Lewis Acid Mediated Domino Intramolecular Cyclization: Synthesis of Dihydrobenzo[ a]fluorenes

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Lewis Acid Mediated Domino Intramolecular Cyclization: Synthesis

of Dihydrobenzo[a]ﬂuorenes

Dakoju Ravi Kishore, Chander Shekhar, and Gedu Satyanarayana*

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ABSTRACT: An eﬃcient and facile method for the regioselective

synthesis of novel dihydrobenzo[a]ﬂuorenes from readily acces-

sible alkynols is presented. The current strategy triggers the

formation of a dual C−C bond intramolecularly via Lewis acid

catalysis under mild reaction conditions. Notably, secondary as well

as tertiary alcohols bearing an alkyne moiety have been smoothly

transformed into the corresponding products. As a result, novel

tetracyclic dihydrobenzo[a]ﬂuorenes have been accomplished using this approach.

INTRODUCTION

■

Benzo[a]ﬂuorenes are nonalternant polycyclic aromatic hydro-

carbons (PAH) with potential applications in material science.

In addition, these structural motifs can serve as ligands in the

ﬁelds of organometallics and coordination chemistry.¹

Although the synthesis of benzo[a]ﬂuorenes has been greatly

explored, the accomplishment of saturated analogues of

benzo[a]ﬂuorenes (i.e., dihydrobenzo[a]ﬂuorenes and

tetrahydrobenzo[a]ﬂuorenes) has not. In addition, the

saturated benzo[a]ﬂuorene skeletal core constitutes various

carbocyclic natural products.²This tetracyclic core skeleton

has gained much attention owing to its interesting biological

and pharmacological activities, namely in isoprekinamycin,³

veratramine,⁴pelorol,⁵and dasyscyphin B.⁶In addition, the

synthetic tetracyclic core of the THBF analogue having a

piperidinyl-ethoxypheny side chain (Figure 1) is known to

show interesting properties, for instance, as estrogen receptor

or bone loss inhibitors.⁷

Cascade or tandem reactions are highly eﬃcient chemical

processes wherein several reactions sequentially take place in

Figure 1. Representative natural/unnatural products bearing benzo-

[a]ﬂuorene skeleton.

the same pot and, as a result, bring in suﬃcient molecular

complexity instantly.⁸In recent years, electrophilic cascade

reactions have gained more attention in the domain of

synthetic organic chemistry.⁹However, the literature prece-

dence disclosing the synthesis of fused tetracyclic

dihydrobenzo[a]ﬂuorene derivatives is very limited. To the

best of our knowledge, until now, only a very few reports are

known in the literature for the synthesis of dihydrobenzo[a]-

ﬂuorenes.

limitations like being utilized a precious catalysts, with limited

substrate scope and longer reaction times. Thus, there is always

enough space for establishing new and eﬃcient strategies

utilizing mild conditions. As part of our ongoing interest

centered on transition-metal catalysis and acid-mediated

domino electrophilic cyclizations,¹²herein we disclose an

Among them, an eﬃcient gold-catalyzed intramolecular [3 +

3] cycloaddition of o-alkynylstyrene was demonstrated for the

synthesis of dihydrobenzo[a]ﬂuororenes by Sanz et al.¹⁰In yet

another report, the research group of Anand established the

synthesis of dihydrobenzo[a]ﬂuorenes starting from alkynated

p-quinonemethides and styrenes.¹¹Although these previous

reports were found to be eﬀective but suﬀer from some

Received: March 4, 2021

Published: June 10, 2021

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

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intramolecular electrophilic cascade cyclization reaction of

alkynol promoted by simple Lewis acid BF₃·OEt₂, which

aﬀords the novel 11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene

derivatives under mild conditions.

5a−5f) and then by intermolecular Sonogashira coupling of

tertiary alcohols 5a−5f with terminal acetylenes 6a, 6d, and 6f

(Scheme 2).

At the outset, we began our optimization studies with simple

1-phenyl-3-(2-(phenylethynyl)phenyl)propan-1-ol 7a (62.4

mg, 0.2 mmol) for its conversion into the desired tetracyclic

product 9a. This, based on our previous experience with acid

catalysis, led us to choose 1,2-DCE as solvents. Thus, initially,

alkynol 7a was treated with p-toluenesulfonic acid with varying

quantities (50 mol % and 1 equiv) at 0 °C to room

temperature. However, the product was formed in moderate

and fair yields, respectively (Table 1, entries 1 and 2), while

the starting material was decomposed with p-TSA at a

temperature of 80 °C (Table 1, entry 3). Thus, switching to

the Lewis acid ZnI₂at ambient temperature furnished the

desired tetracyclic product 9a, but in very poor yield (Table 1,

entry 4). A slightly elevated temperature of 50 °C gave a

moderate yield of 34% of 9a (Table 1, entry 5). The presence

of Lewis acids ZnCl₂/ZnBr₂at ambient temperature and 50 °C

showed little improvement (Table 1, entries 6−9). Notably,

the Lewis acid FeCl₃at room temperature drove the reaction

to give 9a in 50% yield (Table 1, entry 10). Further

improvement was noted with the same FeCl₃catalyst at a

slightly elevated temperature of 50 °C (Table 1, entry 11). In

contrast, the hydrated FeCl₃Lewis acid was found to be much

inferior when compared with the anhydrous one (Table 1,

entry 12). To our delight, when 50 mol % of BF₃·OEt₂(Table

1, entry 13) was used as the Lewis acid at 50 °C, the tetracyclic

product 9a was acquired in 65% yield. The reaction with a

decreased loading of catalyst BF₃·OEt₂to 30 mol % and

decreased temperature to 0 °C, gratifyingly, increased the yield

of 9a to 79% (Table 1, entry 14). However, the reaction

became sluggish upon further decreasing the amount of the

catalyst BF₃·OEt₂at room temperature (Table 1, entry 15). In

contrast, the attempt with AlCl₃was found to be inferior

(Table 1, entries 16). Also, when the reaction was conducted

with 20 and 40 mol % of BF₃·OEt₂under similar conditions of

entry 14 at 0 °C to rt for 1 h, the product 9a was observed in

52% and 60% yields, respectively (Table 1, entries 17 and 18),

while a moderate yield of the product 9a was observed when

TfOH was used as the Bronsted acid at low temperature

(Table 1, entry 19). The attempts to increase the yield were

successful when AgSbF₆was used as an additive under the

standard conditions (entry 14) and obtained 81% 9a (Table 1,

entry 20).

RESULT AND DISCUSSION

■

It was intended that in the presence of an appropriate acid

catalyst the synthetic precursor with suitably positioned

hydroxyl and alkyne functional groups (alkynols) would

undergo the activation of the hydroxyl group, which in turn

initiate the tandem intramolecular cyclization to furnish

dihydrobenzo[a]ﬂuorenes. Thus, the novel tetracyclic products

9a−9ab/10a−10h could be accomplished from alkynols 7a−

7ab/8a−8h in the presence of an acid, as outlined in Scheme

1.

Scheme 1. Anticipated Mode of Tandem Cyclization Path to

Yield Tetracyclic Products 9a−9ab/10a−10h

The required starting material secondary alkynols 7a−7ac

have been readily achieved by adopting a two-pot synthesis, as

depicted in Scheme 2. Thus, the secondary alcohols 4a−4m

were prepared using a sequential one-pot process via one-pot

Heck coupling between allylic alcohols 1a−1j and iodoarenes

2a−2c and reduction sequence.^12fSubsequently, an inter-

molecular Sonogashira coupling between secondary alcohols

4a−4m and terminal aromatic acetylenes 6a−6i aﬀorded the

required synthetic precursors alkynols 7a−7ac (Scheme 2). On

the other hand, the tertiary alkynol precursors 8a−8h were

synthesized by treating the simple Heck products (ketones 3a,

3g, and 3h) with Grignard reagents (to give tertiary alcohols

Scheme 2. Synthesis of Alkynols 7a−7ac/8a−8h Starting from Allylic Alcohols 1a−1j and 1-Bromo-2-iodoarenes 2a−c

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these results, we next turned our attention to checking the

substrate scope on the alkyne-bearing ring (i.e., an aromatic

ring with R³substituents). Consequently, simple functional

groups such as Me- and Et-containing alkynyl arene ring

synthetic precursors were amenable and aﬀorded the products

in fair to very good yields ranging from 64 to 80% (9l, 9o, 9p,

9t, 9w, and 9y). On the other hand, alkynols possessing

electron-donating alkoxy substituents on the arene ring

originating from the terminal alkyne were also well-tolerated

and gave the ﬁnal products 9k, 9m, 9n, 9q, 9r, 9u, and 9x as

anticipated. The structure of 9m was unambiguously

conﬁrmed by X-ray crystallography. However, in the case of

o-anisyl alkyne, the product 9v seemed to accompany its

stereoisomer, which may be attributed to atropisomerism. In

addition, the reaction is quite successful with electron-

withdrawing ﬂuoro (R³) groups containing an arene alkyne

and aﬀorded the corresponding product 9s in 68% of yield. It

is worth mentioning that the reactions were unsuccessful with

aliphatic alkyne and p-amino alkynes 9ac. Furthermore, focus

on the substituents of the arene ring originated from 1-bromo-

2-iodoarene (i.e., R²group-containing aromatic ring). Notably,

electron-donating OMe, as well as ﬂuoro moieties holding

precursors, were smoothly transformed into the corresponding

tetracyclic products 9z, 9aa, and 9ab in 79%, 68%, and 79%

yields, respectively (Table 2).

Furthermore, it was speculated that the reaction would

successful if alkyl or aryl groups are introduced as R⁴in the

form of their tertiary alcohols or not. If the reaction becomes

successful, dihydrobenzo[a]ﬂuorenes will be obtained with a

quaternary center. As shown above, the ketones 3a, 3g, and 3h

have been smoothly transformed into the tertiary alkynols 8a−

8h via the corresponding tertiary alcohols 5a−5f by Grignard

addition and Sonogashira couplings. Gratifyingly, the reaction

of methyl and ethyl tertiary alcohols 8a, 8b, 8c, 8e, 8f, 8g, and

8h was quite successful and delivered dihydrobenzo[a]-

ﬂuorenes with diﬀerent R¹and R³substituents (10a, 10b,

10c, 10e, 10f, 10g, and 10h) in yields ranging from 78 to 82%

in 30 min as shown in Table 3. It is also worth mentioning that

the reaction was amenable with aryl tertiary alcohol 8d and

furnished the product dihydrobenzo[a]ﬂuorene 10d in 79%

yield (Table 3).

Table 1. Screening Conditions for the Formation of

Tetracyclic Product 9a

a−c

entry

acid catalyst

temp (°C)

time

yield 9a (%)

1

2

3

4

5

6

7

8

p-TsOH (50 mol %)

p-TsOH (1 equiv)

ZnI₂(50 mol %)

ZnCl₂(50 mol %)

ZnBr₂(50 mol %)

FeCl₃(50 mol %)

FeCl₃·6H₂O (50 mol %)

BF₃·OEt₂(50 mol %)

BF₃·OEt₂(30 mol %)

BF₃·OEt₂(10 mol %)

AlCl₃(50 mol %)

0 to rt

rt

80

rt

50

rt

50

rt

50

rt

50

rt

50

0 to rt

rt

0 to rt

−10

0 to rt

12 h

2 h

6 h

3 h

6 h

3 h

6 h

3 h

6 h

30 min

1 h

3 h

10 min

1 h

50 min

1 h

42

65

18

34

38

48

32

41

50

61

36

65

79

62

9

10

11

12

13

14

15

16

17

18

19

BF₃·OEt₂(20 mol %)

BF₃·OEt₂(40 mol %)

TfOH (30 mol %)

52

60

62

81

c

20

BF₃·OEt₂(30 mol %)

a

Conditions to synthesize dihydrobenzo[a]ﬂuorene: Reactions were

conducted at ambient temperatures and 50 °C using 62.4 mg (0.20

mmol) of 1-phenyl-3-(2-(phenylethynyl)phenyl)propan-1-ol, in sol-

b

vent 1,2 DCE (1 mL). Yields in parentheses are isolated yields of the

c

tetracyclic product 9a. AgSbF₆(20 mol %) is used as additive.

Overall, out of all the reaction conditions screened, the

conditions of entry 14 from Table 1 were good pertaining to

the yield of dihydrobenzo[a]ﬂuorene 9a, where the Lewis acid

BF₃·OEt₂was used as the sole acid catalyst. Thus, we set out to

explore the scope and limitations of the present strategy on

diﬀerent precursors, in particular, with regard to various

functional groups that are ﬂanked all three aryl rings. First, we

scrutinized the substrate scope concerning the arene ring

derived from allylic alcohol (i.e., with R¹functional moieties).

As anticipated, the reaction is quite compatible with simple

Further, to check the synthetic utility of the current method,

the reaction was also conducted on a molar scale (1.35 mmol

of 7a) experiment for the synthesis of 9a. As expected, 9a was

isolated in 63% yield as outlined in Scheme 3.

In conclusion, we have demonstrated a concise and eﬃcient

method for the synthesis of novel dihydrobenzo[a]ﬂuorene via

an intramolecular cascade cyclization. It was illustrated that

mild Lewis acid BF₃·OEt₂was able to trigger the dual

cyclization process and constructed two C−C bonds

eﬀectively. The strategy showed a broad substrate scope and

quite successful in delivering a variety of dihydrobenzo[a]-

ﬂuorenes.

i

activating alkyl groups (Me, Et, and Pr) placed at the para-

position to the aromatic ring and gave the products 9b, 9c, and

9d in 70%, 65%, and 68% yields, respectively (Table 2). In

addition, the residence of strong electron-donating groups like

dimethoxy and methylenedioxy functional groups facilitated

the formation of the corresponding tetracyclic products 9e−9g

in fair to good yields (Table 2). Notably, the reaction was also

amenable with electron-deactivating Cl and F substituents but

witnessed a slight decrease in yields (9h and 9i, Table 2). This

is probably due to the electron-deactivating nature of Cl and F

groups, which would impede the activation of the hydroxyl

group that is in conjugation to that aromatic ring (i.e., as R¹).

It is worth mentioning that the reaction with naphthalene as

the R¹substituent did not give the desired product; instead, it

gave the isomerized product 9j′. Overall, diﬀerent R¹

substituents with electron-deactivating, simple electron-donat-

ing, and strong electron-donating properties enabled the

formation of desired products smoothly. Encouraged by

EXPERIMENTAL SECTION

■

General Methods. IR spectra were recorded on a Bruker Tensor

1

37 (FTIR) spectrophotometer. H NMR spectra were recorded on

Bruker Avance 400 (400 MHz) spectrometer at 295 K in CDCl₃;

chemical shifts (δ ppm) and coupling constants (hertz) are reported

in standard fashion concerning either internal standard tetramethylsi-

lane (TMS) (δ_H= 0.00 ppm) or CDCl₃(δ_H= 7.25 ppm). ¹³C{¹H}

NMR spectra were recorded on a Bruker Avance 400 (100 MHz)

spectrometer at rt in CDCl₃; chemical shifts (δ ppm) are reported

relative to CDCl₃[δ_C= 77.00 ppm (central line of the triplet)]. In the

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a b

,

Table 2. Substrate Scope of Dihydrobenzo[a]ﬂuorenes 9a−9ab

a

b

Reaction conditions: compound 7a−7ac (0.2 mmol), BF₃·OEt₂(30 mol %), DCE (1 mL), 0 °C to rt, 1 h. Isolated yields of the products 9a−

c

9ab. Double bond is isomerized product 9j′ was obtained.

¹³C{¹H} NMR, the nature of carbons (C, CH, CH₂, and CH₃) was

determined by recording the DEPT-135 spectra and is given in

parentheses and noted as s = singlet (for C), d = doublet (for CH), t

ether with a boiling range of 60−80 °C was used. Pd(OAc)₂, cesium

carbonate, triphenylphosphine (TPP), sodium borohydride, and BF₃·

OEt₂(48−50% essay) were purchased from Sigma-Aldrich and used

as received. Substituted benzaldehydes, vinyl magnesium bromide in

THF, 1-alkynes, and triethylamine were purchased from Sigma/TCI/

local. Solvent THF was dried over sodium metal, whereas DMF was

dried over calcium hydride. Acme’s silica gel (60−120 mesh) was

used for column chromatography (approximately 20 g per 1 g of

crude material).

General Procedure 1 (GP-1): Preparation of 3-(2-Bromo-

phenyl)-1-phenylpropan-1-ols) 4a−4m. To an oven-dried

Schlenk tube under nitrogen atmosphere were added allylic alcohol

1a−1j (134−194 mg, 1 mmol), 1-iodo-2-bromoarene 2a−2c (346−

382 mg, 1.2 mmol), Pd(OAc)₂(4.5 mg, 2 mol %), and triethylamine

1

= triplet (for CH₂), and q = quartet (for CH₃). In the H NMR, the

following abbreviations were used throughout: s = singlet, d =

doublet, t = triplet, q = quartet, qui = quintet, sept = septet, dd =

doublet of doublet, m = multiplet, and br s = broad singlet. The

assignment of signals was conﬁrmed by ¹H, ¹³C{¹H} CPD, and DEPT

spectra. High-resolution mass spectra (HR-MS) were recorded on an

Agilent 6538 UHD Q-TOF electron spray ionization (ESI) mode and

atmospheric pressure chemical ionization (APCI) modes. All small-

scale reactions were carried out using a Schlenk tube. Reactions were

monitored by TLC on silica gel using a combination of hexane and

ethyl acetate as eluents. Solvents were distilled before use; petroleum

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TLC. It was then quenched with saturated aqueous NH₄Cl solution

and extracted with ethyl acetate (3 × 30 mL). The organic layers were

washed with saturated NaCl solution, dried over Na₂SO₄, and ﬁltered.

Evaporation of the solvent and puriﬁcation of the residue over a silica

gel column using petroleum ether/ethyl acetate as eluent furnished

the tertiary alcohols 5a−5f (85−93%).

Table 3. Synthesis of Dihydrobenzo[a]ﬂuorenes with a

Quaternary Center

a b

,

General Procedure 3 (GP-3): Preparation of Alkynols (7a−

7ac). The appropriate arylacetylene 6a−6i (1.5 equiv) was added to a

solution of bromo-secondary/bromo-tertiary alcohol 4a−4m (0.3

mmol), Cs₂CO₃(1.5 equiv), Pd(OAc)₂(0.03 mmol, 3 mol %), and

triphenylphosphine (0.06 mmol, 6 mol %) in DMF (2 mL). The

resulting mixture was heated in a 100 °C oil bath with rapid stirring

until bromo-secondary alcohol was consumed as determined by TLC.

The crude mixture was partitioned between water and ethyl acetate (3

× 30 mL). The organic layers were washed with saturated NaCl

solution, dried (Na₂SO₄), and ﬁltered, and the solvents were removed

under reduced pressure. Puriﬁcation of the residue over silica gel

column using petroleum ether/ethyl acetate as eluent furnished the

corresponding alkynols 7a−7ac/8a−8h (68−89%).

General Procedure 4 (GP-4): Synthesis of Dihydrobenzo-

[a]ﬂuorenes (9a−9ab/10a−10h). To a cold solution (0 °C) of

secondary/tertiary alkynols 7a−7ab/8a−8h (62.4 mg to 88.8 mg, 0.2

mmol) in a Schlenk tube in dry DCE (2 mL) was added BF₃·OEt₂(30

mol %) and the reaction mixture stirred at 0 °C to room temperature.

Completion of the reaction was monitored by TLC (2:98 ethyl

acetate and hexane) for 1−3 h. The reaction mixture was quenched

with aqueous ammonium chloride and extracted with ethyl acetate (3

× 30 mL). The combined organic layers were washed with brine,

dried over (Na₂SO₄), and evaporated under reduced pressure.

Puriﬁcation of the crude residue by column chromatography on

silica gel (100−200 mesh) by using a hexane/ethyl acetate solvent

system as eluent aﬀorded the cyclized product 9a−9ab/10a−10h

(58−82%).

a

3-(2-Bromophenyl)-1-(4-chlorophenyl)propan-1-one (3h).

GP-1 (GP-1 was carried out until ketone stage without further

performing the reduction sequence) was carried out with allylic

alcohol 1h (168 mg, 1 mmol), 1-bromo-2-iodobenzene 2a (346.8 mg,

1.2 mmol), Pd(OAc)₂(4.5 mg, 2 mol %), triethylamine (303 mg, 3

equiv), and dry acetonitrile (2 mL) at 80 °C for 24 h. Puriﬁcation of

the crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 98:1 to 99:2) furnished the ketone 3h (245.5 mg,

76%) as a viscous liquid. TLC (petroleum ether/ethyl acetate 98:2,

R_f(1h) = 0.2, R_f(3h) = 0.75, UV detection. IR (MIR-ATR, 4000-600

Reaction conditions: compound 8a−8h (0.2 mmol), BF₃·OEt₂(30

b

mol %), DCE (1 mL), room temperature, 30 min. Isolated yields of

tetracyclic products 10a−10h.

Scheme 3. Scale-up Experiment on 9a

1

cm⁻¹) ν_max= 3092, 3020, 2842, 1680, 1063, 951, 881, 567 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ = 7.75−7.72 (m, 2H, ArH), 7.37 (m, 1H,

ArH), 7.26−7.24 (m, 2H, ArH), 7.13 (dd, J = 7.6 and 1.7 Hz, 1H,

ArH), 7.07 (ddd, J = 8.8, 6.3, and 2.5 Hz, 1H, ArH), 6.93−6.89 (m,

1H, Ar-H), 3.12−3.09 (m, 2H, CH₂), 3.02−2.99 (m, 2H, CH₂) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 197.6, 140.3, 137.3, 139.5,

134.9, 132.8, 130.7, 129.5 (2 × CH), 128.9 (2 × CH), 128.0, 126.6,

124.3, 38.5, 30.6 ppm.

(303 mg, 3 equiv) followed by dry acetonitrile (2 mL). The resulting

reaction mixture was stirred at 80 °C for 24 h. The progress of the

reaction was monitored by TLC until the reaction was completed. To

the cooled reaction mixture at 0 °C was added NaBH₄(2.0 mmol),

and the reaction mixture was stirred at room temperature for 3 h, with

completion of the reduction monitored by TLC. Then the mixture

was quenched by the addition of an aqueous NH₄Cl solution and then

extracted with ethyl acetate (3 × 30 mL). The organic layers were

washed with saturated NaCl solution, dried (Na₂SO₄), and ﬁltered.

Evaporation of the solvent under reduced pressure and puriﬁcation of

the crude material by silica gel column chromatography (petroleum

ether/ethyl acetate) furnished the alcohols 4a−4m (65−84%) as a

viscous liquid.

General Procedure 2 (GP-2): Preparation of Tertiary

Alcohols 5a−5f. To the ketone 3a, 3g, and 3h (224−249 mg,

0.75 mmol) in a round-bottomed ﬂask in dry diethyl ether or dry

THF (10 mL) at 0 °C was added freshly prepared alkyl magnesium

iodide or arylmagnesium bromide (2.25 mmol) [alkyl/arylmagnesium

halide (bromide or iodide) was prepared from magnesium (45 mg,

1.8 mmol), alkyl halide (142−158 mg, 1.8 mmol), and a catalytic

amount of iodine in 8 mL of dry ether]. The reaction mixture was

stirred at 0 °C for 4 h. Progress of the reaction was monitored by

3-(2-Bromophenyl)-1-(p-tolyl)propan-1-ol (4b). GP-1 was

carried out with allylic alcohol 1b (148 mg, 1 mmol), 1-bromo-2-

iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5 mg, 2 mol %),

triethylamine (303 mg, 3 equiv), and dry acetonitrile (2 mL) at 80 °C

for 24 h and subsequently with NaBH₄(75.6 mg, 2.0 mmol) at room

temperature for 3 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 95:5 to

90:10) furnished the alcohol 4b (231.5 mg, 76%) as a viscous liquid.

TLC (petroleum ether/ethyl acetate 90:10, R_f(1b) = 0.45, R_f(4b) =

0.35, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3334,

1

3064, 2968, 1642, 1463, 1371, 1268, 1085, 938, 756 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ = 7.53 (d, J = 7.9 Hz, 1H, ArH), 7.30−7.24 (m,

2H, ArH), 7.23 (d, J = 4.2 Hz, 2H, ArH), 7.17 (d, J = 7.9 Hz, 2H,

ArH), 7.10−7.02 (m, 1H, ArH), 4.69 (dd, J = 7.6 and 5.5 Hz, 1H,

ArCH(OH)), 2.89 (ddd, J = 13.9, 10.1, and 5.6 Hz, 1H, CH), 2.76

(ddd, J = 13.7, 9.9, and 6.5 Hz, 1H, CH), 2.36 (s, 3H, ArCH₃), 2.19−

1.94 (m, 3H, CH₂and OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃)

δ = 141.3, 141.1, 137.3, 132.8, 130.4, 129.1 (2 × CH), 127.5, 127.4,

125.9 (2 × CH), 124.4, 73.7, 38.7, 32.6, 21.1 ppm. HRMS (ESI) m/z:

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[M + K]⁺calcd for C₁₆H₁₇Br⁷⁹KO 343.0094; Found 343.0092; [M +

K]⁺calcd for C₁₆H₁₇Br⁸¹KO 345.0074; Found 345.0075.

mg, 2 mol %), triethylamine (303.0 mg, 3 equiv), and dry acetonitrile

(2 mL) at 80 °C for 24 h and subsequently with NaBH₄(75.6 mg, 2.0

mmol) at room temperature for 3 h. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

95:5 to 90:10) furnished the alcohol 4h (220.2 mg, 68%) as a viscous

liquid. TLC control (petroleum ether/ethyl acetate 90:10), R_f(1h) =

0.45, R_f(4h) = 0.35, UV detection. IR (MIR-ATR, 4000−600 cm⁻¹):

ν_max= 3382, 3010, 2963, 1606, 1471, 1046, 1022, 832, 750 cm⁻¹. ¹H

NMR (CDCl₃, 400 MHz): δ = 7.56−7.49 (m, 1H, ArH), 7.34−7.24

(m, 4H, ArH), 7.24−7.18 (m, 2H, ArH), 7.06 (ddd, J = 8.0 Hz, 6.3

and 2.8 Hz, 1H, ArH), 4.70 (dd, J = 7.5 and 5.5 Hz, 1H,

ArCH(OH)), 2.96−2.79 (m, 1H, CH), 2.79−2.63 (m, 1H, CH), 2.16

(s, 1H, OH), 2.07−1.91 (m, 2H, CH₂) ppm. ¹³C{¹H} NMR (CDCl₃,

100 MHz): δ = 142.7, 140.8, 133.2, 132.8, 130.3, 128.6 (2 × CH),

127.7, 127.5, 127.2 (2 × CH), 124.3, 73.1, 38.8, 32.4 ppm. HRMS

(ESI) m/z: [(M + NH₄) + (−H₂O)]⁺calcd for C₁₅H₁₆Br⁷⁹ClN

324.0149; Found 324.0139; [(M+NH₄)+ (−H₂O)]⁺calcd for

C₁₅H₁₆Br⁸¹ClN 326.0128; Found 326.0117.

3-(2-Bromophenyl)-1-(4-ﬂuorophenyl)propan-1-ol (4i). GP-

1 was carried out with allylic alcohol 1i (152.1 mg, 1 mmol), 1-

bromo-2-iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5 mg,

2 mol %), triethylamine (303 mg, 3 equiv), and dry acetonitrile (2

mL) at 80 °C for 24 h and subsequently with NaBH₄(75.6 mg, 2.0

mmol) at room temperature for 3 h. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

95:5 to 90:10) furnished the alcohol 4i (200.2 mg, 65%) as yellow

viscous liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(1i) =

0.45, R_f(4i) = 0.40, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

ν_max= 3351, 3061, 2932, 2869, 1653, 1604, 1508, 1223, 1020, 834,

750, 703 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.55−7.50 (m, 1H,

ArH), 7.37−7.31 (m, 2H, ArH), 7.24−7.20 (m, 2H, ArH), 7.11−6.96

(m, 3H, ArH), 4.81−4.60 (m, 1H, ArCH(OH)), 2.88 (ddd, J = 13.7,

10.1, and 5.6 Hz, 1H, CH), 2.75 (ddd, J = 13.7, 9.8, and 6.5 Hz, 1H,

CH), 2.15−1.93 (m, 3H, CH₂and OH) ppm. ¹³C{¹H} NMR (100

MHz, CDCl₃) δ = 162.3 (J_C−F= 244 Hz), 141.9, 140.1 (J_C−F= 3 Hz),

132.9, 130.4, 127.5, 127.6, 127.5 (J_C−F= 2 Hz, 2 × CH), 124.4, 115.3

(J_C−F= 21 Hz, 2 × CH), 73.3, 39.0, 32.5 ppm. HRMS (ESI) m/z:

[(M+NH₄)+ (−H₂O)]⁺calcd for C₁₅H₁₆Br⁷⁹NF 308.0444; Found

308.0449; [(M + NH₄) + (−H₂O)]⁺calcd for C₁₅H₁₆Br⁸¹NF

310.0424; Found 310.0406.

3-(2-Bromophenyl)-1-(naphthalen-1-yl) propan-1-ol (4j).

GP-1 was carried out with allylic alcohol 1j (184.1 mg, 1 mmol), 1-

bromo-2-iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5 mg,

2 mol %), triethylamine (303 mg, 3 equiv), and dry acetonitrile (2

mL) at 80 °C for 24 h and subsequently with NaBH₄(75.6 mg, 2.0

mmol) at room temperature for 3 h. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

90:10 to 88:12) furnished the alcohol 4j (248.2 mg, 73%) as a yellow

viscous liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(1j) =

0.55, R_f(4j) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

ν_max= 3386, 3056, 2928, 2862, 1597, 1510, 1456, 1385, 1025, 778

cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.97 (dt, J = 6.8 and 3.4 Hz,

1H, ArH), 7.91−7.84 (m, 1H, ArH), 7.78 (d, J = 8.2 Hz, 1H, ArH),

7.70 (d, J = 7.1 Hz, 1H, ArH), 7.55 (dd, J = 8.0 and 1.1 Hz, 1H, ArH),

7.50−7.45 (dt, J = 7.1 and 2.8 Hz, 3H, ArH), 7.26−7.23 (m, 2H,

ArH), 7.07 (ddd, J = 7.9, 7.2, and 2.1 Hz, 1H, ArH), 5.51 (dd, J = 8.6

and 3.8 Hz, 1H, ArCH(OH)), 3.11−2.91 (m, 2H, CH₂), 2.37−2.23

(m, 1H, CH), 2.23−2.11 (m, 1H, CH), 2.04 (d, J = 6.1 Hz, 1H,

ArCH(OH)) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 141.1,

140.1, 133.8, 132.8, 130.5, 130.3, 128.9, 128.0, 127.7, 127.4, 126.0,

125.5, 125.4, 124.5, 123.0, 122.7, 70.5, 38.2, 33.0 ppm. HRMS (ESI)

m/z: [(M + H) + (−H₂O)]⁺calcd for C₁₉H₁₆Br⁷⁹323.0430; Found

323.0430; [(M + H) + (−H₂O)]⁺calcd for C₁₉H₁₆Br⁸¹325.0430;

Found 325.0411.

3-(2-Bromophenyl)-1-(4-ethylphenyl)propan-1-ol (4c). GP-1

was carried out with allylic alcohol 1c (162 mg, 1.0 mmol), 1-bromo-

2-iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5 mg, 2 mol

%), triethylamine (303 mg, 3 equiv), and dry acetonitrile (2 mL) at

80 °C for 24 h and subsequently with NaBH₄(75.6 mg, 2.0 mmol) at

room temperature for 3 h. Puriﬁcation of the crude material by silica

gel column chromatography (petroleum ether/ethyl acetate 95:5 to

90:10) furnished the alcohol 4c (257.6 mg, 81%) as a viscous liquid.

TLC control (petroleum ether/ethyl acetate 90:10), R_f(1c) = 0.45, R_f

(4c) = 0.35, UV detection. IR (MIR-ATR, 4000−600 cm⁻¹): ν_max

=

3382, 2930, 2963, 1455, 1471, 1046, 1022, 832 cm⁻¹. ¹H NMR

(CDCl₃, 400 MHz): δ = 7.52 (d, J = 7.7 Hz, 1H, ArH), 7.31−7.29

(m, 2H, ArH), 7.24−7.16 (m, 4H, ArH), 7.07−7.03 (m, 1H, ArH),

4.70 (t, J = 5.5 Hz, 1H, ArCH(OH)), 2.94−2.87 (m, 1H, CH), 2.81−

2.74 (m, 1H, CH), 2.65 (q, J = 7.6 Hz, 2H, CH₂CH₃), 2.13−2.01 (m,

2H, CH₂), 1.89 (s, 1H, OH), 1.24 (t, J = 7.6 Hz, 3H, CH₂CH₃) ppm.

¹³C{¹H} NMR (CDCl₃, 100 MHz): δ = 143.8, 141.6, 141.2, 132.8,

130.4, 128.0 (2 × CH), 127.6, 127.4, 125.9 (2 × CH), 124.4, 73.8,

38.7, 32.6, 28.5, 15.6 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺

calcd for C₁₇H₁₈Br⁷⁹301.0586; Found 301.0576; [(M + H) +

(−H₂O)]⁺calcd for C₁₇H₁₈Br⁸¹303.0566; Found 303.0557.

3-(2-Bromophenyl)-1-(4-isopropylphenyl)propan-1-ol (4d).

GP-1 was carried out with allylic alcohol 1d (176 mg, 1 mmol), 1-

bromo-2-iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5 mg,

2 mol %), triethylamine (212.1 mg, 3 equiv), and dry acetonitrile (2

mL) at 80 °C for 24 h and subsequently with NaBH₄(75.6 mg, 2.0

mmol) at room temperature for 3 h. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

95:5 to 90:10) furnished the alcohol 4d (270.5 mg, 78%) as a viscous

liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(1d) = 0.45,

R_f(4d) = 0.35, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3385, 3017, 2957, 2874, 1636, 1511, 1454, 1030, 921, 833, 750 cm⁻¹.

¹H NMR (400 MHz, CDCl₃) δ = 7.49 (d, J = 8.0 Hz, 1H, ArH),

7.31−7.24 (m, 2H, ArH), 7.24−7.15 (m, 4H, ArH), 7.05−6.99 (m,

1H, ArH), 4.67−4.64 (m, 1H, ArCH(OH)), 2.96−2.83 (m, 2H,

CH₂), 2.75 (ddd, J = 13.7, 9.7, and 6.6 Hz, 1H, ArCH(CH₃)₂), 2.12−

1.95 (m, 3H, CH₂and OH), 1.24 (d, J = 5.8 Hz, 6H, CH(CH₃)₂)

ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 148.3, 141.8, 141.2,

132.7, 130.3, 127.5, 127.3, 126.5 (2 × CH), 125.9 (2 × CH), 124.4,

73.7, 38.7, 33.8, 32.7, 24.0 (2 × CH₃) ppm. HRMS (ESI) m/z: [(M +

H) + (−H₂O)]⁺calcd for C₁₈H₂₀Br⁷⁹315.0743; Found 315.0745;

[(M + H) + (−H₂O)]⁺calcd for C₁₈H₂₀Br⁸¹317.0743; Found

317.0726.

3-(2-Bromophenyl)-1-(3,5-dimethoxyphenyl)propan-1-ol

(4f). GP-1 was carried out with allylic alcohol 1f (194.1 mg, 1 mmol),

1-bromo-2-iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5

mg, 2 mol %), triethylamine (303 mg, 3 equiv), and dry acetonitrile (2

mL) at 80 °C for 24 h and subsequently with NaBH₄(75.6 mg, 2.0

mmol) at room temperature for 3 h. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

85:15 to 80:20) furnished the alcohol 4f (280.3 mg, 80%) as a viscous

liquid. TLC (petroleum ether/ethyl acetate 80:20, R_f(1f) = 0.50,

R_f(4f) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3421, 3000, 2935, 2837, 1595, 1469, 1428, 1203, 1152, 750 cm⁻¹. ¹H

NMR (400 MHz, CDCl₃) δ = 7.52 (d, J = 7.7 Hz, 1H, ArH), 7.25−

7.18 (m, 2H, ArH), 7.05 (ddd, J = 8.0 Hz, 5.7 and 3.4 Hz, 1H, ArH),

6.54 (d, J = 2.2 Hz, 2H, ArH), 6.37 (t, J = 7.3 Hz, 1H, ArH), 4.67 (dd,

J = 7.4 and 5.6 Hz, 1H, ArCH(OH)), 3.80 (s, 6H, 2 × ArOCH₃),

2.93−2.86 (m, 1H, CH), 2.82−2.75 (m, 1H, CH), 2.08−2.01 (m, 3H,

CH₂and OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 160.8 (2

× C), 146.9, 141.1, 132.8, 130.4, 127.6, 127.4, 124.3, 103.7 (2 × CH),

99.6, 73.9, 55.4 (2 × OCH₃), 38.7, 32.5 ppm. HRMS (ESI) m/z: [(M

+ H) + (−H₂O)]⁺calcd for C₁₇H₁₈Br⁷⁹O₂333.0484; Found

333.0485; [(M + H) + (−H₂O)]⁺calcd for C₁₇H₁₈Br⁸¹O₂

335.0464; Found 335.0468.

3-(2-Bromo-4-methoxyphenyl)-1-phenylpropan-1-ol (4k).

GP-1 was carried out with allylic alcohol 1k (134.1 mg, 1 mmol),

2-bromo-1-iodo-4-methoxybenzene 2b (382.8 mg, 1.2 mmol),

Pd(OAc)₂(4.5 mg, 2 mol %), triethylamine (303 mg, 3 equiv), and

dry acetonitrile (2 mL) at 80 °C for 24 h and subsequently with

NaBH₄(75.6 mg, 2.0 mmol) at room temperature for 3 h. Puriﬁcation

3-(2-Bromophenyl)-1-(4-chlorophenyl)propan-1-ol (4h).

GP-1 was carried out with allylic alcohol 1h (168.0 mg, 1 mmol),

1-bromo-2-iodobenzene 2a (346.8 mg, 1.2 mmol), Pd(OAc)₂(4.5

8711

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

of the crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 90:10 to 85:15) furnished the alcohol 4k (249.6

mg, 78%) as a viscous liquid. TLC control (petroleum ether/ethyl

acetate 85:15), R_f(1k) = 0.55, R_f(4k) = 0.45, UV detection. IR (MIR-

ATR, 4000−600 cm⁻¹): ν_max= 3374, 2922, 1604, 1578, 1469, 1234,

acetate 93:07), R_f(3a) = 0.85, R_f(5a) = 0.55, UV detection. IR (MIR-

ATR, 4000−600 cm⁻¹): ν_max= 3529, 3026, 2939, 2898, 1429, 1358,

1330, 1251, 1115, 928, 879 cm⁻¹. ¹H NMR (CDCl₃, 400 MHz): δ =

7.54−7.46 (m, 3H, ArH), 7.40−7.33 (m, 2H, ArH), 7.29−7.23 (m,

1H, ArH), 7.20−7.15 (m, 1H, ArH), 7.13 (dd, J = 7.6 Hz, 1.9 Hz, 1H,

CH), 7.05−6.97 (m, 1H, ArH), 2.80−2.72 (m, 1H, CH), 2.60−2.52

(m, 1H, CH), 2.17−2.06 (m, 2H, CH₂), 1.85 (s, 1H, OH), 1.63 (s,

3H, CH₃) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz): δ = 147.3, 141.6,

132.7, 130.3, 128.2 (2 × CH), 127.5, 127.5, 126.7, 124.8 (2 × CH),

124.3, 74.6, 44.3, 31.1, 30.3 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺calcd for C₁₆H₁₆Br⁷⁹287.0430; Found 287.0431; [(M +

H) + (−H₂O)]⁺calcd for C₁₆H₁₆Br⁸¹289.0409; Found 289.0411.

3-(2-Bromophenyl)-1,1-diphenylpropan-1-ol (5b). GP-2 was

carried out with ketone 3a (288.1 mg, 1 mmol) and PhMgBr

[prepared from Mg (48, 2.0 mmol), PhBr (312 mg, 2.0 mmol), and

dry diethyl ether (10 mL)] in diethyl ether (2 mL) at 0 °C for 2 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 95:5 to 90:10) furnished the

alcohol 5b (311.1 mg, 85%) as a viscous liquid. TLC control

(petroleum ether/ethyl acetate 95:05), R_f(3a) = 0.8, R_f(5b) = 0.45,

UV detection. IR (MIR-ATR, 4000−600 cm⁻¹): ν_max= 3385, 2921,

1

1028, 816 cm⁻¹. H NMR (CDCl₃, 400 MHz): δ = 7.40−7.32 (m,

4H, ArH), 7.29−7.27 (m, 1H, ArH), 7.13 (d, J = 8.5 Hz, 1H, ArH),

7.09 (d, J = 2.6 Hz, 1H, ArH), 6.79 (dd, J = 8.5 and 2.6 Hz, 1H, ArH),

4.71 (t, J = 6.4 Hz, 1H, ArCH(OH)), 3.77 (s, 3H, ArOCH₃), 2.85−

2.79 (m, 1H, CH), 2.77−2.65 (m, 1H, CH), 2.12−1.94 (m, 3H, CH₂

and OH) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz): δ = 158.3, 144.4,

133.0, 130.6, 128.5 (2 × CH), 127.6, 125.9 (2 × CH), 124.5, 117.9,

113.6, 73.9, 55.5, 39.1, 31.6 ppm. HRMS (ESI) m/z: [(M+NH₄)+

(−H₂O)]⁺calcd for C₁₆H₁₉Br⁷⁹NO 320.0644; Found 320.0637; [(M

+ NH₄) + (−H₂O)]⁺calcd for C₁₆H₁₉Br⁸¹NO 322.0624; Found

322.0617.

3-(2-Bromo-4-methoxyphenyl)-1-(4-ethylphenyl)propan-1-

ol (4l). GP-1 was carried out with allylic alcohol 1c (162.2 mg, 1

mmol), 2-bromo-1-iodo-4-methoxybenzene 2b (382.8 mg, 1.2

mmol), Pd(OAc)₂(4.5 mg, 2 mol %), triethylamine (303 mg, 3

equiv), and dry acetonitrile (2 mL) at 80 °C for 24 h and

subsequently with NaBH₄(75.6 mg, 2.0 mmol) at room temperature

for 3 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 90:10 to 85:15)

furnished the alcohol 4l (281.9 mg, 81%) as a viscous liquid. TLC

(petroleum ether/ethyl acetate 85:15, R_f(1c) = 0.50, R_f(4l) = 0.45,

UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3382, 2906,

2809, 1581, 1446, 1456, 1415, 1187, 1138 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ = 7.32−7.26 (dd, J = 8.6 and 6.9 Hz, 2H, ArH), 7.19 (d, J =

8.1 Hz, 2H, ArH), 7.13 (d, J = 8.5 Hz, 1H, ArH), 7.08 (d, J = 2.6 Hz,

1H, ArH), 6.78 (dd, J = 8.5 and 2.6 Hz, 1H, ArH), 4.68 (dd, J = 7.8

and 5.4 Hz, 1H, ArCH(OH)), 3.77 (s, 3H, ArOCH₃), 2.83 (ddd, J =

14.0, 9.9, and 5.6 Hz, 1H, CH), 2.75−2.62 (m, 3H, CH, ArCH₂CH₃),

2.14−2.00 (m, 2H, CH₂), 1.95 (br.s, 1H, OH), 1.30 (t, J = 7.6 Hz,

3H, ArCH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 158.3,

143.7, 141.7, 133.1, 130.7, 128.0 (2 × CH), 126.0 (2 × CH), 124.5,

117.9, 113.6, 73.7, 55.5, 39.0, 31.7, 28.6, 15.6 ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺calcd for C₁₈H₂₀Br⁷⁹O 331.0692; Found

331.0679; [(M + H) + (−H₂O)]⁺calcd for C₁₈H₂₀Br⁸¹O 333.0671;

Found 333.0662.

1

1596, 1580, 1497, 1273, 1227, 1067, 959, 818, 755 cm⁻¹. H NMR

(CDCl₃, 400 MHz): δ = 7.53−7.46 (m, 5H, ArH), 7.36−7.30 (m, 4H,

ArH), 7.27−7.20 (m, 3H, ArH), 7.19−7.14 (m, 1H, ArH), 7.07−7.00

(m, 1H, CH), 2.78−2.68 (m, 2H, CH₂), 2.62−2.53 (m, 2H, CH₂),

2.23 (s, 1H, OH) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz): δ = 146.6

(2 × C), 141.7, 132.8, 130.5, 128.2 (4 × CH), 127.6, 127.5, 127.0 (2

× CH), 126.9, 126.0 (3 × CH), 124.3, 78.0, 42.3, 30.9 ppm. HRMS

(ESI) m/z: [(M + H) + (−H₂O)]⁺calcd for C₂₁H₁₈Br⁷⁹349.0586;

Found 349.0575; [(M + H) + (−H₂O)]⁺calcd for C₂₁H₁₈Br⁸¹

351.0566; Found 351.0556.

4-(2-Bromophenyl)-2-(4-chlorophenyl)butan-2-ol (5c). GP-2

was carried out with ketone 3h (321 mg, 1 mmol) and MeMgI

[prepared from Mg (48, 2.0 mmol), MeI (312 mg, 2.0 mmol), and

dry diethyl ether (10 mL)] in diethyl ether (2 mL) at 0 °C for 2 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 95:5 to 90:10) furnished the

alcohol 5c (304.2 mg, 90%) as a viscous liquid. TLC control

(petroleum ether/ethyl acetate 95:05), R_f(3h) = 0.80, R_f(5c) = 0.45,

UV detection. IR (MIR-ATR, 4000−600 cm⁻¹): ν_max= 3434, 2972,

1

1595, 1566, 1488, 1470, 1170, 1093, 930, 888, 832 cm⁻¹. H NMR

3-(2-Bromo-5-ﬂuorophenyl)-1-(p-tolyl)propan-1-ol (4m).

GP-1 was carried out with allylic alcohol 1b (150 mg, 1 mmol), 1-

bromo-4-ﬂuoro-2-iodobenzene 2c (382.8 mg, 1.2 mmol), Pd(OAc)₂

(4.5 mg, 2 mol %), triethylamine (303 mg, 3 equiv), and dry

acetonitrile (2 mL) at 80 °C for 24 h and subsequently with NaBH₄

(75.6 mg, 2.0 mmol) at room temperature for 3 h. Puriﬁcation of the

crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 95:5 to 90:10) furnished the alcohol 4m (257.6

mg, 80%) as a viscous liquid. TLC control (petroleum ether/ethyl

acetate 90:10), R_f(1b) = 0.45, R_f(4m) = 0.35, UV detection. IR (MIR-

ATR, 4000−600 cm⁻¹): ν_max= 3430, 2924, 1607, 1597, 1457, 1470,

(CDCl₃, 400 MHz): δ = 7.49 (dd, J = 8.0 and 1.2 Hz, 1H, ArH),

7.46−7.42 (m, 2H, ArH), 7.36−7.31 (m, 2H, ArH), 7.19 (td, J = 7.4

and 1.2 Hz, 1H, ArH), 7.13 (dd, J = 7.6 and 1.8 Hz, 1H, ArH), 7.07−

6.98 (m, 1H, ArH), 2.78−2.66 (m, 1H, CH), 2.61−2.54 (m, 1H,

CH), 2.12−2.04 (m, 2H, CH₂), 1.82 (s, 1H, OH), 1.62 (s, 3H,

ArCH₃) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz): δ = 145.9, 141.3,

132.8, 132.5, 130.3, 128.3 (2 × CH), 127.6, 127.5, 126.4 (2 × CH),

124.3, 74.3, 44.2, 31.0, 30.5 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺calcd for C₁₆H₁₅Br⁷⁹Cl 321.0040; Found 321.0025; [(M +

H) + (−H₂O)]⁺calcd for C₁₆H₁₅Br⁸¹Cl 323.0019; Found 323.0004.

2-(Benzo[d][1,3]dioxol-5-yl)-4-(2-bromophenyl)butan-2-ol

(5d). GP-2 was carried out with ketone 3g (332.2 mg, 1 mmol) and

MeMgI [prepared from Mg (48, 2.0 mmol), MeI (312 mg, 2.0

mmol), and dry diethyl ether (10 mL)] in diethyl ether (2 mL) at 0

°C for 2 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 95:5 to 90:10)

furnished the alcohol 5g (306.2 mg, 88%) as a viscous liquid. TLC

control (petroleum ether/ethyl acetate 90:10), R_f(3g) = 0.80, R_f( 5g)

= 0.65, UV detection. IR (MIR-ATR, 4000−600 cm⁻¹): ν_max= 3386,

1

1155, 1061, 751 cm⁻¹. H NMR (CDCl₃, 400 MHz): δ = 7.32 (m,

1H, ArH), 7.11 (d, J = 8.1 Hz, 2H, ArH), 7.03 (d, J = 8.0 Hz, 2H,

ArH), 6.81 (dd, J = 9.4 and 3.0 Hz, 1H, ArH), 6.65 (td, J = 8.5 and

3.0 Hz, 1H, ArH), 4.52 (dd, J = 7.6 and 5.5 Hz, 1H, ArCH(OH)),

2.78−2.66 (m, 1H, CH), 2.61−2.54 (m, 1H, CH), 2.22−2.10 (m, 4H,

ArCH₃, OH), 1.97−1.83 (m, 2H, CH₂) ppm. ¹³C{¹H} NMR (CDCl₃,

100 MHz): δ = 162.0 (J_C−F= 245 Hz), 143.4 (J_C−F= 7 Hz), 141.3,

137.5, 133.8 (J = 9 Hz), 129.3 (2 × CH), 125.9 (2 × CH), 118.5 (J =

3 Hz), 117.2 (J = 23 Hz), 114.7 (J = 22 Hz), 73.7, 38.4, 32.7, 21.2

ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺calcd for

C₁₆H₁₅Br⁷⁹F 305.0335; Found 305.0324; [(M + H) + (−H₂O)]⁺

calcd for C₁₆H₁₅Br⁸¹F 307.0315; Found 307.0305.

4-(2-Bromophenyl)-2-phenylbutan-2-ol (5a). GP-2 was car-

ried out with ketone 3a (288.1 mg, 1 mmol), MeMgI [prepared from

Mg (48, 2.0 mmol), MeI (300 mg, 2.0 mmol), and dry diethyl ether

(10 mL)] in diethyl ether (2 mL) at 0 °C for 2 h. Puriﬁcation of the

crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 95:5 to 90:10) furnished the alcohol 5a (270.6

mg, 89%) as a viscous liquid. TLC control (petroleum ether/ethyl

1

2905, 1585, 1551, 1480, 1436, 1305, 1264, 1176, 847, 812 cm⁻¹. H

NMR (CDCl₃, 400 MHz): δ = 7.49 (dd, J = 8.0 and 1.2 Hz, 1H,

ArH), 7.26−7.14 (m, 2H, ArH), 7.06−7.03 (m, 2H, ArH), 6.97 (d, J

= 8.1 and 1.9 Hz, 1H, ArH), 6.80 (d, J = 8.1 Hz, 1H, ArH), 6.00−

5.91(m, 2H, −OCH₂O−), 2.78−2.68 (m, 1H, CH), 2.62−2.54 (m,

1H, CH), 2.11−1.98 (m, 2H, CH₂), 1.87 (s, 1H, OH), 1.61 (s, 3H,

CH₃) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz): δ = 147.5, 146.2,

141.6, 141.5, 132.7, 130.3, 127.5 (2 × CH), 124.3, 117.9, 107.8,

105.9, 100.9, 74.5, 44.3, 31.1, 30.4 ppm. HRMS (ESI) m/z: [(M + H)

+ (−H₂O)]⁺calcd for C₁₇H₁₆Br⁷⁹O₂331.0328; Found 331.0276; [(M

8712

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+ H) + (−H₂O)]⁺calcd for C₁₇H₁₆Br⁸¹O₂333.0307; Found

333.0255.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 93:07 to 90:10) furnished the

product 7b (80.2 mg, 80%) as a brown oil. TLC (petroleum ether/

ethyl acetate 90:10, R_f(4b) = 0.50, R_f(6a) = 0.95, R_f(7b) = 0.45, UV

detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3753, 3414, 3053,

1-(2-Bromophenyl)-3-(4-chlorophenyl)pentan-3-ol (5e). GP-

2 was carried out with ketone 3h (321 mg, 1 mmol) and EtMgI

[prepared from Mg (48, 2.0 mmol), CH₂CH₃I (312 mg, 2.0 mmol),

and dry diethyl ether (10 mL)] in diethyl ether (2 mL) at 0 °C for 2

h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 95:5 to 90:10)

furnished the alcohol 5e (327.4 mg, 93%) as a viscous liquid. TLC

control (petroleum ether/ethyl acetate 95:05), R_f(3h) = 0.80, R_f(5e)

= 0.55, UV detection. IR (MIR-ATR, 4000−600 cm⁻¹): ν_max= 3468,

1

2925, 1683, 1603, 1449, 1267, 814, 742 cm⁻¹. H NMR (400 MHz,

CDCl₃) δ = 7.52−7.47 (m, 3H, Ar-H), 7.36−7.32 (m, 3H, Ar-H),

7.26−7.23 (m, 3H, Ar-H), 7.23−7.17 (m, 2H, Ar-H), 7.11 (d, J = 7.9

Hz, 2H, Ar-H), 4.71−4.66 (m, 1H, ArCH(OH)), 3.01−2.87 (m, 2H,

CH₂), 2.32 (s, 3H, Ar-CH₃), 2.20−2.09 (m, 2H, CH₂), 2.01 (d, J =

2.9 Hz, 1H, OH) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz) δ = 143.9,

141.4, 137.1, 132.2, 131.5 (2 × CH), 129.1 (2 × CH), 128.7, 128.4,

128.3 (2 × CH), 128.2, 125.9, 125.8 (2 × CH), 123.3, 122.5, 93.0,

88.1, 73.8, 39.6, 31.0, 21.1 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺Calcd for C₂₄H₂₁309.1637; Found 309.1637.

1-(4-Ethylphenyl)-3-(2-(phenylethynyl)phenyl)propan-1-ol

(7c). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

ethylphenyl)propan-1-ol 4c (95.4 mg, 0.3 mmol), ethynylbenzene

6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7

mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at

100 °C for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 93:07 to 90:10)

furnished the product 7c (84.6 mg, 83%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 90:10, R_f(4c) = 0.50, R_f(6a) = 0.95,

1

3056, 2878, 1566, 1470, 1093, 1012, 1024, 1094, 827, 753 cm⁻¹. H

NMR (CDCl₃, 400 MHz): δ = 7.49 (dd, J = 8.0 and 1.2 Hz, 1H,

ArH), 7.43−7.38 (m, 2H, ArH), 7.37−7.31 (m, 2H, ArH), 7.21−7.16

(m, 1H, ArH), 7.12 (dd, J = 7.6 and 1.8 Hz, 1H, ArH), 7.07−6.98 (m,

1H, ArH), 2.80−2.73 (m, 1H, CH), 2.47−2.40 (m, 1H, CH), 2.12−

2.01 (m, 2H, CH₂), 1.92−1.82 (m, 2H, CH₂) 1.76 (s, 1H, OH), 0.78

(s, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz): δ =

143.8, 141.5, 132.8, 132.3, 130.3, 128.2 (2 × CH), 127.6, 127.5, 126.9

(2 × CH), 124.3, 76.9, 42.9, 35.7, 31.0, 7.6 ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺calcd for C₁₇H₁₇Br⁷⁹Cl 335.0196; Found

335.0181; [(M + H) + (−H₂O)]⁺calcd for C₁₇H₁₇Br⁸¹Cl 337.0176;

Found 337.0161.

3-(Benzo[d][1,3]dioxol-5-yl)-1-(2-(phenylethynyl)phenyl)-

pentan-3-ol (5f). GP-2 was carried out with ketone 3g (332.2 mg, 1

mmol), EtMgI [prepared from Mg (48, 2.0 mmol), and CH₂CH₃I

(312 mg, 2.0 mmol) and dry diethyl ether (10 mL)] in diethyl ether

(2 mL) at 0 °C for 2 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 95:5 to

90:10) furnished the alcohol 5f (333.1 mg, 92%) as a viscous liquid.

TLC control (petroleum ether/ethyl acetate 90:10), R_f(3g) = 0.60,

R_f(7c) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3366, 3021, 2960, 2926, 2209, 1496, 1447, 1057, 832, 754 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ = 7.51−7.46 (m, 3H, Ar-H), 7.36−7.31

(m, 3H, Ar-H), 7.24−7.22 (m, 4H, Ar-H), 7.20−7.15 (m, 1H, Ar-H),

7.14−7.12 (m, 2H, Ar-H), 4.69 (t, 1H, J = 6.3 Hz, ArCH(OH)),

3.03−2.90 (m, 2H, CH₂), 2.61 (q, J = 7.6 Hz, 2H, CH₂CH₃), 2.24−

2.21 (m, 2H, CH₂), 1.96 (s, 1H, OH), 1.20 (t, J = 7.6 Hz, 3H,

CH₂CH₃) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz) δ = 144.0, 143.5,

141.7, 132.2, 131.5 (2 × CH), 128.9, 128.5, 128.3 (2 × CH), 128.2,

127.9 (2 × CH), 125.9 (2 × CH), 125.9, 123.4, 122.6, 93.2, 88.1,

73.9, 39.6, 31.0, 28.5, 15.5 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺Calcd for C₂₅H₂₃323.1794; Found 323.1797.

1

R_f(5f) = 0.45, UV detection. IR (MIR-ATR, 4000−600 cm⁻¹): ν_max

=

3559, 2878, 1503, 1487, 1238, 1040, 1025, 752, 731 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ = 7.49 (dd, J = 8.0 and 1.2 Hz, 1H, ArH), 7.19

(td, J = 7.5 and 1.2 Hz, 1H, ArH), 7.14 (dd, J = 7.6 and 1.9 Hz, 1H,

ArH), 7.06−7.00 (m, 1H, ArH), 6.97 (d, J = 1.8 Hz, 1H, ArH), 6.92

(dd, J = 8.1 and 1.8 Hz, 1H, ArH), 6.81 (d, J = 8.1 Hz, 1H, ArH), 5.97

(s, 2H, ArOCH₂O), 2.80−2.72 (m, 1H, CH), 2.52−2.47 (m, 1H,

CH), 2.10−2.01 (m, 2H, CH₂), 1.94−1.78 (m, 2H, CH₂), 1.75 (s,

1H, ArC(OH)), 0.80 (t, J = 7.4 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ = 147.6, 146.0, 141.7, 139.4, 132.7,

130.4, 127.5, 127.4, 124.3, 118.5, 107.7, 106.3, 100.9, 77.0, 43.0, 35.7,

30.7, 7.7 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺calcd for

C₁₈H₁₈Br⁷⁹O₂345.0484; Found 345.0475; [(M + H) + (−H₂O)]⁺

calcd for C₁₈H₁₈Br⁸¹O₂347.0464; Found 347.0456.

1

1-(4-Isopropylphenyl)-3-(2-(phenylethynyl)phenyl)propan-

1-ol (7d). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

isopropylphenyl)propan-1-ol 4d (99.6 mg, 0.3 mmol), ethynylben-

zene 6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃

(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2

mL) at 100 °C for 12 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 93:07 to

90:10) furnished the product 7d (73.3 mg, 69%) as a brown liquid.

TLC (petroleum ether/ethyl acetate 90:10, R_f(4d) = 0.50, R_f(6a) =

0.95, R_f(7d) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

ν_max= 3350, 2894, 2827, 1476, 1251, 1078, 820, 743 cm⁻¹. ¹H NMR

(400 MHz, CDCl₃) δ = 7.51−7.48 (m, 3H, Ar-H), 7.37−7.32 (m, 3H,

Ar-H), 7.28−7.23 (m, 4H, Ar-H), 7.20−7.15 (m, 3H, Ar-H), 4.71−

4.68 (m, 1H, ArCH(OH)), 3.03−2.83 (m, 3H, CH₂and CH(CH₃)₂),

2.24−2.12 (m, 2H, CH₂), 1.96 (s, 1H, OH), 1.22 (d, J = 6.9 Hz, 6H,

CH(CH₃)₂) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 148.2,

143.9, 141.8, 132.2, 131.5 (2× CH), 128.9, 128.5, 128.3 (2 × CH),

128.2, 126.5 (2 × CH), 125.9 (2 × CH), 125.8, 123.4, 122.6, 93.0,

88.1, 73.9, 39.6, 33.8, 31.1, 23.9 (2 × CH₃) ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺Calcd for C₂₆H₂₅337.1950; Found 337.1937.

1-(3,4-Dimethoxyphenyl)-3-(2-(phenylethynyl)phenyl)-

propan-1-ol (7e). GP-3 was carried out with 3-(2-bromophenyl)-1-

(3,4-dimethoxyphenyl)propan-1-ol 4e (105.0 mg, 0.3 mmol),

ethynylbenzene 6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3

mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol),

and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 85:15 to 80:20) furnished the product 7e (90.3 mg, 81%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 75:25, R_f(4e) =

0.50, R_f(6a) = 0.95, R_f(7e) = 0.42, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3466, 2933, 1594, 1516, 1462, 1263, 1234,

1-Phenyl-3-(2-(phenylethynyl)phenyl)propan-1-ol (7a). GP-

3 was carried out with 3-(2-bromophenyl)-1-phenylpropan-1-ol 4a

(87.0 mg, 0.3 mmol), ethynylbenzene 6a (45.9 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 93:07 to 90:10) furnished the

product 7a (73.9 mg, 79%) as a brown liquid. TLC (petroleum ether/

ethyl acetate 90:10, R_f(4a) = 0.50, R_f(6a) = 0.95, R_f(7a) = 0.45, UV

detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3387, 3064, 2922,

1599, 1492, 1452, 1057, 755, 700 cm⁻¹. ¹H NMR (400 MHz, CDCl₃)

δ = 7.51−7.45 (m, 3H, Ar-H), 7.38−7.32 (m, 5H, Ar-H), 7.29−7.27

(m, 2H, Ar-H), 7.26−7.22 (m, 3H, Ar−H), 7.18 (ddd, J = 7.5, 6.2,

and 2.6 Hz, 1H, Ar-H), 4.73 (t, J = 5.2 Hz, 1H, ArCH(OH)), 3.06−

2.87 (m, 2H, CH₂), 2.27−2.04 (m, 2H, CH₂), 1.99 (d, J = 2.9 Hz, 1H,

OH) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz) δ = 144.5, 143.9,

132.3, 131.5 (2 × CH), 128.9, 128.5, 128.4 (2 × CH), 128.3 (2 ×

CH), 128.2, 127.5, 126.0, 125.9 (2× CH), 123.3, 122.6, 93.0, 88.1,

74.0, 39.8, 31.0 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺

Calcd for C₂₃H₁₉295.1481; Found 295.1487.

3-(2-(Phenylethynyl)phenyl)-1-(p-tolyl)propan-1-ol (7b).

GP-3 was carried out with 3-(2-bromophenyl)-1-(p-tolyl)propan-1-

ol 4b (91.2 mg, 0.3 mmol), ethynylbenzene 6a (45.9 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

1

1027, 757, 691 cm⁻¹. H NMR (400 MHz, CDCl₃) δ = 7.52 (d, J =

7.5 Hz, 1H, Ar-H), 7.48−7.46 (m, 2H, Ar-H), 7.36−7.34 (m, 3H, Ar-

H), 7.29−7.23 (m, 2H, Ar-H), 7.20−7.16 (m, 1H, Ar-H), 6.89−6.85

8713

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(m, 2H, Ar-H), 6.77 (d, J = 8.1 Hz, 1H, Ar-H), 4.68 (dd, J = 7.5 and

5.6 Hz, 1H, ArCH(OH)), 3.84 (s, 3H, ArOCH₃), 3.81 (s, 3H,

ArOCH₃), 3.06−2.88 (m, 2H, CH₂), 2.27−2.04 (m, 3H, CH₂and

OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 149.0, 148.4,

143.9, 137.1, 132.3, 131.5 (2 × CH), 128.9, 128.6, 128.4 (2 × CH),

128.3, 125.9, 123.3, 122.6, 118.2, 110.9, 109.1, 93.0, 88.1, 73.9, 55.8,

55.7, 39.6, 31.1 ppm. HRMS (ESI) m/z: [M+NH₄]⁺Calcd for

C₂₅H₂₈NO₃390.2064; Found 390.2049.

39.8, 30.7 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for

C₂₃H₁₈Cl 329.1091; Found 329.1084.

1-(4-Fluorophenyl)-3-(2-(phenylethynyl)phenyl)propan-1-

ol (7i). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

ﬂuorophenyl)propan-1-ol 4i (92.4 mg, 0.3 mmol), ethynylbenzene

6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7

mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at

100 °C for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 93:07 to 90:10)

furnished the product 7i (71.3 mg, 72%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 90:10, R_f(4i) = 0.50, R_f(6a) = 0.95,

1-(3,5-Dimethoxyphenyl)-3-(2-(phenylethynyl)phenyl)-

propan-1-ol (7f). GP-3 was carried out with 3-(2-bromophenyl)-1-

(3,5-dimethoxyphenyl)propan-1-ol 4f (105 mg, 0.3 mmol), ethynyl-

benzene 6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %),

PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF

(2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by silica

gel column chromatography (petroleum ether/ethyl acetate 85:15 to

80:20) furnished the product 7f (92.6 mg, 83%) as a brown liquid.

TLC (petroleum ether/ethyl acetate 75:25, R_f(4f) = 0.50, R_f(6a) =

0.95, R_f(7f) = 0.42 UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

R_f(7i) = 0.42, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3387, 3058, 2927, 1678, 1601, 1468, 1267, 1139, 748 cm⁻¹. ¹H NMR

(CDCl₃400 MHz) δ = 7.51−7.49 (d, 1H, J = 7.5 and 0.9 Hz, Ar-H),

7.48−7.43 (m, 2H, Ar-H), 7.37−7.33 (m, 3H, Ar-H), 7.33−7.28 (m,

2H, Ar-H), 7.27−7.22 (m, 2H, Ar-H), 7.21−7.15 (m, 1H, Ar-H),

6.99−6.94 (m, 2H, Ar-H), 4.72 (t, 1H, J = 6.4 Hz, ArCH(OH)),

2.96−2.89 (m, 2H, CH₂), 2.25−2.00 (m, 3H, CH₂and OH) ppm.

¹³C{¹H} NMR (CDCl₃, 100 MHz) δ = 162.1 (J_C−F= 244 Hz), 143.7,

140.1, 132.3, 131.5 (2 × CH), 128.9, 128.6, 128.4 (2× CH), 128.3,

1

ν_max= 3022, 1582, 1439, 1250, 1040, 723, 659 cm⁻¹. H NMR (400

MHz, CDCl₃) δ = 7.53−7.49 (m, 3H, Ar-H), 7.37−7.33 (m, 3H, Ar-

H), 7.28−7.26 (m, 2H, Ar-H), 7.22−7.17 (m, 1H, Ar-H), 6.52 (d, J =

2.3 Hz, 2H, Ar-H), 6.35 (t, J = 2.3 Hz, 1H, Ar-H), 4.69 (dd, J = 7.4

and 5.5 Hz, 1H, ArCH(OH)), 3.73 (s, 6H, 2 × ArOCH₃), 3.04−2.93

(m, 2H, CH₂), 2.19−2.05 (m, 3H, CH₂and OH) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ = 160.8 (2× C), 147.1, 143.8, 132.2,

131.5 (2 × CH), 128.9, 128.5, 128.3 (2 × CH), 128.2, 125.9, 123.3,

122.6, 103.6 (2 × CH), 99.5, 93.1, 88.1, 74.1, 55.2 (2 × OCH₃), 39.6,

31.1 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₅H₂₅O₃

373.1798; Found 373.1776.

126.6 (J_C−F= 8.0 Hz, 2 × Ar-CH), 126.0, 123.2, 122.6, 115.3 (J_C−F

=

21.2 Hz, 2 × Ar-CH), 93.0, 87.9, 73.2, 39.9, 30.9 ppm. HRMS (ESI)

m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₃H₁₈F 313.1387; Found

313.1393.

3-(2-((4-Methoxyphenyl)ethynyl)phenyl)-1-(naphthalen-1-

yl)propan-1-ol (7j). GP-3 was carried out with 3-(2-bromophenyl)-

1-(naphthalen-1-yl)propan-1-ol 4j (102 mg, 0.3 mmol), 1-ethynyl-4-

methoxybenzene 6d (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol

%), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and

DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

88:12 to 85:15) furnished the product 7j (90.2 mg, 83%) as a brown

liquid. TLC (petroleum ether/ethyl acetate 88:12, R_f(4j) = 0.50,

R_f(6d) = 0.90, R_f(7j) = 0.45, UV detection. IR (MIR-ATR, 4000-600

cm⁻¹) ν_max= 3431, 2930, 2368, 1605, 1509, 1248, 1030, 801 cm⁻¹. ¹H

NMR (400 MHz, CDCl₃) δ = 7.89 (d, J = 8.5 Hz, 1H, Ar-H), 7.84 (d,

J = 8.1 Hz, 1H, Ar-H), 7.75 (d, J = 8.2 Hz, 1H, Ar-H), 7.70 (d, J = 7.1

Hz, 1H, Ar-H), 7.54−7.50 (d, J = 7.2 Hz, 1H, Ar-H), 7.46 (d, J = 7.2

Hz, 1H, Ar-H), 7.44−7.37 (m, 3H, Ar-H), 7.34−7.23 (m, 3H, Ar-H),

7.23−7.17 (m, 1H, Ar-H), 6.91−6.83 (m, 2H, Ar-H), 5.53 (d, J = 8.3

Hz, 1H, ArCH(OH)), 3.84 (s, 3H, ArOCH₃), 3.26−3.05 (m, 2H,

CH₂), 2.41−2.22 (m, 2H, CH₂), 2.17 (s, 1H, OH) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 159.6 (s, Ar-C), 143.6 (s, Ar-C), 140.2

(s, Ar-C), 133.7 (s, Ar-C), 132.9 (d, 2 × Ar-CH), 132.1 (d, Ar-CH),

130.2 (s, Ar-C), 129.0 (d, Ar-CH), 128.8 (d, Ar-CH), 128.2 (d, Ar-

CH), 127.8 (d, Ar-CH), 126.0 (d, Ar-CH), 125.9 (d, Ar-CH), 125.4

(d, 2 × Ar-CH), 123.0 (d, Ar-CH), 123.0 (s, Ar-C), 122.6 (d, Ar-

CH), 115.4 (s, Ar-C), 114.0 (d, 2 × Ar-CH), 93.0 (s, CC), 86.8 (s,

CC), 70.4 (d, ArCH(OH)), 55.3 (s, ArOCH₃), 39.3 (t, CH₂), 31.4

(t, CH₂) ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for

C₂₈H₂₃O 375.1743; Found 375.1730.

1-(Benzo[d][1,3]dioxol-5-yl)-3-(2-(phenylethynyl)phenyl)-

propan-1-ol (7g). GP-3 was carried out with 1-(benzo[d][1,3]-

dioxol-5-yl)-3-(2-bromophenyl)propan-1-ol 4g (100.2 mg, 0.3

mmol), ethynylbenzene 6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0

mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45

mmol), and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 90:10 to 85:15) furnished the product 7g (75.7 mg, 71%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 85:15, R_f(4g) =

0.50, R_f(6a) = 0.95, R_f(7g) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3567, 3056, 2969, 1598, 1487, 1434, 1373,

1039, 916 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.50−7.44 (m, 3H,

Ar-H), 7.35−7.30 (m, 3H, Ar-H), 7.26−7.21 (m, 2H, Ar-H), 7.18−

7.13 (m, 1H, Ar-H), 6.84 (d, J = 1.6 Hz, 1H, Ar-H), 6.79−6.72 (m,

1H, Ar-H), 6.69 (d, J = 7.9 Hz, 1H, Ar-H), 5.85 (d, J = 1.5 Hz, 1H,

−OCH_aCH_bO−), 5.84 (d, J = 1.5 Hz, 1H, -OCH_aCH_bO−), 4.60 (dd,

J = 7.4 and 5.7 Hz, 1H, ArCH(OH)), 3.00−2.80 (m, 2H, CH₂),

2.22−1.98 (m, 3H, CH₂and OH) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 147.7, 146.8, 143.8, 138.5, 132.2, 131.4 (2 × CH), 128.8,

128.4, 128.3 (2 × CH), 128.2, 125.9, 123.3, 122.5, 119.3, 108.0,

106.4, 100.9, 93.0, 88.0, 73.8, 39.7, 30.9 ppm. HRMS (ESI) m/z: [(M

+ H) + (−H₂O)]⁺Calcd for C₂₄H₁₉O₂339.1379; Found 339.1372.

1-(4-Chlorophenyl)-3-(2-(phenylethynyl)phenyl)propan-1-

ol (7h). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

chlorophenyl)propan-1-ol 4h (97.2 mg, 0.3 mmol), ethynylbenzene

6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7

mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at

100 °C for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 93:07 to 90:10)

furnished the product 7h (78.1 mg, 75%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 90:10, R_f(4h) = 0.50, R_f(6a) = 0.95,

3-(2-((3,4-Dimethoxyphenyl)ethynyl)phenyl)-1-phenylpro-

pan-1-ol (7k). GP-3 was carried out with 3-(2-bromophenyl)-1-

phenylpropan-1-ol 4a (87.2 mg, 0.3 mmol), 4-ethynyl-1,2-dimethox-

ybenzene 6e (72.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %),

PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF

(2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by silica

gel column chromatography (petroleum ether/ethyl acetate 85:15 to

80:20) furnished the product 7k (88.1 mg, 79%) as a brown liquid.

TLC (petroleum ether/ethyl acetate 75:25, R_f(4a) = 0.50, R_f(6e) =

0.9, R_f(7k) = 0.48, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

R_f(7h) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

1

= 3516, 2934, 1597, 1513, 1453, 1249, 1132, 1024, 759 cm⁻¹. H

3566, 3368, 2924, 2318, 1596, 1491, 1445, 1082, 1013, 755 cm⁻¹. ¹H

NMR (CDCl₃400 MHz) δ = 7.50 (d, 1H, J = 7.5 and 0.9 Hz, Ar-H),

7.46−7.43 (m, 2H, Ar-H), 7.38−7.33 (m, 3H, Ar-H), 7.28−7.21 (m,

6H, Ar-H), 7.19−7.14 (m, 1H, Ar-H), 4.69 (t, 1H, J = 5.9 Hz,

ArCH(OH)), 2.95−2.87 (m, 2H, CH₂), 2.19−2.03 (m, 3H, CH₂and

OH) ppm. ¹³C{¹H} NMR (CDCl₃, 100 MHz) δ = 143.6, 142.9,

133.1, 132.3, 131.4 (2 × CH), 128.9, 128.6, 128.6 (2 × CH), 128.4 (2

× CH), 128.3, 127.3 (2 × CH), 126.0, 123.2, 122.6, 93.1, 88.0, 73.2,

NMR (400 MHz, CDCl₃) δ = 7.48 (d, J = 7.3 Hz, 1H, Ar-H), 7.36−

7.32 (m, 2H, Ar-H), 7.28 (ddd, J = 5.9, 2.4, and 0.6 Hz, 2H, Ar-H),

7.26−7.20 (m, 3H, Ar-H), 7.16 (ddd, J = 7.6, 5.7, and 3.1 Hz, 1H, Ar-

H), 7.08 (dd, J = 8.3 and 1.9 Hz, 1H, Ar-H), 7.02 (d, J = 1.9 Hz, 1H,

Ar-H), 6.83 (d, J = 8.3 Hz, 1H, Ar-H), 4.71 (dd, J = 8.0 and 5.0 Hz,

1H, ArCH(OH)), 3.88 (s, 3H, ArOCH₃), 3.87 (s, 3H, ArOCH₃),

2.97 (dddd, J = 16.1, 13.4, 9.5, and 6.2 Hz, 2H, CH₂), 2.25−2.09 (m,

2H, CH₂), 2.08 (s, 1H, OH) ppm. ¹³C{¹H} NMR (100 MHz,

8714

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

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Article

CDCl₃) δ 149.5, 148.6, 144.5, 143.7, 132.1, 128.9, 128.4 (2 × CH),

128.3, 127.4, 125.9, 125.8 (2 × CH), 124.8, 122.8, 115.5, 114.1,

111.0, 93.1, 86.6, 73.9, 55.9, 55.8, 39.8, 31.1 ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺Calcd for C₂₅H₂₃O₂355.1692; Found

355.1675.

1-(p-Tolyl)-3-(2-(p-tolylethynyl)phenyl)propan-1-ol (7l). GP-

3 was carried out with 3-(2-bromophenyl)-1-(p-tolyl)propan-1-ol 4b

(91.2 mg, 0.3 mmol), 1-ethynyl-4-methylbenzene 6b (52.2 mg, 0.45

mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %),

Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12

h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 93:07 to 90:10)

furnished the product 7l (76.5 mg, 75%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 90:10, R_f(4b) = 0.50, R_f(6b) = 0.95,

1-(4-Ethylphenyl)-3-(2-(p-tolylethynyl)phenyl)propan-1-ol

(7o). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

ethylphenyl)propan-1-ol 4c (95.4 mg, 0.3 mmol), 1-ethynyl-4-

methylbenzene 6b (52.6 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3

mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol),

and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 93:07 to 90:10) furnished the product 7o (83.9 mg, 79%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(4c) =

0.50, R_f(6b) = 0.95, R_f(7o) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3409, 2964, 2928, 2313, 1509, 1451, 1045,

816, 706 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.49 (d, J = 7.4 Hz,

1H, Ar-H), 7.39 (d, J = 8.1 Hz, 2H, Ar-H), 7.28 (s, 1H, Ar-H), 7.27−

7.22 (m, 3H, Ar-H), 7.20−7.17 (m, 1H, Ar-H), 7.15 (dd, J = 7.8, 5.8

Hz, 4H, Ar-H), 4.70 (dd, J = 7.6 and 5.5 Hz, 1H, ArCH(OH)), 3.05−

2.88 (m, 2H, CH₂), 2.61 (q, J = 7.6 Hz, 2H, CH₂CH₃), 2.38 (s, 3H,

ArCH₃), 2.28−2.10 (m, 2H, CH₂), 1.96 (s, 1H, OH), 1.22 (t, J = 7.6

Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ =

143.9, 143.5, 141.7, 138.3, 132.2, 131.4 (2 × CH), 129.1 (2 × CH),

128.8, 128.3, 127.9 (2 × CH), 125.9 (2 × CH), 125.8, 122.8, 120.3,

93.2, 87.5, 73.9, 39.7, 31.1, 28.5, 21.5, 15.5 ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺Calcd for C₂₆H₂₅337.1950; Found 337.1940.

1-(4-Ethylphenyl)-3-(2-((4-ethylphenyl)ethynyl)phenyl)-

propan-1-ol (7p). GP-3 was carried out with 3-(2-bromophenyl)-1-

(4-ethylphenyl)propan-1-ol 4c (95.4 mg, 0.3 mmol), 1-ethyl-4-

ethynylbenzene 6c (58.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3

mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol),

and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 90:10 to 88:12) furnished the product 7p (79.5 mg, 72%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(4c) =

0.50, R_f(6c) = 0.95 R_f(7p) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3736, 2964, 1590, 1456, 1205, 1156, 1064,

757 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ 7.50−7.48 (m, 1H, Ar-H),

7.42−7.39 (m, 2H, Ar-H), 7.27 (s, 1H, Ar-H), 7.26−7.22 (m, 3H, Ar-

H), 7.20−7.15 (m, 3H, Ar-H), 7.15−7.13 (m, 2H, Ar-H), 4.69 (m,

1H, ArCH(OH)), 3.00−2.88 (m, 2H, CH₂), 2.66 (q, J = 7.6 Hz, 2H,

CH₂CH₃), 2.61 (q, J = 7.7 Hz, 2H, CH₂CH₃), 2.20−2.10 (m, 2H,

CH₂), 1.97 (d, J = 3.2 Hz, 1H, OH), 1.24 (t, J = 7.6 Hz, 3H,

CH₂CH₃), 1.20 (t, J = 7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ = 144.6, 143.9, 143.5, 141.8, 132.2, 131.5 (2 ×

CH), 128.9, 128.3, 127.9 (2 × CH), 127.9 (2 × CH), 125.9 (2 ×

CH), 125.8, 122.8, 120.5, 93.2, 87.4, 73.8, 39.6, 31.0, 28.8, 28.5, 15.5,

15.5 ppm. HRMS (ESI) m/z: [M + Na]⁺Calcd for C₂₇H₂₈ONa

391.2032; Found 391.2030.

R_f(7l) = 0.30, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3391, 3055, 2919, 2213, 1605, 1509, 1058, 816, 756 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ 7.51 (d, J = 7.4 Hz, 1H, Ar-H), 7.39 (d, J = 8.1

Hz, 2H, Ar-H), 7.30−7.25 (m, 4H, Ar-H), 7.22−7.10 (m, 5H, Ar-H),

4.72−4.69 (m, 1H, ArCH(OH)), 3.09−2.82 (m, 2H, CH₂), 2.39 (s,

3H, ArCH₃), 2.34 (s, 3H, ArCH₃), 2.28−2.07 (m, 2H, CH₂), 2.00 (s,

1H, OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 143.8, 141.5,

138.3, 137.1, 132.1, 131.4 (2 × CH), 129.1 (2 × CH), 129.0 (2 ×

CH), 128.8, 128.3, 125.8 (3 × CH), 122.7, 120.2, 93.2, 87.4, 73.8,

39.7, 31.1, 21.6, 21.2 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺

Calcd for C₂₅H₂₃323.1794; Found 323.1775.

1

3-(2-((4-Methoxyphenyl)ethynyl)phenyl)-1-(p-tolyl)propan-

1-ol (7m). GP-3 was carried out with 3-(2-bromophenyl)-1-(p-

tolyl)propan-1-ol 4b (91.2 mg, 0.3 mmol), 1-ethynyl-4-methoxyben-

zene 6d (59.4 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃

(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2

mL) at 100 °C for 12 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 90:10 to

85:15) furnished the product 7m (87.6 mg, 82%) as a brown liquid.

TLC (petroleum ether/ethyl acetate 85:15, R_f(4b) = 0.60, R_f(6d) =

0.90, R_f(7m) = 0.55, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

ν_max= 3384, 2915, 2825, 2150, 2061, 1361, 1238, 1172, 946, 888

cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ = 7.47 (d, J = 7.4 Hz, 1H, Ar-

H), 7.42−7.38 (m, 2H, Ar-H), 7.24−7.20 (m, 4H, Ar-H), 7.16 (ddd, J

= 7.6, 5.2, and 3.7 Hz, 1H, Ar-H), 7.11 (d, J = 7.8 Hz, 2H, Ar-H),

6.90−6.84 (m, 2H, Ar-H), 4.69 (dd, J = 7.5 and 5.5 Hz, 1H,

ArCH(OH)), 3.82 (s, 3H, ArOCH₃), 3.06−2.81 (m, 2H, CH₂), 2.31

(s, 3H, ArCH₃), 2.27−2.05 (m, 2H, CH₂), 2.02 (s, 1H, OH) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 159.6, 143.7, 141.5, 137.1,

132.9 (2 × CH), 132.0, 129.1 (2 × CH), 128.8, 128.1, 125.9 (3 ×

CH), 122.9, 115.5, 113.9 (2 × CH), 93.1, 86.8, 73.8, 55.3, 39.7, 31.0,

21.1 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for

C₂₅H₂₃O 339.1743; Found 339.1732.

1-(4-Ethylphenyl)-3-(2-((4-methoxyphenyl)ethynyl)phenyl)-

propan-1-ol (7q). GP-3 was carried out with 3-(2-bromophenyl)-1-

(4-ethylphenyl)propan-1-ol 4c (95.4 mg, 0.3 mmol), 1-ethynyl-4-

methoxybenzene 6d (59.4 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol

%), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and

DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

90:10 to 88:12) furnished the product 7q (83.2 mg, 75%) as a brown

liquid. TLC (petroleum ether/ethyl acetate 85:15, R_f(4c) = 0.50,

R_f(6d) = 0.9, R_f(7q) = 0.45, UV detection. IR (MIR-ATR, 4000-600

cm⁻¹) ν_max= 3374, 2923, 2859, 2323, 1492, 1446, 1051, 753, 694

3-(2-((3,4-Dimethoxyphenyl)ethynyl)phenyl)-1-(p-tolyl)-

propan-1-ol (7n). GP-3 was carried out with 3-(2-bromophenyl)-1-

(p-tolyl)propan-1-ol 4b (91.2 mg, 0.3 mmol), 4-ethynyl-1,2-

dimethoxybenzene 6e (72.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3

mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol),

and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 85:15 to 80:20) furnished the product 7n (90.3 mg, 78%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 75:25, R_f(4b) =

0.50, R_f(6e) = 0.90, R_f(7n) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3389, 2927, 1584, 1449, 1484, 1251, 1227,

1

cm⁻¹. H NMR (400 MHz, CDCl₃) δ = 7.48−7.46 (m, 1H, Ar-H),

7.45−7.40 (m, 2H, Ar-H), 7.27−7.26 (m, 2H, Ar-H), 7.23 (dd, J =

4.9 and 1.1 Hz, 2H, Ar-H), 7.17−7.14 (m, 1H, Ar-H), 7.12 (t, J = 8.1

Hz, 2H, Ar-H), 6.91−6.84 (m, 2H, Ar-H), 4.68 (dd, J = 7.7 and 5.4

Hz, 1H, ArCH(OH)), 3.81 (s, 3H, ArOCH₃), 2.97−2.88 (m, 2H,

CH₂), 2.61 (q, J = 7.6 Hz, 2H, CH₂CH₃), 2.27−2.05 (m, 2H, CH₂),

2.02 (s, 1H, OH), 1.22 (t, J = 7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ = 159.6, 143.7, 143.5, 141.7, 132.9 (2 ×

CH), 132.0, 128.8, 128.1, 127.9 (2 × CH), 125.9 (2 × CH), 125.8,

122.9, 115.5, 114.0 (2 × CH), 93.0, 86.8, 73.8, 55.3, 39.6, 31.0, 28.5,

15.5 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for

C₂₆H₂₅O 353.1900; Found 353.1903.

1

1041, 822 cm⁻¹. H NMR (400 MHz, CDCl₃) δ 7.51−7.49 (m, 1H,

Ar-H), 7.25−7.21 (m, 4H, Ar-H), 7.18 (ddd, J = 7.6, 5.7, and 3.2 Hz,

1H, Ar-H), 7.13−7.07 (m, 3H, Ar-H), 7.05 (d, J = 1.8 Hz, 1H, Ar-H),

6.84 (d, J = 8.3 Hz, 1H, Ar-H), 4.70 (dd, J = 8.0 and 5.0 Hz, 1H,

ArCH(OH)), 3.91 (s, 3H, ArOCH₃), 3.90 (s, 3H, ArOCH₃), 2.97

(dddd, J = 16.1, 13.4, 9.6, and 6.1 Hz, 2H, CH₂), 2.32 (s, 3H,

ArCH₃), 2.16 (ddddd, J = 13.7, 11.8, 9.8, 7.4, and 5.3 Hz, 2H, CH₂),

1.97 (s, 1H, OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 149.4,

148.7, 143.8, 141.5, 137.1, 132.1, 129.1 (2 × CH), 128.9, 128.3,

125.9, 125.8 (2 × CH), 124.8, 122.8, 115.6, 114.2, 111.1, 93.1, 86.7,

73.8, 55.9, 55.9, 39.7, 31.1, 21.1 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺Calcd for C₂₆H₂₅O₂369.1849; Found 369.1837.

3-(2-((3,5-Dimethoxyphenyl)ethynyl)phenyl)-1-(4-

ethylphenyl)propan-1-ol (7r). GP-3 was carried out with 3-(2-

8715

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

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Article

bromophenyl)-1-(4-ethylphenyl)propan-1-ol 4c (95.4 mg, 0.3 mmol),

1-ethynyl-3,5-dimethoxybenzene 6f (45.9 mg, 0.45 mmol), Pd(OAc)₂

(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45

mmol), and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 85:15 to 80:20) furnished the product 7r (94.8 mg, 79%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 75:25, R_f(4c) =

0.50, R_f(6f) = 0.90, R_f(7r) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3338, 2895, 2836, 1496, 1250, 1016, 801, 729

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 90:10 to 85:15) furnished the

product 7u (93.3 mg, 81%) as a brown liquid. TLC (petroleum ether/

ethyl acetate 85:15, R_f(4d) = 0.50, R_f(6d) = 0.90, R_f(7u) = 0.45, UV

detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3410, 2958, 2372,

1606, 1509, 1287, 1248, 831, 756 cm⁻¹. ¹H NMR (400 MHz, CDCl₃)

δ 7.49 (d, J = 7.4 Hz, 1H, Ar-H), 7.47−7.43 (m, 2H, Ar-H), 7.30−

7.28 (m, 2H, Ar-H), 7.27−7.23 (m, 2H, Ar-H), 7.21−7.16 (m, 3H,

Ar-H), 6.91−6.87 (m, 2H, Ar-H), 4.71 (dd, J = 6.2 Hz, 1H,

ArCH(OH)), 3.84 (s, 3H, ArOCH₃), 3.09−2.82 (m, 3H, CH₂and

CH(CH₃)₂), 2.26−2.07 (m, 2H, CH₂), 1.99 (s, 1H, OH), 1.24 (d, J =

6.9 Hz, 6H, CH(CH₃)₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

159.6, 148.2, 143.7, 141.9, 132.9 (2 × CH), 132.0, 128.8, 128.2, 126.5

(2 × CH), 125.9 (2 × CH), 125.9, 122.9, 115.5, 113.9 (2 × CH),

93.0, 86.8, 73.8, 55.3, 39.6, 33.8, 31.1, 23.9, 23.8 ppm. HRMS (ESI)

m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₇H₂₇O 367.2056; Found

367.2036.

1-(4-Isopropylphenyl)-3-(2-((2-methoxyphenyl)ethynyl)-

phenyl)propan-1-ol (7v). GP-3 was carried out with 3-(2-

bromophenyl)-1-(4-isopropylphenyl)propan-1-ol 4d (99.6 mg, 0.3

mmol), 1-ethynyl-2-methoxybenzene 6h (59.4 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 90:10 to 85:15) furnished the

product 7v (91.0 mg, 79%) as a brown liquid. TLC (petroleum ether/

ethyl acetate 85:15, R_f(4d) = 0.50, R_f(6h) = 0.90, R_f(7v) = 0.45, UV

detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3441, 2933, 1596,

1493, 1455, 1204, 1154, 1060, 756 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ ¹H NMR (400 MHz, CDCl₃) δ 7.58 (d, J = 7.4 Hz, 1H, Ar-

H), 7.52 (dd, J = 7.6, 1.7 Hz, 1H, Ar-H), 7.40−7.15 (m, 8H, Ar-H),

6.98 (td, J = 7.5, 0.9 Hz, 1H, Ar-H), 6.94 (d, J = 8.3 Hz, 1H, Ar-H),

4.73 (s, 1H, ArCH(OH)), 3.92 (s, 3H, ArOCH₃), 3.07 (t, J = 7.7 Hz,

2H, CH₂), 2.90 (dt, J = 13.8, 6.9 Hz, 1H, ArCH(CH₃)₂), 2.40 (br. s,

1H, OH), 2.34−2.08 (m, 2H, CH₂), 1.25 (d, J = 6.9 Hz, 6H,

ArCH(CH₃)₂) ppm. ¹³C{H} NMR (100 MHz, CDCl₃) δ 159.7,

148.0, 144.0, 142.0, 133.4, 132.3, 129.7, 129.0, 128.4, 126.4 (2 ×

CH), 125.8 (2 × CH), 125.8, 123.0, 120.6, 112.7, 110.8, 92.4, 89.4,

73.3, 55.9, 40.1, 33.8, 31.0, 24.0 (2× CH₃) ppm. HRMS (ESI) m/z:

[(M+H)]⁺Calcd for C₂₇H₂₉O₂385.2162, Found 385.2184.

1-(3,5-Dimethoxyphenyl)-3-(2-(p-tolylethynyl)phenyl)-

propan-1-ol (7w). GP-3 was carried out with 3-(2-bromophenyl)-1-

(3,5-dimethoxyphenyl)propan-1-ol 4f (105.0 mg, 0.3 mmol), 1-

ethynyl-4-methylbenzene 6b (52.5 mg, 0.45 mmol), Pd(OAc)₂(2.0

mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45

mmol), and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 85:15 to 80:20) furnished the product 7w (96.1 mg, 83%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 75:25, R_f(4f) =

0.50, R_f(6b) = 0.98, R_f(7w) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3399, 2966, 2901, 1583, 1445, 1250, 1141,

1047, 724 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ 7.52 (d, J = 7.4 Hz,

1H, Ar-H), 7.41 (d, J = 8.1 Hz, 2H, Ar-H), 7.31−7.24 (m, 2H, Ar-H),

7.22−7.12 (m, 3H, Ar-H), 6.53 (d, 2H, Ar-H), 6.37 (t, J = 2.3 Hz, 1H,

Ar-H), 4.73−4.63 (m, 1H, ArCH(OH)), 3.75 (s, 6H, 2 × ArOCH₃),

3.07−2.95 (m, 2H, CH₂), 2.39 (s, 3H, Ar-CH₃), 2.15 (ddt, J = 9.7 Hz,

7.2 and 5.4 Hz, 3H, CH₂and OH) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 160.9 (2 × C), 147.2, 143.8, 138.4, 132.2, 131.4 (2 × CH),

129.2 (2 × CH), 128.9, 128.4, 125.4, 122.9, 120.3, 103.8 (2 × CH),

99.5, 93.3, 87.5, 74.1, 55.3 (2 × OCH₃), 39.7, 31.1, 21.5 ppm. HRMS

(ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₆H₂₅O₂369.1849;

Found 369.1829.

1

cm⁻¹. H NMR (400 MHz, CDCl₃) δ 7.42 (dd, J = 7.2 and 0.8 Hz,

1H, Ar-H), 7.21−7.13 (m, 4H, Ar-H), 7.12−7.08 (m, 1H, Ar-H), 7.05

(t, J = 6.7 Hz, 2H, Ar-H), 6.61 (d, J = 2.3 Hz, 2H, Ar-H), 6.38 (t, J =

2.3 Hz, 1H, Ar-H), 4.62 (dd, J = 8.0 and 5.1 Hz, 1H, ArCH(OH)),

3.72 (s, 6H, 2 × ArOCH₃), 2.93−2.82 (m, 2H, CH₂), 2.52 (q, J = 7.6

Hz, 3H, CH₂CH₃and OH), 2.19−1.99 (m, 2H, CH₂), 1.12 (t, 3H,

CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 160.5 (2 × C),

144.1, 143.6, 141.7, 132.3, 128.9, 128.5, 127.9 (2 × CH), 125.9 (3 ×

CH), 124.7, 122.4, 109.4 (2 × CH), 101.6, 93.0, 87.7, 73.9, 55.4 (2 ×

OCH₃), 39.6, 31.2, 28.5, 15.5 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺Calcd for C₂₇H₂₇O₂383.2005; Found 383.2007.

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

propan-1-ol (7s). GP-3 was carried out with 3-(2-bromophenyl)-1-

(4-ethylphenyl)propan-1-ol 4c (95.4 mg, 0.3 mmol), 1-ethynyl-4-

ﬂuorobenzene 6g (54.2 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol

%), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and

DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

93:07 to 90:10) furnished the product 7s (73.0 mg, 68%) as a brown

liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(4c) = 0.50,

R_f(6g) = 0.95, R_f(7s) = 0.46, UV detection. IR (MIR-ATR, 4000-600

cm⁻¹) ν_max= 3352, 2988, 2930, 1582, 1492, 1277, 1215, 825, 749

1

cm⁻¹. H NMR (400 MHz, CDCl₃) δ 7.53−7.47 (m, 3H, Ar-H),

7.31−7.28 (m, 4H, Ar-H), 7.23−7.18 (m, 1H, Ar-H), 7.17 (d, J = 4.9

and 1.1 Hz, 2H, Ar-H), 7.10−7.05 (m, 2H, Ar-H), 4.73 (dd, J = 7.7

and 5.4 Hz, 1H, ArCH(OH)), 3.04−2.92 (m, 2H, CH₂), 2.66 (q, J =

7.6 Hz, 2H, CH₂CH₃), 2.24−2.14 (m, 2H, CH₂), 2.02 (s, 1H, OH),

1.25 (t, J = 7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 162.4 (J_C−F= 248 Hz), 143.9, 143.6, 141.7, 133.3 (J_C−F

=

8.0 Hz, 2 × CH), 132.6, 128.9, 128.5, 127.9 (2 × CH), 125.9 (2 ×

CH), 125.9, 122.4, 119.4 (J_C−F= 4.0 Hz), 115.5 (J_C−F= 22 Hz, 2 ×

CH), 91.9, 87.8, 73.9, 39.6, 31.1, 28.5, 15.5 ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺Calcd for C₂₅H₂₂F 341.1700; Found

341.1689.

1-(4-Isopropylphenyl)-3-(2-(p-tolylethynyl)phenyl)propan-

1-ol (7t). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

isopropylphenyl)propan-1-ol 4d (99.6 mg, 0.3 mmol), 1-ethynyl-4-

methylbenzene 6b (52.6 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol

%), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and

DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

93:07 to 90:10) furnished the product 7t (86.2 mg, 78%) as a brown

liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(4d) = 0.50,

R_f(6b) = 0.95, R_f(7t) = 0.45, UV detection. IR (MIR-ATR, 4000-600

cm⁻¹) ν_max= 3390, 2939, 2898, 1451, 1429, 1251, 1057, 741, 693

cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ 7.56 (d, J = 7.4 Hz, 1H, Ar-H),

7.51−7.44 (m, 2H, Ar-H), 7.34 (d, J = 8.1 Hz, 2H, Ar-H), 7.32−7.29

(m, 2H, Ar-H), 7.28−7.23 (m, 5H, Ar-H), 4.76 (dd, J = 7.3 and 5.7

Hz, 1H, ArCH(OH)), 3.09−2.87 (m, 3H, CH₂and CH), 2.44 (s, 3H,

ArCH₃), 2.32−2.12 (m, 2H, CH₂), 2.05 (s, 1H, OH), 1.29 (d, 6H,

CH(CH₃)₂) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 148.2,

143.8, 141.8, 138.3, 132.2, 131.4 (2 × CH), 129.1 (2 × CH), 128.8,

128.3, 126.5 (2 × CH), 125.9 (2 × CH), 125.8, 122.8, 120.3, 93.2,

87.4, 73.8, 39.6, 33.8, 31.1, 23.9 (2 × CH₃), 21.6 ppm. HRMS (ESI)

m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₇H₂₇351.2107; Found

351.2086.

1-(3,5-Dimethoxyphenyl)-3-(2-((4-methoxyphenyl)ethynyl)-

phenyl)propan-1-ol (7x). GP-3 was carried out with 3-(2-

bromophenyl)-1-(3,5-dimethoxyphenyl)propan-1-ol 4f (105 mg, 0.3

mmol), 1-ethynyl-4-methoxybenzene 6d (59.4 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

Puriﬁcation of the crude material by silica gel column chromatog-

1-(4-Isopropylphenyl)-3-(2-((4-methoxyphenyl)ethynyl)-

phenyl)propan-1-ol (7u). GP-3 was carried out with 3-(2-

bromophenyl)-1-(4-isopropylphenyl)propan-1-ol 4d (99.6 mg, 0.3

mmol), 1-ethynyl-4-methoxybenzene 6d (59.4 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

8716

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

raphy (petroleum ether/ethyl acetate 85:15 to 80:20) furnished the

product 7x (92.9 mg, 77%) as a brown liquid. TLC (petroleum ether/

ethyl acetate 75:25, R_f(4f) = 0.50, R_f(6d) = 0.98, R_f(7x) = 0.45, UV

detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3452, 2936, 2367,

CDCl₃) δ 7.45−7.41 (m, 2H, Ar-H), 7.26−7.24 (m, 2H, Ar-H), 7.14

(dd, J = 8.3 and 3.6 Hz, 3H, Ar-H), 7.02 (d, 1H, Ar-H), 6.90−6.86

(m, 2H, Ar-H), 6.82 (dd, J = 8.5 and 2.8 Hz, 1H, Ar-H), 4.73−4.65

(m, 1H, ArCH(OH)), 3.84 (s, 3H, ArOCH₃), 3.80 (s, 3H, ArOCH₃),

2.98−2.79 (m, 2H, CH₂), 2.63 (q, J = 7.6 Hz, 2H, CH₂CH₃), 2.25−

2.03 (m, 2H, CH₂), 1.97 (s, 1H, OH), 1.22 (t, J = 7.6 Hz, 3H,

CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 159.6, 157.4,

143.5, 141.8, 136.0, 132.9 (2 × CH), 129.9, 127.9 (2 × CH), 125.9 (2

× CH), 123.5, 116.3, 115.3, 114.9, 114.0 (2 × CH), 92.7, 86.8, 73.8,

55.3 (2 × OCH₃), 40.1, 30.1, 28.5, 15.5 ppm. HRMS (ESI) m/z: [(M

+ H) + (−H₂O)]⁺Calcd for C₂₇H₂₇O₂383.2005; Found 383.1989.

3-(5-Fluoro-2-(phenylethynyl)phenyl)-1-(p-tolyl)propan-1-

ol (7ab). GP-3 was carried out with 3-(2-bromo-5-ﬂuorophenyl)-1-

(p-tolyl)propan-1-ol 4m (96.6 mg, 0.3 mmol), ethynylbenzene 6a

(45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6

mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C

for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 93:07 to 90:10)

furnished the product 7ab (84.6 mg, 82%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 90:10, R_f(4m) = 0.50, R_f(6a) = 0.95,

1

1596, 1606, 1456, 1248, 1155, 832, 757 cm⁻¹. H NMR (400 MHz,

CDCl₃) δ 7.49 (d, J = 7.4 Hz, 1H, Ar-H), 7.45−7.40 (m, 2H, Ar-H),

7.24 (dd, J = 4.2 and 3.4 Hz, 2H, Ar-H), 7.21−7.15 (m, 1H, Ar-H),

6.90−6.85 (m, 2H, Ar-H), 6.51 (d, J = 2.2 Hz, 2H, Ar-H), 6.35 (t, J =

2.3 Hz, 1H, Ar-H), 4.68 (t, J = 5.3 Hz, 1H, ArCH(OH)), 3.83 (s, 3H,

ArOCH₃), 3.74 (s, 6H, 2 × ArOCH₃), 3.04−2.89 (m, 2H, CH₂),

2.21−2.08 (m, 2H, CH₂), 2.03 (s, 1H, OH) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ 160.8 (2 × C), 159.6, 147.2, 143.6, 132.9 (2 ×

CH), 132.0, 128.8, 128.2, 125.9, 122.9, 115.4, 114.0 (2 × CH), 103.7

(2 × CH), 99.4, 93.1, 86.8, 74.1, 55.3, 55.3 (2 × OCH₃), 39.7, 31.0

ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₆H₂₇O₄403.1904;

Found 403.1882.

1-(4-Chlorophenyl)-3-(2-(p-tolylethynyl)phenyl)propan-1-ol

(7y). GP-3 was carried out with 3-(2-bromophenyl)-1-(4-

chlorophenyl)propan-1-ol 4h (97.2 mg, 0.3 mmol), 1-ethynyl-4-

methylbenzene 6b (53.1 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol

%), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and

DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

93:07 to 90:10) furnished the product 7y (91.8 mg, 85%) as a brown

liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(4h) = 0.50,

R_f(6b) = 0.95, R_f(7y) = 0.45, UV detection. IR (MIR-ATR, 4000-600

cm⁻¹) ν_max= 3410, 3340, 3029, 2927, 1598, 1456, 1257, 813 cm⁻¹. ¹H

NMR (400 MHz, CDCl₃) δ 7.51 (d, J = 7.5 Hz, 1H, Ar-H), 7.37 (d, J

= 8.1 Hz, 2H, Ar-H), 7.30−7.24 (m, 5H, Ar-H), 7.24−7.21 (m, 1H,

Ar-H), 7.21−7.16 (m, 3H, Ar-H), 4.71 (dd, J = 7.5 and 5.4 Hz, 1H,

ArCH(OH)), 2.94 (dd, J = 9.1 and 6.8 Hz, 2H, CH₂), 2.38 (s, 3H,

Ar-CH₃), 2.21−2.04 (m, 3H, CH₂and OH) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ = 143.5, 142.9, 138.4, 133.0, 132.2, 131.3 (2 ×

CH), 129.2 (2 × CH), 128.8, 128.5 (2 × CH), 128.3, 127.3 (2 ×

CH), 126.0, 122.7, 120.1, 93.3, 87.3, 73.2, 39.8, 30.7, 21.5 ppm.

HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₄H₂₀Cl

343.1248; Found 343.1252.

R_f(7ab) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

1

3385, 2921, 1580, 1596, 1497, 1273, 1227, 959, 818 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ 7.53−7.49 (m, 3H, Ar-H), 7.41−7.34 (m, 3H,

Ar-H), 7.27 (d, J = 7.9 Hz, 2H, Ar-H), 7.15 (d, J = 7.9 Hz, 2H, Ar-H),

7.07−6.88 (m, 2H, Ar-H), 4.73−4.70 (m, 1H, ArCH(OH)), 3.10−

2.83 (m, 2H, CH₂), 2.36 (s, 3H, ArCH₃), 2.22−1.95 (m, 3H, CH₂

and OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 162.5 (J_C−F

=

248 Hz), 146.8 (J_C−F= 8 Hz), 141.4, 137.3, 134.0 (J_C−F= 8 Hz),

131.5 (2 × CH), 129.2 (2 × CH), 128.4 (2 × CH), 128.3, 125.9 (2 ×

CH), 123.3, 118.7 (J_C−F= 4 Hz), 115.9 (J_C−F= 22 Hz), 113.2 (J_C−F

=

22 Hz), 92.7, 88.2, 74.0, 55.4, 40.1, 30.1 ppm. HRMS (ESI) m/z: [(M

+ H) + (−H₂O)]⁺Calcd for C₂₄H₂₀F 327.1543; Found 327.1529.

2-Phenyl-4-(2-(phenylethynyl)phenyl)butan-2-ol (8a). GP-3

was carried out with 4-(2-bromophenyl)-2-phenylbutan-2-ol 5a (91.2

mg, 0.3 mmol), ethynylbenzene 6a (45.9 mg, 0.45 mmol), Pd(OAc)₂

(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45

mmol), and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 95:05 to 93:07) furnished the product 8a (87.0 mg, 89%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 90:10, R_f(5a) =

0.50, R_f(6a) = 0.95, R_f(8a) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 3566, 3435, 2967, 2213, 1492, 1445, 1370,

3-(4-Methoxy-2-(phenylethynyl)phenyl)-1-phenylpropan-

1-ol (7z). GP-3 was carried out with 3-(2-bromo-4-methoxyphenyl)-

1-phenylpropan-1-ol 4k (96.0 mg, 0.3 mmol), ethynylbenzene 6a

(45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6

mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C

for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 90:10 to 85:15)

furnished the product 7z (81.1 mg, 79%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 85:15, R_f(4k) = 0.50, R_f(6a) = 0.95,

1

1026, 755, 695 cm⁻¹. H NMR (400 MHz, CDCl₃) H NMR (400

MHz, CDCl₃) δ 7.49−7.44 (m, 5H, Ar-H), 7.37−7.32 (m, 3H, Ar-H),

7.30−7.25 (m, 2H, Ar-H), 7.23−7.18 (m, 2H, Ar-H), 7.16−7.11 (m,

2H, Ar-H), 2.86 (td, J = 12.4 and 5.2 Hz, 1H, CH), 2.73−2.64 (m,

1H, CH), 2.16 (qdd, J = 13.7, 11.9, and 5.1 Hz, 2H, ArC(CH₃)-

(OH)CH₂CH₂), 1.87 (s, 1H, OH), 1.59 (s, 3H, ArCH₃(OH)) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 147.5, 144.3, 132.2, 131.5 (2 ×

R_f(7z) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3338, 2895, 2836, 1496, 1250, 1016, 861, 725 cm⁻¹. H NMR (400

MHz, CDCl₃) δ 7.44 (dd, J = 6.6 and 3.1 Hz, 2H, Ar-H), 7.34−7.27

(m, 6H, Ar-H), 7.25−7.19 (m, 2H, Ar-H), 7.13−7.06 (m, 1H, Ar-H),

7.01 (d, J = 2.7 Hz, 1H, Ar-H), 6.80 (dd, J = 8.5 and 2.8 Hz, 1H, Ar-

H), 4.67 (dd, J = 7.6 and 5.4 Hz, 1H, ArCH(OH)), 3.75 (s, 3H,

ArOCH₃), 2.86 (td, J = 9.0 and 6.4 Hz, 2H, CH₂), 2.22−1.91 (m, 3H,

CH₂and OH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 157.4,

144.5, 136.2, 131.5 (2 × CH), 129.9, 128.4 (2 × CH), 128.3 (2 ×

CH), 128.2, 127.4, 125.9 (2 × CH), 123.2, 123.1, 116.5, 115.3, 92.7,

88.1, 73.9, 55.3, 39.9, 30.0 ppm. HRMS (ESI) m/z: [(M + H) +

(−H₂O)]⁺Calcd for C₂₄H₂₁O 325.1587; Found 325.1578.

1

CH), 128.7, 128.5, 128.3 (2 × CH), 128.2 (3 × CH), 126.5, 125.8,

124.8 (2 × CH), 123.3, 122.4, 92.8, 88.0, 74.6, 45.2, 30.4, 29.5 ppm.

HRMS (ESI) m/z: [M + Na]⁺Calcd for C₂₄H₂₂ONa 349.1563;

Found 349.1565.

4-(2-((4-Methoxyphenyl)ethynyl)phenyl)-2-phenylbutan-2-

ol (8b). GP-3 was carried out with 4-(2-bromophenyl)-2-phenyl-

butan-2-ol 5a (91.2 mg, 0.3 mmol), 1-ethynyl-4-methoxybenzene 6d

(45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6

mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C

for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 93:07 to 90:10)

furnished the product 8b (84.4 mg, 79%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 85:15, R_f(5a) = 0.50, R_f(6d) = 0.90,

1-(4-Ethylphenyl)-3-(4-methoxy-2-((4-methoxyphenyl)-

ethynyl)phenyl)propan-1-ol (7aa). GP-3 was carried out with 3-

(2-bromo-4-methoxyphenyl)-1-(4-ethylphenyl)propan-1-ol 4l (104.5

mg, 0.3 mmol), 1-ethynyl-4-methoxybenzene 6d (59.4 mg, 0.45

mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %),

Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12

h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 88:12 to 85:15)

furnished the product 7aa (91.0 mg, 82%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 85:15, R_f(4l) = 0.50, R_f(6d) = 0.95,

R_f(8b) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3503, 2972, 1731, 1243, 1040, 913, 734 cm⁻¹. H NMR (400 MHz,

CDCl₃) δ 7.48−7.44 (m, 3H, Ar-H), 7.43−7.38 (m, 2H, Ar-H),

7.30−7.26 (m, 2H, Ar-H), 7.26−7.20 (m, 2H, Ar-H), 7.17−7.13

(ddd, J = 7.1, 4.0, and 1.4 Hz, 2H, Ar-H), 6.94−6.87 (m, 2H, Ar-H),

3.85 (s, 3H, ArOCH₃), 2.88−2.81 (m, 1H, CH), 2.71−2.64 (m, 1H,

CH), 2.19 (ddt, J = 13.8, 12.0, and 8.6 Hz, 2H, CH₂), 1.63 (s, 3H,

ArCH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 159.6, 147.6,

1

R_f(7aa) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

3741, 2962, 1602, 1510, 1248, 1034, 832 cm⁻¹. ¹H NMR (400 MHz,

=

8717

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J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

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Article

144.1, 133.0 (2 × CH), 132.1, 128.7, 128.2 (3 × CH), 126.5, 125.8,

124.8 (2 × CH), 122.8, 115.5, 114.0 (2 × CH), 92.9, 86.7, 74.6, 55.3,

45.2, 30.5, 29.6 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺

Calcd for C₂₅H₂₃O 339.1743; Found 339.1747.

and DMF (2 mL) at 100 °C for 12 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 90:10 to 88:12) furnished the product 8f (91.0 mg, 82%) as a

brown liquid. TLC (petroleum ether/ethyl acetate 85:15, R_f(5d) =

0.50, R_f(6a) = 0.95, R_f(8f) = 0.45, UV detection. IR (MIR-ATR,

4000-600 cm⁻¹) ν_max= 2953, 1718, 1357, 1219, 1032 cm⁻¹. ¹H NMR

(400 MHz, CDCl₃) δ 7.47 (ddd, J = 6.5 Hz, 3.7 and 2.4 Hz, 3H, Ar-

H), 7.40−7.30 (m, 3H, Ar-H), 7.25−7.20 (m, 1H, Ar-H), 7.14 (dd, J

= 11.6 and 4.3 Hz, 2H, Ar-H), 7.00 (d, J = 1.8 Hz, 1H, Ar-H), 6.93

(dd, J = 8.1 and 1.8 Hz, 1H, Ar-H), 6.69 (d, J = 8.1 Hz, 1H, Ar-H),

5.88 (d, J = 1.5 Hz, 1H, −-OCH_aCH_b−, 5.87 (d, J = 1.5 Hz, 1H,

−OCH_aCH_b−), 2.91−2.81 (m, 1H, CH), 2.71 (m, 1H, CH), 2.21−

2.04 (m, 2H, CH₂), 1.84 (s, 1H, OH), 1.57 (s, 3H, ArCH₃) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ 147.5, 146.0, 144.2, 141.7,

4-(2-((3,5-Dimethoxyphenyl)ethynyl)phenyl)-2-phenylbu-

tan-2-ol (8c). GP-3 was carried out with 4-(2-bromophenyl)-2-

phenylbutan-2-ol 5a (91.2 mg, 0.3 mmol), 1-ethynyl-3,5-dimethox-

ybenzene 2f (72.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %),

PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF

(2 mL) at 100 °C for 12 h. Puriﬁcation of the crude material by silica

gel column chromatography (petroleum ether/ethyl acetate 85:15 to

80:20) furnished the product 8c (92.6 mg, 80%) as a brown liquid.

TLC (petroleum ether/ethyl acetate 75:25, R_f(5a) = 0.50, R_f(6a) =

0.98, R_f(8c) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

ν_max= 3477, 2934, 1589, 1453, 1420, 1205, 1156, 1064, 757 cm⁻¹. ¹H

NMR (400 MHz, CDCl₃) δ 7.47 (dt, J = 7.6 and 1.4 Hz, 3H, Ar-H),

7.32−7.24 (m, 2H, Ar-H), 7.24−7.17 (m, 2H, Ar-H), 7.14 (dd, J =

10.7 and 4.5 Hz, 2H, Ar-H), 6.68 (d, J = 2.3 Hz, 2H, Ar-H), 6.50 (t, J

= 2.3 Hz, 1H, Ar-H), 3.83 (s, 6H, 2 × ArOCH₃), 2.93−2.86 (m, 1H,

CH), 2.74−2.65 (m, 1H, CH), 2.23−2.16 (m, 2H, CH₂), 1.83 (s, 1H,

OH), 1.62 (s, 3H, ArC(CH₃)OH) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 160.5 (2 × C), 147.5, 144.4, 132.3, 128.1, 128.6, 128.2 (2 ×

CH), 126.6, 125.8, 124.7 (2 × CH), 124.6, 122.3, 109.4 (2 × CH),

101.7, 92.9, 86.7, 74.6, 55.4 (2 × OCH₃), 45.2, 30.4, 29.6 ppm.

HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₆H₂₅O₂

369.1849; Found 369.1842.

132.4, 131.4 (2 × CH), 128.8, 128.5, 128.3 (2 × CH), 128.2, 125.8,

123.3, 122.4, 117.8, 107.8, 105.9, 100.9, 92.8, 88.0, 74.5, 45.4, 30.6,

29.5 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for

C₂₅H₂₁O₂353.1536; Found 353.1520.

3-(4-Chlorophenyl)-1-(2-((4-methoxyphenyl)ethynyl)-

phenyl)pentan-3-ol (8g). GP-3 was carried out with 1-(2-

bromophenyl)-3-(4-chlorophenyl)pentan-3-ol 5e (105.6 mg, 0.3

mmol), 1-ethynyl-4-methoxybenzene 6d (45.9 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 95:05 to 93:07) furnished the

product 8g (88.6 mg, 79%) as a brown liquid. TLC (petroleum ether/

ethyl acetate 90:10, R_f(5e) = 0.50, R_f(6d) = 0.95, R_f(8g) = 0.45, UV

detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3448, 2930, 1599,

1,1-Diphenyl-3-(2-(phenylethynyl)phenyl)propan-1-ol (8d).

GP-3 was carried out with 3-(2-bromophenyl)-1,1-diphenylpropan-1-

ol 5b (109.4 mg, 0.3 mmol), ethynylbenzene 6a (45.9 mg, 0.45

mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %),

Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12

h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 95:05 to 93:07)

furnished the product 8d (82.6 mg, 71%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 90:10, R_f(5b) = 0.50, R_f(6a) = 0.95,

1

1493, 1444, 1280, 1067, 755 cm⁻¹. H NMR (400 MHz, CDCl₃) δ

7.48−7.44 (m, 1H, Ar-H), 7.40−7.34 (m, 4H, Ar-H), 7.25−7.19 (m,

3H, Ar-H), 7.18−7.12 (m, 2H, Ar-H), 6.95 (m, 2H, Ar-H), 3.86 (s,

3H, ArOCH₃), 2.85 (td, J = 12.5 and 4.8 Hz, 1H, CH), 2.58−2.30

(m, 1H, CH), 2.20−2.10 (m, 2H, CH₂), 1.91−1.76 (m, 2H,

CH₂CH₃), 1.75 (s, 1H, OH), 0.77 (t, J = 7.4 Hz, 3H, CH₂CH₃)

ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 159.6, 143.9 (2 × C),

132.9 (2 × CH), 132.1, 132.1, 128.8, 128.3, 128.2 (2 × CH), 126.9 (2

× CH), 125.8, 122.7, 115.3, 114.1 (2 × CH), 92.8, 86.7, 77.0, 55.3,

43.8, 35.8, 29.1, 7.67 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺

Calcd for C₂₆H₂₄ClO 387.1510; Found 387.1482.

3-(Benzo[d][1,3]dioxol-5-yl)-1-(2-((3,4-dimethoxyphenyl)-

ethynyl)phenyl)pentan-3-ol (8h). GP-3 was carried out with 1-(2-

bromophenyl)-3-(4-chlorophenyl)pentan-3-ol 5f (108.6 mg, 0.3

mmol), 4-ethynyl-1,2-dimethoxybenzene 6e (72.9 mg, 0.45 mmol),

Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃

(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for 12 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 90:10 to 85:15) furnished the

product 8h (107.8 mg, 81%) as a brown liquid. TLC (petroleum

ether/ethyl acetate 80:20, R_f(5f) = 0.50, R_f(6e) = 0.90, R_f(8h) = 0.45,

UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3536, 3060,

2963, 2934, 2835, 1486, 1439, 1326, 1248, 1133, 1038, 930 cm⁻¹. ¹H

NMR (400 MHz, CDCl₃) δ 7.51−7.42 (m, 1H, Ar-H), 7.25−7.18 (m,

1H, Ar-H), 7.19−7.02 (m, 4H, Ar-H), 6.95 (d, J = 1.7 Hz, 1H, Ar-H),

6.93−6.83 (m, 2H, Ar-H), 6.71 (d, J = 8.1 Hz, 1H, Ar-H), 5.90 (dd, J

= 8.6, 1.4 Hz, 2H, OCH₂), 3.92 (d, J = 0.9 Hz, 6H, ArOCH₃), 2.90

(ddd, J = 13.0, 10.4, and 6.6 Hz, 1H, CH₂), 2.76−2.51 (m, 1H, CH),

2.42−2.06 (m, 2H, CH₂), 1.96−1.70 (m, 3H, CH₂and OH), 0.77 (t,

J = 7.4 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ

149.5, 148.7, 147.6, 145.9, 144.3, 139.8, 132.1, 128.9, 128.3, 125.9,

124.8, 122.6, 118.5, 115.6, 114.2, 111.1, 107.8, 106.4, 100.9, 93.1,

86.7, 76.8, 55.9, 55.8, 43.7, 35.8, 29.1, 7.67 ppm. HRMS (ESI) m/z:

[(M + H) + (−H₂O)]⁺Calcd for C₂₈H₂₇O₄427.1904; Found

427.1878.

R_f(8d) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3724, 2923, 1681, 1597, 1455, 1248, 1026, 758 cm⁻¹. ¹H NMR (400

MHz, CDCl₃) δ 7.42−7.32 (m, 7H, Ar-H), 7.26−7.20 (m, 3H, Ar-H),

7.17−7.11 (m, 5H, Ar-H), 7.11−7.03 (m, 4H, Ar-H), 2.81−2.72 (m,

2H, CH₂), 2.59−2.51 (m, 2H, CH₂), 2.14 (s, 1H, OH) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 146.8 (2 × C), 144.5, 132.3, 131.4 (2 ×

CH), 128.9, 128.6, 128.3 (2 × CH), 128.2, 128.2 (4 × CH), 126.8 (2

× CH), 126.0 (4 × CH), 125.9, 123.3, 122.5, 92.9, 88.1, 78.1, 43.2,

29.3 ppm. HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for

C₂₉H₂₃371.1794; Found 371.1805.

2-(4-Chlorophenyl)-4-(2-(phenylethynyl)phenyl)butan-2-ol

(8e). GP-3 was carried out with 4-(2-bromophenyl)-2-(4-

chlorophenyl)butan-2-ol 5c (101.4 mg, 0.3 mmol), ethynylbenzene

6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7

mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at

100 °C for 12 h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate 95:05 to 93:07)

furnished the product 8e (82.1 mg, 76%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 93:07, R_f(5c) = 0.50, R_f(6a) = 0.95,

R_f(8e) = 0.45, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max

=

3448, 2930, 1599, 1493, 1444, 1280, 1067, 755 cm⁻¹. ¹H NMR (400

MHz, CDCl₃) δ 7.51−7.45 (m, 2H, Ar-H), 7.45−7.41 (m, 2H, Ar-H),

7.41−7.32 (m, 4H, Ar-H), 7.25−7.20 (m, 3H, Ar-H), 7.18 (dd, J =

10.9 and 4.4 Hz, 2H, Ar-H), 2.87 (td, J = 12.4 and 5.1 Hz, 1H, CH),

2.67 (td, J = 12.4 and 5.2 Hz, 1H, CH), 2.25−2.04 (m, 2H, CH₂),

1.83 (s, 1H, OH), 1.60 (s, 3H, CH₃) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 145.9, 144.0 (2 × C), 132.3, 131.4 (2 × CH), 128.8, 128.6,

128.4 (2 × CH), 128.3 (3 × CH), 125.4 (2 × CH), 125.9, 123.2,

122.4, 92.9, 87.9, 74.4, 45.4, 30.7, 29.4 ppm. HRMS (ESI) m/z: [(M

+ H) + (−H₂O)]⁺Calcd for C₂₄H₂₀Cl 343.1248; Found 343.1235.

2-(Benzo[d][1,3]dioxol-5-yl)-4-(2-(phenylethynyl)phenyl)-

butan-2-ol (8f). GP-3 was carried out with 2-(benzo[d][1,3]dioxol-

5-yl)-4-(2-bromophenyl)butan-2-ol 5d (104.4 mg, 0.3 mmol),

ethynylbenzene 6a (45.9 mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3

mol %), PPh₃(4.7 mg, 6 mol %), Cs₂CO₃(146.3 mg, 0.45 mmol),

3-(2-((3-Aminophenyl)ethynyl)phenyl)-1-(p-tolyl)propan-1-

ol (7ac). GP-3 was carried out with 3-(2-bromophenyl)-1-(p-

tolyl)propan-1-ol 4b (91.2 mg, 0.3 mmol), 3-ethynylaniline 6i (52.6

mg, 0.45 mmol), Pd(OAc)₂(2.0 mg, 3 mol %), PPh₃(4.7 mg, 6 mol

%), Cs₂CO₃(146.3 mg, 0.45 mmol), and DMF (2 mL) at 100 °C for

12 h. Puriﬁcation of the crude material by silica gel column

8718

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

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Article

chromatography (petroleum ether/ethyl acetate 90:10 to 95:15)

furnished the product 7ac (107.8 mg, 81%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 80:20, R_f(4b) = 0.50, R_f(7ac) = 0.45,

UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3536, 3432,

3360, 2934, 2835, 1486, 1439, 1326, 1248, 1133, 1038, 930 cm⁻¹. ¹H

NMR (400 MHz, CDCl₃) δ 7.49 (d, J = 7.7 Hz, 2H, Ar-H), 7.28−

7.22 (m, 2H, Ar-H), 7.17 (ddd, J = 8.9 Hz, 6.0 and 3.0 Hz, 2H, Ar-H),

7.14−7.10 (m, 3H, Ar-H), 6.90 (d, J = 7.6 Hz, 1H, Ar-H), 6.81−6.78

(m, 1H, Ar-H), 6.63 (ddd, J = 8.1 Hz, 2.4 and 0.9 Hz, 1H, Ar-H), 4.93

(t, J = 6.3 Hz, 1H, ArCH(OH)), 3.72 (br. s, 2H, ArNH₂), 3.06−3.03

(m, 2H, CH₂), 2.16 (s, 3H, ArCH₃), 2.16−2.02 (m, 3H, CH₂and

OH). ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 146.2, 143.9, 142.7, 134.4,

132.4, 130.1, 129.2, 128.9, 128.4, 127.3, 126.9, 125.9, 125.0, 123.9,

122.6, 121.9, 117.7, 115.3, 93.2, 87.6, 69.2, 38.8, 31.9, 18.7 ppm.

HRMS (ESI) m/z: [(M + H) + (−H₂O)]⁺Calcd for C₂₄H₂₂N

310.1590; Found:--- .

11-Phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene (9a). GP-4 was

carried out with 1-phenyl-3-(2-(phenylethynyl)phenyl)propan-1-ol 7a

(62.4 mg, 0.2 mmol), BF₃·OEt₂(16.9 mg, 30 mol %) in dry DCE (2

mL) at 0 °C to room temperature for 1 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate/hexane to 99:1) furnished the product 9a (46.4 mg, 79%) as

colorless liquid.

1.35 mmol Scale-up Reaction of 9a. GP-4 was carried out with

1-phenyl-3-(2-(phenylethynyl)phenyl)propan-1-ol 7a (422 mg, 1.35

mmol), BF₃·OEt₂(114 mg, 30 mol %) in dry DCE (10 mL) at 0 °C

to room temperature for 1 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate/

hexane to 99:1) furnished the product 9a (262 mg, 63%) as a

colorless liquid. TLC (petroleum ether/ethyl acetate 99:1, R_f(7a) =

0.20, R_f(9a) = 0.9, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹)

ν_max= 2921, 2363, 1488, 1240, 1039, 756 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ = 7.52 (d, J = 6.8 Hz, 1H, Ar-H), 7.48−7.42 (m, 2H, Ar-

H), 7.38 (t, J = 6.8 Hz, 3H, Ar-H), 7.26−7.13 (m, 4H, Ar-H), 7.09−

7.06 (m, 2H, Ar-H), 6.87 (t, J = 7.6 Hz, 1H, Ar-H), 3.61 (dd, J = 13.5

and 4.3 Hz, 1H, CH), 3.20−3.05 (m, 2H, CH₂), 2.72−2.66 (m, 1H,

CH), 1.67−1.52 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ = 147.2, 145.8, 142.1, 137.6, 136.4, 136.2, 132.2, 129.3 (2 ×

CH), 129.0, 128.9 (2 × CH), 127.4, 127.1, 126.9 (2 × CH), 125.5,

124.8, 122.5, 120.2, 42.2, 30.6, 28.4 ppm. HRMS (ESI) m/z: [M]⁺

Calcd for C₂₃H₁₈294.1403; Found 294.1399.

9-Methyl-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9b). GP-4 was carried out with 3-(2-(phenylethynyl)phenyl)-1-(p-

tolyl)propan-1-ol 7b (65.2 mg, 0.2 mmol) and BF₃·OEt₂(16.9 mg, 30

mol %) in dry DCE (2 mL) at 0 °C to room temperature for 1 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate/exane to 99:1) furnished the

product 9b (43.1 mg, 70%) as a colorless liquid. TLC (petroleum

ether/ethyl acetate 99:1, R_f(7b) = 0.20, R_f(9b) = 0.90, UV detection.

IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3535, 3054, 2924, 2853, 1452,

746 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ 7.51 (t, J = 7.2 Hz, 2H, Ar-

H), 7.47−7.37 (m, 4H, Ar-H), 7.22 (d, J = 7.6 Hz, 1H, Ar-H), 7.15−

7.07 (m, 3H, Ar-H), 6.92−6.89 (m, 2H, Ar-H), 3.62 (dd, J = 13.5 and

4.3 Hz, 1H, CH), 3.30−3.16 (m, 2H, CH₂), 2.77−2.65 (m, 1H, CH),

2.36 (s, 3H, ArCH₃), 1.67−1.57 (m, 1H, CH) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ = 147.3, 143.0, 142.4, 137.6, 136.7, 136.5,

136.2, 132.3, 129.3 (2 × CH), 129.0, 128.9 (2 × CH), 127.4, 127.1,

126.9, 125.7, 125.4, 122.2, 120.9, 48.9, 30.6, 28.5, 21.5 ppm. HRMS

(ESI) m/z: [M]⁺Calcd for C₂₄H₂₀308.1560; Found 308.1568.

9-Ethyl-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene (9c).

GP-4 was carried out with 1-(4-ethylphenyl)-3-(2-(phenylethynyl)-

phenyl)propan-1-ol 7c (68.0 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30

mol %) in dry DCE (2 mL) at 0 °C to room temperature for 1 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate/hexane to 99:1) furnished the

product 9c (41.9 mg, 65%) as colorless liquid. TLC (petroleum

ether/ethyl acetate 99:1, R_f(7c) = 0.20, R_f(9c) = 0.90, UV detection.

IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2923, 1597, 1492, 1443, 1090,

756 cm⁻¹. ¹H NMR (400 MHz, CDCl₃) δ 7.55−7.43 (m, 6H, Ar-H),

7.24 (d, J = 7.3 Hz, 1H, Ar-H), 7.17−7.11 (m, 3H, Ar-H), 6.97 (d, J =

0.8 Hz, 1H, Ar-H), 6.92 (t, J = 7.6 Hz, 1H, Ar-H), 3.64 (dd, J = 13.5

and 4.3 Hz, 1H, CH), 3.24−3.17 (m, 2H, CH₂), 2.74−2.68 (m, 1H,

CH), 2.67 (q, J = 7.7 Hz, CH₂CH₃), 1.69−1.64 (m, 1H, CH), 1.25 (t,

J = 7.7 Hz, CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ =

147.4, 143.3, 143.2, 142.4, 137.6, 136.5, 136.3, 132.3, 129.3 (2 ×

CH), 129.0, 128.9 (2 × CH), 127.3, 127.0, 126.8, 125.4, 124.5, 122.3,

119.7, 48.9, 30.6, 29.0, 28.5, 16.0 ppm. HRMS (ESI) m/z: [M + H]⁺

Calcd for C₂₅H₂₃323.1794; Found 323.1797.

9-Isopropyl-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9d). GP-4 was carried out with 1-(4-isopropylphenyl)-3-(2-

(phenylethynyl)phenyl)propan-1-ol 7d (70.8 mg, 0.2 mmol) and

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate/hexane to

99:1) furnished the product 9d (45.7 mg, 68%) as a yellow liquid.

TLC (petroleum ether/ethyl acetate 99:1, R_f(7d) = 0.20, R_f(9d) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3054,

2925, 2958, 1608, 1469, 814, 745 cm⁻¹. ¹H NMR (400 MHz, CDCl₃)

δ ¹H NMR (400 MHz, CDCl₃) δ 7.57−7.25 (m, 6H, Ar-H), 7.22 (d, J

= 7.6 Hz, 1H, Ar-H), 7.18−7.06 (m, 3H, Ar-H), 6.96 (d, J = 1.4 Hz,

1H, Ar-H), 6.90 (t, J = 7.5 Hz, 1H, Ar-H), 3.61 (dd, J = 13.5, 4.3 Hz,

1H, CH), 3.34−3.05 (m, 2H, CH₂), 2.91 (dt, J = 13.8, 6.9 Hz, 1H,

ArCH(CH₃)₂), 2.83−2.57 (m, 1H, CH), 1.80−1.59 (m, 1H, CH),

1.24 (dd, J = 6.9 and 1.6 Hz, 6H, ArCH(CH₃)₂) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ = 147.9, 147.2, 143.5, 142.4, 137.6, 136.5,

136.3, 132.3, 129.4 (2 × CH), 129.0, 128.9 (2 × CH), 127.3, 127.0,

126.8, 125.4, 122.9, 122.3, 118.4, 48.9, 34.3, 30.6, 28.4, 24.3, 24.2

ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₆H₂₅337.1951;

Found 337.1930.

8,9-Dimethoxy-11-phenyl-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9e). GP-4 was carried out with 1-(3,4-dimethoxyphenyl)-

3-(2-(phenylethynyl)phenyl)propan-1-ol 7e (74.4 mg, 0.2 mmol),

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9e (48.1 mg, 68%) as a brown liquid. TLC

(petroleum ether/ethyl acetate 95:05, R_f(7e) = 0.20, R_f(9e) = 0.85,

UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3446, 3060,

2924, 2854, 1673, 1271, 1118, 1071 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ = 7.50 (t, J = 7.2 Hz, 2H, Ar-H), 7.46−7.38 (m, 3H, Ar-H),

7.21−7.20 (m, 1H, Ar-H), 7.14 (s, 1H, Ar-H), 7.10−7.06 (m, 2H, Ar-

H), 6.89 (t, J = 7.6 Hz, 1H, Ar-H), 6.64 (s, 1H, Ar-H), 3.96 (s, 3H,

ArOCH₃), 3.81 (s, 3H, ArOCH₃), 3.58 (dd, J = 13.5 and 4.2 Hz, 1H,

CH), 3.20−3.15 (m, 2H, CH₂), 2.72−2.66 (m, 1H, CH), 1.67−1.57

(m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 148.8,

147.6, 141.0, 139.8, 138.5, 137.1, 136.6, 136.1, 132.3, 129.3 (2 ×

CH), 129.0 (3 × CH), 127.4, 126.7, 126.4, 125.5, 106.8, 103.9, 56.4,

56.1, 48.9, 30.6, 28.8 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₅H₂₃O₂355.1698; Found 355.1693.

8,10-Dimethoxy-11-phenyl-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9f). GP-4 was carried out with 1-(3,5-dimethoxyphenyl)-3-

(2-(phenylethynyl)phenyl)propan-1-ol 7f (74.4 mg, 0.2 mmol) and

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9f (50.2 mg, 71%) as lightyellow liquid.

TLC (petroleum ether/ethyl acetate 95:05, R_f(7f) = 0.20, R_f(9f) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2936,

2836, 1596, 1493, 1204, 1154, 756 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ = 7.50−7.30 (m, 4H, Ar-H), 7.19−7.16 (m, 2H, Ar-H),

7.04 (td, J = 7.4 Hz, and 1.4 Hz, 1H, Ar-H), 6.89 (dd, J = 8.0 Hz, and

1.2 Hz, 1H, Ar-H), 6.82 (t, J = 7.5 Hz, 1H, Ar-H), 6.77 (dd, J = 2.0

and 0.8 Hz, 1H, Ar-H), 6.38 (d, J = 2.0 Hz, 1H, Ar-H), 3.87 (s, 3H,

ArOCH₃), 3.57 (dd, J = 13.4 and 4.3 Hz, 1H, CH), 3.49 (s, 3H,

ArOCH₃), 3.19−3.08 (m, 2H, CH₂), 2.72−2.59 (m, 1H, CH), 1.73−

1.58 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ =

159.4, 155.2, 149.5, 139.1, 138.7, 137.0, 135.8, 132.7, 128.9, 127.9,

127.6, 126.6 (2 × CH), 126.5 (2 × CH), 126.3 (2 × CH), 125.4,

100.6, 98.2, 55.6, 55.6, 49.5, 30.6, 28.8 ppm. HRMS (ESI) m/z: [M +

H]⁺Calcd for C₂₅H₂₃O₂355.1698; Found 355.1692.

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12-Phenyl-6,6a-dihydro-5H-benzo[7,8]ﬂuoreno[2,3-d][1,3]-

dioxole (9g). GP-4 was carried out with 1-(benzo[d][1,3]dioxol-5-

yl)-3-(2-(phenylethynyl)phenyl)propan-1-ol 7g (71.2 mg, 0.2 mmol),

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9g (49.3 mg, 73%) as a brown liquid.

1605, 1507, 1249, 1178, 1031, 1345, 840 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ 7.64 (d, J = 8.2 Hz, 1H, Ar-H), 7.59 (dd, J = 8.1 and 1.9

Hz, 2H, Ar-H), 7.50−7.39 (m, 3H, Ar-H), 7.39−7.32 (m, 1H, Ar-H),

7.29−7.22 (m, 2H, Ar-H), 7.16−6.04 (m, 3H, Ar-H), 6.68−6.61 (m,

2H, Ar-H), 5.63 (s, 1H, CH), 3.63 (s, 3H, ArOCH₃), 3.15−3.10 (m,

1H, CH), 2.94−2.91 (m, 2H, CH₂), 2.76−2.69 (m, 1H, CH) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 157.9, 139.2, 138.6, 136.7,

TLC (petroleum ether/ethyl acetate 95:05, R_f(7g) = 0.20, R_f(9g) =

0.85, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3057,

2146, 2073, 1687, 1372, 1263, 730 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ 7.46 (t, J = 7.2 Hz, 2H, Ar-H), 7.41−7.34 (m, 3H, Ar-H),

7.17 (d, J = 7.2 Hz, 1H, Ar-H), 7.06 (ddd, J = 8.8, 7.2, and 3.4 Hz,

2H, Ar-H), 7.02 (s, 1H, Ar-H), 6.86 (t, J = 7.6 Hz, 1H, Ar-H), 6.56 (s,

1H, Ar-H), 5.94 (d, J = 1.5 Hz, 1H, -OCH_aCH_bO−), 5.92 (d, J = 1.5

Hz, 1H, -OCH_aCH_bO−), 3.51 (dd, J = 13.5 and 4.2 Hz, 1H, CH),

3.20−3.08 (m, 2H, CH₂), 2.70−2.59 (m, 1H, CH), 1.65−1.56 (m,

1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 147.0, 145.9,

141.1, 141.1, 139.9, 137.1, 136.3, 136.0, 132.2, 129.2 (2 × CH),

129.0, 128.9 (2 × CH), 127.4, 126.7, 126.4, 125.5, 104.0, 101.4,

100.9, 48.9, 30.6, 28.7 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₄H₁₉O₂339.1385; Found 339.1381.

9-Chloro-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9h). GP-4 was carried out with 1-(4-chlorophenyl)-3-(2-

(phenylethynyl)phenyl)propan-1-ol 7h (71.2 mg, 0.2 mmol), BF₃·

OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate/hexane to

99:1) furnished the product 9h (39.3 mg, 60%) as colorless liquid.

TLC (petroleum ether/ethyl acetate 98:2, R_f(7h) = 0.20, R_f(9h) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3064,

2923, 1722, 1449, 1289, 1073, 700 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ = 7.52 (t, J = 7.1 Hz, 2H, Ar-H), 7.48−7.37 (m, 4H, Ar-H),

7.28−7.20 (m, 2H, Ar-H), 7.16 (dd, J = 14.0 and 7.6 Hz, 2H, Ar-H),

7.08 (d, J = 1.6 Hz, 1H, Ar-H), 6.93 (t, J = 7.6 Hz, 1H, Ar-H), 3.62

(dd, J = 13.5 and 4.4 Hz, 1H, CH), 3.28−3.10 (m, 2H, CH₂), 2.78−

2.65 (m, 1H, CH), 1.63 (dd, J = 12.8 and 5.9 Hz, 1H, CH) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 148.8, 144.0, 143.8, 137.6,

134.7, 133.2, 133.0, 132.4, 130.4, 128.0 (2 × CH), 127.3, 127.2,

126.7, 126.6, 126.3, 126.3, 126.1, 125.9, 125.5, 123.9, 120.0, 114.1 (2

× CH), 55.0, 46.3, 28.5, 23.4 ppm. HRMS (ESI) m/z: [M + H]⁺

Calcd for C₂₈H₂₃O 375.1743; Found 375.1728.

11-(3,4-Dimethoxyphenyl)-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9k). GP-4 was carried out with 1-phenyl-3-(2-

(phenylethynyl)phenyl)propan-1-ol 7k (74.4 mg, 0.2 mmol), BF₃·

OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9k (55.2 mg, 78%) as white solid with M.P =

130−132 °C.

TLC (petroleum ether/ethyl acetate 95:05, R_f(7k) = 0.30, R_f(9k) =

0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2923,

2853, 1509, 1460, 1249, 1026, 762 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ 7.56−7.54 (m, 1H, Ar-H), 7.32−7.25 (m, 3H, Ar-H), 7.23

(dd, J = 6.6 and 2.8 Hz, 1H, Ar-H), 7.16 (ddd, J = 4.4 Hz, 2.7 and 0.9

Hz, 1H, Ar-H), 7.12 (dd, J = 7.5 and 1.3 Hz, 1H, Ar-H), 7.04−6.98

(m, 2H, Ar-H), 6.98−6.90 (m, 2H, Ar-H), 3.99 (s, 3H, ArOCH₃),

3.85 (s, 3H, ArOCH₃), 3.64 (dd, J = 13.5 and 4.3 Hz, 1H, CH),

3.28−3.10 (m, 2H, CH₂), 2.79−2.67 (m, 1H, CH), 1.72−1.59 (m,

1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 149.3, 148.3,

147.2, 145.7, 141.9, 137.5, 135.9, 132.2, 129.0, 128.7, 127.1, 126.9 (2

× CH), 125.5, 124.8, 122.5, 121.5, 120.2, 112.2, 111.6, 55.9, 55.8,

49.2, 30.6, 28.2 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₅H₂₃O₂355.1693; Found 355.1685.

9-Methyl-11-(p-tolyl)-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9l). GP-4 was carried out with 1-(p-tolyl)-3-(2-(p-tolylethynyl)-

phenyl)propan-1-ol 7l (70.8 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30

mol %) in dry DCE (2 mL) at 0 °C to room temperature for 1 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate/hexane to 99:1) furnished the

product 9l (53.8 mg, 80%) as yellow oil.

TLC (petroleum ether/ethyl acetate 99:01, R_f(7l) = 0.10, R_f(9l) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3743,

3005, 2937, 2298, 2252, 1438, 1378, 1038, 748 cm⁻¹. ¹H NMR (400

MHz, CDCl₃) δ 7.38 (d, J = 7.5 Hz, 1H, Ar-H), 7.32−7.21 (m, 4H,

Ar-H), 7.21−7.13 (m, 2H, Ar-H), 7.10−7.00 (m, 2H, Ar-H), 6.88 (s,

1H, Ar-H), 6.85 (d, J = 7.6 Hz, 1H, Ar-H), 3.56 (dd, J = 13.5 and 4.2

Hz, 1H, CH), 3.23−3.05 (m, 2H, CH₂), 2.70−2.61 (m, 1H, CH),

2.41 (s, 3H, ArCH₃), 2.31 (s, 3H, ArCH₃), 1.69−1.51 (m, 1H, CH)

ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 147.4, 143.0, 142.2,

137.5, 136.9, 136.6, 136.2, 133.4, 132.4, 129.6 (2 × CH), 129.2 (2 ×

CH), 129.0, 126.9, 126.8, 125.6, 125.4, 122.2, 120.9, 48.8, 30.6, 28.5,

21.5, 21.4 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₅H₂₃

323.1794; Found 323.1786.

11-(4-Methoxyphenyl)-9-methyl-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9m). GP-4 was carried out with 3-(2-((4-methoxyphenyl)-

ethynyl)phenyl)-1-(p-tolyl)propan-1-ol 7m (70.8 mg, 0.2 mmol),

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9m (53.8 mg, 80%) as white solid with melting

point = 124−122 °C.

135.6, 135.5, 133.1, 131.9, 129.2 (2 × CH), 129.1 (3 × CH), 127.7,

127.5, 126.9, 125.6, 124.6, 123.4, 120.3, 48.8, 30.4, 28.3 ppm. HRMS

(ESI) m/z: [M]⁺Calcd for C₂₃H₁₇Cl 328.1013; Found 328.1016.

9-Fluoro-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene (9i).

GP-4 was carried out with 1-(4-ﬂorophenyl)-3-(2-(phenylethynyl)-

phenyl)propan-1-ol 7i (66.1 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30

mol %) in dry DCE (2 mL) at 0 °C to room temperature for 1 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate/hexane to 99:1) furnished the

product 9i (36.2 mg, 58%) as colorless liquid.

TLC (petroleum ether/ethyl acetate 98:2, R_f(7i) = 0.20, R_f(9i) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2922,

1

1749, 1614, 1465, 1345, 1286, 1129, 1060, 920, 761, 695 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ 7.50 (t, J = 7.1 Hz, 2H, Ar-H), 7.48−7.42

(m, 2H, Ar-H), 7.41−7.36 (m, 2H, Ar-H), 7.23 (d, J = 7.6 Hz, 1H,

Ar-H), 7.20−7.10 (m, 2H, Ar-H), 6.96−6.90 (m, 2H, Ar-H), 6.79

(dd, J = 9.3 and 2.4 Hz, 1H, Ar-H), 3.61 (dd, J = 13.6 and 4.4 Hz, 1H,

CH), 3.29−3.08 (m, 2H, CH₂), 2.78−2.65 (m, 1H, CH), 1.72−1.57

(m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 162.8

(J_C−F= 241 Hz), 149.0 (J_C−F= 8.6 Hz), 144.2, 141.2, 137.6, 135.3,

133.5 (J_C−F= 3.2 Hz), 131.8, 129.2 (2 × CH), 129.1, 129.0 (2 ×

CH), 127.7, 127.5, 126.9, 125.5, 123.2 (J_C−F= 9 Hz), 111.4 (J_C−F

=

22 Hz), 107.3 (J_C−F= 23.4 Hz), 48.6, 30.5, 28.5 ppm. HRMS (ESI)

m/z: [M]⁺Calcd for C₂₃H₁₇F 312.1309; Found 312.1291.

TLC (petroleum ether/ethyl acetate 90:10, R_f(7m) = 0.30, R_f(9m)

= 0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_m₁_ax= 3384,

2915, 2825, 2150, 2060, 1361, 1172, 946, 888, 831 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ 7.30 (d, J = 7.5 Hz, 1H, Ar-H), 7.21 (d, J = 7.9

Hz, 2H, Ar-H), 7.12−7.06 (m, 2H, Ar-H), 7.00−6.91 (m, 4H, Ar-H),

6.81 (dd, J = 12.5 and 3.9 Hz, 2H, Ar-H), 3.78 (s, 3H, ArOCH₃), 3.47

(dd, J = 13.5 and 4.3 Hz, 1H, CH), 3.15−2.95 (m, 2H, CH₂), 2.61−

2.52 (m, 1H, CH), 2.24 (s, 3H, ArCH₃), 1.56−1.41 (m, 1H, CH)

ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 158.9, 147.5, 143.0,

13-(4-Methoxyphenyl)-6,6a-dihydro-5H-dibenzo[a,g]-

ﬂuorene (9j′). GP-4 was carried out with 1-(naphthalen-1-yl)-3-(2-

(phenylethynyl)phenyl)propan-1-ol 7j (78.4 mg, 0.2 mmol), BF₃·

OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9j′ (60.6 mg, 81%) as yellow liquid.

TLC (petroleum ether/ethyl acetate 95:5, R_f(7j) = 0.20, R_f(9j′) =

0.70, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2936,

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Article

142.3, 137.5, 136.6, 135.8, 132.4, 130.4 (2 × CH), 129.0, 128.5,

126.9, 126.8, 125.6, 125.4, 122.2, 120.8, 114.3 (2 × CH), 55.2, 48.8,

30.6, 28.5, 21.5 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₅H₂₃O 339.1743; Found 339.1734.

11-(3,4-Dimethoxyphenyl)-9-methyl-6,6a-dihydro-5H-

benzo[a]ﬂuorene (9n). GP-4 was carried out with 3-(2-((3,4-

dimethoxyphenyl)ethynyl)phenyl)-1-(p-tolyl)propan-1-ol 7n (71.2

mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2

mL) at 0 °C to room temperature for 1 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 95:5−93:7) furnished the product 9n (66.4 mg, 89%) as

yellow oily.

TLC (petroleum ether/ethyl acetate 85:15, R_f(7n) = 0.30, R_f(9n) =

0.85, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3024,

2971, 1709, 1542, 1495, 1241, 1157, 1018, 856 cm⁻¹. ¹H NMR (400

MHz, CDCl₃) δ 7.43 (d, J = 7.5 Hz, 1H, Ar-H), 7.23 (dd, J = 10.9 and

4.0 Hz, 2H, Ar-H), 7.14−7.05 (m, 2H, Ar-H), 7.02 (d, J = 8.2 Hz, 1H,

Ar-H), 6.98−6.80 (m, 3H, Ar-H), 6.81−6.87 (m, 1H, Ar-H), 3.99 (s,

3H, ArOCH₃), 3.83 (s, 3H, ArOCH₃), 3.60 (dd, J = 13.5 and 4.3 Hz,

1H, CH), 3.18−3.14 (m, 2H, CH₂), 2.72−2.68 (m, 1H, CH), 2.36 (s,

3H, ArCH₃), 1.67−1.56 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100

MHz, CDCl₃) δ = 149.3, 148.3, 147.4, 143.0, 142.2, 137.5, 136.7,

135.9, 132.3, 129.0, 128.9, 127.0, 126.9, 125.6, 125.4, 122.2, 121.5,

120.9, 112.3, 111.6, 55.9, 55.8, 48.8, 30.7, 28.4, 21.5 ppm. HRMS

(ESI) m/z: [M + H]⁺Calcd for C₂₆H₂₅O₂369.1849; Found

369.1835.

9-Ethyl-11-(p-tolyl)-6,6a-dihydro-5H-benzo[a]ﬂuorene (9o).

GP-4 was carried out with 1-(4-ethylphenyl)-3-(2-(p-tolylethynyl)-

phenyl)propan-1-ol 7o (70.8 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30

mol %) in dry DCE (2 mL) at 0 °C to room temperature for 1 h.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate 97:3−95:5) furnished the

product 9o (53.8 mg, 78%) as white liquid.

9-Ethyl-11-(4-methoxyphenyl)-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9q). GP-4 was carried out with 1-(4-ethylphenyl)-3-(2-

((4-methoxyphenyl)ethynyl)phenyl)propan-1-ol 7q (74.0 mg, 0.2

mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to

room temperature for 1 h. Puriﬁcation of the crude material by silica

gel column chromatography (petroleum ether/ethyl acetate 97:3−

95:5) furnished the product 9q (52.8 mg, 75%) as colorless liquid.

TLC (petroleum ether/ethyl acetate 93:07, R_f(7q) = 0.20, R_f(9q) =

0.75, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3010,

1

2534, 1694, 1508, 1462, 1290, 1245, 1130, 951, 815, 660 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ = 7.45 (d, J = 7.5 Hz, 1H, Ar-H), 7.33

(m, J = 7.9 Hz, 2H, Ar-H), 7.24−7.17 (m, 2H, Ar-H), 7.13−7.07 (m,

2H, Ar-H), 7.04−7.01 (m, 2H, Ar-H), 6.95 (s, 1H, Ar-H), 6.92 (t, J =

7.6 Hz, 1H, Ar-H), 3.91 (s, 3H, ArOCH₃), 3.59 (dd, J = 13.5 and 4.3

Hz, 1H, CH), 3.16 (ddd, J = 17.1 Hz, 12.7 and 8.2 Hz, 2H, CH₂),

2.73−2.59 (m, 3H, CH and CH₂CH₃), 1.70−1.56 (m, 1H, CH), 1.23

(t, J = 7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ = 158.9, 147.5, 143.3, 143.2, 142.3, 137.5, 135.9, 132.5,

130.5 (2 × CH), 129.0, 128.5, 126.9, 126.8, 125.4, 124.5, 122.3,

119.7, 114.4 (2 × CH), 55.2, 48.8, 30.9, 29.0, 28.4, 16.1 ppm. HRMS

(ESI) m/z: [M]⁺Calcd for C₂₆H₂₄O 352.1822; Found 352.1813.

11-(3,5-Dimethoxyphenyl)-9-ethyl-6,6a-dihydro-5H-benzo-

[a]ﬂuorene (9r). GP-4 was carried out with 3-(2-((3,5-

dimethoxyphenyl)ethynyl)phenyl)-1-(4-ethylphenyl)propan-1-ol 7r

(80.0 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE

(2 mL) at 0 °C to room temperature for 1 h. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 97:3−95:5) furnished the product 9r (60.3 mg, 79%) as

yellow oil.

TLC (petroleum ether/ethyl acetate 95:05, R_f(7r) = 0.20, R_f(9r) =

0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2923,

1

2852, 1605, 1486, 1252, 1037, 753, 701 cm⁻¹. H NMR (400 MHz,

CDCl₃) δ 7.42 (d, J = 7.5 Hz, 1H, Ar-H), 7.28−7.24 (m, 1H, Ar-H),

7.17 (t, J = 5.5 Hz, 1H, Ar-H), 7.09−7.07 (m, 2H, Ar-H), 6.97 (s, 1H,

Ar-H), 6.92 (t, J = 7.4 Hz, 1H, Ar-H), 6.55−6.53 (m, 3H, Ar-H), 3.76

(s, 6H, 2 × ArOCH₃), 3.57 (dd, J = 13.5 and 4.3 Hz, 1H, CH), 3.24−

3.01 (m, 2H, CH₂), 2.74−2.66 (m, 1H, CH), 2.63 (q, J = 7.6 Hz, 2H,

CH₂CH₃), 1.64−1.53 (m, 1H, CH), 1.21 (t, J = 7.6 Hz, 3H,

CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 161.2 (2 × C),

147.1, 143.2, 143.1, 142.2, 138.6, 137.5, 136.1, 132.1, 128.9, 127.1,

127.0, 125.5, 124.5, 122.3, 119.8, 106.9, 99.9 (2 × CH), 55.3 (2 ×

OCH₃), 48.9, 30.6, 29.0, 28.3, 16.1 ppm. HRMS (ESI) m/z: [M+ H]⁺

Calcd for C₂₇H₂₇O₂383.2006; Found 383.1997.

9-Ethyl-11-(4-ﬂuorophenyl)-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9s). GP-4 was carried out with 1-(4-ethylphenyl)-3-(2-((4-

ﬂuorophenyl)ethynyl)phenyl)propan-1-ol 7s (71.6 mg, 0.2 mmol),

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate/hexane to

99:1) furnished the product 9s (46.2 mg, 68%) as colorless liquid.

TLC (petroleum ether/ethyl acetate 99:01, R_f(7s) = 0.20, R_f(9s) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2923,

2852, 1728, 1605, 1252, 1037, 753 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ = 7.53 (d, J = 7.5 Hz, 1H, Ar-H), 7.44−7.26 (m, 2H, Ar-

H), 7.27 (dt, J = 8.9 and 6.5 Hz, 3H, Ar-H), 7.19 (ddd, J = 6.7 Hz,

3.3.Hz and 1.4 Hz, 3H, Ar-H), 6.99 (dd, J = 7.4 and 4.2 Hz, 2H, Ar-

H), 3.67 (dd, J = 13.5 and 4.3 Hz, 1H, CH), 3.32−3.14 (m, 2H,

CH₂), 2.84−2.74 (m, 1H, CH), 2.76−2.66 (m, 2H, CH₂CH₃), 1.76−

1.61 (m, 1H, CH), 1.30 (t, J = 7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ = 162.2 (J_C−F= 245 Hz), 147.1, 143.3,

143.3, 142.9, 137.6, 135.1, 132.3 (J = 4 Hz), 132.1, 131.1, 130.1,

129.1, 127.2, 126.7, 125.5, 124.7, 122.4, 119.6, 116.1, 115.9, 48.8,

30.6, 29.0, 28.4, 16.1 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₅H₂₂F 341.1700; Found 341.1687.

TLC (petroleum ether/ethyl acetate 99:1, R_f(7o) = 0.20, R_f(9o) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3018,

1

2924, 1676, 1605, 1360, 1147, 880, 732 cm⁻¹. H NMR (400 MHz,

CDCl₃) δ 7.46 (d, J = 7.5 Hz, 1H, Ar-H), 7.32−7.27 (m, 4H, Ar-H),

7.21 (t, J = 7.7 Hz, 2H, Ar-H), 7.13−7.09 (m, 2H, Ar-H), 6.96 (s, 1H,

Ar-H), 6.92 (t, J = 7.5 Hz, 1H, Ar-H), 3.61 (dd, J = 13.5 and 4.2 Hz,

1H, CH), 3.25−3.12 (m, 2H, CH₂), 2.73−2.63 (m, 3H, CH and

CH₂CH₃), 2.46 (s, 3H, ArCH₃), 1.69−1.51 (m, 1H, CH), 1.24 (t, J =

7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ =

147.4, 143.4, 143.2, 142.2, 137.5, 136.9, 136.3, 133.4, 132.4, 129.6 (2

× CH), 129.2 (2 × CH), 129.0, 126.9, 126.9, 125.4, 124.4, 122.3,

119.8, 48.8, 30.7, 29.4, 28.5, 21.5, 16.0 ppm. HRMS (ESI) m/z: [M +

H]⁺Calcd for C₂₆H₂₅337.1951; Found 337.1940.

9-ethyl-11-(4-ethylphenyl)-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9p). GP-4 was carried out with 1-(4-ethylphenyl)-3-(2-

((4-ethylphenyl)ethynyl)phenyl)propan-1-ol 7p (73.6 mg, 0.2

mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0

°C to room temperature for 1 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate/

hexane to 99:1) furnished the product 9p (50.4 mg, 72%) as white

liquid.

TLC (petroleum ether/ethyl acetate 99:1, R_f(7p) = 0.20, R_f(9p) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2974,

1

1749, 1614, 1465, 1345, 1286, 1129, 1060, 920, 761, 695 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ = 7.46 (d, J = 7.5 Hz, 1H, Ar-H), 7.33−

7.32 (m, 4H, Ar-H), 7.24−7.17 (m, 2H, Ar-H), 7.14−7.07 (m, 2H,

Ar-H), 6.97 (s, 1H, Ar-H), 6.92 (t, J = 7.4 Hz, 1H, Ar-H), 3.60 (dd, J

= 13.5 and 4.3 Hz, 1H, CH), 3.22−3.08 (m, 2H, CH₂), 2.78 (q, J =

7.6 Hz, 2H, CH₂CH₃), 2.75−2.68 (m, 1H, CH), 2.66 (q, J = 7.3 Hz,

2H, CH₂CH₃), 1.69−1.58 (m, 1H, CH), 1.36 (t, J = 7.3 Hz, 3H,

CH₂CH₃), 1.24 (t, J = 7.5 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR

(100 MHz, CDCl₃) δ = 147.4, 143.3, 143.2 (2 × C), 142.2, 137.5,

136.3, 133.5, 132.4, 129.2 (2 × CH), 129.0, 128.3 (2 × CH), 126.9,

126.8, 125.4, 124.4, 122.3, 119.9, 48.8, 30.6, 29.0, 28.6, 28.4, 16.1,

15.4 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₇H₂₇351.2107;

Found 351.2112.

9-Isopropyl-11-(p-tolyl)-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9t). GP-4 was carried out with 1-(4-isopropylphenyl)-3-(2-(p-

tolylethynyl)phenyl)propan-1-ol 7t (73.6 mg, 0.2 mmol), BF₃·OEt₂

(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

8721

https://doi.org/10.1021/acs.joc.1c00525

J. Org. Chem. 2021, 86, 8706−8725

The Journal of Organic Chemistry

pubs.acs.org/joc

Article

column chromatography (petroleum ether/ethyl acetate/hexane to

99:1) furnished the product 9t (54.6 mg, 78%) as yellow oil.

TLC (petroleum ether/ethyl acetate 99:1, R_f(7t) = 0.20, R_f(9t) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3049,

(400 MHz, CDCl₃) δ 7.33−7.12 (m, 5H, Ar-H), 7.03 (td, J = 7.5 and

1.3 Hz, 1H, Ar-H), 6.93 (d, J = 8.0 Hz, 1H, Ar-H), 6.84 (t, J = 7.6 Hz,

1H, Ar-H), 6.76 (dd, J = 2.0 and 0.9 Hz, 1H, Ar-H), 6.39 (d, J = 1.8

Hz, 1H, Ar-H), 3.87 (s, 3H, ArOCH₃), 3.55 (dd, J = 13.6 and 4.3 Hz,

1H, CH), 3.51 (s, 3H, ArOCH₃), 3.23−3.05 (m, 2H, CH₂), 2.64−

2.63 (m, 1H, CH), 2.44 (s, 3H, ArCH₃), 1.70−1.57 (m, 1H, CH)

ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 159.3, 155.2, 149.5, 139.0,

137.0, 136.0, 135.8, 135.5, 132.8, 128.8, 128.6 (2 × CH), 127.7, 126.5

(2 × CH), 126.2 (2 × CH), 125.3, 100.6, 98.3, 55.6, 55.6, 49.5, 30.7,

28.8, 21.4 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₆H₂₅O₂

369.1849; Found 369.1834.

8,10-dimethoxy-11-(4-methoxyphenyl)-6,6a-dihydro-5H-

benzo[a]ﬂuorene (9x). GP-4 was carried out with 1-(3,5-

dimethoxyphenyl)-3-(2-((4-methoxyphenyl)ethynyl)phenyl)propan-

1-ol 7x (73.6 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry

DCE (2 mL) at 0 °C to room temperature for 1 h. Puriﬁcation of the

crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 93:7−95:5) furnished the product 9x (44.9 mg,

64%) as yellow oil.

1

2858, 1608, 1469, 1359, 1048, 811, 738 cm⁻¹. H NMR (400 MHz,

CDCl₃) δ 7.46 (d, J = 7.5 Hz, 1H, Ar-H), 7.32−7.27 (m, 4H, Ar-H),

7.21−7.16 (t, 2H, Ar-H), 7.15−7.10 (m, 2H, Ar-H), 6.97 (s, 1H, Ar-

H), 6.90 (t, J = 7.5 Hz, 1H, Ar-H), 3.58 (dd, J = 13.5 and 4.2 Hz, 1H,

CH), 3.17−3.14 (m, 2H, CH₂), 2.90 (dt, J = 13.8 and 6.9 Hz, 1H,

CH), 2.76−2.64 (m, 1H, CH(CH₃)₂), 2.47 (s, 3H, ArCH₃), 1.72−

1.52 (m, 1H, CH), 1.24 (dd, J = 6.9 and 1.0 Hz, 6H, CH(CH₃)₂)

ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 147.9, 147.3, 143.5,

142.2, 137.5, 136.9, 136.4, 133.4, 132.5, 129.6 (2 × CH), 129.2 (2 ×

CH), 129.0, 126.9, 126.9, 125.4, 122.8, 122.3, 118.5, 48.8, 34.3, 30.7,

28.4, 24.3, 24.2, 21.4 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₇H₂₇351.2107; Found 351.2099.

9-Isopropyl-11-(4-methoxyphenyl)-6,6a-dihydro-5H-benzo-

[a]ﬂuorene (9u). GP-4 was carried out with 1-(4-isopropylphenyl)-

3-(2-((4-methoxyphenyl)ethynyl)phenyl)propan-1-ol 7u (76.8 mg,

0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0

°C to room temperature for 1 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

98:2−97:3) furnished the product 9u (59.3 mg, 81%) as yellow oil.

TLC (petroleum ether/ethyl acetate 95:5, R_f(7u) = 0.20, R_f(9u) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2924,

2958, 1599, 1508, 1244, 1244, 1033, 765 cm⁻¹. ¹H NMR (400 MHz,

CDCl₃) δ 7.49 (d, J = 7.6 Hz, 1H, Ar-H), 7.36 (d, J = 7.8 Hz, 2H, Ar-

H), 7.25−7.20 (m, 2H, Ar-H), 7.20−7.10 (m, 2H, Ar-H), 7.07 (d, J =

8.6 Hz, 2H, Ar-H), 7.01 (s, 1H, Ar-H), 6.95 (t, J = 7.6 Hz, 1H, Ar-H),

3.94 (s, 3H, ArOCH₃), 3.61 (dd, J = 13.5 and 4.3 Hz, 1H, CH),

3.30−3.06 (m, 2H, CH₂), 2.94 (dt, J = 13.8 and 6.9 Hz, 1H, CH),

2.77−2.68 (m, 1H, CH), 1.70−1.59 (m, 1H, CH(CH₃)₂), 1.28 (dd, J

= 6.9 and 1.1 Hz, 6H, CH(CH₃)₂) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ = 158.9, 148.0, 147.5, 143.5, 142.3, 137.6, 136.1, 132.5,

130.6 (2 × CH), 129.2, 128.6, 127.0, 126.9, 125.5, 123.0, 122.4,

118.5, 114.4 (2 × CH), 55.3, 48.8, 34.3, 30.7, 28.4, 24.4 (2 × CH₃)

ppm. HRMS (ESI) m/z: [M+H⁺]+[-H₂O] Calcd for C₂₇H₂₅

349.1950; Found 349.1958.

TLC (petroleum ether/ethyl acetate 90:10, R_f(7x) = 0.20, R_f(9x) =

0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3410,

1

2927, 1691, 1598, 1456, 1257, 1075, 873, 813, 752, 654 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ 7.44−7.10 (m, 3H, Ar-H), 7.06 (td, J =

7.4 and 1.3 Hz, 1H, Ar-H), 7.02−6.80 (m, 4H, Ar-H), 6.78 (dd, J =

2.1, 0.8 Hz, 1H, Ar-H), 6.41 (d, J = 2.1 Hz, 1H, Ar-H), 3.91 (s, 3H,

ArOCH₃), 3.89 (s, 3H, ArOCH₃), 3.50−3.52 (m, 4H, CH and

ArOCH₃), 3.26−3.09 (m, 2H, CH₂), 2.76−2.59 (m, 1H, CH), 1.73−

1.60 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 159.3,

158.4, 155.2, 149.5, 139.2, 137.1, 135.5, 132.8, 130.9, 128.9, 127.7,

126.5 (2 × CH), 126.4 (2 × CH), 125.4, 125.3, 113.4, 110.7, 98.3,

55.6 (2 × ArOCH₃), 55.2, 49.4, 30.6, 28.8 ppm. HRMS (ESI) m/z:

[M + H]⁺Calcd for C₂₆H₂₅O₃385.1798; Found 385.1784.

9-Chloro-11-(p-tolyl)-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9y). GP-4 was carried out with 1-(4-chlorophenyl)-3-(2-(p-

tolylethynyl)phenyl)propan-1-ol 7y (72.0 mg, 0.2 mmol), BF₃·OEt₂

(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate/hexane to

99:1) furnished the product 9y (46.5 mg, 68%) as yellow oil.

TLC (petroleum ether/ethyl acetate 99:1, R_f(7y) = 0.20, R_f(9y) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3410,

9-Isopropyl-11-(2-methoxyphenyl)-6,6a-dihydro-5H-benzo-

[a]ﬂuorene (9v). GP-4 was carried out with 1-(4-isopropylphenyl)-

3-(2-((2-methoxyphenyl)ethynyl)phenyl)propan-1-ol 7v (76.8 mg,

0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0

°C to room temperature for 1 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate

98:2−97:3) furnished the product 9v (48.2 mg, 70%) as yellow oil.

TLC (petroleum ether/ethyl acetate 95:5, R_f(7v) = 0.20, R_f(9v) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 2924,

2958, 1599, 1508, 1244, 1244, 1033, 765 cm⁻¹. ¹H NMR according to

the major isomer (400 MHz, CDCl₃) δ 7.53 (dd, J = 7.6, 3.4 Hz, 2H,

Ar-H), 7.27 (d, J = 4.2 Hz, 1H, Ar-H), 7.23−7.16 (m, 4H, Ar-H), 7.07

(d, J = 6.6 Hz, 1H, Ar-H), 6.98 (t, J = 7.3 Hz, 2H, Ar-H), 6.91 (s, 1H,

Ar-H), 3.90 (s, 3H, ArOCH₃), 3.73 (dd, J = 13.6, 4.4 Hz, 1H, CH),

3.33−3.21 (m, 2H), 3.00 (dd, J = 13.8 and 6.9 Hz, 1H, CH), 2.81−

2.76 (m, 1H, CH), 1.74−1.67 (m, 1H, CH), 1.31 (dd, J = 4.2, 2.7 Hz,

1

2927, 1691, 1598, 1456, 1257, 1075, 873, 813, 752, 654 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ 7.42 (d, J = 7.9 Hz, 1H, Ar-H), 7.34−

7.25 (m, 4H, Ar-H), 7.20 (dd, J = 6.4 Hz, 5.4 and 4.0 Hz, 3H, Ar-H),

7.13 (td, J = 7.5 and 1.2 Hz, 1H, Ar-H), 7.07 (d, J = 1.9 Hz, 1H, Ar-

H), 6.93 (t, J = 7.6 Hz, 1H, Ar-H), 3.59 (dd, J = 13.5 and 4.3 Hz, 1H,

CH), 3.28−3.08 (m, 2H, CH₂), 2.75−2.63 (m, 1H, CH), 2.46 (s, 3H,

ArCH₃), 1.72−1.57 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 149.0, 144.0, 143.6, 137.6, 137.4, 135.4, 132.9, 132.5, 131.9,

129.8 (2 × CH), 129.0 (3 × CH), 127.4, 127.0, 125.6, 124.6, 123.3,

120.4, 48.8, 30.5, 28.3, 21.4 ppm. HRMS (ESI) m/z: [M]⁺Calcd for

C₂₄H₁₉Cl 342.1170; Found 342.1173.

2-Methoxy-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene

(9z). GP-4 was carried out with 3-(4-methoxy-2-(phenylethynyl)-

phenyl)-1-phenylpropan-1-ol 7z (68.4 mg, 0.2 mmol), BF₃·OEt₂(16.8

mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room temperature for 3

h. Puriﬁcation of the crude material by silica gel column

chromatography (petroleum ether/ethyl acetate/hexane to 95:5)

furnished the product 9z (51.2 mg, 79%) as yellow oil.

1

6H, 2 × CH₃). H NMR according to the major isomer: ¹³C{H}

NMR (100 MHz, CDCl₃) δ 158.1, 147.6, 146.8, 143.5, 143.0, 142.9,

137.6, 133.5, 132.6, 131.0, 129.01, 128.9 (2 × CH), 127.0, 125.5,

122.8, 122.2, 121.2, 118.8, 111.3, 55.6, 49.0, 34.3, 30.8, 28.5, 24.5,

24.2 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₇H₂₇O

367.2056; Found 367.2041.

TLC (petroleum ether/ethyl acetate 95:5, R_f(7z) = 0.20, R_f(9z) =

8,10-dimethoxy-11-(p-tolyl)-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9w). GP-4 was carried out with 1-(3,5-dimethoxyphenyl)-

3-(2-(p-tolylethynyl)phenyl)propan-1-ol 7w (73.6 mg, 0.2 mmol),

BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 1 h. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 97:3−95:5)

furnished the product 9w (44.9 mg, 64%) as yellow oil. TLC

(petroleum ether/ethyl acetate 90:10, R_f(7w) = 0.20, R_f(9w) = 0.80,

UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3410, 2927,

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3054,

1

2924, 2853, 1686, 1599, 1452, 1265, 746, 701 cm⁻¹. H NMR (400

MHz, CDCl₃) δ = 7.61−7.51 (m, 3H, Ar-H), 7.50−7.40 (m, 3H, Ar-

H), 7.35−7.26 (m, 2H, Ar-H), 7.20−7.09 (m, 2H, Ar-H), 6.75 (dd, J

= 4.6 and 1.8 Hz, 2H, Ar-H), 3.66 (dd, J = 13.5 and 4.2 Hz, 1H, CH),

3.39 (s, 3H, ArOCH₃), 3.26−3.00 (m, 2H, CH₂), 2.85−2.65 (m, 1H,

CH), 1.70−1.48 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ = 157.0, 146.9, 145.8, 142.4, 136.5 (2 × C), 132.7, 129.8,

129.9, 129.4 (2 × CH), 128.9 (2 × CH), 127.4, 126.9, 124.9, 122.5,

1

1691, 1598, 1456, 1257, 1075, 873, 813, 752, 654 cm⁻¹. H NMR

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120.2, 115.1, 109.9, 56.4, 49.2, 29.8, 28.5 ppm. HRMS (ESI) m/z: [M

+ H]⁺Calcd for C₂₄H₂₁O 325.1587; Found 325.1565.

0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at

0 °C to room temperature for 30 min. Puriﬁcation of the crude

material by silica gel column chromatography (petroleum ether/ethyl

acetate 98:2−97:3) furnished the product 10b (52.7 mg, 78%) as

white solid with melting point = 108−110 °C.

9-Ethyl-3-methoxy-11-(4-methoxyphenyl)-6,6a-dihydro-

5H-benzo[a]ﬂuorene (9aa). GP-4 was carried out with 1-(4-

ethylphenyl)-3-(4-methoxy-2-((4-methoxyphenyl)ethynyl)phenyl)-

propan-1-ol 7aa (80.0 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %)

in dry DCE (2 mL) at 0 °C to room temperature for 1 h. Puriﬁcation

of the crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 98:2 to 97:3) furnished the product 9aa (76.4 mg,

68%) as yellow oil.

TLC (petroleum ether/ethyl acetate 95:5, R_f(8b) = 0.20, R_f(10b) =

0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_ma₁_x= 3009,

2917, 1593, 1501, 1360, 1284, 1169, 1024, 826, 749 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ 7.44−7.41 (m, 1H, Ar-H), 7.30 (d, J = 8.3 Hz,

2H, Ar-H), 7.25−7.19 (m, 3H, Ar-H), 7.16−7.14 (m, 2H, Ar-H), 7.10

(dd, J = 7.5 and 1.4 Hz, 1H, Ar-H), 6.98 (dd, J = 7.6 and 1.3 Hz, 2H,

Ar-H), 6.92 (t, J = 7.3 Hz, 1H, Ar-H), 3.85 (s, 3H, ArOCH₃), 3.29−

3.15 (m, 1H, CH), 3.02 (dd, J = 17.7 and 6.3 Hz, 1H, CH), 2.41−

2.36 (m, 1H, CH), 1.67 (td, J = 12.7 and 6.5 Hz, 1H, CH), 1.28 (s,

3H, CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 158.8, 152.4,

146.8, 145.2, 136.7, 134.0, 131.6, 130.6 (2 × CH), 128.9, 128.0,

127.8, 127.0, 126.7, 125.3, 125.0, 121.2, 120.5, 114.2 (2 × CH), 55.2,

48.9, 32.5, 26.7, 20.6 ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for

C₂₅H₂₃O 339.1743; Found 339.1730.

11-(3,5-Dimethoxyphenyl)-6a-methyl-6,6a-dihydro-5H-

benzo[a]ﬂuorene (10c). GP-4 was carried out with 4-(2-((3,5-

dimethoxyphenyl)ethynyl)phenyl)-2-phenylbutan-2-ol 8c (77.3 mg,

0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0

°C to room temperature for 30 min. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

98:2−97:3) furnished the product 10c (64.8 mg, 80%) as white solid

with Melting point = 126−128 °C.

TLC (petroleum ether/ethyl acetate 90:10, R_f(8c) = 0.20, R_f(10c)

= 0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_m₁_ax= 3055,

2926, 1688, 1357, 1313, 1188, 1145, 940, 748, 695 cm⁻¹. H NMR

(400 MHz, CDCl₃) δ 7.44−7.40 (m, 1H, Ar-H), 7.26−7.20 (m, 5H,

Ar-H), 7.11 (td, J = 7.4 and 1.3 Hz, 1H, Ar-H), 6.94 (t, J = 7.4 Hz,

1H, Ar-H), 6.52−6.49 (m, 3H, Ar-H), 3.76 (s, 6H, 2 × ArOCH₃),

3.26−3.17 (m, 1H, CH), 3.02 (dd, J = 17.7 and 6.2 Hz, 1H, CH),

2.44−2.34 (m, 1H, CH), 1.68 (td, J = 12.7 and 6.5 Hz, 1H, CH), 1.29

(s, 3H, ArCH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 161.1

(2 × C), 152.3, 146.9, 144.8, 138.0, 136.7, 134.3, 131.3, 128.9, 127.9,

127.2, 126.8, 125.4, 125.1, 121.2, 120.6, 107.1 (2 × CH), 99.9, 55.4

(2 × OCH₃), 49.0, 32.4, 26.4, 20.6 ppm. HRMS (ESI) m/z: [M+K]⁺

Calcd for C₂₆H₂₄O₂K 407.1408; Found 407.1381.

TLC (petroleum ether/ethyl acetate 95:5, R_f(7aa) = 0.20, R_f(9aa)

= 0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3054,

1

2924, 2853, 1686, 1599, 1452, 1265, 746, 701 cm⁻¹. H NMR (400

MHz, CDCl₃) δ = 7.46 (d, J = 7.5 Hz, 1H, Ar-H), 7.36 (d, J = 7.7 Hz,

2H, Ar-H), 7.14−7.09 (m, 2H, Ar-H), 7.06 (d, J = 8.8 Hz, 2H, Ar-H),

6.97 (d, J = 0.9 Hz, 1H, Ar-H), 6.78 (d, J = 2.7 Hz, 1H, Ar-H), 6.71

(dd, J = 8.4 and 2.7 Hz, 1H, Ar-H), 3.90 (s, 3H, ArOCH₃), 3.58 (dd, J

= 13.5 and 4.2 Hz, 1H, CH), 3.42 (s, 3H, ArOCH₃), 3.15−3.01 (m,

2H, CH₂), 2.74−2.61 (m, 3H, CH₂CH₃and CH), 1.66−1.51 (m, 1H,

CH), 1.24 (t, J = 7.6 Hz, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100

MHz, CDCl₃) δ = 158.9, 157.0, 147.4, 143.3, 143.2, 142.5, 136.2,

133.1, 130.6 (2 × CH), 129.8, 128.6 (2 × C), 124.5, 122.4, 119.7,

114.8, 114.4 (2 × CH), 110.1, 55.3, 54.7, 48.8, 29.9, 29.0, 28.6, 16.1

ppm. HRMS (ESI) m/z: [M + H]⁺Calcd for C₂₇H₂₇O₂383.2006;

Found 383.1988.

3-Fluoro-9-methyl-11-phenyl-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (9ab). GP-4 was carried out with 3-(5-ﬂuoro-2-

(phenylethynyl)phenyl)-1-(p-tolyl)propan-1-ol 7ab (68.8 mg, 0.2

mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0

°C to room temperature for 1 h. Puriﬁcation of the crude material by

silica gel column chromatography (petroleum ether/ethyl acetate/

hexane to 99:1) furnished the product 9ab (51.5 mg, 79%) as yellow

oil.

TLC (petroleum ether/ethyl acetate 99:1, R_f(7ab) = 0.20, R_f(9ab)

= 0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3054,

1

2924, 2853, 1686, 1599, 1452, 1265, 746, 701 cm⁻¹. H NMR (400

MHz, CDCl₃) δ = 7.54 (t, J = 7.3 Hz, 2H, Ar-H), 7.49−7.41 (m, 4H,

Ar-H), 7.15−7.10 (m, 2H, Ar-H), 6.95−6.92 (m, 2H, Ar-H), 6.66−

6.61 (m, 1H, Ar-H), 3.61 (dd, J = 13.5 and 4.3 Hz, 1H, CH), 3.22−

3.13 (m, 2H, CH₂), 2.74−2.70 (m, 1H, CH), 2.39 (s, 3H, ArCH₃),

1.73−1.58 (m, 1H, CH) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ =

161.7 (J_C−F= 246 Hz), 147.2, 142.8, 141.5, 140.0 (J_C−F= 7 Hz),

136.8, 136.4, 135.8, 129.4 (2 × CH), 129.1 (2 × CH), 128.6 (J_C−F= 4

6a,11-Diphenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene (10d).

GP-4 was carried out with 1,1-diphenyl-3-(2-(phenylethynyl)phenyl)-

propan-1-ol 8d (77.6 mg, 0.2 m mol), BF₃·OEt₂(16.8 mg, 30 mol %)

in dry DCE (2 mL) at 0 °C to room temperature for 30 min.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate:Hexane to 99:1) furnished the

product 10d (58.5 mg, 79%) as white solid with melting point = 130−

132 °C.

Hz), 128.5, 125.8, 122.3, 120.9, 115.4 (J_C−F= 21 Hz), 112.8 (J_C−F

=

21 Hz), 48.8, 30.9, 28.3, 21.6 ppm. HRMS (ESI) m/z: [M]⁺Calcd for

C₂₄H₁₉F 326.1465; Found 326.1454.

6a-Methyl-11-phenyl-6,6a-dihydro-5H-benzo[a]ﬂuorene

(10a). GP-4 was carried out with 1-phenyl-3-(2-(phenylethynyl)-

phenyl)propan-1-ol 8a (65.2 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30

mol %) in dry DCE (2 mL) at 0 °C to room temperature for 30 min.

Puriﬁcation of the crude material by silica gel column chromatog-

raphy (petroleum ether/ethyl acetate/hexane to 99:1) furnished the

product 10a (50.5 mg, 82%) as colorless solid with melting point =

124−126 °C.

TLC (petroleum ether/ethyl acetate 99:1, R_f(8d) = 0.20, R_f(10d)

= 0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3052,

1

2965, 2923, 1455, 751, 703 cm⁻¹. H NMR (400 MHz, CDCl₃) δ

7.47−7.34 (m, 8H, Ar-H), 7.16−7.11 (m, 4H, Ar-H), 7.10−7.03 (m,

3H, Ar-H), 6.97−6.94 (m, 2H, Ar-H), 6.85−6.81 (m, 1H, Ar-H), 3.16

(ddd, J = 13.4, 4.6, and 2.3 Hz, 1H, Ar-H), 2.89 (dt, J = 7.4 and 6.9

Hz, 2H, CH₂), 1.99 (ddd, J = 13.4, 11.1, and 7.3 Hz, 1H, CH) ppm.

¹³C{¹H} NMR (100 MHz, CDCl₃) δ = 151.3, 145.6, 144.6, 140.9,

137.2, 136.9, 135.7, 132.1, 129.4 (2 × CH), 128.8 (2 × CH), 128.7,

128.6 (2 × CH), 127.6, 127.5, 127.2, 126.8, 126.5, 126.3 (2 × CH),

125.5, 125.3, 122.5, 120.7, 57.5, 32.5, 27.1 ppm. HRMS (ESI) m/z:

[M+NH₄]⁺Calcd for C₂₉H₂₆N 388.2060; Found 388.2060.

TLC (petroleum ether/ethyl acetate 99:1, R_f(8a) = 0.20, R_f(10a) =

0.90, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3015,

1

1703, 1596, 1452, 1213, 1150, 1011, 838, 747, 697, 599 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ 7.46−7.42 (m, 3H, Ar-H), 7.39−7.36 (m,

3H, Ar-H), 7.25−7.21 (m, 3H, Ar-H), 7.14−7.11 (m, 2H, Ar-H),

7.10−7.07 (m, 1H, Ar-H), 6.90 (t, J = 7.5 Hz, 1H, Ar-H), 3.30−3.17

(m, 1H, CH), 3.03 (dd, J = 17.7 and 6.4 Hz, 1H, CH), 2.40 (dd, J =

13.0 and 5.6 Hz, 1H, CH), 1.70 (td, J = 12.7 and 6.5 Hz, 1H, CH),

1.30 (s, 3H, CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 152.4,

147.0, 145.0, 136.7, 136.0, 134.4, 131.5, 129.4 (2 × CH), 128.9, 128.7

(2 × CH), 127.8, 127.3, 127.1, 126.8, 125.3, 125.1, 121.3, 120.5, 49.0,

32.5, 26.7, 20.5 ppm. HRMS (ESI) m/z: [M]⁺Calcd for C₂₄H₂₀

308.1560; Found 308.1555.

9-Chloro-6a-methyl-11-phenyl-6,6a-dihydro-5H-benzo[a]-

ﬂuorene (10e). GP-4 was carried out with 2-(4-chlorophenyl)-4-(2-

(phenylethynyl)phenyl)butan-2-ol 8e (72.0 mg, 0.2 m mol), BF₃·

OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 30 min. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate/hexane to

99:1) furnished the product 10e (56.1 mg, 82%) as yellow oily.

TLC (petroleum ether/ethyl acetate 99:1, R_f(8e) = 0.20, R_f(10e) =

0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3015,

11-(4-Methoxyphenyl)-6a-methyl-6,6a-dihydro-5H-benzo-

[a]ﬂuorene (10b). GP-4 was carried out with 4-(2-((4-

methoxyphenyl)ethynyl)phenyl)-2-phenylbutan-2-ol 8b (71.2 mg,

1

1703, 1596, 1452, 1213, 1150, 1011, 838, 747, 697, 599 cm⁻¹. H

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NMR (400 MHz, CDCl₃) δ 7.40 (dd, J = 11.0 and 4.6 Hz, 2H, Ar-H),

7.33 (ddd, J = 6.2 Hz, 3.0 and 1.5 Hz, 1H, Ar-H), 7.27 (dd, J = 11.5

and 3.7 Hz, 3H, Ar-H), 7.18−7.11 (td, J = 7.5 and 1.3 Hz, 2H, Ar-H),

7.07 (td, J = 7.5 and 1.3 Hz, 1H, Ar-H), 7.00 (dd, J = 9.1 and 1.3 Hz,

2H, Ar-H), 6.85 (t, J = 7.5 Hz, 1H, Ar-H), 3.20−3.15 (m, 1H, CH),

3.03−2.94 (dd, J = 17.7 and 6.4 Hz, 1H, CH), 2.34−2.29 (m, 1H,

CH), 1.65−1.57 (m, 1H, CH), 1.22 (s, 3H, CH₃) ppm. ¹³C{¹H}

NMR (100 MHz, CDCl₃) δ 150.6, 148.6, 146.7, 136.7, 135.3, 133.5,

132.7, 131.7, 129.3 (2 × CH), 129.0 (2 × CH), 128.9, 127.8, 127.5,

127.5, 125.4, 124.9, 122.2, 120.6, 48.8, 32.4, 26.5, 20.6 ppm. HRMS

(ESI) m/z: [M + H]⁺Calcd for C₂₄H₂₀Cl 343.1248; Found 343.1251.

6a-Methyl-12-phenyl-6,6a-dihydro-5H-benzo[7,8]ﬂuoreno-

[2,3-d][1,3]dioxole (10f). GP-4 was carried out with 2-(benzo[d]-

[1,3]dioxol-5-yl)-4-(2-(phenylethynyl)phenyl)butan-2-ol 8f (74.0 mg,

0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0

°C to room temperature for 30 min. Puriﬁcation of the crude material

by silica gel column chromatography (petroleum ether/ethyl acetate

98:2 to 97:3) furnished the product 10f (56.3 mg, 80%) as yellow oil.

TLC (petroleum ether/ethyl acetate 95:5, R_f(8f) = 0.20, R_f(10f) =

0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3015,

CH), 1.82−1.64 (m, 3H, CH₂and CH), 0.52 (t, J = 7.3 Hz, 3H,

CH₂CH₃) ppm. ¹³C{¹H} NMR (100 MHz, CDCl₃) δ 149.1, 148.2,

146.6, 145.8, 144.6, 144.3, 140.2, 136.4, 135.1, 131.6, 128.8, 128.3,

127.2, 126.7, 125.2, 121.6, 112.3, 111.3, 103.2, 101.4, 100.8, 55.8,

55.7, 52.4, 31.7, 26.4, 26.3, 8.1 ppm. HRMS (ESI) m/z: [M + H]⁺

Calcd for C₂₈H₂₇O₄427.1904; Found 427.1874.

ASSOCIATED CONTENT

* Supporting Information

The Supporting Information is available free of charge at

https://pubs.acs.org/doi/10.1021/acs.joc.1c00525.

■

sı

1

Copies of H and ¹³C{¹H} NMR spectra for all starting

materials and ﬁnal compounds (PDF)

Accession Codes

CCDC 2063966−2063967 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.

1

1703, 1596, 1452, 1213, 1150, 1011, 838, 747, 697, 599 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ 7.47−7.40 (m, 2H, Ar-H), 7.39−7.35 (m,

3H, Ar-H), 7.22 (d, J = 7.7 Hz, 1H, Ar-H), 7.11 (td, J = 7.5 and 1.3

Hz, 1H, Ar-H), 7.03 (dd, J = 7.9 and 1.0 Hz, 1H, Ar-H), 6.96 (s, 1H,

Ar-H), 6.90 (t, J = 7.4 Hz, 1H, Ar-H), 6.61 (s, 1H, Ar-H), 5.95 (dd, J

= 9.8 and 1.4 Hz, 2H, -OCH₂O−), 3.25−3.15 (m, 1H, CH), 3.03 (dd,

J = 17.7 and 6.4 Hz, 1H, CH), 2.36−2.31 (m, 1H, CH), 1.72−1.64

(m, 1H, CH), 1.27 (s, 3H, Ar-CH₃) ppm. ¹³C{¹H} NMR (100 MHz,

CDCl₃) δ 146.8, 146.8, 146.1, 145.9, 138.8, 136.3, 136.0, 134.2, 131.6,

129.3 (2 × CH), 128.3, 128.8 (2 × CH), 127.4, 127.3, 126.7, 125.3,

102.9, 101.7, 100.9, 48.7, 32.8, 26.7, 20.7 ppm. HRMS (ESI) m/z: [M

+ H]⁺Calcd for C₂₅H₂₁O₂353.1536; Found 353.1522.

AUTHOR INFORMATION

Corresponding Author

■

Gedu Satyanarayana − Department of Chemistry, Indian

Institute of Technology (IIT) Hyderabad, Kandi 502 285,

Telangana, India; orcid.org/0000-0002-6410-5421;

Phone: (040) 2301 6251; Email: gvsatya@chy.iith.ac.in;

Fax: (040) 2301 6003/32

9-Chloro-6a-ethyl-11-(4-methoxyphenyl)-6,6a-dihydro-5H-

benzo[a]ﬂuorene (10g). GP-4 was carried out with 3-(4-

chlorophenyl)-1-(2-((4-methoxyphenyl)ethynyl)phenyl)pentan-3-ol

8g (74.8 mg, 0.2 mmol), BF₃·OEt₂(16.8 mg, 30 mol %) in dry DCE

(2 mL) at 0 °C to room temperature for 30 min. Puriﬁcation of the

crude material by silica gel column chromatography (petroleum

ether/ethyl acetate 98:2−97:3) furnished the product 10g (57.7 mg,

82%) as yellow oil.

Authors

Dakoju Ravi Kishore − Department of Chemistry, Indian

Institute of Technology (IIT) Hyderabad, Kandi 502 285,

Telangana, India

Chander Shekhar − Department of Chemistry, Indian

Institute of Technology (IIT) Hyderabad, Kandi 502 285,

Telangana, India

TLC (petroleum ether/ethyl acetate 95:05, R_f(8g) = 0.20, R_f(10g)

= 0.80, UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3015,

Complete contact information is available at:

https://pubs.acs.org/10.1021/acs.joc.1c00525

1

1703, 1596, 1452, 1213, 1150, 1011, 838, 747, 697, 599 cm⁻¹. H

NMR (400 MHz, CDCl₃) δ 7.28−7.24 (m, 3H, Ar-H), 7.16 (ddd, J =

9.2 Hz, 8.6 and 4.5 Hz, 2H, Ar-H), 7.12−7.07 (m, 3H, Ar-H), 6.96 (d,

J = 8.8 Hz, 2H, Ar-H), 6.91 (t, J = 7.5 Hz, 1H, Ar-H), 3.85 (s,

ArOCH₃), 3.23−3.15 (m, 1H, CH), 2.88 (dd, J = 17.7 and 6.4 Hz,

1H, CH), 2.41 (dd, J = 13.2 and 5.8 Hz, 1H, CH), 1.84−1.59 (m, 3H,

CH₂CH₃and CH), 0.48 (s, 3H, CH₂CH₃) ppm. ¹³C{¹H} NMR (100

MHz, CDCl₃) δ 158.9, 148.6, 148.2, 146.9, 136.9, 134.2, 132.6, 131.2,

130.4 (2 × CH), 128.9, 127.6, 127.4, 127.3, 125.4, 124.6, 122.4,

120.4, 114.3 (2 × CH), 55.2, 52.6, 31.3, 26.2, 26.1, 8.1 ppm. HRMS

(ESI) m/z: [M + H]⁺Calcd for C₂₆H₂₄ClO 387.1510; Found

387.1484.

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

■

We greatly acknowledge the ﬁnancial support from DST-SERB

(Department of Science and Technology, Science and

Engineering Research Board, Grant EMR/2017/005312),

New Delhi. D.R.K and C.S gratefully acknowledge UGC and

CSIR, respectively, for providing fellowships.

12-(3,4-Dimethoxyphenyl)-6a-ethyl-6,6a-dihydro-5H-

benzo[7,8]ﬂuoreno[2,3-d][1,3]dioxole (10h). GP-4 was carried

out with 3-(benzo[d][1,3]dioxol-5-yl)-1-(2-((3,4-dimethoxyphenyl)-

ethynyl)phenyl)pentan-3-ol 8h (88.8 mg, 0.2 mmol), and BF₃·OEt₂

(16.8 mg, 30 mol %) in dry DCE (2 mL) at 0 °C to room

temperature for 30 min. Puriﬁcation of the crude material by silica gel

column chromatography (petroleum ether/ethyl acetate 98:2−97:3)

furnished the product 10h (68.1 mg, 80%) as yellow oil. TLC

(petroleum ether/ethyl acetate 95:5, R_f(8h) = 0.20, R_f(10h) = 0.80,

UV detection. IR (MIR-ATR, 4000-600 cm⁻¹) ν_max= 3015, 1703,

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J. Org. Chem. 2021, 86, 8706−8725

Article Doi

Lewis Acid Mediated Domino Intramolecular Cyclization: Synthesis of Dihydrobenzo[ a]fluorenes

DOI: 10.1021/acs.joc.1c00525

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