Substitution controlled functionalization of ortho -bromobenzylic alcohols via palladium catalysis: Synthesis of chromenes and indenols

Article

pubs.acs.org/joc

Substitution Controlled Functionalization of ortho-Bromobenzylic

Alcohols via Palladium Catalysis: Synthesis of Chromenes

and Indenols

Lodi Mahendar and Gedu Satyanarayana*

Department of Chemistry, Indian Institute of Technology, Hyderabad Ordnance Factory Estate Campus, Yeddumailaram 502 205,

Medak District, Andhra Pradesh, India

S

* Supporting Information

ABSTRACT: An eﬃcient domino Pd-catalyzed transforma-

tion of simple ortho-bromobenzyl tertiary alcohols to chromenes

is presented. Their formation is believed to proceed via the

formation of a ﬁve-membered palladacycle, which, in turn,

involves in an intermolecular homocoupling with the second

ortho-bromobenzyltertiary alcohol to yield the homo-biaryl

bond followed by intramolecular C−O bond formation. Inter-

estingly, when there is an allylic substituent on the benzylic

carbon atom, a chemoselective switch was observed, which

preferred intramolecular Heck coupling and gave indenols.

Further, it has been conﬁrmed that the tertiary alcohol func-

tionality is indispensible to give the coupled products, whereas

the use of primary/secondary benzylic alcohols furnished the

simple carbonyl products via a possible reductive debromination followed by oxidation due to the availability of β-hydrogen(s).

transformations through the disconnection of sp³(C)−sp³(C)

INTRODUCTION

■

bond, in strained cyclic systems, have also been reported.⁷⁻¹⁰

Domino reactions facilitate construction of complex molecules

Furthermore, it was also noticed that the sp³(C)−sp³(C) bond

in one-pot operation without the need to isolate reaction inter-

mediates.¹Transition metal catalysis plays a major role in the

ﬁssion is facilitated by a six-membered palladium-cyclic transi-

tion state.¹¹

development of useful synthetic methods, particularly in the

organic synthesis,²as it enables construction of both C−C as

In continuation of our ongoing interest in the development

of transition catalysis,¹²very recently we have developed a

well as C−X (heteroatom) bonds most eﬃciently, through

novel method¹³involving a palladium-catalyzed domino reac-

which it is possible to achieve molecular complexity. In this

tion for the conversion of α,α-disubstituted-(2-haloaryl)-

methanols to 6,6-dialkyl-6H-benzo[c]chromenes via homo-

biaryl coupling. During the course of this process, the reaction

drives to form two bonds (C−C and C−O) in a sequential

fashion. Herein, we report a successful application and thorough

study of the method, the conversion of various ortho-

bromobenzyl tertiary alcohols to the corresponding chromenes.

In addition, it was observed that when there is an oleﬁn sub-

tituent on the benzylic carbon atom, preferred intramolecular

Heck coupling furnished indenols. Overall, this entire study

relies on preferential chemoselective coordination of the initially

formed arylpalladium species either with the hydroxy group or

insertion into the double bond of oleﬁn. Moreover, it was further

proved that the tertiary alcohol functionality is vital to promote

the coupling, whereas the reaction of primary/secondary bromo-

benzyl alcohols, under the adopted reaction conditions,¹³fur-

nished simple carbonyl compounds as shown in Scheme 1.

context, palladium plays a special role, since it can be able to

drive a wide variety of organic transformations. For example,

in one case, a palladium catalyst can be used for reduction

(catalytic hydrogenation), whereas, on the other hand, it can

be applied for oxidation (Wacker oxidation), while there are

many coupling reactions (Heck, Stille, Suzuki, Shonogashira,

Buchwald−Hartwig, etc.) that fall in-between these two

extreme cases. This sort of diversity, in Pd-catalysis, is feasible

because of the reason that the fate of Pd-catalyzed trans-

formations can be changed by the environment (i.e., reaction

conditions) around the palladium−metal center as well as the

nature of the reactant. Of late, many domino processes have

been developed by using Pd-catalysis,³predominantly for

the construction of useful heterocyclic systems.⁴Particularly,

a unique and rare method was reported that involves a

Pd-catalyzed β-carbon cleavage via the coordination of hydroxy

group to the Pd-metal center. This type of process is selectively

observed in the case of tertiary alcohols such as 2-methyl-4-

arylbut-3-yn-2-ol⁵and α,α-disubstitued arylmethanols⁶through

cleavage of sp(C)−sp³(C) and sp²(C)−sp³(C) bonds,

respectively (Scheme 1). In addition, Pd-catalyzed ring-opening

Received: December 12, 2013

Published: February 14, 2014

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all the starting material to the product 5a. This extra activation

required for the present systems can be attributed to the steric

constraints. The selective formation of chromene 5a over

ﬂuorenol 6a may be justiﬁed on the basis of the preferential

chelation of hydroxy group with arylpalladium species.

Recently, the research group of Catellani reported the syn-

thesis of such 6H-dibenzo[b,d]pyrans using sequential Pd/

norbornene-catalysis through heterobiaryl coupling.¹⁴Very

recently, Nishihara and co-workers reported the synthesis of

triphenylenes by coupling between tertiary bromobenzyl

alcohols and ortho-iodobiphenyls.¹⁵

Scheme 1. Representative Previous Approaches vs Present

Study on Pd-Mediated Propargyl/Benzyl Tertiary Alcohol

Cleavage Followed by Coupling

To further check the scope and generality of the method,

these optimized reaction conditions were applied to other

systems. In general, these results were fairly comparable to that

obtained for chromene 5a and furnished chromenes 5b−5f

possessing simple as well as electron rich 2-bromoaryl moiety

(i.e., R¹= H/OMe/OBn, R²= alkyl, R³= phenyl), in very good

yields (Table 1). However, the formation of chromene 5g was

impeded, maybe due to the presence of o,o′ dimethoxy groups

that might induce tremendous strain and thus would prevent

both aromatic rings to adopt coplanar structure, since the entire

tricyclic chromene core is in plane. Further, it was observed that

the method was applicable to other tertiary alcohols 4h−4m,

with meta-anisyl substituent on the benzylic carbon center (i.e.,

R¹= H/OMe/OBn, R²= alkyl, R³= m-MeOC₆H₄), therefore

giving the corresponding products 5h−5m. Also, the reaction

was successful on alcohols 4n−4p with heteroaryl substituent

(i.e., R¹= H/OMe/OBn, R²= alkyl, R³= thiophene) and fur-

nished the chromenes 5n−5p. Furthermore, the diphenyl sub-

stituted tertiary alcohols 4q−4s (i.e., R¹= H/OMe, R²= R³=

phenyl) smoothly transformed into the corresponding

chromenes 5q−5s. However, it was noticed that the reaction

of the tertiary alcohol 4t with acetylene substituent was unclear

and failed to deliver the chromene 5t. This is presumably due

to the interfering ability of the reactive triple bond with the so-

formed aryl palladium intermediate. It is worth mentioning that

in each of the reaction, the formation of cleaved byproduct

ketone 7 has also been isolated. The carbonyl byproducts (7a,

7b, and 7d) were isolated in most of the cases and characterized

by NMR spectroscopy (except for the ketone 7c, for which the

TLC spot was not clean and therefore unable to obtain a clean

NMR spectrum), which, in turn, supports the reaction mech-

anism proposed in our previous report.

Further, to the check the scope and applicability of the

method and to extend for other chromene derivatives, we ex-

plored the reaction with benzyl substituent (i.e., R¹= H/OMe,

R²= alkyl, R³= benzyl). The required alcohols 4u, 4v were

prepared using α-arylation (this α-arylation was speciﬁcally

developed on 2-bromoacetophenoes, very recently, in our

laboratory)^12jfollowed by methylmagnesium iodide addition of

2-bromoacetophenones 3a, 3b (for details, see the Supporting

Information). Gratifyingly, the method was found to be ame-

nable and furnished the expected chromenes 5u, 5v in fair

yields (Scheme 2).

Moreover, it was concluded that the tertiary alcohol func-

tionality of 4 is essential to selectively deliver to the coupled

(chromene) product 5, because the corresponding primary 9a,

9b¹³or secondary alcohols 9c−9e were unable to furnish the

expected chromenes 5, rather furnishing the benzaldehydes/

ketones 10a−10e, as shown in Table 2. The formation of benz-

aldehydes 10a, 10b can be explained via the oxidation followed

by reductive debromination sequence, after the formation of ﬁve-

membered palladacycle (for details, see the plausible mechanism

RESULTS AND DISCUSSION

■

The study was initiated with the preparation of requisite tertiary

bromobenzyl alcohols 4 from 2-bromobenzaldehydes 1 using

the protocol of arylmagnesiumbromide addition, followed by

oxidation of the resulting secondary alcohol 2 to the corre-

sponding ketone and then alkylmagnesiumiodide reaction of

the ketone 3. Unlike the previous study,¹³herein, the second

aromatic substituent of the tertiary alcohol 4a may pose a che-

moselectivity problem in competition to the hydroxyl group.

Therefore, if there is a preferential intramolecular coordination

of the hydroxy group to the arylpalladium species, the chro-

mene 5a would result. On the other hand, if the arylpalladium

species preferentially inserts into the second aromatic ring, the

intramolecular Heck product ﬂuorenol 6a would be the end

product. With the tertiary alcohols 4 in hand, initially the key

Pd-mediated domino catalysis was attempted on tertiary

bromobenzyl alcohol 4a. Thus, the reaction under established

conditions [Pd(OAc)₂(5 mol %), PPh₃(10 mol %), Cs₂CO₃

(2 equiv), DMF (2 mL), 80 °C for 12 h],¹³led to the chro-

mene 5a as the end product, in a highly chemoselective manner

along with a considerable amount of starting material recovery.

Even prolonged reaction time (24 h) at the same temperature

(80 °C) was still unable to convert all the starting material to

product. Gratifyingly, further prolonged reaction time (48 h) at

high temperature variation (120 °C) was successful to deliver

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ab c

, ,

Table 1. Synthesis of Chromenes 5 from Tertiary Alcohols 4 under Optimized Conditions

a

Reaction conditions: 4a−4t (100 mg, 0.21−0.47 mmol), Cs₂CO₃(2 equiv), Pd(OAc)₂(5 mol %), PPh₃(10 mol %), 0.14−0.23 M in DMF, at 120 °C for

b

c

24−48 h. Yields in the parentheses are isolated yields of chromatographically pure products. The corresponding ketone byproducts 7 have been iso-

lated in most of the cases and characterized by NMR spectroscopic data. Most of the starting material was recovered. The reaction was not clean.

d

e

Scheme 2. Pd-Catalyzed Transformation of Tertiary

Alcohols 4 to the Chromenes 5

to give the corresponding ketones 10a, 10b, whereas the sec-

ondary alcohols 9c−9e furnished a mixture of unclear prod-

ucts. Interestingly, for such systems 9c−9e, the catalyst

Pd(dppf)₂Cl₂(5 mol %) was found to be the best and gave

the corresponding ketones 10c−10e (Table 2).

Further, to better understand whether homo-biaryl coupling

is preferred or not, reaction was performed with the primary

and tertiary alcohols (9b and 4w) together. As a result, the

products obtained are the benzaldehyde 10b and the chromene

5w. On the basis of this observation, we realized that the com-

pound 4w predominantly reacted in its own independent

tandem path, without much intervention from the other alcohol

9b (i.e., majorly preferred homocoupling rather than the het-

erocoupling), as described in Scheme 3.

as described in Scheme 6). It is worth mentioning that the

standard catalytic [Pd(OAc)₂(5 mol %)/PPh₃(10 mol %),

DMF] conditions are suitable only for primary alcohols 9a, 9b

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Table 2. Pd-Catalysis of Primary and Secondary Alcohols

(2 and 9)

Scheme 5. Reaction of Silyl Ethers 11 in the Presence of Pd

Catalyst

Scheme 3. Pd-Catalysis of Primary and Tertiary Alcohols

(9b and 4w)

basic reaction conditions) followed by the usual Pd-catalyzed

transformation of tertiary alcohols 4x−4y. The deprotection of

TMS-group was further conﬁrmed by a blank reaction in the

presence of base, without the palladium catalyst.¹⁷The slow

rate of the reaction and the isolation of the deprotected tertiary

alcohols 4x−4y in the presence of active Pd catalyst even after

24 h may be due to the interference of deprotected silyl species

with the Pd catalyst.

In addition to the spectroscopic identiﬁcation of the com-

pounds 5, the complete structures were further conﬁrmed by

single crystal X-ray diﬀraction analysis of compounds 5b and 5r

(for details, see the Supporting Information).

Similarly, to check whether the intermolecular Buchwald−

Hartwig coupling or formation of chromene 5w product, the

reaction was carried out in the presence of phenol as an ex-

ternal coupling agent. However, the chromene 5w was obtained

as the sole product, which clearly indicates that the intra-

molecular trapping of the aryl palladium intermediate by the

hydroxy group works eﬃciently rather than the intermolecular

coupling (Scheme 4).

To further understand the scope and limitations of the meth-

od, oleﬁn variants were also explored (i.e., R¹= R²= H/OMe,

R³= methyl/phenyl). Thus, in contrary to our expectation,

unlike the above case [Table 1 and Scheme 2], the fate of che-

moselectivity totally changed in the presence of an isolated

double bond, therefore furnishing unusual regioisomeric mix-

ture of indenols 13a−13d (major regioisomer) and 13a′−13d′

(minor regioisomer), as inseparable mixture, from alcohols

4aa−4ad, via simple intramolecular Heck coupling. The ob-

served chemoselectivity switch may be justiﬁed on the basis of

preferential insertion of arylpalladium species into reactive

isolated double bond. In addition, this chemoselectivity switch

is in good agreement with that reported by Oestreich et al.,¹⁸

wherein preferential involvement of oleﬁn was observed to give

the Heck product. Interestingly, in the case of electron rich

bromoaryl moiety, the formation of indenene 14e¹⁹was

observed from the indenols (13e and 13e′), after leaving the

sample in CDCl₃within the NMR tube, for a reasonable

amount of time, 12 h (Table 3). This could be due to mild

acidic nature of the NMR solvent CDCl₃, when electron rich

aromatic ring is in conjugation to the hydroxy group connected

carbon atom. To better understand this phenomenon, the

NMR sample of the mixture (13e + 13e′ + 14e) was left as

such in CDCl₃in the NMR tube, and NMR spectra were

measured after 24 h, 48 h, and four days, respectively. As

expected, the slow dehydration of the indenols (13e and 13e′)

mixture was observed with increase in concentration of 14e, as

described in Table 3. To further prove that the dehydration

may be triggered by acidic DCl component of CDCl₃, we

Scheme 4. Pd-Catalysis of 4w in the Presence of External

Phenol

Furthermore, to check the scope and application of the

method, we attempted the reaction of silyl ether, anticipating

intramolecular sp³C−H activation to generate cyclic silyl ethers

12a, 12b (Scheme 5). This sort of sp³C−H activation of

methyl groups of silyl group is expected on the basis of the

existing reports.¹⁶However, the reaction failed to furnish the

expected cyclic silyl ethers 12a, 12b, rather producing simple

chromenes 5x−5y along with the recovery of TMS-group

deprotected starting tertiary alcohols 4x−4y. The formation of

simple chromenes 5x−5y can be explained on the basis of in

situ deprotection of TMS-group (this would be feasible under

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Table 3. Pd-Catalyzed Chemoselective Intramolecular Heck Coupling of Tertiary Alcohols 4 to the Region-Isomeric Mixture of

Indenols 13 and Indenenes 14

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a

Scheme 6. Plausible Catalytic Cycle Reaction Mechanism for the Formation of Chromenes 5 and the Carbonyl Compounds 10

a

For simplicity, ligands are omitted.

recorded the NMR spectra in regular intervals, with the CDCl₃

kept over K₂CO₃. As anticipated, no dehydration product 14e

was observed. Moreover, when the reaction was performed for

suﬃciently longer reaction time (12 h), the indenene 14e was

formed as the sole product (Table 3). This can be explained by

the electron releasing eﬀect of the aromatic ring that facilitates

the dehydration of the chelated intermediate of the tertiary

alcohol with the palladium species.

the Pd(0) catalyst along with the formation of corresponding

carbonyl product 10. On the other hand, the aryl palladium

species A from 4aa−4ad insert into the double bond rather

than coupling with the hydroxy group and yields the ﬁve-

membered intermediate I, which on reductive elimination and

double bond isomerization furnishes the regioisomeric mixture

of cyclic oleﬁns 13 and 13′.

CONCLUSION

The reaction mechanism for the formation of chromenes

5 can be explained via the formation of ﬁve-membered

palladacycle(II) B through the insertion of the initially formed

aryl-palladium(II) species A from 4a−4v, onto the O−H bond

of the tertiary alcohol (Scheme 6). Now, the oxidative addition

of second aryl bromide on to the palladacycle(II) B would

generate new Pd(IV) intermediate C. Intramolecular migration

of aryl group leads to the Pd(II) intermediate D via simul-

taneous reductive ring-opening of palladacycle(IV) and homo-

biaryl bond formation. Now β-carbon cleavage of biaryl

intermediate D gives the ketone byproduct 7 and the

biarylpalladium(II) species E. Finally, intramolecular coupling

of the 7-membered palladacycle(II) F via a reductive elimina-

tion delivers the active Pd(0) catalyst as well as the end product

chromene 5. Though the formation of transmetalation inter-

mediate that contains two Pd(II) centers would also be possible

between two Pd(II)-centers (A and B) for those less sterically

hindered Pd(II)-intermediates followed by aryl migration,²⁰the

present case seems probable for the formation of higher

oxidation state Pd(IV) intermediate, since sterically crowded

palladacycle(II) prefers oxidative addition with second aryl

halide.²¹In the case of primary/secondary benzylic alcohols

9a−9e the same intermediacy of ﬁve-membered palldacycle G

can be predicted to that of B. Because of the availability of

β-hydrogen the ﬁve-membered palladacycle opens up to the

intermediate H, which upon reductive elimination regenerates

■

In summary, we developed an eﬃcient domino Pd-catalysis for

the conversion of simple ortho-bromobenzyl tertiary alcohols to

chromenes. The reaction might proceed via the formation of a

ﬁve-membered palladacycle, which in turn couples with the

second aryl bromide to facilitate biaryl C−C bond followed by

intramolecular C−O bond formation. Interestingly, when there

is isolated double bond functionality in the near vicinity a

chemoselective switch is preferred, furnishing indenols via intra-

molecular Heck reaction. Overall, the study has been carried

out in a reasonably divergent fashion to show the ability and ap-

plicability of Pd-catalysis, which in turn reveals the potentiality

of transition metal catalysis.

EXPERIMENTAL SECTION

■

General Considerations. IR spectra were recorded on a FTIR

spectrophotometer. ¹H NMR spectra were recorded on 400 MHz

spectrometer at 295 K in CDCl₃; chemical shifts (δ ppm) and cou-

pling constants (Hz) are reported in standard fashion with reference

to either internal standard tetramethylsilane (TMS) (δ_H= 0.00 ppm)

or CHCl₃(δ_H= 7.25 ppm). ¹³C NMR spectra were recorded on

100 MHz spectrometer at RT in CDCl₃; chemical shifts (δ ppm) are

reported relative to CHCl₃[δ_C= 77.00 ppm (central line of triplet)].

In the ¹³C 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 =

1

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

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

t = triplet, q = quartet, qui = quintet, m = multiplet and br s. = broad

singlet. The assignment of signals was conﬁrmed by ¹H, ¹³C CPD, and

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

using Q-TOF multimode source. Melting points were determined

on an electrothermal melting point apparatus and are uncorrected.

Benzaldehydes, aryl halideds, allyl bromide, methyl iodide, Zn and Mg

metal, lithium acetylide, Pd(OAc)₂, Pd(dppf)₂Cl₂, PPh₃, xantphos,

Cs₂CO₃, ^tBuOK, Phenol, imidazole and trimethylsilyl chloride,

Na₂SO₄, and NH₄Cl were commercially available and used without

further puriﬁcation. All dry solvents were used, diethylether and THF

were dried over sodium metal, DCM and DMF were dried over

calcium hydride, and dry DMSO was purchased from Sigma Aldrich.

All these solvents (diethylether, THF, DCM, DMF, and DMSO) are

commercially available. All small scale dry reactions were carried out

using standard syringe-septum technique. Reactions were monitored

by TLC on silica gel using a combination of petroleum ether and ethyl

acetate as eluents. Reactions were generally run under argon or a

nitrogen atmosphere. Solvents were distilled prior to use; petroleum

ether with a boiling range of 40 to 60 °C was used. Acme’s silica gel

(60−120 mesh) was used for column chromatography (approximately

20 g per one gram of crude material).

General Procedure GP-1 for Alcohols (2 or 4). To a cold

(0 °C), magnetically stirred solution of a bromobenzaldehyde 1 or

ketone 3 (1 mmol) in dry THF or dry ether (2 mL) was added phe-

nylmagnesium bromide (5 mmol) [prepared from magnesium (5 mmol)

and bromobenzene or bromothiophene or 3-bromoanisole or

methyliodide (5 mmol) and a catalytic amount of iodine in 10 mL

of dry THF or dry ether]. The reaction mixture was stirred at 0 °C to

room temperature for 3 h. It was then poured into saturated aqueous

NH₄Cl solution and extracted with ethyl acetate (3 × 15 mL). The

combined organic layers were dried (Na₂SO₄) and concentrated in

vacuo. The crude secondary alcohol 2 or tertiary alcohol 4 was puriﬁed

by column chromatography on silica using petroleum ether/ethyl

acetate as eluent.

General Procedure GP-2 for Ketones (3). To a magnetically

stirred solution of the secondary alcohol 2 (1 mmol) in dry CH₂Cl₂

(10 mL) was added a homogeneous mixture (1:1) of PCC (3 mmol)

and silica gel. The resulting reaction mixture was stirred at room

temperature for 2 h. Filtration of the reaction mixture through a short

silica column with excess CH₂Cl₂furnished the pure ketone 3.

General Procedure GP-3 for α-Aryl Ketones (8). In an oven-

dried Schlenk tube under nitrogen atmosphere were added aryliodide

(0.50 mmol), ortho-bromoacetophenone 3 (0.55 mmol), Pd(OAc)₂

(2 mol %), xantphos (4 mol %) and ^tBuOK (0.65 mmol) followed by

addition of dry toluene (4 mL). The resulting reaction mixture was

stirred at 80 °C for 45 min. Progress of the reaction was monitored by

TLC until the reaction is completed. The reaction mixture was then

quenched with saturated aqueous NH₄Cl, and the aqueous layer was

extracted with ethyl acetate (3 × 20 mL). The combined organic layers

were dried (Na₂SO₄) and concentrated in vacuo. The crude ketone 8

was puriﬁed by column chromatography on silica using petroleum

ether/ethyl acetate as eluent.

General Procedure GP-4 for Homoallylic Alcohol (4). Allyl

bromide (0.60 mL−0.70 mL, 6.98−8.04 mmol) in THF (1 mL) was

added dropwise to a sonicated suspension of zinc dust (457 mg−525 mg,

6.98−8.04 mmol) or lithium acetylide in THF (2 mL) at room tem-

perature, and the mixture was further sonicated for 30 min, and then

ortho-bromoacetophenone 3 (400 mg, 1.74−2.01 mmol) in THF

(3 mL) was added and continued sonication at room temperature for

2 h. Progress of the reaction was monitored by TLC. The reaction

mixture was quenched by addition of aqueous NH₄Cl solution and

extracted with ethyl acetate (3 × 15 mL). The collected organic layers

were dried (Na₂SO₄) and concentrated in vacuo. Puriﬁcation of the

residue on a silica gel column chromatography (petroleum ether/ethyl

acetate) as eluent furnished homoallylic alcohol 4.

stirred at room temperature for 4 h. The reaction mixture was

quenched and extracted with CH₂Cl₂(3 × 15 mL). The collected

organic layers were dried (Na₂SO₄) and concentrated under reduced

pressure. Puriﬁcation of the residue on a silica gel column chroma-

tography (petroleum ether/ethyl acetate) as eluent furnished trimethyl

silylether of corresponding alcohol 11.

General Procedure GP-6 for Cyclization (5). In an oven-dried

Schlenk tube under nitrogen atmosphere were added Pd(OAc)₂

(5 mol %), PPh₃(10 mol %), Cs₂CO₃(1.0 mmol), and tertiary

alcohol 4 (0.50 mmol) followed by addition of DMF (2 mL) [or

DMSO (2 mL) in case of silyl ethers 11a, 11b]. The resulting reaction

mixture was stirred at 120 °C for 24−48 h. Progress of the reaction

was monitored by TLC until the reaction is completed. The reaction

mixture was quenched by addition of aq. NH₄Cl solution and extracted

with CH₂Cl₂(3 × 10 mL). The organic layers were dried (Na₂SO₄)

and concentrated in vacuo. Puriﬁcation of the residue on a silica gel

column chromatography using petroleum ether/ethyl acetate as eluent

furnished the cyclic ethers 5.

[5-(Benzyloxy)-2-bromo-4-methoxyphenyl](phenyl)methanol

(2e). This compound was prepared according to the GP-1 and isolated

1

as yellow color viscous liquid 96% yield (597 mg): H NMR (CDCl₃

400 MHz) δ = 7.41 (d, 2H, J = 7.4 Hz), 7.37 (d, 2H, J = 7.8 Hz),

7.35−7.28 (m, 5H), 7.25 (t, 1H, J = 7.8 Hz), 7.08 (s, 1H), 7.02 (s,

1H), 6.08 (s, 1H), 5.07 (s, 2H), 3.79 (s, 3H), 2.61 (br. s, 1H) ppm;

¹³C NMR (CDCl₃, 100 MHz) δ = 149.3 (C_q), 148.0 (C_q), 142.4 (C_q),

136.3 (C_q), 135.2 (C_q), 128.5 (2 × CH), 128.3 (2 × CH), 128.0

(CH), 127.6 (CH), 127.3 (2 × CH), 126.7 (2 × CH), 117.6 (CH),

112.3 (C_q), 111.3 (CH), 74.3 (CH), 71.1 (CH₂), 56.0 (C_q) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3552, 2939, 1499, 1379, 1257,

1152, 1027, 809, 735, 697 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₁H₁₈⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺381.0485, found 381.0486.

[4-(Benzyloxy)-2-bromo-5-methoxyphenyl](phenyl)methanol

(2f). This compound was prepared according to the GP-1 and iso-

1

lated as brown color viscous liquid 96% yield (597 mg): H NMR

(CDCl₃400 MHz) δ = 7.38 (d, 2H, J = 7.1 Hz), 7.32 (dd, 4H,

J = 7.5 and 7.1 Hz), 7.29−7.24 (m, 3H), 7.21 (d, 1H, J = 7.1 Hz), 7.04

(s, 1H), 6.98 (s, 1H), 6.02 (s, 1H), 5.02 (s, 2H), 3.74 (s, 3H), 2.75 (br.

s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 149.1 (C_q), 147.9

(C_q), 142.3 (C_q), 136.2 (C_q), 135.2 (C_q), 128.5 (2 × CH), 128.3 (2 ×

CH), 128.0 (CH), 127.5 (CH), 127.3 (2 × CH), 126.6 (2 × CH),

117.4 (CH), 112.2 (C_q), 111.2 (CH), 74.2 (CH), 71.0 (CH₂), 55.9

(CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3505, 2934,

1497, 1383, 1257, 1154, 1044, 865, 737, 698 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₂₁H₁₈⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺381.0485,

found 381.0486.

(2-Bromo-3,4,5-trimethoxyphenyl)(phenyl)methanol (2g).

This compound was prepared according to the GP-1 and isolated

1

as brown color viscous liquid 98% yield (632 mg): H NMR (CDCl₃

400 MHz) δ = 7.39 (d, 2H, J = 7.3 Hz), 7.33 (dd, 2H, J = 7.8 and

6.8 Hz), 7.27 (d, 1H, J = 6.8 Hz), 6.97 (s, 1H), 6.18 (s, 1H), 3.86

(s, 6H), 3.82 (s, 3H), 2.52 (br. s, 1H) ppm; ¹³C NMR (CDCl₃, 100

MHz) δ = 152.9 (C_q), 150.6 (C_q), 142.4 (C_q), 142.1 (C_q), 138.1 (C_q),

128.4 (2 × CH), 127.7 (CH), 126.9 (2 × CH), 109.1 (C_q), 107.0

(CH), 74.6 (CH), 61.0 (2 × CH₃), 56.1 (CH₃) ppm; IR (MIR-ATR,

4000−600 cm⁻¹) ν_max= 3450, 2937, 1568, 1479, 1391, 1324, 1237,

1159, 1104, 1007, 921, 816, 700, 607 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₁₆H₁₆⁷⁹BrO₃]⁺= [(M + H) − H₂O]⁺335.0283, found

335.0287.

(2-Bromo-5-methoxyphenyl)(3-methoxyphenyl)methanol

(2i). This compound was prepared according to the GP-1 and isolated

1

as colorless viscous liquid 94% yield (706 mg): H NMR (CDCl₃

400 MHz) δ = 7.45 (d, 1H, J = 8.8 Hz), 7.29 (dd, 1H, J = 8.2 and 8.1

Hz), 7.20 (d, 1H, J = 2.9 Hz), 7.03 (d, 2H, J = 7.5 Hz), 6.86 (dd, 1H,

J = 7.0 and 2.5 Hz), 6.74 (dd, 1H, J = 8.8 and 2.9 Hz), 6.13 (s, 1H),

3.81 (s, 3H), 3.80 (s, 3H), 2.79 (br. s, 1H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 159.5 (C_q), 159.1 (C_q), 143.6 (C_q), 143.4 (C_q), 133.3

(CH), 129.4 (CH), 119.2 (CH), 114.9 (CH), 113.8 (CH), 113.0

(CH), 112.9 (C_q), 112.7 (CH), 74.4 (CH), 55.3 (CH₃), 55.1 (CH₃)

ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3416, 2937, 1593, 1465,

1235, 1149, 1038, 907, 874, 729, 693 cm⁻¹; HR-MS (ESI+) m/z

General Procedure GP-5 for Trimethylsilylether (11). To a

magnetically stirred solution of the tertiary alcohol 4 (1.5 mmol) and

imidazole (3 mmol) in dry CH₂Cl₂(6 mL) trimethylsilyl chloride

(3 mmol) was added at 0 °C. The resulting reaction mixture was

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calculated for [C₁₅H₁₄⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺305.0172, found

305.0164.

(2-Bromo-4,5-dimethoxyphenyl)(thiophen-2-yl)methanol

(2p). This compound was prepared according to the GP-1 and isolated

1

as black semisolid 90% yield (604 mg): H NMR (CDCl₃400 MHz)

(2-Bromo-4, 5-dimethoxyphenyl)(3-methoxyphenyl)-

methanol (2j). This compound was prepared according to the

δ = 7.27 (dd, 1H, J = 5.4 and 1.5 Hz), 7.21 (s, 1H), 6.96 (s, 1H), 6.92

(dd, 1H, J = 5.4 and 3.4 Hz), 6.88 (d, 1H, J = 3.4 Hz), 6.01 (s, 1H),

3.86 (s, 3H), 3.80 (s, 3H), 1.59 (br. s, 1H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 149.2 (C_q), 148.9 (C_q), 144.4 (C_q), 132.2 (C_q), 126.5

(CH), 126.1 (CH), 125.7 (CH), 114.9 (CH), 112.7 (C_q), 110.7 (CH),

75.6 (CH), 56.1 (CH₃), 56.0 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3525, 2924, 1492, 1382, 1254, 1153, 1042, 862,

734, 692 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₁₃H₁₂⁷⁹BrSO₂]⁺=

[(M + H) − H₂O]⁺310.9736, found 310.9737.

1

GP-1 and isolated as colorless viscous liquid 95% yield (684 mg): H

NMR (CDCl₃400 MHz) δ = 7.25 (dd, 1H, J = 8.1 and 8.1 Hz), 7.07

(s, 1H), 7.03−6.93 (m, 3H), 6.81 (dd, 1H, J = 8.1 and 2.3 Hz), 6.11 (s,

1H), 3.86 (s, 3H), 3.83 (s, 3H), 3.79 (s, 3H), 2.65 (br. s, 1H) ppm;

¹³C NMR (CDCl₃, 100 MHz) δ = 159.6 (C_q), 148.9 (C_q), 148.7 (C_q),

144.2 (C_q), 134.7 (C_q), 129.4 (CH), 118.9 (CH), 115.3 (CH), 112.8

(CH), 112.6 (C_q), 112.4 (CH), 110.9 (CH), 74.2 (CH), 56.1 (CH₃),

56.0 (CH₃), 55.1 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3486, 2934, 1599, 1498, 1378, 1253, 1148, 1027, 809, 740, 697 cm⁻¹;

HR-MS (ESI+) m/z calculated for [C₁₆H₁₆⁷⁹BrO₃]⁺= [(M + H) −

H₂O]⁺335.0277, found 335.0269.

(6-Bromobenzo[d][1,3]dioxol-5-yl)(phenyl)methanone (3d).

This compound was prepared according to the GP-2 and isolated as

1

white solid 96% yield (476 mg): mp 110−115 °C; H NMR (CDCl₃

400 MHz) δ = 7.80 (d, 2H, J = 7.1 Hz), 7.57 (dd, 1H, J = 7.7 and

7.1 Hz), 7.44 (dd, 2H, J = 7.8 and 7.7 Hz), 7.05 (s, 1H), 6.81 (s, 1H),

6.03 (s, 2H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 195.1 (C_q),

149.7 (C_q), 147.1 (C_q), 136.3 (2 × C_q), 133.5 (CH), 130.1 (2 × CH),

128.5 (2 × CH), 113.2 (CH), 111.4 (C_q), 109.2 (CH), 102.2 (CH₂)

ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2932, 1663, 1592, 1434,

1331, 1262, 1170, 1021, 853, 715, 699 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₁₄H₁₀⁷⁹BrO₃]⁺= [M + H]⁺304.9808, found 304.9806.

[5-(Benzyloxy)-2-bromo-4-methoxyphenyl](phenyl)-

methanone (3e). This compound was prepared according to the GP-

2 and isolated as white solid 96% yield (477 mg): mp 108−110 °C; ¹H

NMR (CDCl₃400 MHz) δ = 7.72 (d, 2H, J = 7.3 Hz), 7.57 (dd, 1H,

J = 7.4 and 7.3 Hz), 7.41 (dd, 2H, J = 7.8 and 7.8 Hz), 7.38−7.26 (m,

5H), 7.10 (s, 1H), 6.92 (s, 1H), 5.08 (s, 2H), 3.93 (s, 3H) ppm; ¹³C

NMR (CDCl₃, 100 MHz) δ = 195.3 (C_q), 151.6 (C_q), 146.9 (C_q),

136.5 (C_q), 136.0 (C_q), 133.3 (CH), 131.9 (C_q), 130.2 (2 × CH),

128.6 (2 × CH), 128.5 (2 × CH), 128.1 (CH), 127.4 (2 × CH), 116.3

(CH), 115.1 (CH), 111.7 (C_q), 71.2 (CH₂), 56.3 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 2934, 1666, 1593, 1439, 1330,

1261, 1174, 1024, 850, 718, 697 cm⁻¹; HR-MS (ESI+) m/z calculated

for [C₂₁H₁₈⁷⁹BrO₃]⁺= [M + H]⁺397.0434, found 397.0435.

(6-Bromobenzo[d][1,3]dioxol-5-yl)(3-methoxyphenyl)-

methanol (2k). This compound was prepared according to the GP-1

1

and isolated as pale yellow viscous liquid 88% yield (650 mg): H

NMR (CDCl₃400 MHz) δ = 7.27 (d, 1H, J = 8.2 and 8.0 Hz), 7.08−

7.94 (m, 4H), 6.83 (dd, 1H, J = 8.2 and 2.3 Hz), 6.13 (s, 1H), 5.98 (d,

1H, J = 1.2 Hz), 5.95 (d, 1H, J = 1.4 Hz), 3.81 (s, 3H), 2.60 (br. s, 1H)

ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 159.6 (C_q), 147.7 (C_q), 147.6

(C_q), 144.0 (C_q), 136.0 (C_q), 129.5 (CH), 118.9 (CH), 113.1 (C_q),

112.9 (CH), 112.4 (CH), 112.3 (CH), 108.3 (CH), 101.7 (CH₂), 74.2

(CH), 55.2 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3394,

2900, 1473, 1230, 1105, 1035, 905, 726, 647 cm⁻¹; HR-MS (ESI+) m/

z calculated for [C₁₅H₁₂⁷⁹BrO₃]⁺= [(M + H) − H₂O]⁺318.9964,

found 318.9950.

[5-(Benzyloxy)-2-bromo-4-methoxyphenyl](3-methoxyphenyl)-

methanol (2l). This compound was prepared according to the GP-1

1

and isolated as white solid 93% yield (623 mg): mp 110−112 °C; H

NMR (CDCl₃400 MHz) δ = 7.44−7.26 (m, 5H), 7.23 (dd, 1H, J =

8.0 and 7.8 Hz), 7.08 (s, 1H), 7.03 (s, 1H), 6.92 (s, 1H), 6.88 (d, 1H,

J = 7.8 Hz), 6.82 (dd, 1H, J = 8.0 and 2.5 Hz), 6.01 (s, 1H), 5.11 (d,

1H, J = 12.2 Hz), 5.10 (d, 1H, J = 12.2 Hz), 3.87 (s, 3H), 3.78 (s, 3H),

2.42 (br. s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 159.6 (2 ×

C_q), 149.6 (C_q), 147.6 (C_q), 144.0 (C_q), 136.5 (C_q), 134.5 (C_q), 129.4

(CH), 128.5 (2 × CH), 127.9 (CH), 127.5 (2 × CH), 118.9 (CH),

115.8 (CH), 113.8 (CH), 113.0 (CH), 112.3 (CH), 74.2 (CH), 71.0

(CH₂), 56.2 (CH₃), 55.1 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3479, 2937, 1496, 1377, 1254, 1146, 1028, 908,

729, 695 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₂₂H₂₀⁷⁹BrO₃]⁺=

[(M + H) − H₂O]⁺411.0590, found 411.0578.

[4-(Benzyloxy)-2-bromo-5-methoxyphenyl](phenyl)-

methanone (3f). This compound was prepared according to the GP-

2 and isolated as white solid 94% yield (468 mg): mp 120−122 °C; ¹H

NMR (CDCl₃400 MHz) δ = 7.82 (d, 2H, J = 7.6 Hz), 7.58 (dd, 1H,

J = 7.6 and 7.0 Hz), 7.51−7.42 (m, 4H), 7.40 (dd, 2H, J = 7.6 and

7.0 Hz), 7.34 (d, 1H, J = 7.0 Hz), 7.13 (s, 1H), 6.91 (s, 1H), 5.17 (s,

2H), 3.83 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 195.5 (C_q),

150.0 (C_q), 148.7 (C_q), 136.5 (C_q), 135.8 (C_q), 133.4 (CH), 132.7

(C_q), 130.2 (2 × CH), 128.6 (2 × CH), 128.5 (2 × CH), 128.2 (CH),

127.4 (2 × CH), 117.8 (CH), 112.6 (CH), 110.6 (C_q), 71.2 (CH₂),

56.2 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2928, 1649,

1588, 1497, 1379, 1264, 1146, 987, 839, 719, 696 cm⁻¹; HR-MS

(ESI+) m/z calculated for [C₂₁H₁₈⁷⁹BrO₃]⁺= [M + H]⁺397.0434,

found 397.0425.

[4-(Benzyloxy)-2-bromo-5-methoxyphenyl](3-methoxyphenyl)-

methanol (2m). This compound was prepared according to the GP-1

and isolated as pale yellow solid 92% yield (615 mg): mp 108−

1

110 °C; H NMR (CDCl₃400 MHz) δ = 7.40 (d, 2H, J = 7.4 Hz),

7.35 (dd, 2H, J = 7.4 and 7.0 Hz), 7.30 (d, 1H, J = 7.0 Hz), 7.23 (dd,

1H, J = 8.0 and 8.0 Hz), 7.06 (s, 1H), 7.02 (s, 1H), 6.99−6.90 (m,

2H), 6.79 (dd, 1H, J = 8.0 and 2.5 Hz), 6.07 (d, 1H, J = 3.5 Hz), 5.08

(s, 2H), 3.81 (s, 3H), 3.77 (s, 3H), 2.37 (d, 1H, J = 3.5 Hz) ppm; ¹³C

NMR (CDCl₃, 100 MHz) δ = 159.6 (2 × C_q), 149.3 (C_q), 148.1 (C_q),

144.1 (C_q), 136.3 (C_q), 135.0 (C_q), 129.5 (CH), 128.6 (2 × CH),

128.1 (CH), 127.4 (2 × CH), 119.0 (CH), 117.6 (CH), 112.9 (CH),

112.4 (CH), 111.3 (CH), 74.3 (CH), 71.2 (CH₂), 56.1 (CH₃), 55.2

(CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3476, 2939,

1495, 1374, 1253, 1152, 1023, 904, 725, 694 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₂₂H₂₀⁷⁹BrO₃]⁺= [(M + H) − H₂O]⁺411.0590,

found 411.0579.

(2-Bromo-5-methoxyphenyl)(thiophen-2-yl)methanol (2o).

This compound was prepared according to the GP-1 and isolated as

black color semisolid 93% yield (646 mg): ¹H NMR (CDCl₃400 MHz)

δ = 7.38 (d, 1H, J = 8.8 Hz), 7.23 (dd, 2H, J = 7.3 and 3.4 Hz), 6.90 (s,

2H), 6.70 (dd, 1H, J = 8.3 and 2.5 Hz), 6.28 (s, 1H), 3.76 (s, 3H), 2.98

(br. s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 159.2 (C_q), 146.0

(C_q), 143.0 (C_q), 133.3 (CH), 126.6 (CH), 125.5 (CH), 125.4 (CH),

115.4 (CH), 113.0 (CH), 112.5 (C_q), 70.9 (CH), 55.4 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3515, 2914, 1487, 1380, 1237,

1144, 1014, 835, 735, 688 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₂H₁₁⁷⁹BrNaSO₂]⁺= [M + Na]⁺322.9535, found 322.9523.

(2-Bromo-3,4,5-trimethoxyphenyl)(phenyl)methanone (3g).

This compound was prepared according to the GP-2 and isolated as

1

yellow color solid 97% yield (482 mg): mp 72−73 °C; H NMR

(CDCl₃400 MHz) δ = 7.82 (d, 2H, J = 7.8 Hz), 7.60 (t, 1H, J = 7.3

Hz), 7.46 (dd, 2H, J = 7.8 and 7.3 Hz), 6.69 (s, 1H), 3.94 (s, 3H), 3.92

(s, 3H), 3.83 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 195.4

(C_q), 153.0 (2 × C_q), 151.1 (C_q), 144.3 (C_q), 136.1 (C_q), 133.7 (CH),

130.2 (2 × CH), 128.6 (2 × CH), 107.7 (CH), 106.3 (C_q), 61.2

(CH₃), 61.1 (CH₃), 56.3 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 2937, 1669, 1562, 1479, 1383, 1336, 1227, 1162,

1103, 1003, 926, 837, 726, 689 cm⁻¹; HR-MS (ESI+) m/z calculated

for [C₁₆H₁₅⁷⁹BrNaO₄]⁺= [M + Na]⁺373.0046, found 373.0042.

(2-Bromo-5-methoxyphenyl)(3-methoxyphenyl)methanone

(3i). This compound was prepared according to the GP-2 and isolated

1

as white solid 98% yield (486 mg): mp 63−70 °C; H NMR (CDCl₃

400 MHz) δ = 7.49 (d, 1H, J = 8.8 Hz), 7.44 (s, 1H), 7.34 (dd, 1H, J =

7.8 and 7.8 Hz), 7.29 (d, 1H, J = 7.6 Hz), 7.14 (ddd, 1H,

J = 8.8, 7.8, and 2.5 Hz), 6.88 (dd, 1H, J = 8.8 and 3.0 Hz), 6.86 (d,

1H, J = 3.0 Hz), 3.84 (s, 3H), 3.79 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 195.4 (C_q), 159.9 (C_q), 158.7 (C_q), 141.4 (C_q), 137.2

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1

(C_q), 133.9 (CH), 129.6 (CH), 123.5 (CH), 120.5 (CH), 117.3 (CH),

114.1 (CH), 113.7 (CH), 109.7 (C_q), 55.6 (CH₃), 55.4 (CH₃) ppm;

IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2937, 1671, 1593, 1464, 1288,

1019, 788, 681 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₅H₁₃⁷⁹BrKO₃]⁺= [M + K]⁺358.9680, found 358.9674.

as black color solid 97% yield (477 mg): mp 84−86 °C; H NMR

(CDCl₃400 MHz) δ = 7.74 (d, 1H, J = 4.9 Hz), 7.49 (d, 1H, J =

8.8 Hz), 7.41 (d, 1H, J = 3.4 Hz), 7.10 (dd, 1H, J = 4.9 and 3.9 Hz),

6.92 (d, 1H, J = 2.9 Hz), 6.88 (dd, 1H, J = 8.8 and 2.9 Hz), 3.79 (s,

3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 187.5 (C_q), 158.5 (C_q),

143.1 (C_q), 141.1 (C_q), 136.1 (CH), 135.7 (CH), 134.0 (CH), 128.3

(CH), 117.3 (CH), 114.1 (CH), 109.5 (C_q), 55.6 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 2932, 1662, 1591, 1373, 1252,

1171, 1035, 753, 628 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₂H₁₃⁸¹BrNO₂S]⁺= [M + NH₄]⁺315.9824, found 315.9811.

(2-Bromo-4,5-dimethoxyphenyl)(thiophen-2-yl)methanone

(3p). This compound was prepared according to the GP-2 and isolated

(4,5-Dimethoxy-2-methylphenyl)(3-methoxyphenyl)-

methanone (3j). This compound was prepared according to the

1

GP-2 and isolated as brown viscous liquid 98% yield (487 mg): H

NMR (CDCl₃400 MHz) δ = 7.30 (s, 1H), 7.24−7.14 (m, 2H), 7.02

(d, 1H, J = 7.7 Hz), 6.97 (s, 1H), 6.78 (s, 1H), 3.81 (s, 3H), 3.73 (s,

6H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 195.3 (C_q), 159.8 (C_q),

150.9 (C_q), 148.2 (C_q), 138.0 (C_q), 132.4 (C_q), 129.5 (CH), 123.3

(CH), 120.0 (CH), 115.9 (CH), 113.9 (CH), 112.3 (CH), 110.9 (C_q),

56.3 (CH₃), 56.2 (CH₃), 55.4 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 2936, 1665, 1593, 1373, 1256, 1172, 1034, 751,

629 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₁₆H₁₅⁷⁹BrNaO₄]⁺=

[M + Na]⁺373.0046, found 373.0056.

1

as black color solid 95% yield (472 mg): mp 118−120 °C; H NMR

(CDCl₃400 MHz) δ = 7.71 (dd, 1H, J = 4.9 and 1.0 Hz), 7.43 (dd,

1H, J = 3.4 and 1.0 Hz), 7.09 (dd, 1H, J = 4.9 and 3.4 Hz), 7.06 (s,

1H), 6.92 (s, 1H), 3.90 (s, 3H), 3.82 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 187.3 (C_q), 150.8 (C_q), 147.9 (C_q), 143.5 (C_q), 135.7

(CH), 135.3 (CH), 132.2 (C_q), 128.2 (CH), 115.9 (CH), 111.8 (CH),

110.5 (C_q), 56.2 (CH₃), 56.1 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 2931, 1668, 1591, 1378, 1259, 1178, 1035, 752,

628 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₁₃H₁₁⁷⁹BrNaO₃S]⁺=

[(M + Na)]⁺348.9504, found 348.9495.

(6-Bromobenzo[d][1,3]dioxol-5-yl)(3-methoxyphenyl)-

methanone (3k). This compound was prepared according to the

GP-2 and isolated as yellow color solid 98% yield (490 mg): mp 98−

1

100 °C; H NMR (CDCl₃400 MHz) δ = 7.41 (dd, 1H, J = 2.4 and

1.5 Hz), 7.33 (d, 1H, J = 7.8 Hz), 7.29 (ddd, 1H, J = 7.8, 6.3, and

1.4 Hz), 7.17−7.08 (m, 1H), 7.06 (s, 1H), 6.81 (s, 1H), 6.05 (s, 2H),

3.84 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 195.0 (C_q),

159.8 (C_q), 149.7 (C_q), 147.2 (C_q), 137.7 (C_q), 133.7 (C_q), 129.5

(CH), 123.3 (CH), 120.2 (CH), 113.8 (CH), 113.3 (CH), 111.5 (C_q),

109.2 (CH), 102.3 (CH₂), 55.5 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 2933, 1668, 1500, 1450, 1381, 1263, 1038, 843, 737,

698 cm⁻¹; HR-MS (APCI+) m/z calculated for [C₁₅H₁₁⁷⁹BrNaO₄]⁺=

[M + Na]⁺356.9733, found 356.9717.

[5-(Benzyloxy)-2-bromo-4-methoxyphenyl](3-methoxyphenyl)-

methanone (3l). This compound was prepared according to the GP-2

and isolated as pale yellow color solid 98% yield (489 mg): mp 106−

108 °C; ¹H NMR (CDCl₃400 MHz) δ = 7.42−7.23 (m, 7H), 7.19 (d,

1H, J = 7.7 Hz), 7.11 (dd, 1H, J = 8.7 and 2.6 Hz), 7.10 (s, 1H), 6.92

(s, 1H), 5.08 (s, 2H), 3.92 (s, 3H), 3.82 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 195.1 (C_q), 159.8 (C_q), 151.6 (C_q), 147.0

(C_q), 137.9 (C_q), 136.1 (C_q), 132.1 (C_q), 129.4 (CH), 128.6 (2 ×

CH), 128.1 (CH), 127.4 (2 × CH), 123.3 (CH), 120.1 (CH), 116.4

(CH), 115.1 (CH), 113.7 (CH), 111.7 (C_q), 71.2 (CH₂), 56.3 (CH₃),

55.4 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2932, 1667,

1590, 1510, 1448, 1391, 1260, 1036, 841, 735, 693 cm⁻¹; HR-MS

(ESI+) m/z calculated for [C₂₂H₂₀⁷⁹BrO₄]⁺= [M + H]⁺427.0539,

found 427.0521.

1-(2-Bromo-5-methoxyphenyl)-1-phenylethanol (4b). This

compound was prepared according to the GP-1 and isolated as

brown color viscous liquid 96% yield (405 mg): H NMR (CDCl₃

1

400 MHz) δ = 7.40 (dd, 2H, J = 8.6 and 3.1 Hz), 7.33−7.20 (m, 5H),

6.72 (dd, 1H, J = 8.6 and 3.1 Hz), 3.84 (s, 3H), 3.42 (br. s, 1H), 1.94

(s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 158.7 (C_q), 147.3

(C_q), 146.0 (C_q), 135.4 (CH), 128.1 (2 × CH), 126.9 (CH), 125.6

(2 × CH), 115.4 (CH), 113.5 (CH), 112.4 (C_q), 77.3 (C_q), 55.5

(CH₃), 29.9 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3458, 2936, 1569, 1463, 1289, 1039, 764, 699 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₁₅H₁₄⁷⁹BrO]⁺= [(M + H) − H₂O]⁺289.0223,

found 289.0222.

1-(2-Bromo-4,5-dimethoxyphenyl)-1-phenylethanol (4c).

This compound was prepared according to the GP-1 and isolated as

brown color viscous liquid 98% yield (411 mg): ¹H NMR (CDCl₃400

MHz) δ = 7.33 (s, 1H), 7.27−7.12 (m, 5H), 6.92 (s, 1H), 3.86 (s,

3H), 3.78 (s, 3H), 1.89 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz)

δ = 148.5 (C_q), 147.7 (C_q), 147.5 (C_q), 137.6 (C_q), 128.1 (2 × CH),

126.9 (CH), 125.7 (2 × CH), 117.6 (CH), 112.1 (C_q), 111.7 (CH),

77.0 (C_q), 56.1 (2 × CH₃), 29.8 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3514, 2935, 1598, 1500, 1442, 1373, 1255, 1157,

1027, 764, 618 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₆H₁₆⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺319.0328, found 319.0327.

1-(6-bromo-1,3-benzodioxol-5-yl)-1-phenylethanol (4d).

This compound was prepared according to the GP-1 and isolated as

[4-(Benzyloxy)-2-bromo-5-methoxyphenyl](3-methoxy-

phenyl)methanone (3m). This compound was prepared according

to the GP-2 and isolated as white color solid 97% yield (483 mg): mp

1

104−106 °C; H NMR (CDCl₃400 MHz) δ = 7.45 (d, 2H, J =

yellow color viscous liquid 97% yield (410 mg): H NMR (CDCl₃

7.1 Hz), 7.42−7.37 (m, 3H), 7.36−7.26 (m, 3H), 7.18−7.08 (m, 2H),

6.89 (s, 1H), 5.17 (s, 2H), 3.84 (s, 6H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 195.4 (C_q), 159.8 (C_q), 150.0 (C_q), 148.7 (C_q), 137.9

(C_q), 135.9 (C_q), 132.8 (C_q), 129.5 (CH), 128.7 (2 × CH), 128.3

(CH), 127.4 (2 × CH), 123.4 (CH), 120.2 (CH), 117.9 (CH), 113.7

(CH), 112.5 (CH), 110.6 (C_q), 71.2 (CH₂), 56.2 (CH₃), 55.4 (CH₃)

ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2933, 1668, 1591, 1500,

1450, 1381, 1263, 1038, 843, 738, 698 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₂₂H₂₀⁷⁹BrO₄]⁺= [M + H]⁺427.0539, found 427.0527.

(2-Bromophenyl)(thiophen-2-yl) methanone (3n). This com-

pound was prepared according to the GP-2 and isolated as black color

400 MHz) δ = 7.32 (s, 1H), 7.28−7.18 (m, 5H), 6.94 (s, 1H), 5.99 (d,

1H, J = 1.4 Hz), 5.98 (d, 1H, J = 1.4 Hz), 3.34 (br. s, 1H), 1.87 (s, 3H)

ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 147.7 (C_q), 147.4 (C_q), 147.2

(C_q), 138.8 (C_q), 128.1 (2 × CH), 126.9 (CH), 125.5 (2 × CH),

114.7 (CH), 112.9 (C_q), 108.8 (CH), 102.0 (CH₂), 77.2 (C_q), 30.5

(CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3514, 2936,

1597, 1502, 1432, 1353, 1245, 1151, 1047, 761, 675 cm⁻¹; HR-MS

(ESI+) m/z calculated for [C₁₅H₁₂⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺

303.0015, found 303.0011.

1-[5-(Benzyloxy)-2-bromo-4-methoxyphenyl]-1-phenyletha-

nol (4e). This compound was prepared according to the GP-1 and

1

viscous liquid 98% yield (486 mg): H NMR (CDCl₃400 MHz) δ =

isolated as yellow color viscous liquid 97% yield (405 mg): H NMR

7.75 (dd, 1H, J = 4.9 and 1.5 Hz), 7.64 (d, 1H, J = 7.8 Hz), 7.45−7.37

(m, 3H), 7.36−7.30 (m, 1H), 7.11 (dd, 1H, J = 4.9 and 3.9 Hz) ppm;

¹³C NMR (CDCl₃, 100 MHz) δ = 187.8 (C_q), 143.4 (C_q), 140.4 (C_q),

136.0 (CH), 135.6 (CH), 133.3 (CH), 131.3 (CH), 128.7 (CH),

128.3 (CH), 127.0 (CH), 119.4 (C_q) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 2936, 1669, 1583, 1371, 1253, 1171, 1032, 750,

(CDCl₃400 MHz) δ = 7.37 (d, 2H, J = 7.3 Hz), 7.31 (d, 2H, J =

7.0 Hz), 7.28 (s, 1H), 7.24 (d, 1H, J = 7.0 Hz), 7.23−7.05 (m, 5H),

6.94 (s, 1H), 5.13 (s, 2H), 3.79 (s, 3H), 1.76 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 149.3 (C_q), 147.6 (C_q), 146.5 (C_q), 137.2

(C_q), 136.6 (C_q), 128.6 (2 × CH), 128.1 (3 × CH), 127.6 (2 × CH),

126.8 (CH), 125.6 (2 × CH), 118.1 (CH), 115.2 (CH), 112.9 (C_q),

77.0 (C_q), 71.5 (CH₂), 56.2 (CH₃), 30.2 (CH₃) ppm; IR (MIR-ATR,

4000−600 cm⁻¹) ν_max= 3512, 2933, 1596, 1494, 1373, 1252, 1151,

1023, 760, 691 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₂H₂₀⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺395.0641, found 395.0639.

622 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₁₁H₈⁷⁹BrOS]⁺

=

[(M + H)]⁺266.9474, found 266.9475.

(2-Bromo-5-methoxyphenyl)(thiophen-2-yl)methanone

(3o). This compound was prepared according to the GP-2 and isolated

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Article

1-[4-(Benzyloxy)-2-bromo-5-methoxyphenyl]-1-phenyletha-

and 7.9 Hz), 6.97 (s, 1H), 6.88 (dd, 1H, J = 2.3 and 2.0 Hz), 6.81 (d,

1H, J = 7.8 Hz), 6.77 (dd, 1H, J = 8.0 and 2.5 Hz), 6.01 (d, 2H, J = 1.4

Hz), 3.77 (s, 3H), 3.44 (br. s, 1H), 1.88 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 159.5 (C_q), 149.6 (C_q), 147.4 (C_q), 147.2

(C_q), 138.7 (C_q), 129.2 (CH), 118.1 (CH), 114.7 (CH), 113.0 (C_q),

111.9 (CH), 111.8 (CH), 108.8 (CH), 102.0 (CH₂), 77.2 (C_q), 55.2

nol (4f). This compound was prepared according to the GP-1 and

1

isolated as brown color viscous liquid 98% yield (408 mg): H NMR

(CDCl₃400 MHz) δ = 7.43 (dd, 3H, J = 7.5 and 6.3 Hz), 7.38 (dd,

2H, J = 7.5 and 7.1 Hz), 7.33 (d, 1H, J = 7.1 Hz), 7.31−7.22 (m, 5H),

7.05 (d, 1H, J = 7.1 Hz), 5.10 (s, 2H), 3.94 (s, 3H), 1.96 (s, 3H) ppm;

¹³C NMR (CDCl₃, 100 MHz) δ = 148.3 (C_q), 147.7 (C_q), 147.5 (C_q),

138.0 (C_q), 136.3 (C_q), 128.6 (2 × CH), 128.1 (3 × CH), 127.4 (2 ×

CH), 126.9 (CH), 125.7 (2 × CH), 119.9 (CH), 112.2 (CH), 112.0

(C_q), 77.1 (C_q), 71.2 (CH₂), 56.3 (CH₃), 29.9 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 3511, 2934, 1598, 1497, 1370, 1253,

1154, 1025, 763, 699 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₂H₂₀⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺395.0641, found 395.0637.

1-(2-Bromo-3,4,5-trimethoxyphenyl)-1-phenylethanol (4g).

This compound was prepared according to the GP-1 and isolated as

(CH₃), 30.5 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3545, 2898, 1583, 1473, 1230, 1100, 1031, 928, 863, 701, 634 cm⁻¹;

HR-MS (ESI+) m/z calculated for [C₁₆H₁₄⁷⁹BrO₃]⁺= [(M + H) −

H₂O]⁺333.0121, found 333.0127.

1-[5-(Benzyloxy)-2-bromo-4-methoxyphenyl]-1-(3-

methoxyphenyl)ethanol (4l). This compound was prepared

according to the GP-1 and isolated as yellow color viscous liquid

96% yield (402 mg): ¹H NMR (CDCl₃400 MHz) δ = 7.44 (d, 2H, J =

7.0 Hz), 7.39 (s, 1H), 7.38 (dd, 2H, J = 7.5 and 7.0 Hz), 7.33 (d, 1H,

J = 7.0 Hz), 7.21 (dd, 1H, J = 7.9 and 7.9 Hz), 7.06 (s, 1H), 6.89 (dd,

1H, J = 2.0 and 2.0 Hz), 6.83 (d, 1H, J = 7.7 Hz), 6.78 (dd, 1H, J = 8.0

and 2.3 Hz), 5.10 (s, 2H), 3.93 (s, 3H), 3.77 (s, 3H), 3.32 (br. s, 1H),

1.94 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 159.4 (C_q),

149.4 (C_q), 148.3 (C_q), 147.7 (C_q), 137.8 (C_q), 136.3 (C_q), 129.1

(CH), 128.6 (2 × CH), 128.0 (CH), 127.4 (2 × CH), 119.9 (CH),

118.1 (CH), 112.2 (CH), 112.1 (C_q), 112.0 (CH), 111.7 (CH), 77.0

(C_q), 71.2 (CH₂), 56.2 (CH₃), 55.1 (CH₃), 29.9 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3446, 2937, 1597, 1495, 1369,

1249, 1152, 1025, 735, 697 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₃H₂₂⁷⁹BrO₃]⁺= [(M + H) − H₂O]⁺425.0747, found 425.0757.

1-[4-(Benzyloxy)-2-bromo-5-methoxyphenyl]-1-(3-

methoxyphenyl)ethanol (4m). This compound was prepared

according to the GP-1 and isolated as pale yellow color viscous liquid

97% yield (405 mg): ¹H NMR (CDCl₃400 MHz) δ = 7.44 (d, 2H, J =

7.0 Hz), 7.38 (dd, 3H, J = 7.5 and 6.9 Hz), 7.32 (d, 1H, J = 7.0 Hz),

7.21 (dd, 1H, J = 8.0 and 7.9 Hz), 7.06 (s, 1H), 6.90 (s, 1H), 6.83 (d,

1H, J = 7.6 Hz), 6.78 (dd, 1H, J = 8.0 and 2.5 Hz), 5.09 (s, 2H), 3.92

(s, 3H), 3.76 (s, 3H), 3.52 (br. s, 1H), 1.95 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 159.4 (C_q), 149.3 (C_q), 148.3 (C_q), 147.7

(C_q), 137.9 (C_q), 136.3 (C_q), 129.1 (CH), 128.6 (2 × CH), 128.1

(CH), 127.4 (2 × CH), 119.9 (CH), 118.2 (CH), 112.3 (CH), 112.1

(C_q), 112.0 (CH), 111.8 (CH), 77.0 (C_q), 71.2 (CH₂), 56.2 (CH₃),

1

brown color solid 92% yield (385 mg): mp 68−69 °C; H NMR

(CDCl₃400 MHz) δ = 7.38−7.28 (m, 5H), 7.25 (s, 1H), 3.92 (s, 3H),

3.90 (s, 3H), 3.82 (s, 3H), 3.47 (br. s, 1H), 1.95 (s, 3H) ppm; ¹³C

NMR (CDCl₃, 100 MHz) δ = 152.0 (C_q), 151.4 (C_q), 147.4 (C_q),

142.2 (C_q), 140.8 (C_q), 128.1 (2 × CH), 126.9 (CH), 125.5 (2 ×

CH), 109.0 (C_q), 107.8 (CH), 77.5 (C_q), 61.0 (CH₃), 60.9 (CH₃),

56.2 (CH₃), 29.9 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3516, 2945, 1588, 1487, 1360, 1251, 1158, 1024, 754, 686 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₁₇H₁₈⁷⁹BrO₃]⁺= [(M + H) − H₂O]⁺

349.0434, found 349.0430.

1-(2-Bromophenyl)-1-(3-methoxyphenyl)ethanol (4h). This

compound was prepared according to the GP-1 and isolated as col-

orless viscous liquid 94% yield (397 mg): ¹H NMR (CDCl₃400 MHz)

δ = 7.78 (dd, 1H, J = 7.9 and 1.1 Hz), 7.53 (d, 1H, J = 7.9 Hz), 7.38

(dd, 1H, J = 7.6 and 7.5 Hz), 7.24−7.10 (m, 2H), 6.88 (s, 1H), 6.78

(d, 2H, J = 8.6 Hz), 3.76 (s, 3H), 3.54 (br. s. 1H), 1.94 (s, 3H) ppm;

¹³C NMR (CDCl₃, 100 MHz) δ = 159.5 (C_q), 149.5 (C_q), 144.7 (C_q),

134.8 (CH), 129.1 (2 × CH), 128.4 (CH), 127.3 (CH), 122.4 (C_q),

118.0 (CH), 111.8 (CH), 111.7 (CH), 77.4 (C_q), 55.1 (CH₃), 30.3

(CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3453, 2937,

1582, 1429, 1249, 1129, 1037, 754, 698 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₁₅H₁₄⁷⁹BrO]⁺= [(M + H) − H₂O]⁺289.0223, found

289.0223.

55.1 (CH₃), 29.9 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

1-(2-Bromo-5-methoxyphenyl)-1-(3-methoxyphenyl)-

ethanol (4i). This compound was prepared according to the GP-1

and isolated as pale yellow color viscous liquid 95% yield (399 mg):

¹H NMR (CDCl₃400 MHz) δ = 7.40 (d, 1H, J = 8.7 Hz), 7.37 (d, 1H,

3443, 2934, 1598, 1497, 1370, 1253, 1154, 1025, 763, 699 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₂₃H₂₂⁷⁹BrO₃]⁺= [(M + H) − H₂O]⁺

425.0747, found 425.0755.

1-(2-Bromophenyl)-1-thien-2-ylethanol (4n). This compound

was prepared according to the GP-1 and isolated as black color viscous

liquid 97% yield (412 mg): ¹H NMR (CDCl₃400 MHz) δ = 7.83 (dd,

1H, J = 7.8 and 2.0 Hz), 7.56 (dd, 1H, J = 7.8 and 1.5 Hz), 7.37 (ddd,

1H, J = 8.8, 7.8, and 1.5 Hz), 7.23 (dd, 1H, J = 4.9 and 1.5 Hz), 7.17

(ddd, 1H, J = 8.8, 7.8, and 1.5 Hz), 6.91 (dd, 1H, J = 4.9 and 3.4 Hz),

6.73 (dd, 1H, J = 3.4 and 1.5 Hz), 3.39 (br. s, 1H), 2.10 (s, 3H) ppm;

¹³C NMR (CDCl₃, 100 MHz) δ = 152.5 (C_q), 144.6 (C_q), 134.9

(CH), 129.2 (CH), 127.9 (CH), 127.3 (CH), 126.6 (CH), 124.7

(CH), 124.4 (CH), 122.1 (C_q), 75.2 (C_q), 30.2 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 3456, 2933, 1595, 1498, 1363, 1247,

1151, 1023, 733, 692 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₂H₁₀⁷⁹BrS]⁺= [(M + H) − H₂O]⁺264.9681, found 264.9679.

1-(2-Bromo-5-methoxyphenyl)-1-thien-2-ylethanol (4o).

This compound was prepared according to the GP-1 and isolated as

J = 3.0 Hz), 7.19 (dd, 1H, J = 8.0 and 8.0 Hz), 6.89 (dd, 1H, J = 2.0

and 1.9 Hz), 6.85−6.74 (m, 2H), 6.70 (dd, 1H, J = 8.7 and 3.0 Hz),

3.84 (s, 3H), 3.76 (s, 3H), 3.45 (br. s, 1H), 1.92 (s, 3H) ppm; ¹³C

NMR (CDCl₃, 100 MHz) δ = 159.5 (C_q), 158.8 (C_q), 149.1 (C_q),

145.9 (C_q), 135.4 (CH), 129.1 (CH), 118.1 (CH), 115.4 (CH), 113.6

(CH), 112.5 (C_q), 112.0 (CH), 111.8 (CH), 77.3 (C_q), 55.5 (CH₃),

55.2 (CH₃), 30.0 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3472, 2937, 1584, 1462, 1234, 1159, 1036, 755, 700 cm⁻¹; HR-MS

(ESI+) m/z calculated for [C₁₆H₁₆⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺

319.0328, found 319.0329.

1-(2-Bromo-4,5-dimethoxyphenyl)-1-(3-methoxyphenyl)-

ethanol (4j). This compound was prepared according to the GP-1

and isolated as yellow color solid 96% yield (402 mg): mp 72−74 °C;

¹H NMR (CDCl₃400 MHz) δ = 7.35 (s, 1H), 7.20 (dd, 1H, J = 8.0

and 7.9 Hz), 6.99 (s, 1H), 6.88 (dd, 1H, J = 2.0 and 2.0 Hz), 6.82 (d,

1H, J = 7.6 Hz), 6.77 (dd, 1H, J = 8.0 and 2.0 Hz), 3.92 (s, 3H), 3.85

(s, 3H), 3.76 (s, 3H), 3.29 (br. s, 1H), 1.93 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 159.5 (C_q), 149.4 (C_q), 148.5 (C_q), 147.7

(C_q), 137.4 (C_q), 129.1 (CH), 118.2 (CH), 117.5 (CH), 112.3 (C_q),

112.0 (CH), 111.7 (CH), 111.6 (CH), 77.0 (C_q), 56.1 (2 × CH₃),

1

yellow color viscous liquid 93% yield (410 mg): H NMR (CDCl₃

400 MHz) δ = 7.47−7.37 (m, 2H), 7.22 (dd, 1H, J = 4.9 and 1.0 Hz),

6.90 (dd, 1H, J = 4.9 and 3.4 Hz), 6.75 (dd, 1H, J = 3.4 and 1.0 Hz),

6.71 (dd, 1H, J = 8.8 and 3.4 Hz), 3.81 (s, 3H), 3.34 (br. s, 1H), 2.07

(s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 158.7 (C_q), 152.0

(C_q), 145.8 (C_q), 135.3 (CH), 126.5 (CH), 124.8 (CH), 124.6 (CH),

114.5 (CH), 113.9 (CH), 112.2 (C_q) 74.9 (C_q), 55.4 (CH₃), 29.7

(CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3441, 2933,

1595, 1494, 1368, 1247, 1153, 1024, 738, 692 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₁₃H₁₂⁷⁹BrOS]⁺= [(M + H) − H₂O]⁺294.9787,

found 294.9790.

55.2 (CH₃), 29.9 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3465, 2937, 1584, 1461, 1232, 1153, 1032, 751, 646 cm⁻¹; HR-MS

(ESI+) m/z calculated for [C₁₇H₁₇⁷⁹BrO₃]⁺= [M−H₂O]⁺348.0356,

found 348.0354.

1-(6-Bromo-1,3-benzodioxol-5-yl)-1-(3-methoxyphenyl)-

ethanol (4k). This compound was prepared according to the GP-1

and isolated as white color solid 96% yield (405 mg): mp 74−76 °C;

¹H NMR (CDCl₃400 MHz) δ = 7.32 (s, 1H), 7.19 (dd, 1H, J = 8.0

1-(2-Bromo-4,5-dimethoxyphenyl)-1-thien-2-ylethanol (4p).

This compound was prepared according to the GP-1 and isolated as

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Article

black color semisolid 95% yield (400 mg): ¹H NMR (CDCl₃

400 MHz) δ = 7.42 (s, 1H), 7.20 (d, 1H, J = 4.9 Hz), 6.99 (s, 1H),

6.89 (dd, 1H, J = 4.9 and 3.9 Hz), 6.79 (d, 1H, J = 3.4 Hz), 3.88 (s,

3H), 3.84 (s, 3H), 3.19 (br. s, 1H), 2.07 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 152.3 (C_q), 148.4 (C_q), 147.6 (C_q), 137.2

(C_q), 126.5 (CH), 124.8 (CH), 124.6 (CH), 117.4 (CH), 111.9 (C_q),

111.0 (CH), 74.5 (C_q), 56.0 (CH₃), 55.9 (CH₃), 29.7 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3441, 2933, 1596, 1495, 1362,

1249, 1151, 1024, 735, 697 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₄H₁₅⁷⁹BrO₃S]⁺= [M]⁺343.9900, found 343.9887.

(2-Bromophenyl)(diphenyl)methanol (4q). This compound

was prepared according to the GP-1 and isolated as color less viscous

liquid 91% yield (460 mg): ¹H NMR (CDCl₃400 MHz) δ = 7.38 (dd,

2H, J = 8.3 and 1.5 Hz), 7.34−7.18 (m, 12H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 145.5 (2 × C_q), 145.0 (C_q), 134.8 (CH), 131.9 (CH),

129.2 (CH), 127.9 (8 × CH), 127.3 (2 × CH), 126.8 (CH), 122.9

(C_q), 83.1 (C_q) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3544,

3057, 1583, 1446, 1338, 1265, 1158, 1023, 890, 755, 698 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₁₉H₁₄⁷⁹Br]⁺= [(M + H) − H₂O]⁺

321.0273, found 321.0277.

(2-Bromo-5-methoxyphenyl)(diphenyl)methanol (4r). This

compound was prepared according to the GP-1 and isolated as

color less viscous liquid 61% yield (310 mg): ¹H NMR (CDCl₃

400 MHz) δ = 7.45 (d, 1H, J = 8.8 Hz), 7.33−7.17 (m, 10H), 6.65

(dd, 1H, J = 8.8 and 2.9 Hz), 6.25 (d, 1H, J = 2.9 Hz), 4.53 (s, 1H),

3.55 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 158.1 (C_q),

146.1 (C_q), 145.3 (2 × C_q), 135.3 (CH), 127.9 (4 × CH), 127.8 (4 ×

CH), 127.3 (2 × CH), 119.0 (CH), 113.6 (CH), 113.1 (C_q), 83.0

(C_q), 55.1 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3542,

3053, 1573, 1443, 1358, 1265, 1155, 1024, 893, 752, 695 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₂₀H₁₆⁷⁹BrO]⁺= [(M + H) − H₂O]⁺

351.0379, found 351.0383.

400 MHz) δ = 7.51 (d, 1H, J = 8.8 Hz), 7.24−7.14 (m, 3H), 7.11 (d,

1H, J = 2.9 Hz), 7.05 (dd, 2H, J = 7.3 and 2.9 Hz), 6.64 (dd, 1H, J =

8.8 and 3.4 Hz), 3.70 (s, 3H), 3.67 (d, 1H, J = 13.7 Hz), 3.26 (d, 1H,

J = 13.7 Hz), 2.44 (br. s, 1H), 1.73 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 158.8 (C_q), 146.3 (C_q), 136.6 (C_q), 135.5 (CH), 130.4

(2 × CH), 128.1 (2 × CH), 126.6 (CH), 114.5 (CH), 113.7 (CH),

110.4 (C_q), 75.3 (C_q), 55.3 (CH₃), 45.8 (CH₂), 27.1 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3454, 2939, 1560, 1461, 1289,

1037, 762, 699 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₆H₁₆⁷⁹BrO]⁺= [(M + H) − H₂O]⁺303.0379, found 303.0370.

2-(2-Bromophenyl)pent-4-en-2-ol (4aa). This compound was

prepared according to the GP-4 and isolated as colorless viscous liquid

1

95% yield (460 mg): H NMR (CDCl₃400 MHz) δ = 7.69 (dd, 1H,

J = 7.9 and 1.6 Hz), 7.57 (dd, 1H, J = 7.9 and 1.1 Hz), 7.29 (ddd, 1H,

J = 8.0, 6.9, and 1.1 Hz), 7.08 (ddd, 1H, J = 9.2, 7.4, and 1.6 Hz),

5.65−5.45 (m, 1H), 5.13 (d, 1H, J = 17.1 Hz), 5.08 (d, 1H, J =

10.2 Hz), 3.27 (dd, 1H, J = 14.0 and 6.4 Hz), 2.64 (m, 2H), 1.72 (s,

3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 145.0 (C_q), 135.0 (CH),

133.6 (CH), 128.5 (CH), 128.2 (CH), 127.4 (CH), 119.9 (C_q), 119.3

(CH₂), 74.6 (C_q), 45.0 (CH₂), 27.3 (CH₃) ppm. ; IR (MIR-ATR,

4000−600 cm⁻¹) ν_max= 3443, 2932, 1591, 1490, 1367, 1240, 1151, 1024,

735, 697 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₁₁H₁₂⁷⁹Br]⁺

[(M + H) − H₂O]⁺223.0117, found 223.0117.

=

1-(2-Bromophenyl)-1-phenylbut-3-en-1-ol (4ab). This com-

pound was prepared according to the GP-4 and isolated as colorless

1

viscous liquid 89% yield (413 mg): H NMR (CDCl₃400 MHz) δ =

7.80 (dd, 1H, J = 7.9 and 1.5 Hz), 7.49 (d, 1H, J = 7.9 Hz), 7.35 (dd,

1H, J = 7.9 and 7.4 Hz), 7.32−7.18 (m, 5H), 7.12 (ddd, 1H, J = 7.7,

7.5, and 1.4 Hz), 5.78−5.58 (m, 1H), 5.11 (dd, 1H, J = 17.2 and

1.4 Hz), 5.06 (d, 1H, J = 10.2 Hz), 3.42 (dd, 1H, J = 14.1 and 6.6 Hz),

3.22 (br. s, 1H), 2.99 (dd, 1H, J = 14.1 and 7.3 Hz) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 145.5 (C_q), 143.9 (C_q), 135.0 (CH), 133.6

(CH), 129.1 (CH), 128.9 (CH), 128.0 (2 × CH), 127.1 (CH), 127.0

(CH), 126.5 (2 × CH), 122.1 (C_q), 118.9 (CH₂), 78.3 (C_q), 44.8

(CH₂) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3440, 2942,

1581, 1450, 1360, 1230, 1156, 1021, 739, 689 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₁₆H₁₄⁷⁹Br]⁺= [(M + H) − H₂O]⁺285.0273,

found 285.0280.

(2-Bromo-4,5-dimethoxyphenyl)(diphenyl)methanol (4s).

This compound was prepared according to the GP-1 and isolated as

color less viscous liquid 81% yield (402 mg): ¹H NMR (CDCl₃

400 MHz) δ = 7.35−7.18 (m, 10H), 7.02 (s, 1H), 6.19 (s, 1H), 4.39

(s, 1H), 3.82 (s, 3H), 3.42 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100

MHz) δ = 148.5 (C_q), 147.0 (C_q), 145.7 (2 × C_q), 137.4 (C_q), 127.9

(8 × CH), 127.3 (2 × CH), 117.4 (CH), 115.3 (CH), 112.9 (C_q),

82.9 (C_q), 56.1 (CH₃), 55.4 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3545, 3059, 2933, 1597, 1500, 1442, 1369, 1253,

1149, 1019, 730, 699 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₁H₁₈⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺381.0485, found 381.0482.

1-(2-Bromo-5-methoxyphenyl)-1-phenylprop-2-yn-1-ol (4t).

This compound was prepared according to the GP-4 and isolated as

pale yellow color crystalline solid 63% yield (275 mg): mp 97−98 °C;

¹H NMR (CDCl₃400 MHz) δ = 7.64 (d, 1H, J = 2.9 Hz), 7.50 (dd,

2H, J = 7.8 and 1.5 Hz), 7.43 (d, 1H, J = 8.8 Hz), 7.38−7.28 (m, 3H),

6.75 (dd, 1H, J = 8.8 and 2.9 Hz), 3.82 (s, 3H), 3.38 (br. s, 1H), 2.88

(s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 158.7 (C_q), 142.5

(C_q), 142.4 (C_q), 135.4 (CH), 128.3 (2 × CH), 128.1 (CH), 126.7

(2 × CH), 114.9 (CH), 114.8 (CH), 111.9 (C_q), 84.1 (C_q), 76.2

(CH), 74.5 (C_q), 55.5 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹)

ν_max= 3436, 3286, 1591, 1463, 1290, 1236, 1019, 815, 767, 698 cm⁻¹.

2-(2-Bromophenyl)-1-phenylpropan-2-ol (4u). This com-

pound was prepared according to the GP-1 and isolated as color

2-(2-Bromo-5-methoxyphenyl)pent-4-en-2-ol (4ac). This

compound was prepared according to the GP-4 and isolated as color-

1

less viscous liquid 94% yield (445 mg): H NMR (CDCl₃400 MHz)

δ = 7.43 (d, 1H, J = 8.6 Hz), 7.29 (d, 1H, J = 3.0 Hz), 6.62 (dd, 1H,

J = 8.6, and 3.0 Hz), 5.65−5.45 (m, 1H), 5.12 (d, 1H, J = 17.1 Hz),

5.07 (d, 1H, J = 10.0 Hz), 3.76 (s, 3H), 3.27 (dd, 1H, J = 14.0 and

6.3 Hz), 2.67 (br. s, 1H), 2.60 (dd, 1H, J = 14.0 and 8.5 Hz), 1.69 (s,

3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 158.8 (C_q), 146.3 (C_q),

135.5 (CH), 133.5 (CH), 119.2 (CH₂), 114.4 (CH), 113.5 (CH),

110.0 (C_q), 74.4 (C_q), 55.3 (CH₃), 44.8 (CH₂), 27.1 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3442, 2932, 1591, 1493, 1366,

1242, 1150, 1025, 735, 698 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₂H₁₄⁷⁹BrO]⁺= [(M + H) − H₂O]⁺253.0223, found 253.0220.

1-(2-Bromo-5-methoxyphenyl)-1-phenylbut-3-en-1-ol (4ad).

This compound was prepared according to the GP-4 and isolated

1

as red color viscous liquid 91% yield (416 mg): H NMR (CDCl₃

400 MHz) δ = 7.40 (d, 1H, J = 3.0 Hz), 7.36 (d, 1H, J = 8.7 Hz),

7.30−7.15 (m, 5H), 6.65 (dd, 1H, J = 8.7 and 3.1 Hz), 5.78−5.60 (m,

1H), 5.11 (dd, 1H, J = 17.1 and 1.6 Hz), 5.05 (dd, 1H, J = 10.2 and

1.6 Hz), 3.79 (s, 3H), 3.42 (dd, 1H, J = 14.2 and 6.6 Hz), 3.17 (br. s,

1H), 2.99 (dd, 1H, J = 14.2 and 7.3 Hz) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 158.5 (C_q), 145.2 (C_q), 144.9 (C_q), 135.5 (CH), 133.6

(CH), 128.0 (2 × CH), 127.1 (CH), 126.5 (2 × CH), 118.8 (CH₂),

115.9 (CH), 113.7 (CH), 112.2 (C_q), 78.1 (C_q), 55.4 (CH₃), 44.4

(CH₂) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3435, 2930,

1581, 1496, 1366, 1230, 1156, 1029, 734, 686 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₁₇H₁₆⁷⁹BrO]⁺= [(M + H) − H₂O]⁺315.0379,

found 315.0388.

1

less viscous liquid 83% yield (351 mg): H NMR (CDCl₃400 MHz)

δ = 7.63 (d, 1H, J = 7.8 Hz), 7.47 (d, 1H, J = 7.8 Hz), 7.23−7.13 (m,

4H), 7.08 (ddd, 1H, J = 9.3, 7.8, and 1.5 Hz), 7.04−6.96 (m, 2H), 3.66

(d, 1H, J = 13.2 Hz), 3.26 (d, 1H, J = 13.2 Hz), 2.44 (br. s, 1H), 1.75

(s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 144.9 (C_q), 136.7

(C_q), 135.0 (CH), 130.5 (2 × CH), 129.7 (C_q), 128.5 (CH), 128.3

(CH), 128.1 (2 × CH), 127.4 (CH), 126.6 (CH), 75.5 (C_q), 46.0

(CH₂), 27.3 (CH₃) ppm. ; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3456, 2932, 1561, 1462, 1283, 1033, 762, 694 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₁₅H₁₄⁷⁹Br]⁺= [(M + H) − H₂O]⁺273.0273,

found 273.0271.

2-(2-Bromo-4,5-dimethoxyphenyl)pent-4-en-2-ol (4ae). This

2-(2-Bromo-5-methoxyphenyl)-1-phenylpropan-2-ol (4v).

compound was prepared according to the GP-4 and isolated as color-

less viscous liquid 92% yield (427 mg): H NMR (CDCl₃400 MHz)

δ = 7.32 (s, 1H), 7.05 (s, 1H), 5.70−5.50 (m, 1H), 5.17 (d, 1H,

1

This compound was prepared according to the GP-1 and isolated

1

as colorless viscous liquid 87% yield (366 mg): H NMR (CDCl₃

2069

dx.doi.org/10.1021/jo402763m | J. Org. Chem. 2014, 79, 2059−2074

The Journal of Organic Chemistry

Article

J = 17.4 Hz), 5.13 (d, 1H, J = 10.2 Hz), 3.89 (s, 3H), 3.88 (s, 3H),

3.31 (dd, 1H, J = 14.1 and 6.3 Hz), 2.62 (dd, 1H, J = 14.1 and 8.5 Hz),

2.53 (br. s, 1H), 1.72 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ =

147.9 (C_q), 147.8 (C_q), 137.6 (C_q), 133.7 (CH), 119.4 (CH₂), 117.7

(CH), 111.3 (CH), 109.4 (C_q), 74.3 (C_q), 56.1 (CH₃), 55.9 (CH₃),

(s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 149.9 (C_q), 149.0

(C_q), 148.0 (C_q), 147.0 (C_q), 145.1 (C_q), 144.1 (C_q), 129.2 (C_q),

127.9 (2 × CH), 127.4 (CH), 126.4 (2 × CH), 123.0 (C_q), 114.5

(C_q), 109.3 (CH), 105.9 (CH), 105.1 (CH), 102.1 (CH), 80.9 (C_q),

56.7 (CH₃), 56.2 (2 × CH₃), 55.9 (CH₃), 28.2 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 2933, 2833, 1504, 1443, 1332, 1266,

1139, 1035, 910, 861, 770 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₄H₂₅O₅]⁺= [M + H]⁺393.1697, found 393.1689.

45.1 (CH₂), 27.5 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3423, 2938, 1583, 1428, 1321, 1243, 1151, 1035, 745, 696 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₁₃H₁₆⁷⁹BrO₂]⁺= [(M + H) − H₂O]⁺

283.0328, found 283.0323.

6-Methyl-6-phenyl-6H-[1,3]benzodioxolo[5,6-c][1,3]dioxolo-

[4,5-g]chromene (5d). This compound was prepared according to

the GP-6 and isolated as colorless oil 73% yield (66 mg), byproduct

ketone 7a (18 mg, 61%) as colorless oil: ¹H NMR (CDCl₃, 400 MHz)

δ = 7.27 (dd, 2H, J = 7.8 and 1.0 Hz), 7.21 (dd, 2H, J = 7.8 and

6.8 Hz), 7.18 (d, 1H, J = 6.9 Hz), 7.01 (s, 1H), 6.90 (s, 1H), 6.75

(s, 1H), 6.53 (s, 1H), 6.00 (d, 2H, J = 1.6 Hz), 5.88 (d, 1H, J =

1.0 Hz), 5.85 (d, 1H, J = 1.0 Hz), 1.94 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 147.7 (C_q), 147.6 (2 × C_q), 146.6 (C_q), 144.9

(C_q), 142.7 (C_q), 130.3 (C_q), 127.9 (2 × CH), 127.4 (CH), 126.4

(2 × CH), 124.6 (C_q), 116.0 (C_q), 106.2 (CH), 102.5 (CH), 102.0

(CH), 101.2 (CH₂), 101.1 (CH₂), 100.1 (CH), 81.2 (C_q), 28.4 (CH₃)

ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2899, 1502, 1477, 1371,

1255, 1168, 1037, 935, 861, 770, 699 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₂₂H₁₇O₅]⁺= [M + H]⁺361.1071, found 361.1062.

3,8-Bis(benzyloxy)-2,9-dimethoxy-6-methyl-6-phenyl-6H-

benzo[c]chromene (5e). This compound was prepared according to

the GP-6 and isolated as colorless oil 76% yield (102 mg), byproduct

ketone 7a (21 mg, 71%) as colorless oil: ¹H NMR (CDCl₃, 400 MHz)

δ = 7.46−7.26 (m, 11H), 7.20−7.05 (m, 5H), 7.02 (s, 1H), 6.74 (s,

1H), 6.59 (s, 1H), 5.18 (d, 1H, J = 12.4 Hz), 5.17 (d, 1H, J = 12.4 Hz),

5.13 (s, 2H), 3.99 (s, 3H), 3.87 (s, 3H), 1.84 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 149.8 (C_q), 149.0 (C_q), 147.0 (C_q), 146.6

(C_q), 145.0 (C_q), 144.6 (C_q), 136.9 (C_q), 136.7 (C_q), 129.2 (C_q),

128.6 (2 × CH), 128.5 (2 × CH), 127.9 (2 × CH), 127.8 (CH), 127.7

(2 × CH), 127.5 (2 × CH), 127.3 (2 × CH), 127.1 (CH), 126.2

(CH), 123.4 (C_q), 115.0 (C_q), 113.0 (CH), 106.9 (CH), 105.7 (CH),

104.5 (CH), 80.8 (C_q), 71.5 (CH₂), 70.8 (CH₂), 57.0 (CH₃), 56.3

[1-(2-Bromo-5-methoxyphenyl)-1-methylethoxy](trimethyl)-

silane (11a). This compound was prepared according to the GP-5

1

and isolated as 74% yield (383 mg) as colorless viscous liquid: H

NMR (CDCl₃400 MHz) δ = 7.44 (d, 1H, J = 8.3 Hz), 7.32 (d, 1H, J =

3.4 Hz), 6.61 (dd, 1H, J = 8.3 and 3.4 Hz), 3.79 (s, 3H), 1.75 (s, 3H),

0.16 (s, 9H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 158.6 (C_q),

148.5 (C_q), 135.7 (CH), 114.0 (CH), 113.1 (CH), 110.6 (C_q), 76.3

(C_q), 55.2 (CH₃), 29.8 (2 × CH₃), 2.4 (3 × CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 2950, 2874, 1532, 1454, 1372, 1230,

1128, 1022, 831, 750, 694 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₃H₁₉⁸¹BrSiKO]⁺= [(M + K) − H₂O]⁺339.0001, found 339.0011.

[1-(6-Bromo-1,3-benzodioxol-5-yl)-1-methylethoxy](trimethyl)-

silane (11b). This compound was prepared according to the GP-5 and

1

isolated as white color solid 76% yield (388 mg): mp 47−48 °C; H

NMR (CDCl₃400 MHz) δ = 7.23 (s, 1H), 7.02 (s, 1H), 5.95 (s, 2H),

1.72 (s, 6H), 0.14 (s, 9H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ =

147.2 (C_q), 146.8 (C_q), 141.3 (C_q), 115.0 (CH), 110.7 (C_q), 108.1

(CH), 101.8 (CH₂), 76.4 (C_q), 30.2 (2 × CH₃), 2.6 (3 × CH₃) ppm;

IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2957, 2894, 1502, 1474,

1375, 1231, 1126, 1032, 832, 752, 690 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₁₃H₁₉⁷⁹BrSiNaO₃]⁺= [(M + Na)]⁺353.0179, found

353.0172.

6-Methyl-6-phenyl-6H-benzo[c]chromene (5a). This com-

pound was prepared according to the GP-6 and isolated as white

color solid 79% yield (54 mg): mp 120−122 °C, byproduct ketone 7a

1

(20 mg, 68%) as colorless oil; H NMR (CDCl₃, 400 MHz) δ = 7.74

(dd, 1H, J = 7.8 and 1.0 Hz), 7.65 (dd, 1H, J = 7.8 and 1.5 Hz), 7.41

(ddd, 1H, J = 8.8, 7.4, and 1.5 Hz), 7.35 (dd, 1H, J = 7.6 and 1.2 Hz),

7.31 (dd, 2H, J = 8.8 and 1.5 Hz), 7.27 (dd, 1H, J = 7.6 and 1.2 Hz),

7.24−7.12 (m, 4H), 7.02 (dd, 1H, J = 8.0 and 1.0 Hz), 6.95 (ddd, 1H,

J = 8.8, 7.8, and 1.0 Hz), 2.04 (s, 3H) ppm.¹³C NMR (CDCl₃,

100 MHz) δ = 152.9 (C_q), 144.8 (C_q), 137.5 (C_q), 129.5 (C_q), 129.4

(CH), 128.1 (CH), 127.9 (2 × CH), 127.5 (CH), 127.3 (CH), 126.5

(2 × CH), 125.6 (CH), 122.9 (CH), 122.8 (C_q), 122.5 (CH), 121.7

(CH), 118.2 (CH), 81.0 (C_q), 28.4 (C_q) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3060, 2925, 2852, 1591, 1438, 1371, 1245, 1137,

1066, 928, 755, 698 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₀H₁₇O]⁺= [M + H]⁺273.1274, found 273.1262.

3,8-Dimethoxy-6-methyl-6-phenyl-6H-benzo[c]chromene

(5b). This compound was prepared according to the GP-6 and isolated

as yellow color solid 81% yield (68 mg): mp 130−132 °C, byproduct

ketone 7a (19 mg, 63%) as colorless oil; ¹H NMR (CDCl₃, 400 MHz)

δ = 7.59 (d, 1H, J = 8.5 Hz), 7.48 (d, 1H, J = 8.5 Hz), 7.35 (d, 2H, J =

7.8 Hz), 7.29−7.14 (m, 3H), 6.93 (dd, 1H, J = 8.7 and 2.6 Hz), 6.78

(d, 1H, J = 2.0 Hz), 6.59 (d, 1H, J = 2.0 Hz), 6.52 (dd, 1H, J = 8.5 and

2.6 Hz), 3.82 (s, 3H), 3.77 (s, 3H), 2.01 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 160.2 (C_q), 158.5 (C_q), 153.3 (C_q), 144.7

(C_q), 138.0 (C_q), 128.0 (2 × CH), 127.4 (CH), 126.5 (2 × CH),

123.2 (CH), 123.1 (CH), 122.8 (C_q), 115.9 (C_q), 113.0 (CH), 112.0

(CH), 108.3 (CH), 103.2 (CH), 81.4 (C_q), 55.4 (CH₃), 55.3 (CH₃),

28.3 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3061, 2928,

2853, 1592, 1438, 1371, 1246, 1156, 1067, 929, 757, 698 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₂₂H₂₁O₃]⁺= [M + H]⁺333.1485,

found 333.1482.

(CH₃), 28.4 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

3061, 2932, 1608, 1499, 1443, 1374, 1257, 1166, 1019, 905, 848, 737,

696 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₃₆H₃₂NaO₅]⁺= [M +

Na]⁺567.2142, found 567.2123.

2,9-Bis(benzyloxy)-3,8-dimethoxy-6-methyl-6-phenyl-6H-

benzo[c]chromene (5f). This compound was prepared according to

the GP-6 and isolated as colorless oil 75% yield (104 mg), byproduct

ketone 7a (18 mg, 61%) as colorless oil: ¹H NMR (CDCl₃, 400 MHz)

δ = 7.68 (dd, 1H, J = 8.4 and 1.4 Hz), 7.65 (dd, 1H, J = 8.4 and

1.5 Hz), 7.53 (ddd, 1H, J = 7.8, 7.5, and 1.5 Hz), 7.50−7.26 (m, 10H),

7.16−7.09 (m, 2H), 7.08 (s, 1H), 7.02 (s, 1H), 6.73 (s, 1H), 6.59 (s,

1H), 5.18 (d, 1H, J = 12.4 Hz), 5.17 (d, 1H, J = 12.4 Hz), 5.13 (s, 2H),

3.99 (s, 3H), 3.86 (s, 3H), 1.84 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 149.9 (C_q), 148.1 (C_q), 147.1 (C_q), 146.7 (C_q), 145.1

(C_q), 144.7 (C_q), 136.9 (C_q), 136.8 (C_q), 133.0 (C_q), 132.2 (CH),

132.1 (CH), 132.0 (CH), 128.6 (CH), 128.5 (2 × CH), 127.9 (CH),

127.8 (2 × CH), 127.5 (2 × CH), 127.3 (2 × CH), 127.1 (CH), 126.2

(CH), 125.7 (C_q), 123.5 (C_q),115.1 (C_q), 113.1 (CH), 107.0 (CH),

105.7 (CH), 104.5 (CH), 80.9 (C_q), 71.5 (CH₂), 70.8 (CH₂), 57.1

(CH₃), 56.3 (CH₃), 28.4 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3061, 2932, 1500, 1458, 1377, 1261, 1199, 1031,

909, 857, 740, 698 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₃₆H₃₃O₅]⁺= [M + H]⁺545.2323, found 545.2313.

6-(3-Methoxyphenyl)-6-methyl-6H-benzo[c]chromene (5h).

This compound was prepared according to the GP-6 and isolated as

colorless oil 72% yield (55 mg), byproduct ketone 7a 68% yield

1

(25 mg) as colorless oil: H NMR (CDCl₃, 400 MHz) δ = 7.74 (d,

1H, J = 7.8 Hz), 7.65 (dd, 1H, J = 7.8 and 1.1 Hz), 7.41 (ddd, 1H, J =

7.7, 7.3, and 1.1 Hz), 7.34 (dd, 1H, J = 7.7 and 7.3 Hz), 7.29 (d, 1H,

J = 7.5 Hz), 7.20 (ddd, 1H, J = 8.5, 8.0, and 1.1 Hz), 7.13 (dd, 1H, J =

8.0 and 7.9 Hz), 7.04 (d, 1H, J = 8.0 Hz), 6.96 (dd, 1H, J = 7.5 and

7.5 Hz), 6.90 (s, 1H), 6.87 (d, 1H, J = 8.5 Hz), 6.70 (dd, 1H, J = 8.0

and 2.5 Hz), 3.70 (s, 3H), 2.03 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 159.2 (2 × C_q), 152.9 (C_q), 146.6 (C_q), 137.4 (C_q),

2,3,8,9-Tetramethoxy-6-methyl-6-phenyl-6H-benzo[c]-

chromene (5c). This compound was prepared according to the GP-6

and isolated as brown color solid 81% yield (80 mg): mp 158−160 °C,

byproduct ketone 7a (22 mg, 72%) as colorless oil; ¹H NMR (CDCl₃,

400 MHz) δ = 7.30 (d, 2H, J = 7.8 Hz), 7.22 (dd, 2H, J = 7.8 and

6.9 Hz), 7.18 (d, 1H, J = 6.9 Hz), 7.08 (s, 1H), 7.00 (s, 1H), 6.73

(s, 1H), 6.57 (s, 1H), 3.98 (s, 3H), 3.87 (s, 6H), 3.85 (s, 3H), 1.99

2070

dx.doi.org/10.1021/jo402763m | J. Org. Chem. 2014, 79, 2059−2074

The Journal of Organic Chemistry

Article

129.4 (CH), 128.8 (CH), 128.2 (CH), 127.5 (CH), 125.5 (CH),

122.9 (CH), 122.8 (C_q), 122.4 (CH), 121.8 (CH), 119.0 (CH), 118.2

(CH), 112.8 (CH), 112.4 (CH), 81.0 (C_q), 55.1 (CH₃), 28.5 (CH₃)

ppm; IR (MIR−ATR, 4000−600 cm⁻¹) ν_max= 3068, 2933, 1582,

1482, 1371, 1242, 1167, 1039, 928, 876, 726, 616 cm⁻¹; HR-MS

(ESI+) m/z calculated for [C₂₁H₂₃NO]⁺= [(M + NH₄)+(−H₂O)]⁺

305.1774, found 305.1763.

(CH), 105.7 (CH), 104.4 (CH), 80.8 (C_q), 71.5 (CH₂), 70.9 (CH₂),

57.1 (CH₃), 56.3 (CH₃), 55.1 (CH₃), 28.2 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 3063, 2932, 1604, 1499, 1458, 1371,

1253, 1167, 1036, 908, 852, 731, 695 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₃₇H₃₅O₆]⁺= [M + H]⁺575.2428, found 575.2410.

2,9-Bis(benzyloxy)-3,8-dimethoxy-6-(3-methoxyphenyl)-6-

methyl-6H-benzo[c]chromene (5m). This compound was pre-

pared according to the GP-6 and isolated as yellow color semisolid

75% yield (108 mg), byproduct ketone 7b 68% yield (25 mg) as color-

3,8-Dimethoxy-6-(3-methoxyphenyl)-6-methyl-6H-benzo[c]-

chromene (5i). This compound was prepared according to the GP-6

and isolated as red color solid 83% yield (76 mg): mp 74−76 °C,

1

less oil: H NMR (CDCl₃, 400 MHz) δ = 7.48 (d, 2H, J = 7.2 Hz),

1

byproduct ketone 7b 55% yield (20 mg) as colorless oil; H NMR

7.46−7.27 (m, 7H), 7.15 (dd, 1H, J = 8.3 and 8.2 Hz), 6.95 (s, 1H),

6.91 (s, 1H), 6.90−6.84 (m, 2H), 6.76−6.68 (m, 2H), 6.58 (s, 1H),

5.16 (s, 2H), 5.08 (d, 1H, J = 12.0 Hz), 5.04 (d, 1H, J = 12.0 Hz), 3.87

(s, 3H), 3.85 (s, 3H), 3.72 (s, 3H), 1.98 (s, 3H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 159.1 (C_q), 150.7 (C_q), 148.6 (C_q), 148.2

(C_q), 147.4 (C_q), 146.8 (C_q), 143.0 (C_q), 137.6 (C_q), 137.0 (C_q),

129.5 (C_q), 128.8 (CH), 128.6 (2 × CH), 128.5 (2 × CH), 128.0

(CH), 127.8 (CH), 127.5 (2 × CH), 127.4 (2 × CH), 122.7 (C_q),

118.9 (CH), 114.4 (C_q),112.8 (CH), 112.3 (CH), 109.8 (CH), 109.6

(CH), 107.8 (CH), 102.2 (CH), 80.9 (C_q), 72.3 (CH₂), 71.3 (CH₂),

56.3 (CH₃), 56.0 (CH₃), 55.1 (CH₃), 28.2 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 3063, 2931, 1604, 1499, 1372, 1253,

1167, 1036, 908, 852, 731, 695 cm⁻¹; HR-MS (ESI+) m/z calculated

for [C₃₇H₃₈NO₆]⁺= [M + NH₄]⁺592.2694, found 592.2687.

(CDCl₃, 400 MHz) δ = 7.57 (d, 1H, J = 8.3 Hz), 7.47 (d, 1H, J = 8.3

Hz), 7.27 (d, 1H, J = 8.3 Hz), 7.15 (d, 1H, J = 2.0 Hz), 7.12 (d, 1H,

J = 7.8 Hz), 6.97−6.84 (m, 4H), 6.77 (d, 1H, J = 2.4 Hz), 6.71 (dd,

1H, J = 8.3 and 2.4 Hz), 6.57 (d, 1H, J = 2.4 Hz), 6.51 (dd, 1H, J = 8.8

and 2.4 Hz), 3.82 (s, 3H), 3.77 (s, 3H), 3.71 (s, 3H), 1.98 (s, 3H)

ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 160.2 (C_q), 159.2 (C_q), 158.5

(C_q), 153.3 (C_q), 146.4 (C_q), 137.8 (C_q), 128.9 (CH), 123.1 (CH),

123.0 (CH), 122.7 (C_q), 120.5 (CH), 119.0 (CH), 115.9 (C_q), 112.8

(CH), 112.4 (CH), 111.9 (CH), 109.6 (CH), 108.3 (CH), 103.1

(CH), 81.3 (C_q), 55.7 (CH₃), 55.4 (CH₃), 55.3 (CH₃), 55.1 (CH₃),

28.2 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3038, 2937,

2830, 1605, 1489, 1375, 1253, 1194, 1036, 907, 852, 787, 695 cm⁻¹;

HR-MS (ESI+) m/z calculated for [C₂₃H₂₃O₄]⁺= [M + H]⁺363.1591,

found 363.1577.

6-Methyl-6-thien-2-yl-6H-benzo[c]chromene (5n). This com-

pound was prepared according to the GP-6 and isolated as yellow col-

or viscous liquid 77% yield (107 mg), byproduct ketone 7c 69% yield

2,3,8,9-Tetramethoxy-6-(3-methoxyphenyl)-6-methyl-6H-

benzo[c]chromene (5j). This compound was prepared according

to the GP-6 and isolated as brown color viscous liquid 77% yield

1

(21 mg) as black color viscous liquid: H NMR (CDCl₃, 400 MHz)

1

(82 mg), byproduct ketone 7b 58% yield (21 mg) colorless oil: H

δ = 7.77 (d, 1H, J = 7.8 Hz), 7.70 (dd, 1H, J = 7.8 and 1.5 Hz), 7.42

(ddd, 1H, J = 8.8, 7.3, and 1.5 Hz), 7.33 (ddd, 1H, J = 8.8, 7.8, and

1.5 Hz), 7.27 (dd, 1H, J = 7.3 and 1.5 Hz), 7.23−7.14 (m, 2H), 6.99

(dd, 2H, J = 7.3 and 7.3 Hz), 6.78 (dd, 1H, J = 4.9 and 3.4 Hz), 6.67

(dd, 1H, J = 3.4 and 1.5 Hz), 2.13 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 152.4 (C_q), 149.6 (C_q), 137.4 (C_q), 129.5 (CH), 129.2

(C_q), 128.5 (CH), 127.8 (CH), 125.9 (CH), 125.8 (CH), 125.6 (CH),

124.8 (CH), 122.9 (CH), 122.5 (C_q), 122.3 (CH), 122.0 (CH), 118.3

(CH), 79.0 (C_q), 29.0 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹)

ν_max= 3062, 2980, 1591, 1480, 1431, 1245, 1136, 1066, 915, 824, 748,

647 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₁₈H₁₃S]⁺= [(M + H)

− H₂O]⁺261.0732, found 261.0735.

NMR (CDCl₃, 400 MHz) δ = 7.13 (dd, 1H, J = 8.2 and 8.2 Hz), 7.07

(s, 1H), 7.00 (s, 1H), 6.90−6.82 (m, 2H), 6.75 (s, 1H), 6.70 (dd, 1H,

J = 8.2 and 2.5 Hz), 6.58 (s, 1H), 3.97 (s, 3H), 3.87 (s, 6H), 3.84 (s,

3H), 3.70 (s, 3H), 1.98 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz)

δ = 159.1 (C_q), 149.8 (C_q), 149.0 (C_q), 148.0 (C_q), 146.9 (2 × C_q),

144.0 (C_q), 129.0 (C_q), 128.8 (CH), 122.9 (C_q), 118.9 (CH), 114.5

(C_q), 112.8 (CH), 112.2 (CH), 109.2 (CH), 105.9 (CH), 105.1 (CH),

102.1 (CH), 80.8 (C_q), 56.6 (CH₃), 56.1 (2 × CH₃), 55.9 (CH₃), 55.0

(CH₃) 28.3 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

2932, 2834, 1605, 1498, 1371, 1252, 1138, 1036, 908, 852, 730,

695 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₂₅H₂₇O₆]⁺= [M +

H]⁺423.1802, found 423.1786.

3,8-Dimethoxy-6-methyl-6-thien-2-yl-6H-benzo[c]chromene

(5o). This compound was prepared according to the GP-6 and isolated

as brown color semisolid 69% yield (59 mg), byproduct ketone 7c

70% yield (22 mg) black color viscous liquid: ¹H NMR (CDCl3,

400 MHz) δ = 7.22−7.11 (m, 3H), 7.09 (d, 1H, J = 2.4 Hz), 7.07 (d,

1H, J = 2.4 Hz), 6.96 (dd, 1H, J = 8.3 and 2.9 Hz), 6.90 (dd, 1H, J =

8.8 and 2.9 Hz), 6.87 (dd, 1H, J = 4.9 and 3.9 Hz), 6.68 (d, 1H, J =

3.9 Hz), 3.87 (s, 3H), 3.84 (s, 3H), 1.96 (s, 3H) ppm.¹³C NMR

(CDCl₃, 100 MHz) δ = 159.2 (C_q), 158.7 (C_q), 142.6 (C_q), 141.6

(C_q), 134.5 (C_q), 133.1 (CH), 132.4 (C_q), 132.1 (CH), 131.5 (C_q),

127.0 (CH), 126.9 (CH), 126.1 (CH), 116.9 (CH), 115.3 (CH),

113.3 (CH), 112.7 (CH), 55.4 (2 × CH₃), 29.4 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 3063, 2980, 1590, 1484, 1437, 1248,

1139, 1065, 918, 825, 746, 647 cm⁻¹; HR-MS (ESI+) m/z calculated

for [C₂₀H₁₇O₂S]⁺= [(M + H) − H₂O)]⁺321.0944, found 321.0940.

2,3,8,9-Tetramethoxy-6-methyl-6-thien-2-yl-6H-benzo[c]-

chromene (5p). This compound was prepared according to the GP-6

and isolated as yellow color solid 62% yield (62 mg): mp 126−128 °C,

byproduct ketone 7c 55% yield (17 mg) black color viscous liquid; ¹H

NMR (CDCl3, 400 MHz) δ = 7.18 (dd, 1H, J = 4.9 and 1.0 Hz), 7.09

(s, 1H), 7.05 (s, 1H), 6.80 (dd, 1H, J = 4.9 and 3.9 Hz), 6.73 (s, 1H),

6.69 (dd, 1H, J = 3.4 and 1.5 Hz), 6.54 (s, 1H), 3.99 (s, 3H), 3.90 (s,

3H), 3.86 (s, 3H), 3.84 (s, 3H), 2.09 (s, 3H) ppm; ¹³C NMR (CDCl3,

100 MHz) δ = 149.9 (2 × C_q), 149.3 (C_q), 148.2 (C_q), 146.5 (C_q),

144.3 (C_q), 129.1 (C_q), 125.9 (CH), 125.6 (2 × CH), 122.7 (C_q),

114.2 (C_q), 108.4 (CH), 105.9 (CH), 104.9 (CH), 102.2 (CH), 78.9

(C_q), 56.7 (CH₃), 56.1 (2 × CH₃), 55.9 (CH₃), 28.8 (CH₃) ppm;

IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3062, 2982, 1592, 1481,

1433, 1245, 1137, 1067, 918, 824, 745, 648 cm⁻¹; HR-MS (ESI+)

6-(3-Methoxyphenyl)-6-methyl-6H-[1,3]benzodioxolo[5,6-

c][1,3]dioxolo[4,5-g]chromene (5k). This compound was prepared

according to the GP-6 and isolated as yellow color semisolid 87% yield

1

(86 mg), byproduct ketone 7b 57% yield (21 mg) colorless oil: H

NMR (CDCl₃, 400 MHz) δ = 7.13 (dd, 1H, J = 8.3 and 8.1 Hz), 7.01

(s, 1H), 6.91 (s, 1H), 6.87−6.80 (m, 2H), 6.76 (s, 1H), 6.71 (ddd, 1H,

J = 8.3, 2.4, and 0.9 Hz), 6.54 (s, 1H), 5.99 (s, 2H), 5.88 (d, 1H, J =

1.4 Hz), 5.86 (d, 1H, J = 1.4 Hz), 3.72 (s, 3H), 1.94 (s, 3H) ppm; ¹³C

NMR (CDCl₃, 100 MHz) δ = 159.2 (C_q), 147.7 (C_q), 147.6 (2 × C_q),

146.7 (C_q), 146.6 (C_q), 142.7 (C_q), 130.2 (C_q), 128.8 (CH), 124.6

(C_q), 118.9 (CH), 116.0 (C_q), 112.9 (CH), 112.2 (CH), 106.2 (CH),

102.5 (CH), 102.0 (CH), 101.2 (CH₂), 101.0 (CH₂), 100.0 (CH),

81.1 (C_q), 55.1 (CH₃), 28.4 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3030, 2932, 2835, 1604, 1499, 1371, 1253, 1194,

1036, 908, 852, 777, 695 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₃H₁₈NaO₆]⁺= [M + Na]⁺413.0996, found 413.0977.

3,8-Bis(benzyloxy)-2,9-dimethoxy-6-(3-methoxyphenyl)-6-

methyl-6H-benzo[c]chromene (5l). This compound was prepared

according to the GP-6 and isolated as red color viscous liquid 72%

yield (104 mg), byproduct ketone 7b 75% yield (28 mg,) colorless oil:

¹H NMR (CDCl₃, 400 MHz) δ = 7.47−7.27 (m, 11H), 7.07 (s, 1H),

7.03 (s, 1H), 6.78 (dd, 1H, J = 2.0 and 2.0 Hz), 6.73 (s, 1H), 6.68 (dd,

2H, J = 8.3 and 2.0 Hz), 6.64 (d, 1H, J = 8.3 Hz), 6.59 (s, 1H), 5.15 (d,

2H, J = 2.0 Hz), 5.20−5.05 (m, 4H), 3.98 (s, 3H), 3.87 (s, 3H), 3.64

(s, 3H), 1.83 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 159.1

(C_q), 149.9 (C_q), 149.2 (C_q), 147.0 (C_q), 146.8 (2 × C_q), 144.7 (C_q),

136.9 (C_q), 136.8 (C_q), 129.2 (C_q), 128.8 (CH), 128.5 (4 × CH),

127.9 (CH), 127.8 (CH), 127.5 (2 × CH), 127.3 (2 × CH), 123.4

(C_q), 118.8 (CH), 115.1 (C_q), 112.9 (CH), 112.4 (2 × CH), 107.0

2071

dx.doi.org/10.1021/jo402763m | J. Org. Chem. 2014, 79, 2059−2074

The Journal of Organic Chemistry

Article

m/z calculated for [C₂₂H₂₂SO₅]⁺= [(M + Na)]⁺421.1080, found

421.1064.

103.1 (CH), 80.1 (C_q), 55.4 (CH₃), 55.3 (CH₃), 45.6 (CH₂), 24.5

(CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 3002, 2920,

2851, 1580, 1440, 1361, 1236, 1149, 1057, 924, 755, 693 cm⁻¹; HR-

MS (ESI+) m/z calculated for [C₂₃H₂₂O₃]⁺= [(M + H)]⁺347.1642,

found 347.1634.

1-Methyl-3-methyleneindan-1-ol (13a) and 1,3-Dimethyl-

1H-inden-1-ol (13a′). This compound was prepared according to

the GP-6 and isolated as colorless viscous liquid 73% yield (58 mg):

¹H NMR (CDCl₃400 MHz) (for major isomer) δ = 7.42 (dd, 1H, J =

4.9 and 3.9 Hz), 7.35 (dd, 1H, J = 5.5 and 3.3 Hz), 7.28−7.21 (m,

2H), 5.44 (t, 1H, J = 2.3 and 2.3 Hz), 5.01 (s, 1H), 2.85 (q, 2H, J =

16.4 and 7.5 Hz), 1.84 (br. s, 1H), 1.51 (s, 1H) ppm; ¹³C NMR

(CDCl₃, 100 MHz) δ = 150.4 (C_q), 145.9 (C_q), 142.7 (CH), 129.0

(CH), 128.6 (CH), 122.9 (CH), 120.6 (CH), 104.4 (CH₂), 78.7 (C_q),

49.4 (CH₂), 28.1 (CH₃) ppm; ¹H NMR (CDCl₃400 MHz) (for

minor isomer) δ = 7.31 (d, 1H, J = 7.6 Hz), 7.18 (d, 1H, J = 8.4 Hz),

7.13 (dd, 1H, J = 7.4 and 7.3 Hz), 7.07 (d, 1H, J = 7.6 Hz), 5.90 (s,

1H), 1.98 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 143.0 (C_q),

142.7 (C_q), 139.4 (C_q), 137.7 (C_q), 128.3 (CH), 126.3 (CH), 121.2

(CH), 119.2 (CH), 78.7 (C_q), 23.8 (CH₃), 12.7 (CH₃) ppm; IR

(MIR-ATR, 4000−600 cm⁻¹) ν_max= 3062, 2923, 2855, 1591, 1434,

1373, 1240, 1150, 1063, 924, 754, 699 cm⁻¹; HR-MS (ESI+) m/z

calculated for [C₁₁H₁₂O]⁺= [(M + Na)]⁺183.0780, found 183.0787.

3-Methylene-1-phenylindan-1-ol (13b) and 3-Methyl-1-phenyl-

1H-inden-1-ol (13b′). This compound was prepared according to

the GP-6 and isolated as colorless viscous liquid 70% yield (78 mg):

¹H NMR (CDCl₃400 MHz) (for major isomer) δ = 7.56 (d, 1H, J =

6,6-Diphenyl-6H-benzo[c]chromene (5q). This compound was

prepared according to the GP-6 and isolated as color less viscous liquid

73% yield (60 mg), byproduct ketone 7d 58% yield (26 mg) white

1

crystals: H NMR (CDCl3, 400 MHz) δ = 7.77 (d, 1H, J = 7.8 Hz),

7.65 (dd, 1H, J = 7.8 and 1.5 Hz), 7.40 (ddd, 1H, J = 8.8, 7.8, and

1.5 Hz), 7.34−7.12 (m, 12H), 7.04 (dd, 1H, J = 8.3 and 1.5 Hz), 6.94

(ddd, 1H, J = 8.8, 7.8, and 1.5 Hz), 6.71 (dd, 1H, J = 7.3 and 1.0 Hz)

ppm.¹³C NMR (CDCl3, 100 MHz) δ = 152.8 (C_q), 143.6 (2 × C_q),

137.1 (C_q), 130.1 (C_q), 129.5 (CH), 128.9 (5 × CH), 128.3 (2 ×

CH), 127.7 (5 × CH), 127.0 (CH), 123.0 (C_q), 122.9 (CH), 122.3

(CH), 121.9 (CH), 118.6 (CH), 86.6 (C_q) ppm; IR (MIR-ATR,

4000−600 cm⁻¹) ν_max= 3060, 3032, 1591, 1437, 1302, 1234, 1038,

988, 757, 699 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₂₅H₁₈O]⁺=

[M + H]⁺334.1352, found 334.1355.

3,8-Dimethoxy-6,6-diphenyl-6H-benzo[c]chromene (5r). This

compound was prepared according to the GP-6 and isolated as white

color solid 73% yield (71 mg): mp 118−120 °C, byproduct ketone 7d

1

53% yield (24 mg) white crystals; H NMR (CDCl3, 400 MHz) δ =

7.61 (d, 1H, J = 8.8 Hz), 7.47 (d, 1H, J = 8.8 Hz), 7.35−7.17 (m,

10H), 6.92 (dd, 1H, J = 8.3 and 2.4 Hz), 6.59 (d, 1H, J = 2.4 Hz), 6.49

(dd, 1H, J = 8.8 and 2.4 Hz), 6.25 (d, 1H, J = 2.4 Hz), 3.76 (s, 3H),

3.69 (s, 3H) ppm.¹³C NMR (CDCl3, 100 MHz) δ = 160.2 (C_q), 158.0

(C_q), 153.3 (C_q), 143.5 (2 × C_q), 137.4 (C_q), 128.8 (5 × CH), 127.8

(CH), 127.7 (4 × CH), 123.5 (C_q), 123.1 (CH), 122.9 (CH), 116.1

(C_q), 114.7 (CH), 113.1 (CH), 108.4 (CH), 103.5 (CH), 86.9 (C_q),

55.3 (CH₃), 55.2 (CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max

=

7.5 Hz), 7.37 (d, 2H, J = 8.0 Hz), 7.33−7.20 (m, 5H), 7.13 (d, 1H, J =

7.5 Hz), 5.59 (s, 1H, J = 2.3 and 2.3 Hz), 5.12 (s, 1H), 3.19 (q, 2H, J =

19.7 and 6.7 Hz), 2.30 (br. s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz)

δ = 150.3 (C_q), 146.5 (C_q), 146.1 (C_q), 140.2 (C_q), 129.3 (CH), 128.8

(CH), 128.1 (2 × CH), 126.8 (CH), 125.2 (2 × CH), 124.6 (CH),

3060, 2935, 2834, 1617, 1484, 1273, 1157, 1048, 1008, 907, 834, 727,

699 cm⁻¹; HR-MS (ESI+) m/z calculated for [C₂₇H₂₂O₃]⁺= [(M +

H)]⁺395.1642, found 395.1635.

2,3,8,9-Tetramethoxy-6,6-diphenyl-6H-benzo[c]chromene

(5s). This compound was prepared according to the GP-6 and isolated

as brown color semisolid 78% yield (88 mg), byproduct ketone 7d

1

120.6 (CH), 104.8 (CH₂), 82.5 (C_q), 51.8 (CH₂) ppm; H NMR

(CDCl₃400 MHz) (for minor isomer) δ = 7.41 (dd, 1H, J = 7.6 Hz),

7.33 (d, 1H, J = 7.4 Hz), 7.30−7.21 (m, 5H), 7.20−7.15 (m, 2H), 6.07

(s, 1H), 2.10 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 150.5

(C_q), 148.0 (C_q), 143.7 (C_q), 140.0 (C_q), 137.9 (CH), 128.4 (CH),

128.2 (2 × CH), 127.3 (CH), 126.7 (CH), 125.8 (2 × CH), 122.8

(CH), 119.5 (CH), 84.8 (C_q), 12.8 (CH₃) ppm; IR (MIR-ATR,

4000−600 cm⁻¹) ν_max= 3042, 2913, 2845, 1565, 1443, 1337, 1220,

1105, 1066, 923, 765, 656 cm⁻¹.

1

71% yield (32 mg) white crystals: H NMR (CDCl3, 400 MHz) δ =

7.36−7.16 (m, 10H), 7.10 (s, 1H), 7.00 (s, 1H), 6.60 (s, 1H), 6.18 (s,

1H), 3.98 (s, 3H), 3.86 (s, 3H), 3.82 (s, 3H), 3.60 (s, 3H) ppm.¹³C

NMR (CDCl3, 100 MHz) δ = 149.9 (C_q), 149.1 (C_q), 147.5 (C_q),

146.9 (C_q), 144.2 (C_q), 143.8 (2 × C_q), 129.6 (C_q), 128.7 (5 × CH),

127.7 (5 × CH), 123.6 (C_q), 114.7 (C_q), 112.0 (CH), 105.8 (CH),

104.8 (CH), 102.5 (CH), 86.6 (C_q), 56.6 (CH₃), 56.1 (CH₃), 55.9 (2 ×

CH₃) ppm; IR (MIR-ATR, 4000−600 cm⁻¹) ν_max= 2930, 2834, 1502,

1440, 1259, 1197, 1119, 1014, 910, 860, 729, 700 cm⁻¹; HR-MS (ESI+)

m/z calculated for [C₂₉H₂₆O₅]⁺= [M]⁺454.1775, found 454.1772.

6-Benzyl-6-methyl-6H-benzo[c]chromene (5u). This com-

pound was prepared according to the GP-6 and isolated as pale

6-Methoxy-1-methyl-3-methyleneindan-1-ol (13c) and 6-

methoxy-1,3-dimethyl-1H-inden-1-ol (13c′). This compound

was prepared according to the GP-6 and isolated as colorless viscous

1

liquid 78% yield (69 mg): H NMR (CDCl₃400 MHz) (for major

isomer) δ = 7.39 (d, 1H, J = 8.4 Hz), 6.91 (d, 1H, J = 2.3 Hz), 6.86

(dd, 1H, J = 8.4 and 2.4 Hz), 5.34 (t, 1H, J = 2.3 and 2.1 Hz), 4.95 (t,

1H, J = 1.9 and 1.8 Hz), 3.82 (s, 3H), 2.91 (q, 2H, J = 16.4 and 11.0

Hz), 1.56 (s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 160.8 (C_q),

152.1 (C_q), 145.3 (C_q), 135.8 (C_q), 121.8 (CH), 115.9 (CH), 106.7

(CH), 102.1 (CH₂), 78.6 (C_q), 55.5 (CH₃), 49.8 (CH₂), 28.0 (CH₃)

1

yellow color viscous liquid 67% yield (48 mg): H NMR (CDCl₃,

400 MHz) δ = 7.76 (ddd, 2H, J = 7.3, 7.3, and 1.5 Hz), 7.36 (ddd, 1H,

J = 8.3, 7.3, and 1.0 Hz), 7.29 (dd, 1H, J = 8.3 and 2.0 Hz), 7.24−7.14

(m, 4H), 7.05 (dd, 1H, J = 7.8 and 1.5 Hz), 7.02 (d, 2H, J = 7.3 Hz),

7.00−6.94 (m, 2H), 3.15 (d, 1H, J = 13.2 Hz), 2.87 (d, 1H, J =

13.2 Hz), 1.67 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 152.4

(C_q), 138.0 (C_q), 136.6 (C_q), 130.7 (2 × CH), 129.6 (CH), 128.7

(C_q), 127.8 (CH), 127.7 (2 × CH), 127.6 (CH), 126.3 (CH), 124.5

(CH), 122.9 (CH), 122.3 (C_q), 122.0 (CH), 121.6 (CH), 118.2 (CH),

79.7 (C_q), 45.6 (CH₂), 24.5 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3028, 2923, 2851, 1592, 1484, 1437, 1377, 1250,

1154, 1087, 938, 756, 702 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₂₁H₁₈O]⁺= [M + H]⁺287.1430, found 287.1436.

6-Benzyl-3,8-dimethoxy-6-methyl-6H-benzo[c]chromene

(5v). This compound was prepared according to the GP-6 and isolated

as pale yellow color viscous liquid 69% yield (60 mg): ¹H NMR

(CDCl₃, 400 MHz) δ = 7.59 (d, 2H, J = 8.8 Hz), 7.24−7.15 (m, 3H),

7.00 (dd, 2H, J = 7.8 and 2.4 Hz), 7.87 (dd, 1H, J = 8.8 and 2.9 Hz),

6.61 (dd, 1H, J = 8.3 and 2.4 Hz), 6.55 (d, 1H, J = 2.4 Hz), 6.51 (d,

1H, J = 2.4 Hz), 3.83 (s, 3H), 3.75 (s, 3H), 3.13 (d, 1H, J = 13.7 Hz),

2.85 (d, 1H, J = 13.7 Hz), 1.64 (s, 3H) ppm; ¹³C NMR (CDCl₃, 100

MHz) δ = 160.4 (C_q), 158.5 (C_q), 152.8 (C_q), 138.4 (C_q), 136.6 (C_q),

130.8 (2 × CH), 127.7 (2 × CH), 126.4 (CH), 123.1 (CH), 122.6

(CH), 121.9 (C_q), 115.4 (C_q), 113.1 (CH), 110.4 (CH), 108.2 (CH),

1

ppm; H NMR (CDCl₃400 MHz) (for minor isomer) δ = 7.02 (d,

1H, J = 8.2 Hz), 6.98 (d, 1H, J = 2.4 Hz), 6.76 (dd, 1H, J = 8.2 and 2.4

Hz), 5.86 (d, 1H, J = 1.5 Hz), 2.01 (d, 3H, J = 1.5 Hz), 1.54 (s, 3H)

ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 159.1 (C_q), 138.7 (C_q), 135.8

(C_q), 132.2 (C_q), 119.8 (CH), 112.6 (CH), 108.5 (CH), 80.8 (C_q),

55.6 (CH₃) 24.0 (CH₃), 12.8 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3067, 2923, 2851, 1582, 1448, 1361, 1241, 1150,

1062, 922, 758, 699 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₂H₁₄O₂]⁺= [(M + Na)]⁺213.0893, found 213.0886.

6-Methoxy-3-methylene-1-phenylindan-1-ol (13d) and 6-

Methoxy-3-methyl-1-phenyl-1H-inden-1-ol (13d′). This com-

pound was prepared according to the GP-6 and isolated as colorless

1

viscous liquid 74% yield (93 mg): H NMR (CDCl₃400 MHz) (for

major isomer) δ = 7.49 (d, 1H, J = 8.3 Hz), 7.38 (d, 2H, J = 6.8 Hz),

7.31 (dd, 2H, J = 7.8 and 6.8 Hz), 7.24 (d, 1H, J = 5.8 Hz), 6.90 (dd,

1H, J = 8.3 and 2.4 Hz), 6.63 (d, 1H, J = 2.4 Hz), 5.43 (dd, 1H, J = 2.4

and 2.0 Hz), 5.00 (dd, 1H, J = 2.0 and 1.5 Hz), 3.73 (s, 3H), 3.33−

3.08 (m, 2H), 2.32 (br. s, 1H) ppm; ¹³C NMR (CDCl₃, 100 MHz)

δ = 160.9 (C_q), 151.9 (C_q), 146.4 (C_q), 145.5 (C_q), 133.2 (C_q), 128.1

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(2 × CH), 126.9 (CH), 125.1 (2 × CH), 121.8 (CH), 116.5 (CH),

108.0 (CH), 102.4 (CH₂), 82.5 (C_q), 55.4 (CH₃), 52.4 (CH₂) ppm;

¹H NMR (CDCl₃400 MHz) (for minor isomer) δ = 7.43 (d, 1H, J =

(2) For reviews on C−H activations, see: (a) Shibasaki, M.; Vogl, E.

M.; Ohshima, T. Adv. Synth. Catal. 2004, 346, 1533−1552. (b) Souza,

D. M. D.; Muller, T. J. J. Chem. Soc. Rev. 2007, 36, 1095−1108.

̈

(c) Minatti, A.; Muniz, K. Chem. Soc. Rev. 2007, 36, 1142−1152.

6.8 Hz), 7.38 (d, 2H, J = 6.8 Hz), 7.31 (dd, 1H, J = 7.8 and 6.8 Hz),

7.24 (d, 1H, J = 5.8 Hz), 7.09 (d, 1H, J = 7.8 Hz), 6.80 (dd, 1H, J = 3.9

and 2.0 Hz), 6.78 (d, 1H, J = 2.0 Hz), 5.98 (d, 1H, J = 7.8 Hz), 2.10

(d, 3H, J = 2.0 Hz) ppm; ¹³C NMR (CDCl₃, 100 MHz) δ = 160.9

(C_q), 151.9 (C_q), 146.4 (C_q), 145.5 (C_q), 136.1 (C_q), 128.3 (2 × CH),

127.2 (CH), 125.2 (2 × CH), 120.1 (CH), 113.0 (CH), 110.0 (CH),

82.5 (C_q), 55.5 (CH₃), 12.9 (CH₃) ppm; IR (MIR-ATR, 4000−

600 cm⁻¹) ν_max= 3072, 2934, 2845, 1590, 1454, 1345, 1256, 1140,

1054, 943, 756, 645 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₇H₁₆NaO₂]⁺= [(M + Na)]⁺275.1043, found 275.1039.

̃

(d) Catellani, M.; Motti, E.; Della Ca′, N. Acc. Chem. Res. 2008, 41,

1512−1522. (e) Evano, G.; Blanchard, N.; Toumi, M. Chem. Rev.

2008, 108, 3054−3131. (f) Chen, X.; Engle, K. M.; Wang, D.-H.; Yu,

J.-Q. Angew. Chem. 2009, 121, 5196−5217; Angew.Chem. Int. Ed. 2009,

48, 5094−5115. (g) Daugulis, O.; Do, H.-Q.; Shabashov, D. Acc. Chem.

Res. 2009, 42, 1074−1086. (h) Xu, L.-M.; Li, B.-J.; Yang, Z.; Shi, Z.-J.

Chem. Soc. Rev. 2010, 39, 712−733. (i) Lyons, T. W.; Sanford, M. S.

Chem. Rev. 2010, 110, 1147−1169. (j) Bras, J. L.; Muzart, J. Chem. Rev.

2011, 111, 1170−1214. (k) Ackermann, L. Chem. Rev. 2011, 111,

1315−1345.

5,6-Dimethoxy-1-methyl-3-methyleneindan-1-ol (13e) and

5,6-Dimethoxy-1,3-dimethyl-1H-inden-1-ol (13e′). This com-

pound was prepared according to the GP-6 and isolated as colorless

(3) For recent Pd-catalyzed domino transformations, see: (a) Thir-

unavukkarasu, V. S.; Parthasarathy, K.; Cheng, C.-H. Angew. Chem.

2008, 120, 9604−9607; Angew. Chem., Int. Ed. 2008, 47, 9462−9465.

1

viscous liquid 81% yield (89 mg): H NMR (CDCl₃400 MHz) (for

major isomer) δ = 6.92 (s, 1H), 6.89 (s, 1H), 5.31 (dd, 1H, J = 2.4 and

2.0 Hz), 4.95 (dd, 1H, J = 2.0 and 1.5 Hz), 3.91 (s, 3H), 3.90 (s, 3H),

3.05−2.80 (m, 2H), 1.83 (br. s, 1H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 150.8 (C_q), 150.2 (C_q), 145.8 (C_q), 143.1 (C_q), 131.9

(C_q), 104.9 (CH), 102.5 (CH), 101.8 (CH₂), 78.7 (C_q), 56.0 (2 ×

̌

(b) Cvengros, J.; Schutte, J.; Schlorer, N.; Neudorfl, J.; Schmalz, H.-G.

̈

̈ ̈

Angew. Chem. 2009, 121, 6264−6267; Angew.Chem. Int. Ed. 2009, 48,

6148−6151. (c) Hu, Y.; Yu, C.; Ren, D.; Hu, Q.; Zhang, L.; Cheng, D.

Angew. Chem. 2009, 121, 5556−5559; Angew.Chem. Int. Ed. 2009, 48,

5448−5451. (d) Wang, G.-W.; Yuan, T.-T.; Li, D.-D. Angew. Chem.

2011, 123, 1416−1419; Angew. Chem., Int. Ed. 2011, 50, 1380−1383.

(e) Levi, Z. U.; Tilley, T. D. J. Am. Chem. Soc. 2009, 131, 2796−2797.

1

CH₃), 49.8 (CH₂), 28.1 (CH₃) ppm; H NMR (CDCl₃400 MHz)

(for minor isomer) δ = 7.00 (s, 1H), 6.70 (s, 1H), 5.91 (d, 1H, J =

2.0 Hz), 3.87 (s, 3H), 3.85 (s, 3H), 2.03 (d, 3H, J = 1.5 Hz) ppm; ¹³C

NMR (CDCl₃, 100 MHz) δ = 149.2 (C_q), 148.0 (C_q), 142.5 (C_q),

138.5 (C_q), 136.6 (C_q), 133.7 (C_q), 105.7 (CH), 103.6 (CH), 81.0

(C_q), 56.3 (2 × CH₃), 24.0 (CH₃) 12.9 (CH₃) ppm; IR (MIR-ATR,

4000−600 cm⁻¹) ν_max= 3085, 2924, 2835, 1580, 1452, 1325, 1252,

1142, 1044, 942, 751, 642 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₃H₁₇O₃]⁺= [(M + H)]⁺221.1172, found 221.1175.

(f) Tietze, L. F.; Dufert, A.; Lotz, F.; Solter, L.; Oum, K.; Lenzer, T.;

̈

Beck, T.; Herbst-Irmer, R. J. Am. Chem. Soc. 2009, 131, 17879−17884.

(g) Tietze, L. F.; Redert, T.; Bell, H. P.; Hellkamp, S.; Levy, L. M.

Chem.Eur. J. 2008, 14, 2527−2535. (h) Tietze, L. F.; Spiegl, D. A.;

Stecker, F.; Major, J.; Raith, C.; Große, C. Chem.Eur. J. 2008, 14,

8956−8963. (i) Satyanarayana, G.; Maichle-Mossmerzb, C.; Maier, M.

̈

E. Chem. Commun. 2009, 1571−1573. (j) Wang, S.; Xie, K.; Tan, Z.;

An, X.; Zhou, X.; Guo, C.-C.; Peng, Z. Chem. Commun. 2009, 6469−

6471. (k) Zhang, H.-j.; Wei, J.; Zhao, F.; Liang, Y.; Wanga, Z.; Xi, Z.

Chem. Commun. 2010, 46, 7439−7441. (l) Li, R.-J.; Pi, S.-F.; Liang, Y.;

Wang, Z.-Q.; Song, R.-J.; Chen, G.-X.; Li, J.-H. Chem. Commun. 2010,

46, 8183−8185. (m) Chen, X.; Wang, H.; Jin, X.; Feng, J.; Wang, Y.;

Lu, P. Chem. Commun. 2011, 47, 2628−2630. (n) Bryan, C. S.;

Lautens, M. Org. Lett. 2008, 10, 4633−4636. (o) Jana, R.; Chatterjee,

I.; Samanta, S.; Ray, J. K. Org. Lett. 2008, 10, 4795−4797. (p) Luo, Y.;

Pan, X.; Wu, J. Org. Lett. 2011, 13, 1150−1153. (q) Sui, X.; Zhu, R.; Li,

G.; Ma, X.; Gu, Z. J. Am. Chem. Soc. 2013, 135, 9318−9321.

(r) Leibeling, M.; Pawliczek, M.; Kratzert, D.; Stalke, D.; Werz, D. B.

Org. Lett. 2012, 14, 346−349. (s) Lu, Z.; Hu, C.; Guo, J.; Li, J.; Cui, Y.;

Jia, Y. Org. Lett. 2010, 12, 480−483. (t) Tietze, L. F.; Duefert, D. S.;

Clerc, J.; Dipl.-Chem, M. B.; Maaß, C.; Stalke, D. Angew. Chem. 2013,

125, 3273−3276. (u) Hashmi, A. S. K.; Ghanbari, M.; Rudolph, M.;

Rominger, F. Chem.Eur. J. 2012, 18, 8113−8119. (v) Hashmi, A. S.

5,6-Dimethoxy-3-methyl-1-methylene-1H-indene (14e). This

compound was prepared according to the GP-6 and isolated as color-

1

less viscous liquid 86% yield (87 mg): H NMR (CDCl₃400 MHz)

δ = 6.43 (s, 1H), 6.01 (s, 1H), 5.39 (s, 1H), 5.07 (s, 1H), 4.76 (s, 1H),

3.18 (s, 3H), 3.19 (s, 3H), 1.42 (s, 3H) ppm; ¹³C NMR (CDCl₃,

100 MHz) δ = 162.5 (C_q), 149.5 (C_q), 147.5 (C_q), 146.8 (C_q), 142.3

(C_q), 137.8 (C_q), 129.2 (C_q), 124.5 (CH), 110.0 (CH₂), 104.3 (CH),

102.7 (CH), 56.3 (CH₃), 56.1 (CH₃), 13.1 (CH₃) ppm; IR (MIR-

ATR, 4000−600 cm⁻¹) ν_max= 2930, 2861, 1581, 1450, 1380, 1240,

1140, 1022, 926, 770, 689 cm⁻¹; HR-MS (ESI+) m/z calculated for

[C₁₃H₁₅O₂]⁺= [(M + H)]⁺202.1067, found 202.1073.

ASSOCIATED CONTENT

* Supporting Information

■

S

Experimental procedures and characterization for all new

compounds, copies of NMR spectra, and CIF ﬁles for 5b and

5r. This material is available free of charge via the Internet at

http://pubs.acs.org.

K.; Lothschutz, C.; Dopp, R.; Ackermann, M.; Becker, J. D. B.;

̈

Rudolph, M.; Scholz, C.; Rominger, F. Adv. Synth. Catal. 2012, 354,

133−137. (w) Hashmi, A. S. K.; Lothschutz, C.; Dopp, R.; Rudolph,

̈

M.; Ramamurthi, T. D.; Rominger, F. Angew. Chem. 2009, 121, 8392−

8395; Angew. Chem., Int. Ed. 2009, 48, 8243−8246.

AUTHOR INFORMATION

Corresponding Author

*Fax: +91(40) 2301 6032. E-mail: gvsatya@iith.ac.in.

■

(4) For recent Pd-catalyzed transformations on the synthesis of

heterocyclic systems, see: (a) Motti, E.; Faccini, F.; Ferrari, I.;

Catellani, M.; Ferraccioli, R. Org. Lett. 2006, 8, 3967−3970. (b) Furuta,

T.; Kitamura, Y.; Hashimoto, A.; Fujii, S.; Tanaka, K.; Toshiyuki Kan,

T. Org. Lett. 2007, 9, 183−186. (c) Maestri, G.; Larraufie, M.-H.;

Notes

The authors declare no competing ﬁnancial interest.

ACKNOWLEDGMENTS

Derat, E.; Ollivier, C.; Fensterbank, L.; Lacote, E.; Malacria, M. Org.

̂

■

Lett. 2010, 12, 5692−5695. (d) Zhengneng, J.; Jiashou, W.;

Chuanfeng, W.; Guoliang, D.; Shiyong, L.; Jianmei, L.; Huajiang, J.

Mol. Biomol. Spectrosc. 2014, 117, 527−534. (e) Sharma, S.; Kim, A.;

Park, J.; Kim, M.; Kwak, J. H.; Jung, Y. H.; Park, J. S.; Kim, I. S. Org.

Biomol. Chem. 2013, 11, 7869−7876. (f) Ahmed, A.; Ghosh, M.;

Sarkar, P.; Ray, J. K. Tetrahedron Lett. 2013, 54, 6691−6694. (g) Li, S.;

Ye, J.; Yuan, W.; Ma, S. Tetrahedron 2013, 69, 10450−10456. (h) Guo,

H.-M.; Mao, R.-Z.; Wang, Q.-T.; Niu, H.-Y.; Xie, M.-S.; Qu, G.-R. Org.

Lett. 2013, 15, 5460−5463. (i) Yang, Q.; Chai, H.; Liu, T.; Yu, Z.

Tetrahedron Lett. 2013, 54, 6485−6489. (j) Liu, Q.; Zhang, Y. -A.; Xu,

P.; Jia, Y. J. Org. Chem. 2013, 78, 10885−10893. (k) Wang, Z.; Xing,

Financial support by the Council of Scientiﬁc and Industrial

Research [(CSIR), 02(0018)/11/EMR-II], New Delhi, is

gratefully acknowledged. L.M. thank the CSIR of India, for

the award of research fellowship.

REFERENCES

■

(1) For reviews on domino reactions, see: (a) Tietze, L. F. Chem. Rev.

1996, 96, 115−136. (b) Pellissier, H. Chem. Rev. 2013, 113, 442−524.

(c) Shiri, M. Chem. Rev. 2012, 112, 3508−3549. (d) Zeng, X. Chem.

Rev. 2013, 113, 6864−6900.

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The Journal of Organic Chemistry

Article

X.; Xue, L.; Gao, F.; Fang, Ling. Org. Biomol. Chem. 2013, 11, 7334−

7341.

(5) Chow, H.-F.; Wan, C.-W.; Low, K.-H.; Yeung, Y.-Y. J. Org. Chem.

(18) Oestreich, M.; Sempere-Culler, F.; Machotta, A. B. Angew.

Chem. 2005, 117, 7793−7797; Angew. Chem., Int. Ed. 2005, 44, 149−

152.

(19) Cardenas, D. J.; Martín-Matute, B.; Echavarren, A. M. J. Am.

Chem. Soc. 2006, 128, 5033−5040.

2001, 66, 1910−1913.

(6) (a) Terao, Y.; Wakui, H.; Satoh, T.; Miura, M.; Nomura, M. J.

Am. Chem. Soc. 2001, 123, 10407−10408. (b) Terao, Y.; Wakui, H.;

Nomoto, M.; Satoh, T.; Miura, M.; Nomura, M. J. Org. Chem. 2003,

68, 5236−5243.

(20) For reviews of intermediate palladium species with higher

oxidation states, see: (a) Muniz, K. Angew. Chem. 2009, 121, 9576−

̃

9588; Angew. Chem., Int. Ed. 2009, 48, 9412−9423. (b) Desai, L. V.;

Malik, H. A.; Sanford, M. S. Org. Lett. 2006, 8, 1141−1144. (c) Xu, L.-

M.; Li, B.-J.; Yang, Z.; Shi, Z.-J. Chem. Soc. Rev. 2010, 39, 712−733.

(d) Canty, A. J. Platinum Met. Rev. 1993, 37, 2−7. (e) Powers, D. C.;

Xiao, D. Y.; Geibel, M. A. L.; Ritter, T. J. Am. Chem. Soc. 2010, 132,

14530−14536. (f) Sehnal, P.; Taylor, R. J. K.; Fairlamb, I. J. S. Chem.

Soc. Rev. 2010, 110, 824−889. (g) Wu, X-F; Neumann, H.; Beller, M.

Chem. Soc. Rev. 2013, 113, 1−35. (h) Zhang, H.; Lei, A. Dalton Trans.

(7) (a) Harayama, H.; Kuroki, T.; Kimura, M.; Tanaka, S.; Tamaru,

Y. Angew. Chem. 1997, 109, 2449−2451; Angew. Chem., Int. Ed. 1997,

36, 2352−2354. (b) Takao, K.; Nanamiya, R.; Fukushima, Y.; Namba,

A.; Yoshida, K.; Tadano, K. Org. Lett. 2013, 15, 5582−5585.

(c) Kapadia, N.; Harding, W. Tetrahedron 2013, 69, 8914−8920.

(d) Liu, Y.; Wang, H.; Wan, J. Asian J. Org. Chem. 2013, 2, 374−386.

(e) Goel, A.; Taneja, G.; Raghuvanshi, A.; Kantb, R.; Maulik, P. R. Org.

Biomol. Chem. 2013, 11, 5239−5253. (f) Vandekerckhove, S.; Moor, S.

D.; Segers, D.; Kock, C.; Smith, P. J.; Chibale, K.; Kimpe, N. D.;

D’hooghe, M. Med. Chem. Commun. 2013, 4, 724−730.

(8) Arylative ring-opening of cyclobutanols: (a) Larock, R. C.; Reddy,

C. K. Org. Lett. 2000, 2, 3325−3327. (b) Nishimura, T.; Ohe, K.;

Uemura, S. J. Org. Chem. 2001, 66, 1455−1465. (c) Nishimura, T.;

Uemura, S. J. Am. Chem. Soc. 2000, 122, 12049−12050. (d) Nishimura,

T.; Uemura, S. J. Am. Chem. Soc. 1999, 121, 11010−11011.

(e) Chtchemelinine, A.; Rosa, D.; Orellana, A. J. Org. Chem. 2011,

76, 9157−9162. (f) Ethirajan, M.; Oh, H.-S.; Cha, J. K. Org. Lett. 2007,

9, 2693−2696. (g) Schweinitz, A.; Chtchemelinine, A.; Orellana, A.

Org. Lett. 2011, 13, 232−235.

2011, 40, 8745−8754. (i) Fortuno, C.; Martín, A. Inorg. Chem. 2013,

̃

52, 5493−5506. (j) Alberico, D.; Scott, M. E.; Lautens, M. Chem. Rev.

2007, 107, 174−238.

(21) The possible dehydration products 14 have been mentioned

irrespective of whether that particular compound is generated in each

and every entry.

(9) (a) Park, S.-B.; Cha, J. K. Org. Lett. 2000, 2, 147−149.

(b) Okumoto, H.; Jinnai, T.; Shimizu, H.; Harada, Y.; Mishima, H.;

Suzuki, A. Synlett 2000, 629−630.

(10) Waibel, M.; Cramer, N. Angew. Chem. 2009, 121, 4557−4560;

Angew. Chem., Int. Ed. 2010, 49, 4455−4458.

(11) (a) Niwa, T.; Yorimitsu, H.; Oshima, K. Angew. Chem. 2007,

119, 2697−2699; Angew. Chem., Int. Ed. 2007, 46, 2643−2645.

(b) Hayashi, S.; Hirano, K.; Yorimitsu, H.; Oshima, K. J. Am. Chem.

Soc. 2006, 128, 2210−2211.

(12) (a) Reddy, A. G. K.; Krishna, J.; Satyanarayana, G. Synlett 2011,

1756−1760. (b) Krishna, J.; Reddy, A. G. K.; Mahendar, L.; Ramulu,

B. V.; Satyanarayana, G. Synlett 2012, 23, 375−380. (c) Reddy, A. G.

K.; Satyanarayana, G. Tetrahedron 2012, 68, 8003−8010. (d) Reddy,

A. G. K.; Krishna, J.; Satyanarayana, G. Tetrahedron Lett. 2012, 53,

5635−5640. (e) Krishna, J.; Reddy, A. G. K.; Satyanarayana, G. Synlett

2013, 24, 967−972. (f) Reddy, A. G. K.; Krishna, J.; Satyanarayana, G.

Tetrahedron 2013, 69, 10098−10107. (g) Suchand, B.; Krishna, J.;

Ramulu, B. V.; Dibyendu, D.; Reddy, A. G. K.; Mahendar, L.;

Satyanarayana, G. Tetrahedron Lett. 2012, 53, 3861−3864. (h) Ramulu,

B. V.; Mahendar, L.; Krishna, J.; Reddy, A. G. K.; Suchand, B.;

Satyanarayana, G. Tetrahedron 2013, 69, 8305−8315. (i) Krishna, J.;

Reddy, A. G. K.; Satyanarayana, G. Tetrahedron Lett. 2014, 55, 861−

864. (j) Krishna, J.; Reddy, A. G. K.; Satyanarayana, G. Synth. Commun.

in press.

(13) Mahendar, L.; Krishna, J.; Reddy, A. G. K.; Ramulu, B. V.;

Satyanarayana, G. Org. Lett. 2012, 14, 628−631.

(14) Motti, E.; Ca’, N. D.; Xu, D.; Piersimoni, A.; Bedogni, E.; Zhou,

Z.-M.; Catellani, M. Org. Lett. 2012, 14, 5792−5795.

(15) Iwasaki, M.; Iino, S.; Nishihara, Y. Org. Lett. 2013, 15, 5326−

5329.

(16) (a) Liang, Y.; Geng, W.; Wei, J.; Ouyang, K.; Xi, Z. Org. Biomol.

Chem. 2012, 10, 1537−1542. (b) Nakao, Y.; Imanaka, H.; Sahoo, A.

K.; Yada, A.; Hiyama. J. Am. Chem. Soc. 2005, 127, 6952−6953.

(17) The reaction of TMS-ether 11a only with the base Cs₂CO₃(2

equiv) in hot DMSO furnished the alcohol 4x:

2074

dx.doi.org/10.1021/jo402763m | J. Org. Chem. 2014, 79, 2059−2074

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Substitution controlled functionalization of ortho -bromobenzylic alcohols via palladium catalysis: Synthesis of chromenes and indenols

DOI: 10.1021/jo402763m

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