7.92−7.84 (m, 2H), 7.81−7.77 (m, 1H),

7.59 (d, J = 7.6 Hz, 1H), 7.36 (d, J = 8.4 Hz, 2H), 7.22 (d, J = 3.8 Hz,

2H), 7.20−7.17 (m, 2H), 7.15−7.10 (m, 1H), 7.09 (s, 1H), 4.15 (s,

3H), 2.90 (s, 3H), 2.34 (s, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ

161.2, 159.2, 157.0, 149.5 (d, J = 99.8 Hz), 143.6, 139.2, 138.0 (d, J =

44.7 Hz), 132.5, 129.3 (d, J = 18.4 Hz), 128.2 (d, J = 7.3 Hz), 127.7,

M

https://dx.doi.org/10.1021/acs.joc.0c02131

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

10-(4-Ethylphenyl)-11H-benzo[b]ﬂuoren-11-one (3c, Table 3).

The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 96.2 mg, 96%); m.p. =

208−209 °C; R_f= 0.45 in 10% EtOAc/hexanes; ¹H NMR (500 MHz,

CDCl₃): δ 7.92 (s, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.76 (d, J = 7.5 Hz,

1H), 7.69 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.55 (q, J =

7.6 Hz, 2H), 7.40−7.35 (m, 3H), 7.34−7.29 (m, 3H), 2.81 (q, J = 7.6

Hz, 2H), 1.37 (t, J = 7.6 Hz, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃):

δ 192.4, 144.1, 143.9, 141.6, 138.5, 136.7, 136.4, 134.7, 134.1, 132.6,

129.6, 129.2, 128.8, 128.7, 127.6, 126.8, 124.2, 120.7, 118.6, 28.8,

15.4; IR (KBr, cm⁻¹): υ 2958, 1692, 1620, 1579, 1467, 1334, 1186,

1160, 955, 832, 760, 752, 597; HRMS (ESI-TOF) m/z: [M + H]⁺

Calcd for C₂₅H₁₉O 335.1430; found 335.1430.

7.47−7.36 (m, 5H), 7.14 (s, 1H), 5.95 (s, 2H), 5.69 (s, 1H);

¹³C{¹H}NMR (100 MHz, CDCl₃): δ 191.5, 153.2, 148.4, 142.6,

137.2, 136.9, 134.6, 133.3, 133.1, 131.8, 130.6, 129.7, 129.4, 128.8,

128.4, 127.0, 126.7, 124.5, 104.5, 104.3, 102.1; IR (KBr, cm⁻¹): υ

2918, 1693, 1621, 1493, 1451, 1298, 1269, 1028, 927, 818, 747, 727,

554; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₄H₁₅O₃

351.1016; found 351.1017.

8-Ethyl-10-phenyl-11H-benzo[b]ﬂuoren-11-one (3i, Table 3).

The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 89.2 mg, 89%); m.p. =

193−194 °C; R_f= 0.52 in 10% EtOAc/hexanes; ¹H NMR (400 MHz,

CDCl₃): δ 7.89 (s, 1H), 7.80 (d, J = 8.9 Hz, 1H), 7.74 (d, J = 7.5 Hz,

1H), 7.61 (d, J = 7.4 Hz, 1H), 7.58−7.52 (m, 4H), 7.44−7.37 (m,

4H), 7.33−7.28 (m, 1H), 2.67 (q, J = 7.5 Hz, 2H), 1.21 (t, J = 7.6 Hz,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 192.4, 144.2, 143.2, 140.9,

137.7, 136.3, 135.7, 135.1, 134.7, 134.0, 129.7, 129.6, 129.0, 128.8,

128.7, 128.1, 127.9, 127.1, 124.2, 120.6, 118.6, 29.1, 15.5; IR (KBr,

cm⁻¹): υ 2962, 1702, 1599, 1468, 1231, 1023, 958, 888, 762, 700,

600; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₅H₁₉O

335.1430; found 335.1432.

8-Fluoro-10-phenyl-11H-benzo[b]ﬂuoren-11-one (3j, Table 3).

The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 85.2 mg, 85%); m.p. =

220−221 °C; R_f= 0.45 in 10% EtOAc/hexanes; ¹H NMR (400 MHz,

CDCl₃): δ 7.92 (s, 1H), 7.86 (dd, J = 8.9, 5.7 Hz, 1H), 7.75 (d, J = 7.6

Hz, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.59−7.53 (m, 4H), 7.37−7.24 (m,

5H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 192.1, 161.3 (d, J = 245.8

Hz), 144.0, 140.5, 140.4, 138.0, 137.99, 136.1, 135.2 (d, J = 8.3 Hz),

135.0, 134.9, 133.5, 130.8 (d, J = 8.8 Hz), 129.5, 129.4, 129.3, 128.3,

124.3, 120.7, 118.6 (d, J = 24.6 Hz), 112.9 (d, J = 22.2 Hz); IR (KBr,

cm⁻¹): υ 3052, 1698, 1599, 1514, 1468, 1226, 1102, 875, 810, 758,

722, 597; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₃H₁₄FO

325.1023; found 325.1021.

2-Methoxy-10-(p-tolyl)-11H-benzo[b]ﬂuoren-11-one (3k, Table

3). The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 82 mg, 82%); m.p. = 265−

266 °C; R_f= 0.38 in 5% EtOAc/hexanes; ¹H NMR (400 MHz,

CDCl₃): δ 7.81 (d, J = 8.1 Hz, 1H), 7.77 (s, 1H), 7.66−7.62 (m, 2H),

7.53−7.49 (m, 1H), 7.36−7.31 (m, 3H), 7.26 (s, 2H), 7.12 (d, J = 2.3

Hz, 1H), 7.09 (dd, J = 8.3, 2.5 Hz, 1H), 3.85 (s, 3H), 2.49 (s, 3H);

¹³C{¹H}NMR (100 MHz, CDCl₃): δ 192.2, 161.0, 141.6, 138.7,

138.2, 137.7, 137.1, 137.0, 133.5, 132.5, 129.6, 129.2, 129.15, 128.9,

128.8, 128.5, 126.4, 121.9, 121.6, 117.4, 108.0, 55.7, 21.5; IR (KBr,

cm⁻¹): υ 2918, 1688, 1576, 1485, 1438, 1277, 1026, 1010, 792, 764,

586; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₅H₁₉O₂

351.1380; found 351.1380.

10-(4-Fluorophenyl)-11H-benzo[b]ﬂuoren-11-one (3d, Table 3).

The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 97 mg, 97%); m.p. = 192−

1

193 °C; R_f= 0.47 in 10% EtOAc/hexanes; H NMR (500 MHz,

CDCl₃): δ 7.95 (s, 1H), 7.89 (d, J = 8.1 Hz, 1H), 7.77 (d, J = 7.6 Hz,

1H), 7.65−7.60 (m, 2H), 7.60−7.54 (m, 2H), 7.42−7.38 (m, 1H),

7.38−7.32 (m, 3H), 7.26−7.22 (m, 2H); ¹³C{¹H}NMR (125 MHz,

CDCl₃): δ 192.3, 163.7, 161.8, 144.1, 140.2, 138.5, 136.8, 136.3,

134.9, 131.5, 131.4 (d, J = 31.8 Hz), 131.2 (d, J = 14.1 Hz), 129.3,

128.9, 128.85, 128.8, 127.0, 124.3, 120.8, 119.0, 115.2 (d, J = 86.1

Hz); IR (KBr, cm⁻¹): υ 2922, 1701, 1623, 1597, 1499, 1208, 1093,

952, 839, 760, 720, 595; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₃H₁₄FO 325.1023; found 325.1025.

10-(3-Methoxyphenyl)-11H-benzo[b]ﬂuoren-11-one (3e, Table

3). The reaction was carried out using 107 mg of corresponding

aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 93.1 mg, 87%); m.p. =

238−239 °C; R_f= 0.47 in 10% EtOAc/hexanes; ¹H NMR (500 MHz,

CDCl₃): δ 7.93 (s, 1H), 7.87 (d, J = 8.0 Hz, 1H), 7.76 (d, J = 7.5 Hz,

1H), 7.66 (d, J = 8.4 Hz, 1H), 7.63 (d, J = 7.4 Hz, 1H), 7.60−7.52

(m, 2H), 7.46 (t, J = 7.9 Hz, 1H), 7.40−7.36 (m, 1H), 7.33 (t, J = 7.5

Hz, 1H), 7.08−7.05 (m, 1H), 6.96 (d, J = 7.5 Hz, 1H), 6.92 (s, 1H),

3.85 (s, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ 192.1, 159.5,

144.1, 141.0, 138.5, 137.0, 136.7, 136.4, 134.7, 133.8, 129.2, 129.18,

129.1, 128.8, 128.76, 128.6, 126.9, 124.3, 122.0, 120.7, 118.8, 115.3,

113.6, 55.3; IR (KBr, cm⁻¹): υ 2916, 1701, 1622, 1581, 1466, 1335,

1248, 1173, 1032, 957, 762, 700; HRMS (ESI-TOF) m/z: [M + H]⁺

Calcd for C₂₄H₁₇O₂337.1223; found 337.1225.

2-Methoxy-10-phenyl-11H-benzo[b]ﬂuoren-11-one (3f, Table 3).

The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 85.8 mg, 86%); m.p. =

240−241 °C; R_f= 0.55 in 10% EtOAc/hexanes; ¹H NMR (500 MHz,

CDCl₃): δ 8.17 (s, 1H), 7.92−7.89 (m, 1H), 7.62−7.56 (m, 3H),

7.44−7.38 (m, 5H), 7.24 (d, J = 2.6 Hz, 1H), 6.72 (dd, J = 8.5, 2.6

Hz, 1H), 6.22 (d, J = 8.5 Hz, 1H), 3.81 (s, 3H); ¹³C{¹H}NMR (125

MHz, CDCl₃): δ 193.2, 160.4, 138.3, 138.1, 137.6, 137.2, 135.6,

133.2, 133.1, 132.9, 130.8, 129.8, 129.3, 129.0, 128.3, 126.9, 126.5,

125.3, 124.9, 121.5, 108.1, 55.7; IR (KBr, cm⁻¹): υ 2921, 1703, 1602,

1485, 1277, 1118, 1017, 820, 745, 698, 591; HRMS (ESI-TOF) m/z:

[M + H]⁺Calcd for C₂₄H₁₇O₂337.1223; found 337.1224.

2-Fluoro-10-phenyl-11H-benzo[b]ﬂuoren-11-one (3g, Table 3).

The reaction was carried out using 100 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 86.2 mg, 86%); m.p. =

294−295 °C; R_f= 0.47 in 10% EtOAc/hexanes; ¹H NMR (500 MHz,

CDCl₃): δ 7.88 (s, 1H), 7.86 (d, J = 8.1 Hz, 1H), 7.73 (dd, J = 8.3, 4.4

Hz, 1H), 7.62 (d, J = 8.5 Hz, 1H), 7.57−7.51 (m, 4H), 7.40−7.35 (m,

3H), 7.28 (dd, J = 7.4, 2.4 Hz, 1H), 7.26−7.22 (m, 1H); ¹³C{¹H}-

NMR (125 MHz, CDCl₃): δ 190.9, 164.8, 162.8, 141.9, 140.0, 138.5

(d, J = 29.4 Hz), 137.8, 136.8, 135.4, 133.6, 129.6, 129.2, 129.1, 128.9,

128.8, 128.2, 127.0, 122.2 (d, J = 31.0 Hz), 121.5 (d, J = 94.3 Hz),

118.5, 111.3 (d, J = 91.7 Hz); IR (KBr, cm⁻¹): υ 2923, 1698, 1603,

1476, 1261, 1149, 1032, 924, 811, 777, 700, 581; HRMS (ESI-TOF)

m/z: [M + H]⁺Calcd for C₂₃H₁₄FO 325.1023; found 325.1025.

10-Phenyl-11H-benzo[6,7]ﬂuoreno[2,3-d][1,3]dioxol-11-one (3h,

Table 3). The reaction was carried out using 100 mg of corresponding

aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 92.4 mg, 92%); m.p. =

291−292 °C; R_f= 0.27 in 10% EtOAc/hexanes; ¹H NMR (400 MHz,

CDCl₃): δ 8.09 (s, 1H), 7.89 (d, J = 6.9 Hz, 1H), 7.63−7.57 (m, 3H),

10-(4-Fluorophenyl)-2-methoxy-11H-benzo[b]ﬂuoren-11-one

(3l, Table 3). The reaction was carried out using 100 mg of

corresponding aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 84.3

1

mg, 84%); m.p. = 281−282 °C; R_f= 0.42 in 5% EtOAc/hexanes; H

NMR (500 MHz, CDCl₃): δ 7.83 (d, J = 8.1 Hz, 1H), 7.79 (s, 1H),

7.65 (d, J = 8.3 Hz, 1H), 7.57 (d, J = 8.4 Hz, 1H), 7.55−7.51 (m,

1H), 7.37−7.32 (m, 3H), 7.23 (t, J = 8.8 Hz, 2H), 7.14−7.09 (m,

2H), 3.85 (s, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ 192.2, 163.7,

161.5 (d, J = 334.3 Hz), 140.2, 138.4 (d, J = 332.6 Hz), 137.0, 133.2

(d, J = 107.1 Hz), 131.5, 129.8, 129.4 (d, J = 76.6 Hz), 128.8 (d, J =

58.3 Hz), 126.6, 125.0, 121.8 (d, J = 51.2 Hz), 121.5, 117.7, 115.3,

115.1, 111.3, 108.0, 55.8; IR (KBr, cm⁻¹): υ 2993, 1686, 1573, 1486,

1438, 1294, 1217, 1154, 1011, 837, 766, 574; HRMS (ESI-TOF) m/

z: [M + H]⁺Calcd for C₂₄H₁₆FO₂355.1129; found 355.1128.

2-Fluoro-10-(p-tolyl)-11H-benzo[b]ﬂuoren-11-one (3m, Table 3).

The reaction was carried out using 118 mg of corresponding aryl-

fused 1,6-diyn-3-one. Yellow solid (yield = 91.8 mg, 78%); m.p. =

284−285 °C; R_f= 0.48 in 5% EtOAc/hexanes; ¹H NMR (400 MHz,

CDCl₃): δ 8.05 (s, 1H), 7.78 (d, J = 8.2 Hz, 1H), 7.61−7.57 (m, 2H),

7.37 (dd, J = 7.7, 1.7 Hz, 2H), 7.28 (d, J = 1.5 Hz, 1H), 7.13 (s, 2H),

5.94 (s, 2H), 5.64 (s, 1H), 2.36 (s, 3H); ¹³C{¹H}NMR (125 MHz,

CDCl₃): δ191.5, 150.7 (d, J = 605.5 Hz), 142.5, 139.2, 137.4, 137.0,

134.9, 132.8, 132.5, 131.9, 131.2, 130.5, 129.8, 129.5, 129.3, 128.7,

128.4, 125.3 (d, J = 256.1 Hz), 117.4, 104.4 (d, J = 33 Hz), 102.0,

N

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22.0; IR (KBr, cm⁻¹): υ 2915, 1691, 1592, 1262, 1031, 772, 568;

HRMS (ESI-TOF) m/z: [M + Na]⁺Calcd for C₂₄H₁₅FONa

361.0999, found 361.0998.

Hz, 1H), 7.69 (d, J = 7.6 Hz, 1H), 7.59 (dd, J = 8.3, 1.2 Hz, 2H),

7.53−7.45 (m, 2H), 7.41−7.37 (m, 1H), 7.31−7.27 (m, 2H), 7.23 (t,

J = 7.8 Hz, 2H), 6.89 (t, J = 8.8 Hz, 2H), 6.80 (s, 1H), 4.30 (q, J =

13.9, 6.9 Hz, 2H), 1.61 (t, J = 7.0 Hz, 3H); ¹³C{¹H}NMR (125 MHz,

CDCl₃): δ 199.8, 155.6, 138.6, 137.4, 137.0, 133.1, 132.0, 131.1 (d, J

= 32.3 Hz), 129.7, 129.6, 128.4, 128.3, 127.9, 125.5 (d, J = 187.5 Hz),

124.7, 122.4, 115.1 (d, J = 85.9 Hz), 106.2, 100.0, 64.1, 14.9; IR (KBr,

cm⁻¹): υ 2922, 1656, 1591, 1507, 1381, 1219, 1093, 834, 721, 692;

HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for C₂₅H₂₀FO₂371.1442;

found 371.1443.

(4-Ethoxy-2-(4-ethylphenyl)naphthalen-1-yl)(phenyl)methanone

(4d, Table 4). The reaction was carried out using 122 mg of

corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Yellow solid (yield = 100.2 mg, 72%); m.p. = 155−156 °C; R_f= 0.65

in 10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 8.39 (d, J =

7.8 Hz, 1H), 7.70 (d, J = 8.1 Hz, 1H), 7.60 (d, J = 8.0 Hz, 2H), 7.48−

7.39 (m, 2H), 7.31 (t, J = 7.4 Hz, 1H), 7.25 (d, J = 8.1 Hz, 2H), 7.17

(t, J = 7.7 Hz, 2H), 7.01 (d, J = 6.2 Hz, 2H), 6.85 (s, 1H), 4.25 (q, J =

6.9 Hz, 2H), 2.51 (q, J = 7.5 Hz, 2H), 1.55 (t, J = 6.9 Hz, 3H), 1.12

(t, J = 7.6 Hz, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 199.9,

155.4, 143.4, 138.7, 138.6, 138.2, 132.7, 132.0, 129.5, 129.3, 128.1,

127.6, 127.56, 125.3, 125.2, 124.5, 122.3, 122.2, 106.4, 164.0, 28.4,

15.3, 14.8; IR (KBr, cm⁻¹): υ 2924, 1662, 1592, 1386, 1174, 1140,

856, 797, 724, 626; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₇H₂₅O₂381.1849; found 381.1849.

10-(4-Fluorophenyl)-2-methoxy-11H-benzo[b]ﬂuoren-11-one

(3n, Table 3). The reaction was carried out using 100 mg of

corresponding aryl-fused 1,6-diyn-3-one. Yellow solid (yield = 96.8

mg, 97%); m.p. = 234−235 °C; R_f= 0.48 in 10% EtOAc/hexanes; ¹H

NMR (400 MHz, CDCl₃): δ 7.88 (s, 1H), 7.79 (d, J = 8.2 Hz, 1H),

7.72 (d, J = 7.4 Hz, 1H), 7.60 (d, J = 7.4 Hz, 1H), 7.54 (t, J = 7.4 Hz,

1H), 7.41 (d, J = 8.3 Hz, 1H), 7.37−7.27 (m, 4H), 7.25−7.20 (m,

2H), 7.67 (q, J = 7.5 Hz, 2H), 1.20 (t, J = 7.6 Hz, 3H); ¹³C{¹H}NMR

(100 MHz, CDCl₃): δ 192.4, 162.8 (d, J = 245 Hz), 144.2, 143.3,

139.7, 137.7, 136.2, 135.1, 134.8, 134.0, 131.41 (d, J = 8.2 Hz),

131.39, 129.8, 129.0, 128.9, 128.8, 126.7, 124.2, 120.6, 118.8, 115.2

(d, J = 21.3 Hz), 29.1, 15.5; IR (KBr, cm⁻¹): υ 2959, 1700, 1599,

1508, 1468, 1185, 957, 886, 759, 725, 599; HRMS (ESI-TOF) m/z:

[M + H]⁺Calcd for C₂₅H₁₈FO 353.1336, found 353.1337.

6-Methyl-9-nitro-10-phenyl-11H-benzo[b]ﬂuoren-11-one (3o,

Table 3). The reaction was carried out using 100 mg of corresponding

aryl-fused 1,6-diyn-3-one. Pale yellow solid (yield = 77 mg, 77%);

1

m.p. = 262−263 °C; R_f= 0.26 in 10% EtOAc/hexanes; H NMR

(400 MHz, CDCl₃): δ 8.41 (dd, J = 8.5, 2.5 Hz, 1H), 8.32 (s, 1H),

8.22 (d, J = 2.4 Hz, 1H), 8.01 (d, J = 7.7 Hz, 1H), 7.79 (d, J = 7.0 Hz,

1H), 7.69 (d, J = 8.5 Hz, 1H), 7.58−7.48 (m, 2H), 7.33−7.22 (m,

3H), 6.22 (d, J = 7.5 Hz, 1H), 2.17 (s, 3H); ¹³C{¹H}NMR (100

MHz, CDCl₃): δ 192.7, 147.1, 145.6, 144.3, 138.4, 136.5, 135.7,

135.2, 133.6, 132.6, 131.7, 131.3, 130.9, 129.7, 129.3, 127.4, 126.1,

125.9, 125.2, 124.7, 123.7, 122.7, 20.0; IR (KBr, cm⁻¹): υ 2921, 1705,

1513, 1343, 1110, 901, 731; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd

for C₂₄H₁₆NO₃366.1125; found 366.1126.

(4-Ethoxy-2-(3-methoxyphenyl)naphthalen-1-yl)(phenyl)-

methanone (4e, Table 4). The reaction was carried out using 102 mg

of corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Brown solid (yield = 92.5 mg, 80%); m.p. = 203−204 °C; R_f= 0.58 in

10% EtOAc/hexanes; ¹H NMR (500 MHz, CDCl₃): δ 8.35 (d, J = 8.3

Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.37 (t, J = 7.0 Hz, 1H), 7.32 (d, J

= 7.0 Hz, 1H), 7.30 (d, J = 2.5 Hz, 1H), 7.24 (s, 1H), 7.22 (d, J = 7.6

Hz, 2H), 7.19 (d, J = 7.7 Hz, 2H), 7.10 (d, J = 6.9 Hz, 2H), 6.77 (dd,

J = 8.2, 2.4 Hz, 1H), 5.21 (s, 1H), 4.38 (q, J = 7.0 Hz, 2H), 3.90 (s,

3H), 1.63 (t, J = 7.0 Hz, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ

159.5, 155.7, 142.7, 142.4, 142.1, 139.2, 135.6, 131.0, 128.8, 127.9,

126.8, 126.6, 126.0, 125.3, 124.5, 124.3, 123.3, 112.7, 104.8, 97.3,

64.1, 55.6, 52.9, 14.9; IR (KBr, cm⁻¹): υ 2979, 1606, 1583, 1476,

1425, 1234, 1204, 1136, 1029, 739, 701, 626; HRMS (ESI-TOF) m/

z: [M + H]⁺Calcd for C₂₆H₂₃O₃383.1642; found 383.1643.

(4-Ethoxy-6-ﬂuoro-2-phenylnaphthalen-1-yl)(phenyl)-

methanone (4f, Table 4). The reaction was carried out using 85 mg

of corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Yellow solid (yield = 66.6 mg, 69%); m.p. = 154−155 °C; R_f= 0.75 in

Representative Procedure for the Synthesis of (4-Methoxy-

2-phenylnaphthalen-1-yl)(phenyl)methanone 4a Is as Fol-

lows. To a solution of compound 1a (100 mg, 0.326 mmol, 1.0

equiv) in dichloromethane solvent (1.5 mL), trimethyl orthoformate

(35.7 μL, 0.326 mmol, 1.0 equiv) and AgBF₄(3.2 mg, 0.0163 mmol,

0.05 equiv) were charged sequentially at room temperature (25 °C)

under a nitrogen atmosphere. The reaction mixture was allowed to stir

at room temperature under a nitrogen atmosphere until the

completion of the reaction. The progress of the reaction was

monitored by TLC. After that, the solvent was removed under

reduced pressure and (4-methoxy-2-phenylnaphthalen-1-yl)(phenyl)-

methanone (4a) was isolated by column chromatography (using silica

gel, EtOAc/hexanes eluent) as a yellow solid with 70% isolated yield

(77.6 mg); m.p. = 133−134 °C; R_f= 0.41 in 10% EtOAc/hexanes; ¹H

NMR (400 MHz, CDCl₃): δ 8.30 (d, J = 8.2 Hz, 1H), 7.67 (d, J = 8.2

Hz, 1H), 7.55 (d, J = 8.2 Hz, 2H), 7.48−7.38 (m, 2H), 7.29 (d, J =

7.9 Hz, 3H), 7.20−7.08 (m, 5H), 6.81 (s, 1H), 4.02 (s, 3H); IR (KBr,

cm⁻¹): υ 2964, 1658, 1581, 1445, 1383, 1220, 1097, 866, 775, 695,

628; HRMS (ESI-TOF) m/z: [M + Na]⁺Calcd for C₂₄H₁₈O₂Na

361.1199; found 361.1199.

(4-Ethoxy-2-phenylnaphthalen-1-yl)(phenyl)methanone (4b,

Table 4). The reaction was carried out using 100 mg of corresponding

aryl-fused 1,6-diyn-3-one and triethyl orthoformate. Yellow solid

(yield = 91 mg, 79%); the robustness of the reaction was checked by

doing the reaction with 1g of 1a to obtain 4b (823 mg; 72% yield).

m.p. = 235−236 °C; R_f= 0.5 in 10% EtOAc/hexanes; ¹H NMR (400

MHz, CDCl₃): δ 8.41 (d, J = 9 Hz, 1H), 7.73 (d, J = 8.1 Hz, 1H),

7.62 (d, J = 7.4 Hz, 2H), 7.54−7.45 (m, 2H), 7.40−7.33 (m, 3H),

7.25−7.15 (m, 5H), 6.87 (s, 1H), 4.30 (q, J = 7.0 Hz, 2H), 1.61 (t, J =

6.9 Hz, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 199.9, 155.5,

140.9, 138.6, 132.9, 132.0, 129.6, 129.4, 128.2, 128.15, 127.7, 127.4,

125.5, 125.3, 124.6, 122.3, 106.3, 64.0, 14.9; IR (KBr, cm⁻¹): υ 2970,

1655, 1586, 1473, 1380, 1223, 1094, 866, 759, 690, 632; HRMS (ESI-

TOF) m/z: [M + Na]⁺Calcd for C₂₅H₂₀O₂Na 375.1356; found

375.1356.

1

10% EtOAc/hexanes; H NMR (400 MHz, CDCl₃): δ 7.99 (dd, J =

10.4, 2.7 Hz, 1H), 7.72 (dd, J = 9.3, 5.3 Hz, 1H), 7.58 (dd, J = 4.3, 1.3

Hz, 2H), 7.39−7.34 (m, 1H), 7.34−7.30 (m, 2H), 7.25−7.15 (m,

5H), 6.88 (s, 1H), 4.29 (q, J = 7.0 Hz, 2H), 1.60 (t, J = 7.0 Hz, 3H);

¹³C{¹H}NMR (100 MHz, CDCl₃): δ 199.5, 161.8, 159.4, 154.9 (d, J

= 20 Hz), 140.6, 138.5, 138.0, 133.1, 129.6, 129.4, 129.0, 128.23,

128.2, 127.9 (d, J = 34.6 Hz), 127.5, 125.9 (d, J = 44.2 Hz), 117.7 (d,

J = 124.4 Hz), 107.1, 106 (d, J = 89.6 Hz), 64.2, 14.8; IR (KBr,

cm⁻¹): υ 2979, 1645, 1592, 1508, 1460, 1222, 1191, 1022, 872, 792,

715, 584; HRMS (ESI-TOF) m/z: [M + Na]⁺Calcd for

C₂₅H₁₉FO₂Na 393.1261; found 393.1261.

(4-Ethoxy-6-methoxy-2-(p-tolyl)naphthalen-1-yl)(phenyl)-

methanone (4g, Table 4). The reaction was carried out using 100 mg

of corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Yellow solid (yield = 88.2 mg, 78%); m.p. = 148−149 °C; R_f= 0.74 in

10% EtOAc/hexanes; ¹H NMR (500 MHz, CDCl₃): δ 7.56 (d, J = 2.6

Hz, 1H), 7.51 (t, J = 9.3 Hz, 3H), 7.25 (t, J = 7.4 Hz, 1H), 7.14−7.08

(m, 4H), 7.00 (dd, J = 9.2, 2.6 Hz, 1H), 6.90 (d, J = 8.0 Hz, 2H), 6.75

(s, 1H), 4.19 (q, J = 6.9 Hz, 2H), 3.84 (s, 3H), 2.13 (s, 3H), 1.48 (t, J

= 7.0 Hz, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 200.0, 157.4,

134.4, 138.6, 138.0, 136.9, 136.1, 132.9, 129.6, 129.2, 128.9, 128.1,

128.08, 127.3, 127.0, 125.8, 119.8, 107.0, 100.8, 64.0, 55.4, 21.1, 14.9;

IR (KBr, cm⁻¹): υ 2917, 1651, 1593, 1506, 1384, 1280, 1219, 1052,

1024, 814, 724, 629; HRMS (ESI-TOF) m/z: [M + Na]⁺Calcd for

C₂₂H₂₄O₃Na 419.1618; found 419.1618.

(4-Ethoxy-2-(4-ﬂuorophenyl)naphthalen-1-yl)(phenyl)-

methanone (4c, Table 4). The reaction was carried out using 100 mg

of corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Yellow solid (yield = 71.2 mg, 62%); m.p. = 165−166 °C; R_f= 0.52 in

10% EtOAc/hexanes; ¹H NMR (500 MHz, CDCl₃): δ 8.39 (d, J = 7.3

O

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(4-Ethoxy-2-(4-ﬂuorophenyl)-6-methoxynaphthalen-1-yl)-

(phenyl)methanone (4h, Table 4). The reaction was carried out

using 70 mg of corresponding aryl-fused 1,6-diyn-3-one and triethyl

orthoformate. Yellow solid (yield = 55.6 mg, 70%); m.p. = 146−147

°C; R_f= 0.39 in 5% EtOAc/hexanes; ¹H NMR (500 MHz, CDCl₃): δ

7.65 (d, J = 2.7 Hz, 1H), 7.59 (d, J = 9.2 Hz, 1H), 7.56 (d, J = 7.2 Hz,

2H), 7.36 (t, J = 7.4 Hz, 1H), 7.28−7.23 (m, 2H), 7.20 (t, J = 7.8 Hz,

2H), 7.11 (dd, J = 9.2, 2.7 Hz, 1H), 6.86 (t, J = 8.7 Hz, 2H), 6.78 (s,

1H), 4.28 (q, J = 7.0 Hz, 2H), 3.94 (s, 3H), 1.59 (t, J = 7.0 Hz, 3H);

¹³C{¹H}NMR (125 MHz, CDCl₃): δ 199.8, 163.1, 161.1, 157.7,

154.6, 138.6, 137.01 (d, J = 13.3 Hz), 135.0, 133.1, 131.0 (d, J = 32.3

Hz), 129.6, 128.3, 127.9 (d, J = 556.0 Hz), 127.0, 126.0, 120.1, 115.1

(d, J = 85.8 Hz), 106.8, 100.9, 64.1, 55.4, 14.9; IR (KBr, cm⁻¹): υ

2933, 1662, 1592, 1506, 1382,1218, 1163, 1051, 841, 741, 623;

HRMS (ESI-TOF) m/z: [M + Na]⁺Calcd for C₂₆H₂₁FO₃Na

423.1367; found 423.1368.

(R)-11-Methoxy-11-phenyl-11H-benzo[a]ﬂuoren-5-ol (5a,

Scheme 7). To a solution of benzo[a]ﬂuorene 2a (24 mg, 0.068

mmol) in CH₂Cl₂(1 mL) solvent under a nitrogen atmosphere at 0

°C, BBr₃(136 μL, 0.136 mmol, 1 M BBr₃in CH₂Cl₂) was added and

the reaction was allowed to stir at room temperature. Completion of

the reaction was monitored by TLC, and the reaction mixture was

quenched using saturated NaHCO₃solution and extracted with

EtOAc. After that, the combined organic layer was washed with

saturated NaCl solution and dried over anhydrous Na₂SO₄. The

solvent was evaporated under reduced pressure and ﬁnally, the crude

product was puriﬁed by column chromatography (silica gel, hexanes/

EtOAc) to get pure 11-methoxy-11-phenyl-11H-benzo[a]ﬂuoren-5-ol

5a (15.6 mg, 68%). Red solid; m.p. = 212−213 °C; R_f= 0.20 in 5%

EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 8.27 (d, J = 7.7 Hz,

1H), 7.75 (d, J = 7.5 Hz, 1H), 7.68 (d, J = 7.5 Hz, 1H), 7.41(d, J = 6.8

Hz, 2H), 7.38−7.31 (m, 5H), 7.24 (d, J = 7.5 Hz, 2H), 7.21 (s, 1H),

7.17 (s, 1H), 4.13 (s, 3H), 2.49 (bs, 1H); ¹³C{¹H}NMR (100 MHz,

CDCl₃): δ 157.7, 152.8, 143.1, 139.7, 138.3, 136.0, 130.1, 128.7,

128.4, 128.0, 127.3, 127.0, 126.2, 125.1, 124.9, 124.5, 124.0, 123.1,

119.6, 96.4, 84.2, 55.9; IR (KBr, cm⁻¹): υ 2923, 1661, 1584, 1448,

1219, 1141, 756, 699; HRMS (ESI-TOF) m/z: [M - H]⁺Calcd for

C₂₄H₁₇O₂337.1229; found 337.1225.

(4-Ethoxy-6-ﬂuoro-2-(p-tolyl)naphthalen-1-yl)(phenyl)-

methanone (4i, Table 4). The reaction was carried out using 94 mg

of corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Yellow solid (yield = 78.2 mg, 73%); m.p. = 172−173 °C; R_f= 0.78 in

1

10% EtOAc/hexanes; H NMR (500 MHz, CDCl₃): δ 7.90 (dd, J =

10.4, 2.6 Hz, 1H), 7.61 (dd, J = 9.2, 5.4 Hz, 1H), 7.52 (d, J = 8.1 Hz,

2H), 7.28 (t, J = 7.4 Hz, 1H), 7.16−7.09 (m, 5H), 6.92 (d, J = 7.9 Hz,

2H), 6.78 (s, 1H), 4.19 (q, J = 7.0 Hz, 2H), 2.15 (s, 3H), 1.49 (t, J =

7.0 Hz, 3H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ 199.6, 161.5,

159.5, 154.8 (d, J = 19.6 Hz), 138.4, 137.9 (d, J = 8.6 Hz), 137.7,

137.3, 133.0, 129.6, 129.2, 129.0, 128.2, 128.0, 127.8 (d, J = 33.8 Hz),

125.7 (d, J = 35.7 Hz), 117.6 (d, J = 99.6 Hz), 107.3, 106.4 (d, J =

89.4 Hz), 64.1, 21.1, 14.8; IR (KBr, cm⁻¹): υ 2920, 1696, 1651, 1600,

1509, 1447, 1224, 1186, 1025, 873, 746, 713, 659; HRMS (ESI-TOF)

m/z: [M + Na]⁺Calcd for C₂₆H₂₁FO₂Na 407.1418; found 407.1417.

(4-Ethoxy-2-phenylnaphthalen-1-yl)(2-methyl-5-nitrophenyl)-

methanone (4j, Table 4). The reaction was carried out using 100 mg

of corresponding aryl-fused 1,6-diyn-3-one and triethyl orthoformate.

Yellow solid (yield = 39.2 mg, 35%); m.p. = 164−165 °C; R_f= 0.71 in

10% EtOAc/hexanes; ¹H NMR (400 MHz, CDCl₃): δ 8.47−8.44 (m,

1H), 8.07−8.03 (m, 1H), 7.92 (dd, J = 8.4, 2.5 Hz, 1H), 7.83 (d, J =

2.4 Hz, 1H), 7.63−7.55 (m, 2H), 7.17−7.09 (m, 6H), 6.77 (s, 1H),

4.30 (q, J = 7.0 Hz, 2H), 2.47 (s, 3H), 1.61 (t, J = 7.0 Hz, 3H);

¹³C{¹H}NMR (100 MHz, CDCl₃): δ 198.9, 156.5, 146.5, 145.4,

11-Phenyl-5H-benzo[a]ﬂuoren-5-one (6a, Scheme 7). To a

solution of naphthyl ketone (4a) (64 mg, 0.19 mmol) in CH₂Cl₂

(3 mL) solvent under a nitrogen atmosphere at 0 °C, BBr₃(0.4 mL,

0.38 mmol, 1 M BBr₃in CH₂Cl₂) was added and the reaction was

allowed to stir at room temperature. Completion of the reaction was

monitored by TLC, and the reaction mixture was quenched using

saturated NaHCO₃solution and extracted with EtOAc. After that, the

combined organic layer was washed with saturated NaCl solution and

dried over anhydrous Na₂SO₄. The solvent was evaporated under

reduced pressure, and ﬁnally, the crude product was puriﬁed by

column chromatography (silica gel, hexanes/EtOAc) to get pure 11-

phenyl-5H-benzo[a]ﬂuoren-5-one 6a (33 mg, 57%). Dark red solid;

1

m.p. = 190−191 °C; R_f= 0.31 in 10% EtOAc/hexanes; H NMR

(500 MHz, CDCl₃): δ 8.02 (d, J = 7.8 Hz, 1H), 7.52−7.48 (m, 2H),

7.47−7.43 (m, 2H), 7.42−7.39 (m, 2H), 7.22−7.18 (m, 2H), 7.14−

7.09 (m, 3H), 6.80 (s, 2H); ¹³C{¹H}NMR (125 MHz, CDCl₃): δ

186.5, 153.0, 149.0, 146.1, 135.8, 134.4, 133.5, 132.3, 130.9, 130.5,

129.4, 129.2, 128.2, 127.9, 127.6, 125.2, 122.4, 122.0, 121.3; IR (KBr,

cm⁻¹): υ 2921, 1583, 1446, 1374, 1217, 1096, 1026, 741, 700; HRMS

(ESI-TOF) m/z: [M + H]⁺Calcd for C₂₃H₁₅O 307.1117; found

307.1118.

141.3, 140.8, 140.2, 132.2, 129.0, 128.5, 128.2, 127.9, 127.7, 125.9,

125.4, 125.2, 125.0, 124.8, 122.6, 106.2, 64.2, 29.7, 21.4, 14.8; IR

(KBr, cm⁻¹): υ 2926, 1655, 1509, 1340, 1216, 1092, 750, 638; HRMS

(ESI-TOF) m/z: [M + H]⁺Calcd for C₂₆H₂₂FO₂412.1543; found

412.1543.

3-Fluoro-11-phenyl-5H-benzo[a]ﬂuoren-5-one (6b, Scheme 7).

The reaction was carried out using 50 mg of naphthyl ketone (4f).

Dark red solid (yield = 24.7 mg, 56%); m.p. = 216−217 °C; R_f= 0.51

5,11-Dimethoxy-11-phenyl-11H-benzo[a]ﬂuorene (2a-d₆,

Scheme 6). The reaction was carried out using 50 mg of

corresponding aryl-fused 1,6-diyn-3-one. Yellow gummy (yield =

1

in 10% EtOAc/hexanes; H NMR (500 MHz, CDCl₃): δ 7.70 (dd, J

1

= 9.2, 2.8 Hz, 1H), 7.56−7.48 (m, 3H), 7.46−7.44 (m, 1H), 7.42 (d, J

= 8.1 Hz, 2H), 7.23−7.18 (m, 1H), 7.13 (dd, J = 5.3, 3.1 Hz, 2H),

6.88−6.81 (m, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 185.4,

163.2, 161.2, 153.4, 149.0, 145.9, 135.5, 134.0, 132.6 (d, J = 6.8 Hz),

131.0, 129.8 (d, J = 3.4 Hz), 129.4, 129.3, 128.4, 128.2, 127.4 (d, J =

7.2 Hz), 127.1, 122.5, 122.1, 121.0, 119.8 (d, J = 22.3 Hz), 113.6 (d, J

= 22.7 Hz); IR (KBr, cm⁻¹): υ 2920, 1627, 1553, 1439, 1303, 1272,

1049, 758, 700, 576; HRMS (ESI-TOF) m/z: [M + H]⁺Calcd for

C₂₃H₁₄FO 325.1023; found 325.1022.

32.5 mg, 56%); R_f= 0.58 in 5% EtOAc/hexanes; H NMR (400

MHz, CDCl₃): δ 8.34 (d, J = 6.8 Hz, 1H), 7.85 (d, J = 7.8 Hz, 1H),

7.75 (d, J = 7.5 Hz, 1H), 7.45−7.39 (m, 4H), 7.33 (d, J = 8.6 Hz,

1H), 7.29 (d, J = 5.1 Hz, 1H), 7.27−7.25 (m, 2H), 7.24−7.19 (m,

3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 157.7, 149.4, 143.5, 140.9,

139.7, 132.6, 130.7, 128.6, 128.2, 127.7, 127.4, 126.9, 125.9, 125.4,

124.9, 124.4, 124.35, 123.0, 119.4, 96.3, 89.8; IR (KBr, cm⁻¹): υ 2922,

1583, 1446, 1110, 757, 698; HRMS (ESI-TOF) m/z: [M + Na]⁺

Calcd for C₂₅H₁₄D₆O₂Na 381.1732; found 381.1736.

3-Fluoro-9-methyl-11-phenyl-5H-benzo[a]ﬂuoren-5-one (6c,

Scheme 7). The reaction was carried out using 50 mg of naphthyl

ketone (4i). Dark red solid (yield = 25.9 mg, 59%); m.p. = 222−223

°C; R_f= 0.47 in 10% EtOAc/hexanes; ¹H NMR (500 MHz, CDCl₃):

δ 7.73 (dd, J = 9.3, 2.9 Hz, 1H), 7.62−7.53 (m, 3H), 7.47−7.43 (m,

2H), 7.36 (d, J = 7.4 Hz, 1H), 7.20 (dd, J = 8.9, 5.2 Hz, 1H), 6.95 (d,

J = 7.5 Hz, 1H), 6.91−6.85 (m, 1H), 6.79 (s, 1H), 6.65 (s, 1H), 2.26

(s, 3H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 185.4, 163.4, 160.9,

153.5, 148.9, 146.2, 141.6, 134.2, 132.7, 132.6 (d, J = 5.9 Hz), 129.9,

129.4, 129.3, 128.7, 128.2, 127.3 (d, J = 7.3 Hz), 123.6, 122.1, 120.4,

119.7 (d, J = 22.7 Hz), 113.5 (d, J = 22.7 Hz), 21.8; IR (KBr, cm⁻¹):

υ 2919, 1629, 1601, 1476, 1262, 921, 697; HRMS (ESI-TOF) m/z:

[M + H]⁺Calcd for C₂₄H₁₆FO 339.1180; found 339.1178.

(4-Methoxy-2-phenylnaphthalen-1-yl)(phenyl)methanone (4a-

d₃, Scheme 6). The reaction was carried out using 50 mg of

corresponding aryl-fused 1,6-diyn-3-one. Oﬀ-white solid (yield = 42.8

mg, 77%); m.p. = 227−228 °C; R_f= 0.49 in 5% EtOAc/hexanes; H

NMR (500 MHz, CDCl₃): δ 8.38 (d, J = 8.0 Hz, 1H), 7.75 (d, J = 8.1

Hz, 1H), 7.63 (d, J = 7.1 Hz, 2H), 7.57−7.53 (m, 1H), 7.53−7.46 (m,

2H), 7.40−7.36 (m, 3H), 7.25−7.20 (m, 3H), 7.20−7.15 (m, 1H),

6.89 (s, 1H); ¹³C{¹H}NMR (100 MHz, CDCl₃): δ 199.8, 156.1,

140.8, 138.6, 134.7, 132.9, 132.0, 129.6, 129.4, 128.8, 128.2, 127.8,

127.5, 125.7, 125.3, 124.6, 122.2, 120.7, 118.8, 105.6; IR (KBr, cm⁻¹):

υ 2922, 1658, 1580, 1499, 1390, 1225, 1101, 773, 693, 610; HRMS

(ESI-TOF) m/z: [M + Na]⁺Calcd for C₂₄H₁₅D₃O₂Na 364.1387;

found 364.1386.

1

P

https://dx.doi.org/10.1021/acs.joc.0c02131

J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

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ASSOCIATED CONTENT

* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.0c02131.

■

sı

Copies of NMR spectra and HRMS analysis reports of

all the prepared compounds and X-ray crystallographic

data of 2f, 3b, 4b, and 4k (PDF)

̌

̇

O.; Adomeniene, O.; Adomenas, P.; Jankauskas, V.; Jursenas, S.

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Accession Codes

CCDC 1998442−1998445 contain the supplementary crys-

tallographic data for this paper. These data can be obtained

free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by

emailing data_request@ccdc.cam.ac.uk, or by contacting The

Cambridge Crystallographic Data Centre, 12 Union Road,

Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

AUTHOR INFORMATION

Corresponding Author

Rengarajan Balamurugan − School of Chemistry, University of

Hyderabad, Hyderabad 500046, India; orcid.org/0000-

0002-8373-5736; Email: bala@uohyd.ac.in

■

́

Graff, B.; Gigmes, D.; Fouassier, J. P.; Lalevee, J. Julolidine or

Authors

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polychromatic visible light or green light. Macromolecules 2014, 47,

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ative. ChemistrySelect 2019, 4, 10164−10168. (h) Liu, Y.; Tao, X.;

Wang, F.; Dang, X.; Zou, D.; Ren, Y.; Jiang, M. Aggregation-induced

emissions of fluorenonearylamine derivatives: a new kind of materials

for nondoped red organic light-emitting diodes. J. Phys. Chem. C

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Chem. 2004, 12, 4601−4611. (b) Laufer, R. S.; Dmitrienko, G. I.

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potential insights into the molecular mechanism of antibacterial and

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Mou Mandal − School of Chemistry, University of Hyderabad,

Hyderabad 500046, India

Shanmugam Sakthivel − School of Chemistry, University of

Hyderabad, Hyderabad 500046, India

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.0c02131

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

This work was supported by the grants received from SERB-

India. M.M. is grateful to the University Grants Commission

(UGC-BSR), New Delhi for her fellowship. S.S. thanks the

Council of Scientiﬁc and Industrial Research (CSIR), India for

his fellowship. The authors thank the director, ACRHEM,

University of Hyderabad for his help in collecting HRMS data

for some of the compounds.

́

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Br?nsted/Lewis Acid-Promoted Site-Selective Intramolecular Cycloisomerizations of Aryl-Fused 1,6-Diyn-3-ones for Diversity-Oriented Synthesis of Benzo-Fused Fluorenes and Fluorenones and Naphthyl Ketones

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