Diversity-oriented synthesis of functionalized diaryl sulfones by regioselective [3+3] cyclizations of 1,3-bis(siloxy)buta-1,3-dienes with 2-(arylsulfonyl)-3-ethoxy-2-en-1-ones: Scope and limitations

PAPER

2223

Diversity-Oriented Synthesis of Functionalized Diaryl Sulfones by Regio-

selective [3+3] Cyclizations of 1,3-Bis(siloxy)buta-1,3-dienes with 2-(Aryl-

sulfonyl)-3-ethoxy-2-en-1-ones: Scope and Limitations

S

ynthesis of Functiona

o

lized Diaryl

hS

ulfones anad Shkoor,^aAbdolmajid Riahi,^a,bOlumide Fatunsin,^aHelmut Reinke,^aChristine Fischer,^bPeter Langer*^a,b

a

Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany

b

Leibniz-Institut für Katalyse an der Universität Rostock e.V., Albert Einstein Str. 29a, 18059 Rostock, Germany

E-mail: peter.langer@uni-rostock.de

Received 15 January 2009; revised 27 March 2009

Despite their great synthetic utility, the sulfonations out-

lined above, which all rely on the coupling of two arene

moieties, can suffer from several drawbacks, such as

harsh reaction conditions, low regioselectivity, and nar-

row synthetic scope. In addition, it is important to note

that the synthesis of the required starting materials, func-

tionalized or highly substituted aryl halides or triflates,

can be a difficult and tedious task, due to the low o/p-re-

gioselectivity of electrophilic substitutions, competing

isomerization reactions, and other problems.

Abstract: The formal [3+3] cyclization of 1,3-bis(siloxy)buta-1,3-

dienes with 2-(arylsulfonyl)-3-ethoxy-2-en-1-ones, readily avail-

able by reaction of b-keto sulfones with triethyl orthoformate, al-

lows the synthesis of a variety of functionalized diaryl sulfones with

very good regioselectivity.

Key words: arenes, sulfones, cyclizations, regioselectivity, silyl

enol ethers

A number of pharmacologically active compounds con-

tain a 4-(arylsulfonyl)phenol substructure. The wide

range of pharmacological activities reported include, for

example, antibacterial activity,¹inhibition of phospholip-

idase A₂,²inhibition of catechol O-methyltransferase,³in-

hibition of dihydropteroate synthase of Escherichia coli,⁴

hypolipidemic activity,⁵cytotoxicity against HeLa cells

and the antipicornavirus,⁶neuropeptide Y₁receptor bind-

ing activity,⁷anti-HIV activity,⁸anticholesteremic activi-

ty,⁹binding to human muscarinic M₁and M₂

receptors,^8c,10histamine H₃-receptor antagonistic activi-

ty,¹¹antiprotozoal activity,¹²binding to neuroblastoma

cells,¹³binding to the human cannabinoid CB₁receptor,¹⁴

and inhibition of the main protease of the recombinant

SARS coronavirus.¹⁵

An interesting alternative approach to diaryl sulfones is

based on the application of a ‘building block strategy’.

Examples include the reaction of diethyl 2,4-diaryl-3-(ar-

ylsulfonyl)buta-1,3-diene-1,1-dicarboxylates with mal-

ononitrile,²²6p-electrocyclizations of 1-chloro-3-

(phenylsulfonyl)hexa-1,3,5-trienes,²³[4+2] cycloaddi-

tions of 3H-isobenzofuran-1-one with [1-(phenylsulfo-

nyl)vinyl]trimethylsilanes,²⁴reactions of enamines with

1,2,4-tris(phenylsulfonyl)but-2-ene,²⁵the [4+2] cycload-

dition of Danishefsky’s diene with a sulfonyl-substituted

allene,²⁶the [4+2] cycloaddition of a 1,2-bis(arylsulfo-

nyl)ethene with thiophene-1,1-dioxide,²⁷the cyclization

of a 1-(trimethylsiloxy)buta-1,3-diene with an aryl vinyl

sulfone,²⁸6p-electrocyclizations of phenylsulfonyl-sub-

stituted alkenes,²⁹and the [4+2] cycloaddition of furan

with 1,3-bis(phenylsulfonyl)allene.³⁰

Chan and co-workers were the first to report³¹the [3+3]

cyclization mediated by titanium(IV) chloride³²of 1,3-

bis(trimethylsiloxy)buta-1,3-dienes³³with 3-siloxy-2-en-

1-ones, which allows a convenient synthesis of salicy-

lates. In recent years, this methodology has been applied

to the synthesis of various functionalized arenes.³²Most

of the [3+3] cyclizations of 1,3-bis(trimethylsiloxy)buta-

1,3-dienes mediated by titanium(IV) chloride reported to

date involve the use of 3-siloxy-2-en-1-ones as starting

materials. Although a few regioselective cyclizations

have been reported, these reactions are generally not re-

gioselective, because titanium(IV) chloride mediates the

isomerization (silyl shift) of the 3-siloxy-2-en-1-ones. In

their early work in 1980,³¹Chan and Brownbridge report-

ed an isolated example of a successful and regioselective

cyclization of a 3-alkoxy-2-en-1-one, i.e. 1-ethoxybut-1-

en-3-one. On the basis of this observation, we have re-

cently started a synthetic program directed at regioselec-

tive [3+3] cyclizations of acceptor-substituted 3-alkoxy-

A number of synthetic approaches to diaryl sulfones have

been reported. Classic approaches include, for example,

the oxidation of diaryl sulfides.¹⁶In addition, the Friedel–

Crafts-type acylation of anisole with benzenesulfonyl

chloride has been reported.¹⁷However, this reaction pro-

ceeds with low regioselectivity. The reaction of phenol

with benzenesulfonic acid requires harsh conditions

(240 °C).¹⁸In recent years, transition-metal-mediated

syntheses of diaryl sulfones have been developed. Exam-

ples include the copper(I) iodide/proline mediated reac-

tion of aryl iodides with sodium benzenesulfinate,¹⁹the

Suzuki reaction of 4-methoxybenzeneboronic acid with

benzenesulfonyl chloride,²⁰and the copper(II) acetate cat-

alyzed reaction of 4-methoxybenzeneboronic acid with

sodium benzenesulfinate (in the presence of 1,10-phenan-

throline and oxygen).²¹

SYNTHESIS 2009, No. 13, pp 2223–2235

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Advanced online publication: 12.05.2009

DOI: 10.1055/s-0029-1216801; Art ID: T01109SS

2224

M. Shkoor et al.

PAPER

2-en-1-ones. Our strategy takes advantage of the ready tained when the reaction was carried out in a highly

availability of the required enones by reaction of acceptor- concentrated solution (2 mL per 1.0 mmol of 2a). The sto-

substituted ketones (such as b-keto esters or b-keto sul- ichiometry (2a/3a/TiCl₄= 1.0/1.1/1.1), the temperature

fones) with triethyl orthoformate.

(slow warming from –78 to 20 °C), and the reaction time

also played an important role. The yields decreased when

a different stoichiometry (2a/3a/TiCl₄= 1.0/2.0/1.0, 1.0/

2.0/2.0, or 2.0/1.0/1.0) was used, when the reaction time

was too short (2 h), and when the reaction was carried out

at 0 °C rather than –78 °C. The use of trimethylsilyl tri-

fluoromethanesulfonate, boron trifluoride–diethyl ether,

and tin(IV) chloride resulted in the formation of complex

mixtures.

We recently reported³⁴our preliminary results related to

the [3+3] cyclization of 1,3-bis(siloxy)buta-1,3-dienes

with 2-(arylsulfonyl)-3-ethoxy-2-en-1-ones. These reac-

tions provide a convenient and regioselective access to

functionalized 4-(arylsulfonyl)phenols which are not

readily available by other methods. In contrast to the C–S

coupling reactions outlined above, this method constitutes

a new building block methodology and involves the for-

mation of one of the two arene moieties by formation of

two C–C bonds. This full paper provides a comprehensive

report on the scope of this methodology and a discussion

of the regioselectivity.

TMSO

OTMS

O

OH

TiCl₄, CH₂Cl₂

OMe

3a

–78 to 20 °C

14 h

EtO

O

Me

The 1,3-bis(siloxy)buta-1,3-dienes 3a–m required for the

cyclization were prepared by literature procedures from

the corresponding b-keto esters in two steps.^31,35,362-(Ar-

ylsulfonyl)-3-ethoxy-2-en-1-ones 2a–d were prepared, by

a known procedure,³⁷by reaction of b-keto sulfones 1a–d

with triethyl orthoformate and acetic anhydride

(Scheme 1). b-Keto sulfone 1d was prepared by alkyla-

tion of 1a mediated by lithium diisopropylamide

(Scheme 1). Enone 2e was prepared in 90% yield from

b-keto sulfone 1e (Scheme 2).

+

SO₂Ph

Me

SO₂Ph

4a

2a

H₂O

TiCl₄

O

–

TiCl₄

Me

EtO

O

OMe

OTiCl₃

Me

+

SO₂Ph

O

EtO

O

A

D

i

3a

TMSCl

SO₂Ar

TMSCl

1a–c

2a Ar = Ph, 82%

2b Ar = 4-Tol, 80%

2c Ar = 4-ClC₆H₄, 87%

O

TMSO

OMe

ii

TMSO

EtO

OMe

TiCl₃

TMSCl

TiCl₄

O

EtO

O

Me

i

Me

SO₂Ph

TMSOEt

SO₂Ph

SO₂Ar

B

C

1d Ar = Ph, 41%

2d Ar = Ph, 80%

Scheme 3 Possible mechanism of the formation of 4a

Scheme 1 Synthesis of 2a–d. Reagents and conditions: (i) 1 (1.0

equiv), HC(OEt)₃(1.2 equiv), Ac₂O, reflux, 2 h; (ii) LDA, PrI, –78 to

20 °C, 14 h.

It is worth noting that the cyclization proceeded with ex-

cellent regioselectivity. The formation of product 4a

(Scheme 3) might be explained by reaction of 2a with ti-

tanium(IV) chloride to give intermediate A, attack of the

terminal carbon atom of 3a at A to give intermediate B,

then formation of intermediate C, cyclization via the cen-

tral carbon (intermediate D), and subsequent aromatiza-

tion. The regioselectivity of the formation of 4a might be

explained by the steric hindrance at the ketone carbonyl

group.

O

EtO

O

i

Ar

Ts

2e 90%

1e

Ar = 4-O₂NC₆H₄

Scheme 2 Synthesis of 2e. Reagents and conditions: (i) 1e (1.0

equiv), HC(OEt)₃(1.2 equiv), Ac₂O, reflux, 2 h.

The formal [3+3] cyclization of 2-(arylsulfonyl)-3-

ethoxy-2-en-1-ones 2a–e with 1,3-bis(siloxy)buta-1,3-

dienes 3a–m afforded the 4-(arylsulfonyl)phenols 4a–ag

in 42–80% yield (Scheme 4, Table 1). The aryl groups lo-

cated on the sulfonyl group of enones 2 have some influ-

The cyclization of 2a with 3a mediated by titanium(IV)

chloride afforded the novel 4-(arylsulfonyl)phenol 4a in

80% yield (Scheme 3). A thorough optimization was car-

ried out for the synthesis of 4a. The best yields were ob-

Synthesis 2009, No. 13, 2223–2235 © Thieme Stuttgart · New York

PAPER

Synthesis of Functionalized Diaryl Sulfones

2225

Table 1 Synthesis of 4a–ag

Entry

1

2

3

4

Ar

R¹

R²

R³

Yield^a(%)

2a

2b

2c

2d

2e

2f

3a

3b

3c

3d

3e

3f

4a

4b

4c

Ph

Me

H

OMe

OEt

80

77

76

70

78

75

78

57

56

46

65

61

60

59

42

47

48

47

54

50

51

52

48

53

77

79

75

45

49

47

0

2

Ph

Me

3

Ph

Me

Et

4

4d

4e

Ph

Me

n-Bu

i-Bu

OMe

OEt

5

Ph

Me

6

4f

Ph

Me

(CH₂)₅Me

(CH₂)₆Me

(CH₂)₇Me

(CH₂)₈Me

(CH₂)₉Me

H

7

3g

3h

3i

4g

4h

4i

Ph

Me

8

Ph

Me

9

Ph

Me

10

11

12

13

14

15

16

17

18

19

20

21

22

23

24

25

26

27

28

29

30

31

32

33

34

35

3j

4j

Ph

Me

3a

3b

3c

3d

3f

4k

4l

Tol

Me

Tol

Me

4m

4n

4o

4p

4q

4r

Tol

Me

Et

Tol

Me

n-Bu

(CH₂)₅Me

(CH₂)₆Me

(CH₂)₇Me

OMe

H

OMe

OEt

Tol

Me

3g

3h

3k

3a

3b

3c

3d

3f

Tol

Me

Tol

Me

Tol

Me

4s

4-ClC₆H₄

Ph

Me

4t

Me

4u

4v

4w

4x

4y

4z

Me

Et

Me

n-Bu

(CH₂)₅Me

(CH₂)₆Me

(CH₂)₇Me

4-ClC₆H₄

Tol

OMe

Me

3g

3h

3l

Me

3m

3a

3b

3m

3a

3b

3d

3a

3n

4aa

4ab

4ac

4ad

4ae

4af

4ag

4ah

4ai

Me

n-Bu

4-O₂NC₆H₄

Ph

H

Ph

Me

Ph

Tol

H

Tol

Me

Tol

n-Bu

H

Ph

2a

Ph

Me

H

0

^aYields of isolated products.

Synthesis 2009, No. 13, 2223–2235 © Thieme Stuttgart · New York

2226

M. Shkoor et al.

PAPER

TMSO

R²

OTMS

R³

O

OH

R²

TiCl₄, CH₂Cl₂

R³

3a–m

EtO

R¹

–78 to 20 °C

14 h

O

SO₂Ar

+

R¹

4a–ag

SO₂Ar

2a–e

Scheme 4 Synthesis of 4a–ag

ence on the yields. The best yields were obtained for

products 4a–j and 4ab–ad, which are derived from phe-

nyl-substituted enones 2a and 2d, respectively (Table 1,

entries 1–10 and 28–30). In contrast, the presence of a

substituent at C4 of the 1,3-bis(siloxy)buta-1,3-diene 3

has no significant effect on the yield. This can be seen by

comparison of the yield of product 4a with the yields of

products 4b–j (entry 1 vs 2–10), that of 4ab with 4ac and

4ad (entry 28 vs 29 and 30), and by comparison of the

yields of products 4k, 4s, and 4ab with those of the corre-

sponding substituted derivatives (entry 11 vs 12–18, entry

19 vs 20–27, and entry 28 vs 29 and 30, respectively). All

products were formed with excellent regioselectivity. The

formation of only one regioisomer was observed. It is

worth noting that all attempts to carry out cyclizations of

enones containing an aryl group R¹other than 4-nitrophe-

nyl failed (e.g., entry 34). In addition, only b-keto ester-

derived dienes could be successfully employed. All at-

tempts to induce a cyclization using 2,4-bis(trimethylsil-

oxy)-1,3-pentadiene, derived from acetylacetone, failed

(e.g., entry 35). For some derivatives 4 the yields are only

moderate, which might be explained by oxidative dimer-

ization of the diene mediated by titanium(IV) chloride.

This type of reaction has been reported previously.³⁸In

addition, some hydrolysis of the enone was observed.

Figure 1 ORTEP plot of 4ae (30% probability level)

Figure 2 ORTEP plot of 4d (30% probability level)

The structures of all products were confirmed by spectro-

scopic methods. The structures of products 4a, 4k, 4s,

4ab, and 4ae, all containing a hydrogen atom located at

C6, are evident by the presence of large coupling con-

stants for the two neighboring hydrogen atoms. The struc-

ture of 4ae was independently confirmed by X-ray

crystal-structure analysis (Figure 1).³⁹

spectively. Chemical shifts are reported relative to the solvent as in-

ternal standard [CDCl₃, d = 7.26 (¹H) and 77.0 (¹³C)]. MS data were

obtained by EI (70 eV), CI (isobutane), or ESI methods, respective-

ly. Melting points are uncorrected. Anhyd CH₂Cl₂(99.8%) was pur-

chased directly from ACROS and used without further purification,

and TiCl₄was purchased from Aldrich. Analytical TLC was per-

formed on silica gel plates (0.20 mm, 60 Å). Column chromatogra-

phy was performed on silica gel (60–200 mesh, 60 Å). All

cyclization reactions were carried out in anhyd solvents in Schlenk

tubes under an argon atmosphere. Crystallographic data were col-

lected on a Bruker X8Apex system with Mo-Ka radiation

(l = 0.71073 Å). The structures were solved by direct methods us-

ing SHELXS-97 and refined against F²on all data by full-matrix

least-squares analysis with SHELXL-97. All non-hydrogen atoms

were refined anisotropically, and all hydrogen atoms were refined

in the model at geometrically calculated positions and refined by

use of a riding model. 1,3-Bis(siloxy)buta-1,3-dienes 3a–m were

prepared according to the literature from the corresponding b-keto

esters in two steps.^31,35,36

The elucidation of the structures of all other derivatives,

containing an alkyl group at C6, was not so easy and re-

quired extensive 2D NMR experiments (NOESY,

HMBC). The structure of 4d was unambiguously con-

firmed by X-ray crystal-structure analysis (Figure 2).³⁹

In conclusion, we have reported a convenient and regiose-

lective synthesis of 4-(arylsulfonyl)phenols by what are,

to the best of our knowledge, the first formal [3+3] cy-

clizations of 1,3-bis(siloxy)buta-1,3-dienes with 2-(aryl-

sulfonyl)-3-ethoxy-2-en-1-ones. The reactions are easy to

carry out and the starting materials are readily available.

Enones 2a–e; General Procedure

A soln of the appropriate keto sulfone 1 (1 equiv) in HC(OEt)₃(1.2

equiv) and Ac₂O was stirred for 1.5 h at 120 °C and, subsequently,

The NMR spectra of samples in CDCl₃were recorded at 250, 300,

or 500 MHz (¹H), respectively, or 62.5, 75, or 125 MHz (¹³C), re-

Synthesis 2009, No. 13, 2223–2235 © Thieme Stuttgart · New York

PAPER

Synthesis of Functionalized Diaryl Sulfones

2227

for 1.5 h at 140 °C. The Ac₂O was removed in vacuo and the result-

ing solid residue was recrystallized (EtOH).

HRMS (EI): m/z [M]⁺calcd for C₁₂H₁₃O₄ClS: 288.02176; found:

288.021693.

4-Ethoxy-3-(phenylsulfonyl)but-3-en-2-one (2a)

Starting with 1a (2.00 g, 10.1 mmol) and HC(OEt)₃(1.79 g, 2.0 mL,

12.1 mmol), 2a was isolated.

1-Ethoxy-2-(phenylsulfonyl)hept-1-en-3-one (2d)

Starting with 1d (2.00 g, 8.3 mmol) and HC(OEt)₃(1.47 g, 1.66 mL,

10.0 mmol), 2d was isolated.

Yield: 2.10 g (82%); slightly brown solid; mp 46–48 °C.

Yield: 1.97 g (80%); brown solid; mp 79–81 °C.

IR (KBr): 3066 (w), 2986 (w), 2254 (w), 1667 (m), 1599 (s), 1477

(w), 1446 (m), 1393 (m), 1354 (m), 1302 (s), 1189 (m), 1148 (s),

1090 (m), 1047 cm^–1(m).

IR (KBr): 3303 (w), 3071 (w), 2952 (m), 2871 (w), 1721 (w), 1660

(s), 1595 (s), 1448 (m), 1396 (m), 1382 (m), 1340 (m), 1271 (s),

1150 (s), 1113 (s), 1077 (s), 1024 cm^–1(s).

¹H NMR (300 MHz, CDCl₃): d = 1.40 (t, ³J = 7.5 Hz, 3 H,

OCH₂CH₃), 2.25 (s, 3 H, COCH₃), 4.34 (q, ³J = 7.1 Hz, 2 H,

OCH₂CH₃), 7.38–7.50 (m, 3 H, 3CH_Ar), 7.88–7.91 (m, 2 H, 2CH_Ar),

8.20 (s, 1 H, CH).

¹³C NMR (75 MHz, CDCl₃): d = 15.4 (OCH₂CH₃), 31.9 (COCH₃),

74.6 (OCH₂CH₃), 122.0 (C), 128.20 (2CH_Ar), 128.58 (2CH_Ar),

129.4 (CH_Ar), 133.4 (C_Ar), 167.7 (CH), 191.0 (CO).

¹H NMR (250 MHz, CDCl₃): d = 0.77 (t, ³J = 7.4 Hz, 3 H,

(CH₂)₃CH₃), 1.09–1.24 (m, 3 H, OCH₂CH₃), 1.37–1.43 (m, 4 H,

2CH₂), 2.57 (t, ³J = 7.6 Hz, 2 H, COCH₂), 4.34 (q, ³J = 7.4 Hz, 2 H,

OCH₂CH₃), 7.37–7.48 (m, 3 H, 3CH_Ar), 7.87–7.91 (m, 2 H, 2CH_Ar),

8.15 (s, 1 H, CH).

¹³C NMR (75 MHz, CDCl₃): d = 13.8, 15.4 (CH₃), 22.1, 25.4 (CH₂),

43.6 (COCH₂), 74.4 (OCH₂CH₃), 121.3 (C), 128.2 (2CH_Ar), 128.5

(2CH_Ar), 132.9 (CH_Ar), 141.5 (C_Ar), 166.6 (CH), 194.2 (CO).

MS (EI, 70 eV): m/z (%) = 211 (41), 190 (30), 189 (74), 175 (20),

162 (10), 161 (55), 147 (17), 141 (43), 125 (14), 105 (17), 97 (39),

78 (23), 77 (100), 69 (32), 51 (31), 43 (38), 29 (16).

HRMS (EI): m/z [M]⁺calcd for C₁₂H₁₄O₄S: 254.06073; found:

MS (EI, 70 eV): m/z (%) = 239 (36), 232 (12), 231 (27), 212 (11),

211 (100), 203 (15), 190 (15), 175 (10), 161 (37), 141 (41), 105

(10), 78 (10), 77 (68), 51 (11), 29 (13).

HRMS (EI): m/z [M + H]⁺calcd for C₁₅H₂₁O₄S: 297.11551; found:

297.11542; m/z [M + Na]⁺calcd for C₁₅H₂₀NaO₄S: 319.09745;

found: 319.09738; m/z [2M + Na]⁺calcd for C₃₀H₄₀NaO₈S₂:

615.20568; found: 615.20573.

254.060618.

4-Ethoxy-3-tosylbut-3-en-2-one (2b)

Starting with 1b (2.00 g, 9.4 mmol) and HC(OEt)₃(1.67 g, 1.9 mL,

11.3 mmol), 2b was isolated.

3-Ethoxy-1-(4-nitrophenyl)-2-tosylprop-2-en-1-one (2e)

Starting with 1e (2.00 g, 6.3 mmol) and HC(OEt)₃(1.12 g, 1.3 mL,

7.6 mmol), 2e was isolated.

Yield: 2.02 g (80%); slightly brown solid; mp 134–135 °C.

IR (KBr): 3056 (w), 2984 (w), 2925 (w), 2871 (w), 1666 (m), 1597

(s), 1494 (w), 1473 (w), 1394 (m), 1300 (s), 1265 (m), 1187 (m),

1144 (s), 1047 cm^–1(m).

Yield: 2.128 g (90%); yellow solid; mp 133–134 °C.

IR (KBr): 3103 (w), 3069 (w), 2999 (w), 2939 (w), 2866 (w), 1658

(m), 1585 (m), 1523 (m), 1444 (w), 1391 (w), 1348 (m), 1269 (m),

1219 (m), 1147 (m), 1073 (m), 1006 cm^–1(m).

¹H NMR (250 MHz, CDCl₃): d = 1.11 (t, ³J = 7.2 Hz, 3 H,

OCH₂CH₃), 2.30 (s, 3 H, CH₃), 4.07 (q, ³J = 7.1 Hz, 2 H,

OCH₂CH₃), 7.24–7.29 (m, 2 H, 2CH_Ar), 7.74–7.83 (m, 4 H, 4CH_Ar),

7.97 (s, 1 H, CH), 8.15–8.20 (m, 2 H, 2CH_Ar).

¹³C NMR (75 MHz, CDCl₃): d = 15.0 (OCH₂CH₃), 21.6 (PhCH₃),

73.6 (OCH₂CH₃), 120.4 (C), 123.5 (2CH_Ar), 128.1 (2CH_Ar), 129.64

(2CH_Ar), 129.9 (2CH_Ar), 138.4, 142.4, 144.3, 150.2 (C_Ar), 163.8

(CH), 187.1 (CO).

¹H NMR (250 MHz, CDCl₃): d = 1.41 (t, ³J = 7.4 Hz, 3 H,

OCH₂CH₃), 2.24 (s, 3 H, COCH₃), 2.32 (s, 3 H, PhCH₃), 4.33 (q,

³J = 7.3 Hz, 2 H, OCH₂CH₃), 7.19–7.22 (m, 2 H, 2CH_Ar), 7.76–7.79

(m, 2 H, 2CH_Ar), 8.18 (s, 1 H, CH).

¹³C NMR (75 MHz, CDCl₃): d = 15.3 (OCH₂CH₃), 21.5 (PhCH₃),

32.0 (COCH₃), 74.5 (OCH₂CH₃), 122.2 (C), 128.2 (2CH_Ar), 129.2

(2CH_Ar), 138.4, 143.7 (C_Ar), 167.3 (CH), 191.1 (CO).

MS (EI, 70 eV): m/z (%) = 225 (25), 204 (20), 203 (16), 190 (10),

189 (75), 175 (36), 161 (15), 155 (48), 139 (15), 119 (12), 97 (80),

92 (24), 91 (100), 89 (11), 77 (10), 69 (47), 65 (35), 63 (10), 43 (32),

39 (11). 29 (15).

MS (EI, 70 eV): m/z (%) = 312 (11), 311 (68), 310 (11), 296 (64),

283 (11), 282 (38), 204 (93), 176 (100), 155 (10), 150 (25), 139

(14), 104 (19), 92 (19), 91 (73), 76 (11), 65 (16).

HRMS (EI): m/z [M]⁺calcd for C₁₃H₁₆O₄S: 268.07638; found:

268.076825.

3-(4-Chlorophenylsulfonyl)-4-ethoxybut-3-en-2-one (2c)

Starting with 1c (2.00 g, 8.6 mmol) and HC(OEt)₃(1.50 g, 1.7 mL,

10.3 mmol), 2c was isolated.

HRMS (EI): m/z [M]⁺calcd for C₁₈H₁₇NO₆S: 375.07711; found:

375.077049.

4-(Arylsulfonyl)phenols 4a–ag; General Procedure

Yield: 2.16 g (87%); brown solid; mp 120–121 °C.

One of 3a–m (1.1 mmol) and subsequently TiCl₄(1.1 mmol) were

added to a soln of the appropriate 2a–e in CH₂Cl₂(2 mL/1 mmol

of 2a–e) at –78 °C. The stirring soln was allowed to warm to 20 °C

over 14 h. A 10% aq soln of HCl (20 mL) was added to the reaction

mixture, and the organic and aqueous layers were separated. The

latter was extracted with CH₂Cl₂(3 × 20 mL). The combined organ-

ic layers were dried (Na₂SO₄) and filtered, and the filtrate was con-

centrated in vacuo. The residue was purified by chromatography

(silica gel, heptanes–EtOAc) to give the corresponding 4.

IR (KBr): 3087 (w), 2972 (w), 2982 (w), 1657 (m), 1597 (m), 1475

(w), 1438 (w), 1395 (w), 1357 (w), 1330 (m), 1296 (m), 1260 (m),

1193 (m), 1176 (m), 1139 (m), 1085 (m), 1041 (m), 1009 cm^–1(w).

¹H NMR (250 MHz, CDCl₃): d = 1.42 (t, ³J = 7.8 Hz, 3 H,

OCH₂CH₃), 2.26 (s, 3 H, COCH₃), 4.35 (q, ³J = 7.3 Hz, 2 H,

OCH₂CH₃), 7.35–7.41 (m, 2 H, 2CH_Ar), 7.81–7.86 (m, 2 H, 2CH_Ar),

8.19 (s, 1 H, CH).

¹³C NMR (75 MHz, CDCl₃): d = 15.2 (OCH₂CH₃), 31.9 (COCH₃),

74.7 (OCH₂CH₃), 122.1 (C), 129.0 (2CH_Ar), 130.0 (2CH_Ar), 139.5,

140.1 (C_Ar), 168.1 (CH), 191.1 (CO).

Methyl 6-Hydroxy-2-methyl-3-(phenylsulfonyl)benzoate (4a)

Starting with 2a (0.381 g, 1.5 mmol) and 3a (0.429 g, 1.7 mmol), 4a

was isolated after chromatography (silica gel, heptanes–EtOAc).

MS (EI, 70 eV): m/z (%) = 247 (12), 245 (36), 224 (35), 223 (17),

209 (12), 195 (29), 189 (16), 177 (16), 175 (38), 159 (11), 133 (11),

113 (17), 112 (14), 111 (62), 97 (100), 75 (23), 69 (48), 43 (50).

Yellowish solid; yield: 0.365 g (80%); mp 80–83 °C.

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M. Shkoor et al.

PAPER

Methyl 3-Butyl-2-hydroxy-6-methyl-5-(phenylsulfonyl)ben-

IR (KBr): 3070 (w), 3003 (w), 2950 (w), 2923 (w), 2848 (w), 1722

(w), 1667 (m), 1572 (m), 1537 (w), 1461 (w), 1445 (m), 1383 (w),

1349 (m), 1286 (m), 1222 (m), 1140 (s), 1108 (m), 1082 cm^–1(m).

¹H NMR (300 MHz, CDCl₃): d = 2.52 (s, 3 H, PhCH₃), 3.87 (s, 3 H,

OCH₃), 6.96 (d, ³J = 7.6 Hz, 1 H, CH_Ar), 7.40–7.50 (m, 3 H, 3CH_Ar),

7.73–7.77 (m, 2 H, 2CH_Ar), 8.30 (d, ³J = 7.5 Hz, 1 H, CH_Ar), 11.21

(s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 19.0 (CH₃), 52.8 (OCH₃), 115.3

(CCOOCH₃), 115.7 (CH_Ar), 127.2 (2CH_Ar), 129.1 (2CH_Ar), 131.4

(C_Ar), 132.9 (CH_Ar), 135.3 (CH_Ar), 141.9, 142.7 (C_Ar), 165.3 (COH),

171.0 (CO).

MS (EI, 70 eV): m/z (%) = 306 [M]⁺(28), 275 (25), 274 (100), 257

(16), 256 (10), 255 (27), 241 (21), 209 (15), 208 (12), 181 (14), 153

(14), 152 (12), 149 (10), 121 (13), 105 (11), 77 (33), 51 (22).

zoate (4d)

Starting with 2a (0.381 g, 1.5 mmol) and 3d (0.522 g, 1.7 mmol),

4d was isolated after chromatography (silica gel, heptanes–EtOAc).

Yellowish solid; yield: 0.413 g (76%); mp 95–97 °C.

IR (KBr): 3078 (w), 2958 (w), 2927 (w), 1666 (s), 1594 (w), 1567

(w), 1461 (w), 1438 (m), 1402 (m), 1381 (w), 1301 (s), 1215 (m),

1141 (s), 1085 (s), 1022 cm^–1(w).

3

¹H NMR (250 MHz, CDCl₃): d = 0.83 (t, J = 7.5 Hz, 3 H, CH₃),

1.23–1.32 (m, 2 H, CH₂), 1.44–1.56 (m, 2 H, CH₂), 2.42 (s, 3 H,

3

PhCH₃), 2.58 (t, J = 7.6 Hz, 2 H, PhCH₂), 3.80 (s, 3 H, OCH₃),

7.33–7.43 (m, 3 H, 3CH_Ar), 7.66–7.69 (m, 2 H, 2CH_Ar), 8.13 (s, 1

H, CH_Ar), 11.38 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 13.9, 18.8 (CH₃), 22.5, 29.5, 31.2

(CH₂), 52.6 (OCH₃), 114.6 (CCOOCH₃), 127.1 (2CH_Ar), 128.9

(2CH_Ar), 129.6, 130.4 (C_Ar), 132.7, 134.8 (CH_Ar), 139.7, 142.2

(C_Ar), 163.5 (COH), 171.7 (CO).

HRMS (EI): m/z [M]⁺calcd for C₁₅H₁₄O₅S: 306.05565; found:

306.055771.

Methyl 2-Hydroxy-3,6-dimethyl-5-(phenylsulfonyl)benzoate

(4b)

Starting with 2a (0.381 g, 1.5 mmol) and 3b (0.452 g, 1.7 mmol),

4b was isolated after chromatography (silica gel, heptanes–EtOAc).

MS (EI, 70 eV): m/z (%) = 363 (12), 362 [M]⁺(68), 330 (14), 313

(11), 303 (11), 302 (71), 301 (16), 289 (21), 288 (100), 287 (29),

260 (30), 188 (10), 77 (18).

HRMS (EI): m/z [M]⁺calcd for C₁₉H₂₂O₅S: 362.11825; found:

362.117561

White solid; yield: 0.384 g (80%); mp 160–161 °C.

IR (KBr): 3066 (w), 2955 (w), 2255(w), 1736 (w), 1665 (m), 1604

(w), 1571 (w), 1445 (m), 1381 (w), 1344 (m), 1303 (s), 1252 (m),

1201 (m), 1165 (m), 1144 (s), 1087 (m), 1062 (w), 1031 cm^–1(w).

Methyl 2-Hydroxy-3-isobutyl-6-methyl-5-(phenylsulfonyl)ben-

zoate (4e)

Starting with 2a (0.381 g, 1.5 mmol) and 3e (0.522 g, 1.7 mmol), 4e

was isolated after chromatography (silica gel, n-heptane–EtOAc).

¹H NMR (250 MHz, CDCl₃): d = 2.24 (s, 3 H, PhCH₃), 2.46 (s, 3 H,

PhCH₃), 3.85 (s, 3 H, OCH₃), 7.37–7.52 (m, 3 H, 3CH_Ar), 7.71–7.76

(m, 2 H, 2CH_Ar), 8.19 (s, 1 H, CH_Ar), 11.39 (s, 1 H, OH).

Slightly yellow solid; yield: 0.379 g (70%); mp 109–110 °C.

¹³C NMR (75 MHz, CDCl₃): d = 15.9, 18.8 (CH₃), 52.7 (OCH₃),

114.4 (CCOOCH₃), 125.1 (C_Ar), 127.1 (2CH_Ar), 129.0 (2CH_Ar),

130.3 (C_Ar), 132.8, 135.5 (CH_Ar), 139.8, 142.2 (C_Ar), 163.9 (COH),

171.6 (CO).

MS (EI, 70 eV): m/z (%) = 320 [M]⁺(26), 289 (22), 288 (100), 260

(30), 77 (13).

IR (KBr): 2955 (w), 2932 (w), 2870 (w), 1716 (w), 1659 (m), 1600

(w), 1556 (w), 1427 (m), 1383 (w), 1355 (m), 1300 (s), 1254 (m),

1216 (m), 1165 (m), 1141 (s), 1084 (m), 1064 cm^–1(m).

¹H NMR (250 MHz, CDCl₃): d = 0.87 (d, ³J = 6.8 Hz, 6 H, 2CH₃),

1.88–1.99 (m, 1 H, CH), 2.47 (s, 3 H, PhCH₃), 2.52 (d, ³J = 7.2 Hz,

2 H, PhCH₂), 3.85 (s, 3 H, OCH₃), 7.37–7.52 (m, 3 H, 3CH_Ar), 7.69–

7.76 (m, 2 H, 2CH_Ar), 8.14 (s, 1 H, CH_Ar), 11.33 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 17.9, 21.4, 21.4 (CH₃), 27.1 (CH),

37.9 (CH₂), 51.7 (OCH₃), 113.7 (CCOOCH₃), 126.1 (2CH_Ar), 127.4

(C_Ar), 128.0 (2CH_Ar), 129.2 (C_Ar), 131.7, 134.8 (CH_Ar), 138.8, 141.1

(C_Ar), 162.6 (COH), 170.6 (CO).

HRMS (EI): m/z [M]⁺calcd for C₁₆H₁₆O₅S: 320.07130; found:

320.071232.

Ethyl 3-Ethyl-2-hydroxy-6-methyl-5-(phenylsulfonyl)benzoate

(4c)

Starting with 2a (0.381 g, 1.5 mmol) and 3c (0.499 g, 1.7 mmol), 4c

was isolated after chromatography (silica gel, heptanes–EtOAc).

MS (EI, 70 eV): m/z (%) = 362 [M]⁺(40), 331 (12), 330 (28), 315

(15), 303 (18), 302 (100), 288 (33), 287 (84), 260 (13), 238 (14),

219 (25), 188 (11), 129 (17), 125 (11), 116 (22), 99 (33), 97 (10), 81

(32), 71 (15), 69 (19), 57 (18), 55 (12).

HRMS (EI): m/z [M]⁺calcd for C₁₉H₂₂O₅S: 362.11825; found:

362.117994.

White solid; yield: 0.402 g (77%); mp 95–97 °C.

IR (KBr): 3066 (w), 2970 (w), 2934 (w), 2254 (w), 1730 (w), 1658

(m), 1603 (w), 1565 (w), 1445 (m), 1373 (m), 1303 (m), 1288 (m),

1241 (m), 1200 (m), 1143 (s), 1086 (m), 1017 cm^–1(m).

¹H NMR (250 MHz, CDCl₃): d = 1.26 (t, ³J = 7.6 Hz, 3 H,

CH₂CH₃), 1.36 (t, ³J = 7.6 Hz, 3 H, OCH₂CH₃), 2.55 (s, 3 H,

PhCH₃), 2.73 (q, ³J = 7.7 Hz, 2 H, PhCH₂CH₃), 4.40 (q, ³J = 7.2 Hz,

2 H, OCH₂CH₃), 7.45–7.59 (m, 3 H, 3CH_Ar), 7.79–7.82 (m, 2 H,

2CH_Ar), 8.26 (s, 1 H, CH_Ar), 11.53 (s, 1 H, OH).

Methyl 3-Hexyl-2-hydroxy-6-methyl-5-(phenylsulfonyl)ben-

zoate (4f)

Starting with 2a (0.381 g, 1.5 mmol) and 3f (0.568 g, 1.7 mmol), 4f

was isolated after chromatography (silica gel, heptanes–EtOAc).

Slightly yellow viscous oil; yield: 0.456 g (78%).

¹³C NMR (75 MHz, CDCl₃): d = 13.4, 14.0, 19.0 (CH₃), 23.1 (CH₂),

62.4 (OCH₃), 114.7 (CCOOCH₃), 127.1 (2CH_Ar), 129.0 (2CH_Ar),

130.4, 130.8 (C_Ar), 132.79, 134.01 (CH_Ar), 139.7, 142.2 (C_Ar), 163.5

(COH), 171.16 (CO).

IR (KBr): 3067 (w), 2926 (m), 2856 (w), 2256 (w), 1737 (w), 1665

(m), 1602 (w), 1567 (w), 1444 (m), 1345 (m), 1303 (m), 1245 (m),

1201 (m), 1143 (s), 1086 cm^–1(m).

3

MS (EI, 70 eV): m/z (%) = 349 (13), 348 [M]⁺(64), 303 (13), 302

(18), 281 (14), 275 (14), 274 (68), 237 (17), 210 (32), 209 (18), 208

(28), 207 (100), 195 (15), 191 (14), 181 (44), 165 (13), 152 (11),

133 (12), 105 (14), 103 (15), 91 (17), 79 (12), 78(14), 77 (33), 51

(15), 45 (12), 44 (90), 39 (10), 32 (36), 31 (15), 29 (11).

¹H NMR (250 MHz, CDCl₃): d = 0.82 (t, J = 7.1 Hz, 3 H, CH₃),

1.17–1.35 (m, 6 H, 3CH₂), 1.50–1.62 (m, 2 H, CH₂), 2.45 (s, 3 H,

PhCH₃), 2.62 (t, J = 7.5 Hz, 2 H, PhCH₂), 3.91 (s, 3 H, OCH₃),

7.37–7.47 (m, 3 H, 3CH_Ar), 7.70–7.74 (m, 2 H, 2CH_Ar), 8.17 (s, 1

H, CH_Ar), 11.38 (s, 1 H, OH).

3

HRMS (EI): m/z [M]⁺calcd for C₁₈H₂₀O₅S: 348.10260; found:

348.102403.

¹³C NMR (75 MHz, CDCl₃): d = 14.1, 18.9 (CH₃), 22.6, 29.0, 29.1,

29.8, 31.6 (CH₂), 52.7 (OCH₃), 114.6 (CCOOCH₃), 127.1 (2CH_Ar),

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Synthesis of Functionalized Diaryl Sulfones

2229

129.0 (2CH_Ar), 129.6, 130.4 (C_Ar), 132.7, 134.8 (CH_Ar), 139.7,

142.2 (C_Ar), 163.5 (COH), 171.6 (CO).

MS (EI, 70 eV): m/z (%) = 390 [M]⁺(41), 359 (10), 358 (27), 341

(10), 330 (51), 329 (20), 301 (12), 289 (18), 288 (100), 287 (30),

260 (34), 97 (10), 85 (10), 83 (15), 71 (16), 70 (10), 69 (23), 57 (22),

55 (10), 43 (10).

IR (KBr): 2952 (w), 2922 (m), 2852 (w), 1737 (w), 1663 (m), 1602

(w), 1566 (w), 1441 (m), 1344 (m), 1303 (s), 1247 (m), 1200 (m),

1142 (s), 1086 (s), 1062 cm^–1(m).

¹H NMR (250 MHZ, CDCl₃): d = 0.81 (t, ³J = 7.8 Hz, 3 H, (CH₃),

1.18–1.26 (m, 12 H, 6CH₂), 1.50–1.60 (m, 2 H, CH₂), 2.46 (s, 3 H,

3

PhCH₃), 2.63 (t, J = 7.2 Hz, 2 H, PhCH₂), 3.85 (s, 3 H, OCH₃),

7.38–7.50 (m, 3 H, 3CH_Ar), 7.71–7.75 (m, 2 H, 2CH_Ar), 8.18 (s, 1

H, CH_Ar), 11.35 (s, 1 H, OH).

HRMS (EI): m/z [M]⁺calcd for C₂₁H₂₆O₅S: 390.14955; found:

390.149235.

¹³C NMR (75 MHz, CDCl₃): d = 14.0, 18.8 (CH₃), 22.6, 29.0, 29.2,

29.4, 29.4, 29.5, 29.8, 31.8 (CH₂), 52.7 (OCH₃), 114.5

(CCOOCH₃), 127.1 (2CH_Ar), 128.9 (2CH_Ar), 129.6, 130.4 (C_Ar),

132.7 (CH_Ar), 134.8 (CH_Ar), 139.7, 142.2 (C_Ar), 163.5 (COH), 171.6

(CO).

Methyl 3-Heptyl-2-hydroxy-6-methyl-5-(phenylsulfonyl)ben-

zoate (4g)

Starting with 2a (0.254 g, 1.0 mmol) and 3g (0.395 g, 1.1 mmol), 4g

was isolated after chromatography (silica gel, heptanes–EtOAc).

Yellowish oil; yield: 0.303 g (75%).

MS (EI, 70 eV): m/z (%) = 432 [M]⁺(49), 401 (12), 400 (28), 383

(10), 372 (32), 331 (10), 329 (23), 301 (12), 289 (21), 288 (100),

287 (38), 274 (16), 261 (13), 260 (20).

HRMS (EI): m/z [M]⁺calcd for C₂₄H₃₂O₅S: 432.19650; found:

432.196759.

IR (KBr): 3066 (w), 2955 (w), 2926 (m), 2855 (w), 2257 (w), 1734

(w), 1666 (m), 1603 (w), 1568 (w), 1446 (m), 1346 (m), 1305 (m),

1248 (w), 1202 (m), 1161 (m), 1145 (s), 1087 (m), 1064 (w), 1025

cm^–1(w).

¹H NMR (250 MHz, CDCl₃): d = 0.82 (t, J = 7.4 Hz, 3 H, CH₃),

3

Methyl 3-Decyl-2-hydroxy-6-methyl-5-(phenylsulfonyl)ben-

zoate (4j)

Starting with 2a (0.381 g, 1.5 mmol) and 3j (0.661 g, 1.7 mmol), 4j

was isolated after chromatography (silica gel, heptanes–EtOAc).

1.19–1.28 (m, 8 H, 4CH₂), 1.54–1.60 (m, 2 H, CH₂), 2.46 (s, 3 H,

3

PhCH₃), 2.63 (t, J = 7.4 Hz, 2 H, PhCH₂), 3.85 (s, 3 H, OCH₃),

7.37–7.49 (m, 3 H, 3CH_Ar), 7.71–7.75 (m, 2 H, 2CH_Ar), 8.18 (s, 1

H, CH_Ar), 11.36 (s, 1 H, OH).

White solid; yield: 0.521 g (78%); mp 94–95 °C.

¹³C NMR (75 MHz, CDCl₃): d = 13.1, 17.9 (CH₃), 21.7, 28.1, 28.2,

28.5, 28.9, 30.8 (CH₂), 51.7 (OCH₃), 113.7 (CCOOCH₃), 126.2

(2CH_Ar), 128.0 (2CH_Ar), 128.6, 129.4 (C_Ar), 131.8, 133.9 (CH_Ar),

138.7, 141.2 (C_Ar), 162.6 (COH), 170.7 (CO).

IR (KBr): 2953 (w), 2923 (m), 2853 (w), 1734 (w), 1664 (m), 1602

(w), 1567 (w), 1444 (m), 1344 (w), 1303 (s), 1246 (m), 1201 (m),

1143 (s), 1086 (m), 1063 cm^–1(w).

MS (EI, 70 eV): m/z (%) = 404 [M⁺] (81), 372 (40), 355 (15), 344

(61), 329 (28), 301 (19), 288 (100), 260 (40), 230 (9), 188 (8), 165

(7), 146 (8), 125 (7), 91 (8), 77 (13), 41 (9).

¹H NMR (250 MHz, CDCl₃): d = 0.80 (t, J = 6.8 Hz, 3 H, CH₃),

3

1.15–1.26 (m, 14 H, 7CH₂), 1.50–1.56 (m, 2 H, CH₂), 2.46 (s, 3 H,

PhCH₃), 2.62 (t, J = 7.7 Hz, 2 H, PhCH₂), 3.86 (s, 3 H, OCH₃),

3

7.37–7.52 (m, 3 H, 3CH_Ar), 7.69–7.74 (m, 2 H, 2CH_Ar), 8.17 (s, 1

H, CH_Ar), 11.35 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 14.1, 18.9 (CH₃), 22.7, 29.0, 29.3,

29.4, 29.4, 29.5, 29.5, 29.8, 31.8 (CH₂), 52.6 (OCH₃), 114.7

(CCOOCH₃), 127.2 (2CH_Ar), 129.0 (2CH_Ar), 129.6, 130.4 (C_Ar),

132.7, 134.8 (CH_Ar), 139.7, 142.2 (C_Ar), 163.5 (COH), 171.6 (CO).

MS (EI, 70 eV): m/z (%) = 446 [M]⁺(46), 415 (12), 414 (26), 386

(12), 378 (18), 331 (39), 330 (10), 329 (28), 318 (14), 302 (14), 301

(15), 289 (25), 288 (100), 287 (44), 275 (13), 274 (19), 261 (19),

260 (20), 234 (25), 233 (17), 206 (21), 187 (14), 147 (11), 121 (11),

43 (10).

HRMS (EI): m/z [M]⁺calcd for C₂₂H₂₈O₅S: 404.16520; found:

404.165132.

Methyl 2-Hydroxy-6-methyl-3-octyl-5-(phenylsulfonyl)ben-

zoate (4h)

Starting with 2a (0.381 g, 1.5 mmol) and 3h (0.614 g, 1.7 mmol),

4h was isolated after chromatography (silica gel, heptanes–EtOAc).

Slightly yellow viscous oil; yield: 0.471 g (75%).

IR (KBr): 3066 (w), 2925 (m), 2854 (w), 2255 (w), 1737 (w), 1665

(m), 1602 (w), 1567 (w), 1445 (m), 1304 (m), 1247 (w), 1144 (s),

1087 (m), 1064 cm^–1(w).

HRMS (EI): m/z [M]⁺calcd for C₂₅H₃₄O₅S: 446.21215; found:

446.211947.

3

¹H NMR (250 MHz, CDCl₃): d = 0.82 (t, J = 7.4 Hz, 3 H,CH₃),

1.19–1.27 (m, 10 H, 5CH₂), 1.51–1.60 (m, 2 H, CH₂), 2.46 (s, 3 H,

3

PhCH₃), 2.63 (t, J = 7.4 Hz, 2 H, PhCH₂), 3.85 (s, 3 H, OCH₃),

Methyl 6-Hydroxy-2-methyl-3-tosylbenzoate (4k)

Starting with 2b (0.402 g, 1.5 mmol) and 3a (0.429 g, 1.7 mmol),

4k was isolated after chromatography (silica gel, heptanes–EtOAc).

7.38–7.49 (m, 3 H, 3CH_Ar), 7.71–7.75 (m, 2 H, 2CH_Ar), 8.18 (s, 1

H, CH_Ar), 11.31 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 14.0, 18.8 (CH₃), 22.6, 29.0, 29.2,

29.4, 29.4, 29.8, 31.8 (CH₂), 52.7 (OCH₃), 114.6 (CCOOCH₃),

127.1 (2CH_Ar), 128.9 (2CH_Ar), 129.6, 130.40 (C_Ar), 132.7, 134.8

(CH_Ar), 139.6, 142.2 (C_Ar), 163.5 (COH), 171.6 (CO).

MS (EI, 70 eV): m/z (%) = 419 (13), 418 [M]⁺(52), 387 (13), 386

(31), 369 (12), 359 (11), 358 (45), 329 (26), 301 (12), 289 (21), 288

(100), 287 (40), 274 (16), 261 (12), 260 (26).

Yellowish solid; yield: 0.274 g (57%); mp 109–110 °C.

IR (KBr): 3072 (w), 3029 (w), 2953 (w), 2922 (w), 2852 (w), 1715

(w), 1673 (m), 1592 (m), 1574 (m), 1495 (w), 1435 (m), 1348 (m),

1300 (m), 1286 (m), 1218 (m), 1188 (m), 1155 (m), 1142 (s), 1109

(m), 1081 (m), 1040 (w), 1018 cm^–1(w).

¹H NMR (250 MHz, CDCl₃): d = 2.28 (s, 3 H, PhCH₃), 2.47 (s, 3 H,

PhCH₃), 3.81 (s, 3 H, OCH₃), 6.87 (d, ³J = 8.4 Hz, 1 H, CH_Ar), 7.14–

7.17 (m, 2 H, 2 CH_Ar), 7.35–7.58 (m, 2 H, 2CH_Ar), 8.22 (d, ³J = 8.7

Hz, 1 H, CH_Ar), 11.03 (s, 1 H, OH).

HRMS (EI): m/z [M]⁺calcd for C₂₃H₃₀O₅S: 418.18085; found:

418.180994.

Methyl 2-Hydroxy-6-methyl-3-nonyl-5-(phenylsulfonyl)ben-

zoate (4i)

Starting with 2a (0.381 g, 1.5 mmol) and 3i (0.638 g, 1.7 mmol), 4i

was isolated after chromatography (silica gel, heptanes–EtOAc).

¹³C NMR (75 MHz, CDCl₃): d = 19.0, 21.5 (CH₃), 52.7 (OCH₃),

115.1 (CCOOCH₃), 115.6 (CH_Ar), 127.3 (2CH_Ar), 129.6 (2CH_Ar),

131.8 (C_Ar), 135.2 (CH_Ar), 138.9, 142.6, 143.8 (C_Ar), 165.2 (COH),

171.0 (CO).

Yellowish solid; yield: 0.485 g (75%); mp 70–71 °C.

MS (EI, 70 eV): m/z (%) = 320 [M]⁺(34), 289 (27), 288 (100), 271

(23), 269 (18), 256 (9), 255 (48), 224 (16), 223 (20), 222 (17), 181

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M. Shkoor et al.

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(10), 152 (11), 149 (12), 121 (12), 105 (10), 91 (19), 77 (22), 65

(20), 51 (14).

3.89 (s, 3 H, OCH₃), 7.13–7.17 (m, 2 H, 2CH_Ar), 7.53–7.57 (m, 2 H,

2CH_Ar), 8.10 (s, 1 H, CH_Ar), 11.12 (s, 1 H, OH).

HRMS (EI): m/z [M]⁺calcd for C₁₆H₁₆O₅S: 320.07130; found:

320.071076.

¹³C NMR (75 MHz, CDCl₃): d = 13.9, 18.9, 21.5 (CH₃), 22.5, 29.6

31.2 (CH₂), 52.7 (OCH₃), 114.5 (CCOOCH₃), 127.2 (2CH_Ar), 129.4

(C_Ar), 129.6 (2CH_Ar), 130.8 (C_Ar), 134.7 (CH_Ar), 139.2, 139.5, 143.6

(C_Ar), 163.3 (COH), 171.6 (CO).

Methyl 2-Hydroxy-3,6-dimethyl-5-tosylbenzoate (4l)

Starting with 2b (0.402 g, 1.5 mmol) and 3b (0.452 g, 1.7 mmol), 4l

was isolated after chromatography (silica gel, heptanes–EtOAc).

MS (EI, 70 eV): m/z (%) = 377 (12), 376 [M]⁺(49), 344 (16), 327

(12), 317 (19), 316 (87), 315 (16), 303 (19), 302 (100), 301 (23),

274 (32), 188 (11), 91 (14).

Yellowish solid; yield: 0.327 g (65%); mp 175–177 °C.

IR (KBr): 3091 (w), 3054 (w), 2963 (w), 2921 (w), 2853 (w), 1667

(m), 1596 (w), 1568 (w), 1496 (w), 1434 (m), 1374 (m), 1337 (m),

1288 (m), 1247 (m), 1198 (m), 1138 (m), 1120 (m), 1088 (m), 1030

cm^–1(m).

¹H NMR (250 MHz, CDCl₃): d = 2.23 (s, 3 H, PhCH₃), 2.33 (s, 3 H,

PhCH₃), 2.47 (s, 3 H, PhCH₃), 3.81 (s, 3 H, OCH₃), 7.18–7.21 (m,

2 H, 2CH_Ar), 7.60–7.63 (m, 2 H, 2CH_Ar), 8.17 (s, 1 H, CH_Ar), 11.37

(s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 15.9, 18.8, 21.5 (CH₃), 52.7

(OCH₃), 114.3 (CCOOCH₃), 124.9 (C_Ar), 127.2 (2CH_Ar), 129.5

(2CH_Ar), 130.8 (C_Ar), 135.4 (CH_Ar), 139.2, 139.7, 143.6 (C_Ar), 163.7

(COH), 171.5 (CO).

HRMS (EI): m/z [M]⁺calcd for C₂₀H₂₄O₅S: 376.13390; found:

376.133616.

Methyl 3-Hexyl-2-hydroxy-6-methyl-5-tosylbenzoate (4o)

Starting with 2b (0.402 g, 1.5 mmol) and 3f (0.568 g, 1.7 mmol), 4o

was isolated after chromatography (silica gel, heptanes–EtOAc).

Yellowish solid; yield: 0.370 g (61%); mp 95–97 °C.

IR (KBr): 3086 (w), 2954 (w), 2925 (w), 2859 (w), 1660 (m), 1596

(w), 1564 (w), 1495 (w), 1434 (m), 1369 (w), 1335 (m), 1300 (m),

1289 (m), 1243 (m), 1220 (m), 1189 (m), 1138 (s), 1086 (m), 1062

cm^–1(m).

3

¹H NMR (300 MHz, CDCl₃): d = 0.83 (t, J = 7.1 Hz, 3 H, CH₃),

MS (EI, 70 eV): m/z (%) = 334 [M]⁺(31), 303 (23), 302 (100), 274

(31), 91 (12).

1.21–1.32 (m, 6 H, 3CH₂), 1.49–1.56 (m, 2 H, CH₂), 2.33 (s, 3 H,

3

PhCH₃), 2.46 (s, 3 H, PhCH₃), 2.62 (t, J = 7.4 Hz, 2 H, PhCH₂),

3.85 (s, 3 H, OCH₃), 7.19–7.21 (m, 2 H, 2CH_Ar), 7.59–7.62 (m, 2 H,

2CH_Ar), 8.16 (s, 1 H, CH_Ar), 11.21 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 14.0, 18.8, 21.5 (CH₃), 22.6, 29.0,

29.1, 29.8, 31.6 (CH₂), 52.6 (OCH₃), 114.5 (CCOOCH₃), 127.2

(2CH_Ar), 129.5 (C_Ar), 129.6 (2CH_Ar), 130.8 (C_Ar), 134.79 (CH_Ar),

139.2, 139.6, 143.6 (C_Ar), 163.3 (COH), 171.6 (CO).

MS (EI, 70 eV): m/z (%) = 405 (13), 404 [M]⁺(51), 373 (11), 372

(23), 355 (12), 345 (14), 344 (62), 343 (17), 316 (10), 315 (15), 303

(21), 302 (100), 301 (29), 274 (29), 91 (13).

HRMS (EI): m/z [M]⁺calcd for C₁₇H₁₈O₅S: 334.08695; found:

334.087082.

Ethyl 3-Ethyl-2-hydroxy-6-methyl-5-tosylbenzoate (4m)

Starting with 2b (0.402 g, 1.5 mmol) and 3c (0.500 g, 1.7 mmol),

4m was isolated after chromatography (silica gel, heptanes–

EtOAc).

Yellowish solid; yield: 0.250 g (46%); mp 112–114 °C.

IR (KBr): 3078 (w), 2968 (w), 2927 (w), 2872 (w), 1650 (m), 1597

(w), 1556 (w), 1496 (w), 1450 (w), 1417 (m), 1372 (m), 1334 (m),

1287 (m), 1243 (m), 1180 (m), 1141 (m), 1087 (m), 1055 (m), 1017

cm^–1(m).

HRMS (EI): m/z [M]⁺calcd for C₂₂H₂₈O₅S: 404.16250; found:

404.165338.

Methyl 3-Heptyl-2-hydroxy-6-methyl-5-tosylbenzoate (4p)

Starting with 2b (0.268 g, 1.0 mmol) and 3g (0.395 g, 1.1 mmol),

4p was isolated after chromatography (silica gel, heptanes–EtOAc).

¹H NMR (250 MHz, CDCl₃): d = 1.13 (t, ³J = 7.3 Hz, 3 H,

CH₂CH₃), 1.24 (t, ³J = 7.2 Hz, 3 H, OCH₂CH₃), 2.28 (s, 3 H,

PhCH₃), 2.43 (s, 3 H, PhCH₃), 2.59 (q, ³J = 7.5 Hz, 2 H, CH₂CH₃),

4.27 (q, ³J = 7.2 Hz, 2 H, OCH₂CH₃), 7.13–7.17 (m, 2 H, 2CH_Ar),

7.55–7.58 (m, 2 H, 2CH_Ar), 8.12 (s, 1 H, CH_Ar), 11.38 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 15.8, 15.9, 18.8, 21.5 (CH₃), 23.0

(CH₂), 62.4 (OCH₂), 114.3 (CCOOCH₃), 124.9 (C_Ar), 127.2

(2CH_Ar), 129.5 (2CH_Ar), 130.8 (C_Ar), 135.4 (CH_Ar), 139.2, 139.7,

143.6 (C_Ar), 163.7 (COH), 171.5 (CO).

MS (EI, 70 eV): m/z (%) = 362 [M]⁺(36), 317 (31), 316 (96), 290

(10), 289 (19), 288 (100), 91 (25), 77 (13), 57 (33), 289 (19), 41

(10).

HRMS (EI): m/z [M]⁺calcd for C₁₉H₂₂O₅S: 362.11825; found:

362.117378.

Yellowish solid; yield: 0.251 g (60%); mp 67–69 °C.

IR (KBr): 2954 (w), 2925 (w), 2855 (w), 2256 (w), 1737 (w), 1665

(m), 1599 (w), 1567 (w), 1494 (w), 1439 (m), 1345 (w), 1311 (m),

1301 (m), 1288 (m), 1247 (w), 1201 (m), 1160 (m), 1142 (s), 1087

(m), 1063 (w), 1000 cm^–1(w).

¹H NMR (250 MHz, CDCl₃): d = 0.83 (t, ³J = 7.03 Hz, 3 H, CH₃),

1.19–1.28 (m, 8 H, 4CH₂), 1.54–1.60 (m, 2 H, CH₂), 2.34 (s, 3 H,

3

PhCH₃), 2.48 (s, 3 H, PhCH₃), 2.64 (t, J = 7.5 Hz, 2 H, PhCH₂),

3

3.86 (s, 3 H, OCH₃), 7.22 (d, J = 6.0 Hz, 2 H, 2CH_Ar), 7.62 (d,

³J = 9.0 Hz, 2 H, 2CH_Ar), 8.17 (s, 1 H, CH_Ar), 11.33 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 14.1, 18.9, 21.5 (CH₃), 22.6, 29.1,

29.2, 29.4, 29.9, 31.8 (CH₂), 52.7 (OCH₃), 114.6 (CCOOCH₃),

127.2 (2CH_Ar), 129.5 (C_Ar), 129.6 (2CH_Ar), 130.8 (C_Ar), 134.8

(CH_Ar), 139.2, 139.6, 143.7 (C_Ar), 163.4 (COH), 171.7 (CO).

MS (EI, 70 eV): m/z (%) = 418 [M⁺] (90), 386 (32), 358 (82), 343

(25), 315 (20), 302 (100), 288 (15), 274 (34), 230 (8), 188 (8), 165

(8), 139 (11), 121 (6), 91 (21), 77 (9), 43 (10).

Methyl 3-Butyl-2-hydroxy-6-methyl-5-tosylbenzoate (4n)

Starting with 2b (0.402 g, 1.5 mmol) and 3d (0.522 g, 1.7 mmol),

4n was isolated after chromatography (silica gel, heptanes–EtOAc).

Yellowish solid; yield: 0.367 g (65%); mp 95–96 °C.

IR (KBr): 3068 (w), 2932 (w), 2875 (w), 1665 (m), 1595 (w), 1566

(w), 1495 (w), 1439 (m), 1377 (w), 1349 (m), 1299 (m), 1246 (m),

1200 (m), 1161 (m), 1138 (s), 1086 (m), 1002 cm^–1(w).

HRMS (EI): m/z [M]⁺calcd for C₂₃H₃₀O₅S: 418.18085; found:

418.180657.

¹H NMR (300 MHz, CDCl₃): d = 0.83 (t, J = 7.4 Hz, 3 H,CH₃),

3

Methyl 2-Hydroxy-6-methyl-3-octyl-5-tosylbenzoate (4q)

Starting with 2b (0.402 g, 1.5 mmol) and 3h (0.614 g, 1.7 mmol),

4q was isolated after chromatography (silica gel, heptanes–EtOAc).

1.21–1.33 (m, 2 H, 2CH₂), 1.44–1.52 (m, 2 H, CH₂), 2.27 (s, 3 H,

3

PhCH₃), 2.41 (s, 3 H, PhCH₃), 2.57 (t, J = 7.5 Hz, 2 H, PhCH₂),

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Synthesis of Functionalized Diaryl Sulfones

2231

White solid; yield: 0.383 g (59%); mp 79–81 °C.

HRMS (EI): m/z [M]⁺calcd for C₁₅H₁₃O₅ClS: 340.01667; found:

340.017220.

IR (KBr): 3077 (w), 2921 (m), 2851 (m), 1659 (m), 1597 (m), 1495

(w), 1438 (m), 1385 (w), 1348 (m), 1298 (s), 1247 (m), 1199 (s),

1142 (s), 1086 cm^–1(s).

Methyl 3-(4-Chlorophenylsulfonyl)-6-hydroxy-2,5-dimethyl-

benzoate (4t)

Starting with 2c (0.433 g, 1.5 mmol) and 3b (0.452 g, 1.7 mmol), 4t

was isolated after chromatography (silica gel, heptanes–EtOAc).

3

¹H NMR (300 MHz, CDCl₃): d = 0.76 (t, J = 7.4 Hz, 3 H, CH₃),

1.14–1.26 (m, 10 H, 5CH₂), 1.45–1.56 (m, 2 H, CH₂), 2.27 (s, 3 H,

3

PhCH₃), 2.41 (s, 3 H, PhCH₃), 2.56 (t, J = 7.6 Hz, 2 H, PhCH₂),

White solid; yield: 0.255 g (48%); mp 180–182 °C.

3.92 (s, 3 H, OCH₃), 7.13–7.16 (m, 2 H, 2CH_Ar), 7.52–7.58 (m, 2 H,

2CH_Ar), 8.13 (s, 1 H, CH_Ar), 11.22 (s, 1 H, OH).

IR (KBr): 3099 (w), 2969 (w), 2872 (w), 1665 (m), 1602 (w), 1580

(w), 1471 (w), 1415 (m), 1393 (m), 1370 (m), 1304 (m), 1280 (m),

1244 (m), 1202 (m), 1176 (m), 1145 (s), 1086 (s), 1011 cm^–1(m).

¹H NMR (250 MHz, CDCl₃): d = 2.24 (s, 3 H, PhCH₃), 2.46 (s, 3 H,

PhCH₃), 3.86 (s, 3 H, OCH₃), 7.35–7.41 (m, 2 H, 2CH_Ar), 7.64–7.70

(m, 2 H, 2CH_Ar), 8.16 (s, 1 H, CH_Ar), 11.38 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 14.1 18.8, 21.5 (CH₃), 22.6, 29.1,

29.2, 29.4, 29.4, 29.8, 31.8 (CH₂), 52.6 (OCH₃), 114.5

(CCOOCH₃), 127.2 (2CH_Ar), 129.5 (C_Ar), 129.6 (2CH_Ar), 130.8

(C_Ar), 134.8 (CH_Ar), 139.2, 139.5, 143.6 (C_Ar), 163.3 (COH), 171.6

(CO).

MS (EI, 70 eV): m/z (%) = 433 (17), 432 [M]⁺(60), 401 (13), 400

(25), 383 (12), 373 (14), 372 (56), 343 (21), 316 (20), 315 (15), 303

(23), 302 (100), 301 (40), 288 (17), 275 (13), 274 (25), 91 (14).

HRMS (EI): m/z [M]⁺calcd for C₂₄H₃₂O₅S: 432.19650; found:

432.196903.

¹³C NMR (75 MHz, CDCl₃): d = 15.9, 18.9 (CH₃), 52.8 (OCH₃),

114.43 (CCOOCH₃), 125.30 (C_Ar), 128.68 (2CH_Ar), 129.32

(2CH_Ar), 129.94 (C_Ar), 135.45 (CH_Ar), 139.37, 139.79, 140.69 (C_Ar),

164.04 (COH), 171.48 (CO).

MS (EI, 70 eV): m/z (%) = 356 (17), 354 [M]⁺(51), 325 (11), 324

(78), 323 (36), 322 (100), 296 (12), 294 (39), 91 (10).

Methyl 2-Hydroxy-3-methoxy-6-methyl-5-tosylbenzoate (4r)

Starting with 2b (0.402 g, 1.5 mmol) and 3k (0.479 g, 1.7 mmol),

4r was isolated after chromatography (silica gel, heptanes–EtOAc).

HRMS (EI): m/z [M]⁺calcd for C₁₆H₁₅O₅ClS: 354.03232; found:

354.031731.

Yellowish solid; yield: 0.221 g (42%); mp 179–181 °C.

Ethyl 3-(4-Chlorophenylsulfonyl)-5-ethyl-6-hydroxy-2-methyl-

benzoate (4u)

Starting with 2c (0.433 g, 1.5 mmol) and 3c (0.500 g, 1.7 mmol), 4u

was isolated after chromatography (silica gel, heptanes–EtOAc).

IR (KBr): 3411 (w), 3090 (w), 2946 (w), 2845 (w), 1709 (m), 1580

(w), 1483 (m), 1440 (m), 1345 (w), 1289 (m), 1203 (m), 1138 (m),

1089 (m), 1069 (m), 1018 cm^–1(w).

White solid; yield: 0.269 g (47%); mp 144–146 °C.

¹H NMR (250 MHz, CDCl₃): d = 2.30 (s, 3 H, PhCH₃), 2.33 (s, 3 H,

PhCH₃), 3.84 (s, 3 H, OCH₃), 3.93 (s, 3 H, CO₂CH₃), 7.19–7.23 (m,

2 H, 2CH_Ar), 7.60–7.63 (m, 2 H, 2CH_Ar), 7.86 (s, 1 H, CH_Ar), 9.36

(s, 1 H, OH).

IR (KBr): 3100 (w), 2968 (w), 2872 (w), 1666 (m), 1603 (w), 1564

(w), 1471 (w), 1416 (w), 1393 (m), 1370 (m), 1304 (m), 1280 (m),

1254 (m), 1203 (m), 1177 (m), 1145 (s), 1085 (s), 1010 cm^–1(m).

¹³C NMR (75 MHz, CDCl₃): d = 17.4, 21.5 (CH₃), 52.7 (COOCH₃),

56.6 (OCH₃), 114.4 (CH_Ar), 118.4 (CCOOCH₃), 127.30 (2CH_Ar),

129.6 (2CH_Ar), 130.8, 131.6, 138.8, 143.8, 145.6 (C_Ar), 152.4

(COH), 169.52 (CO).

MS (EI, 70 eV): m/z (%) = 350 [M]⁺(50), 320 (11), 319 (40), 318

(100), 290 (45), 289 (11), 288 (11).

¹H NMR (250 MHz, CDCl₃): d = 1.19 (t, ³J = 7.5 Hz, 3 H,

CH₂CH₃), 1.31 (t, ³J = 7.1 Hz, 3 H, OCH₂CH₃), 2.48 (s, 3 H,

PhCH₃), 2.66 (q, ³J = 7.6 Hz, 2 H, CH₂CH₃), 4.35 (q, ³J = 7.1 Hz, 2

H, OCH₂CH₃), 7.36–7.42 (m, 2 H, 2CH_Ar), 7.65–7.70 (m, 2 H,

2CH_Ar), 8.16 (s, 1 H, CH_Ar), 11.51 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 12.3, 13.3, 17.9 (CH₃), 22.0, 61.5

(CH₂), 113.7 (CCOOCH₃), 127.6 (2CH_Ar), 128.3 (2CH_Ar), 129.0,

130.6 (C_Ar), 132.9 (CH_Ar), 138.3, 138.7, 139.7 (C_Ar), 162.8 (COH),

170.0 (CO).

HRMS (EI): m/z [M]⁺calcd for C₁₇H₁₈O₆S: 350.08186; found:

350.081087.

Methyl 3-(4-Chlorophenylsulfonyl)-6-hydroxy-2-methylben-

zoate (4s)

MS (EI, 70 eV): m/z (%) = 384 (16), 382 [M]⁺(46), 339 (10), 338

(52), 337 (31), 336 (100), 310 (43), 309 (16), 308 (94).

Starting with 2c (0.433 g, 1.5 mmol) and 3a (0.429 g, 1.7 mmol), 4s

was isolated after chromatography (silica gel, heptanes–EtOAc).

HRMS (EI): m/z [M]⁺calcd for C₁₈H₁₉O₅ClS: 382.06362; found:

382. 063783.

White solid; yield: 0.240 g (47%); mp 126–127 °C.

Methyl 5-Butyl-3-(4-chlorophenylsulfonyl)-6-hydroxy-2-meth-

ylbenzoate (4v)

Starting with 2c (0.433g, 1.5mmol) and 3d (0.522g, 1.7 mmol), 4v

was isolated after chromatography (silica gel, heptanes–EtOAc).

IR (KBr): 3078 (w), 3024 (w), 2956 (w), 2848 (w), 2789 (w), 1673

(m), 1578 (m), 1503 (w), 1478 (w), 1435 (m), 1351 (m), 1309 (s),

1292 (m), 1223 (m), 1191 (m), 1158 (m), 1145 (s), 1109 (m), 1080

(s), 1031 cm^–1(m).

White solid; yield: 0.321 g (54%); mp 88–90 °C.

¹H NMR (300 MHz, CDCl₃): d = 2.46 (s, 3 H, PhCH₃), 3.82 (s, 3 H,

OCH₃), 6.90 (d, ³J = 7.5 Hz, 1 H, CH_Ar), 7.33–7.35 (m, 2 H, 2CH_Ar),

7.60–7.63 (m, 2 H, 2CH_Ar), 8.23 (d, ³J = 7.5 Hz, 1 H, CH_Ar), 11.11

(s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 19.2 (CH₃), 52.9 (OCH₃), 115.2

(CCOOCH₃), 116.0 (CH_Ar), 128.7 (2CH_Ar), 129.4 (2CH_Ar), 131.0

(C_Ar), 135.3 (CH_Ar), 139.5, 140.4, 142.7 (C_Ar), 165.5 (COH), 171.0

(CO).

IR (KBr): 2956 (w), 2929 (w), 2860 (w), 2257 (w), 1737 (w), 1665

(m), 1602 (w), 1572 (w), 1477 (w), 1439 (m), 1394 (w), 1346 (m),

1310 (m), 1294 (m), 1278 (m), 1245 (w), 1201 (m), 1162 (m), 1144

(s), 1086 (s), 1064 (w), 1014 (w), 1002 (w) cm^–1.

3

¹H NMR (250 MHz, CDCl₃): d = 0.81 (t, J = 6.9 Hz, 3 H, CH₃),

1.18–1.33 (m, 2 H, CH₂), 1.42–1.54 (m, 2 H, CH₂), 2.39 (s, 3 H,

3

PhCH₃), 2.56 (t, J = 8.1 Hz, 2 H, PhCH₂), 3.79 (s, 3 H, OCH₃),

7.21–7.42 (m, 2 H, 2CH_Ar), 7.52–7.67 (m, 2 H, 2CH_Ar), 8.08 (s, 1

H, CH_Ar), 11.31 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 13.9, 18.9 (CH₃), 22.5, 29.6, 31.2

(CH₂), 52.8 (OCH₃), 114.7 (CCOOCH₃), 128.7 (2CH_Ar), 129.3

MS (EI, 70 eV): m/z (%) = 342 [M⁺] (³⁷Cl) (10), 340 [M⁺] (³⁵Cl)

(25), 310 (40), 309 (24), 308 (100), 291 (16), 289 (12), 275 (11),

255 (28), 243 (10), 242 (11), 152 (14), 149 (10), 121 (13), 111 (14),

105 (22), 77 (24), 76 (13), 75 (16), 51(17).

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M. Shkoor et al.

PAPER

(2CH_Ar), 129.8, 130.0 (C_Ar), 134.8 (CH_Ar), 139.4, 139.7, 140.7

(C_Ar), 163.8 (COH), 171.5 (CO).

Methyl 3-(4-Chlorophenylsulfonyl)-6-hydroxy-2-methyl-5-oc-

tylbenzoate (4y)

Starting with 2c (0.288 g, 1.0 mmol) and 3h (0.409 g, 1.1 mmol), 4y

was isolated after chromatography (silica gel, heptanes–EtOAc).

MS (EI, 70 eV): m/z (%) = 398 [M⁺] (³⁷Cl) (13), 396 [M⁺] (³⁵Cl)

(35), 364 (18), 336 (53), 322 (100), 294 (28), 220 (3), 188 (15), 165

(5), 116 (3), 91 (5), 77 (5), 57 (4), 43 (5).

Yellowish solid; yield: 0.235 g (52%); mp 82–82 °C.

HRMS (EI): m/z [M]⁺(³⁵Cl) calcd for C₁₉H₂₁O₅ClS: 396.07927;

found: 396.079088.

IR (KBr): 2953 (w), 2923 (m), 2853 (w), 1663 (m), 1568 (w), 1476

(w), 1436 (m), 1393 (w), 1345 (m), 1312 (m), 1293 (m), 1246 (m),

1200 (m), 1143 (s), 1085 (s), 1062 (m), 1012 (m), 1000 cm^–1(m).

Methyl 3-(4-Chlorophenylsulfonyl)-5-hexyl-6-hydroxy-2-meth-

ylbenzoate (4w)

Starting with 2c (0.288 g, 1.0 mmol) and 3f (0.379 g, 1.1 mmol), 4w

was isolated after chromatography (silica gel, heptanes–EtOAc).

3

¹H NMR (250 MHz, CDCl₃): d = 0.81 (t, J = 6.8 Hz, 3 H, CH₃),

1.16–1.25 (m, 10 H, 5CH₂), 1.50–1.55 (m, 2 H, CH₂), 2.46 (s, 3 H,

PhCH₃), 2.62 (t, J = 7.6 Hz, 2 H, PhCH₂), 3.86 (s, 3 H, OCH₃),

7.36–7.41 (m, 2 H, 2CH_Ar), 7.63–7.69 (m, 2 H, 2CH_Ar), 8.15 (s, 1

H, CH_Ar), 11.39 (s, 1 H, OH).

3

White solid; yield: 0.212 g (50%); mp 91–93 °C.

IR (KBr): 3076 (w), 2954 (w), 2923 (w), 2858 (w), 1660 (m), 1564

(w), 1503 (w), 1479 (w), 1430 (m), 1414 (m), 1395 (m), 1336 (m),

1277 (m), 1243 (m), 1199 (m), 1158 (m), 1139 (s), 1086 (m), 1064

(m), 1011 cm^–1(m).

¹³C NMR (75 MHz, CDCl₃): d = 13.0, 17.9 (CH₃), 21.6, 28.0, 28.2,

28.4, 28.5, 28.8, 30.8 (CH₂), 51.7 (OCH₃), 113.6 (CCOOCH₃),

127.6 (2CH_Ar), 128.3 (2CH_Ar), 128.8, 129.0 (C_Ar), 133.7 (CH_Ar),

138.3, 138.6, 139.7 (C_Ar), 162.7 (COH), 170.5 (CO).

¹H NMR (250 MHz, CDCl₃): d = 0.83 (t, J = 7.0 Hz, 3 H, CH₃),

MS (EI, 70 eV): m/z (%) = 454 [M⁺] (³⁷Cl) (23), 452 [M⁺] (³⁵Cl)

(68), 422 (13), 420 (30), 403 (11), 394 (10), 392 (28), 363 (23), 335

(13), 324 (44), 322 (100), 308 (15).

3

1.21–1.31 (m, 6 H, 3CH₂), 1.53–1.57 (m, 2 H, CH₂), 2.46 (s, 3 H,

PhCH₃), 2.63 (t, J = 7.4 Hz, 2 H, PhCH₂), 3.87 (s, 3 H, OCH₃),

3

7.36–7.42 (m, 2 H, 2CH_Ar), 7.46–7.70 (m, 2 H, 2CH_Ar), 8.15 (s, 1

H, CH_Ar), 11.40 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 14.0, 18.9 (CH₃), 22.6, 29.0, 29.1,

29.8, 31.6 (CH₂), 52.7 (OCH₃), 114.3 (CCOOCH₃), 128.6 (2CH_Ar),

129.3 (2CH_Ar), 129.8, 130.0 (C_Ar), 134.8 (CH_Ar), 139.3, 139.6,

140.7 (C_Ar), 163.7 (COH), 171.5 (CO).

MS (EI, 70 eV): m/z (%) = 426 [M⁺] (³⁷Cl) (25), 424 [M⁺] (³⁵Cl)

(73), 394 (14), 392 (35), 375 (15), 366 (16), 365 (17), 364 (47), 363

(25), 336 (12), 335 (18), 324 (61), 323 (45), 322 (100), 321 (44),

296 (14), 294 (40).

HRMS (EI): m/z [M]⁺(³⁵Cl) calcd for C₂₃H₂₉O₅ClS: 452.14187;

found: 452.141122.

Methyl 4¢-Chloro-5-(4-chlorophenylsulfonyl)-2-hydroxy-4-

methylbiphenyl-3-carboxylate (4z)

Starting with 2c (0.433 g, 1.5 mmol) and 3l (0.612 g, 1.7 mmol), 4z

was isolated after chromatography (silica gel, heptanes–EtOAc).

Yellow solid; yield: 0.325 g (48%); mp 178–180 °C.

IR (KBr): 3070 (w), 3004 (w), 2955 (w), 2929 (w), 2852 (w), 2256

(w), 1741 (w), 1723 (w), 1665 (m), 1583 (w), 1552 (w), 1492 (w),

1477 (w), 1434 (m), 1393 (m), 1311 (m), 1279 (w), 1206 (m), 1178

(m), 1148 (m), 1090 (m), 1042 (w), 1014 cm^–1(m).

HRMS (EI): m/z [M]⁺(³⁵Cl) calcd for C₂₁H₂₅O₅ClS: 424.11057;

found: 424.109531.

¹H NMR (250 MHz, CDCl₃): d = 2.53 (s, 3 H, PhCH₃), 3.90 (s, 3 H,

OCH₃), 7.33–7.48 (m, 6 H, 6CH_Ar), 7.54–7.82 (m, 2 H, 2CH_Ar),

8.35 (s, 1 H, CH_Ar), 11.55 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 19.1 (CH₃), 53.1 (OCH₃), 115.9

(CCOOCH₃), 127.6 (C_Ar), 128.6 (2CH_Ar), 128.8 (2CH_Ar), 129.5

(2CH_Ar), 130.7 (2CH_Ar), 130.9, 131.1, 134.1 (C_Ar), 135.4 (CH_Ar),

139.7, 140.3, 141.6 (C_Ar), 162.4 (COH), 171.3 (CO).

MS (EI, 70 eV): m/z (%) = 452 [M⁺] (³⁷Cl) (9), 450 [M⁺] (³⁵Cl) (12),

422 (10), 421 (14), 420 (66), 419 (23), 418 (100), 384 (2), 291 (3),

214 (12), 186 (13), 152 (26), 139 (12), 111 (11), 86 (12), 67 (15), 43

(27).

Methyl 3-(4-Chlorophenylsulfonyl)-5-heptyl-6-hydroxy-2-

methylbenzoate (4x)

Starting with 2c (0.433 g, 1.5 mmol) and 3g (0.591 g, 1.7 mmol), 4x

was isolated after chromatography (silica gel, heptanes–EtOAc).

Yellowish oil; yield: 0.335 g (51%).

IR (KBr): 2954 (w), 2926 (m), 2855 (w), 2257 (w), 1737 (w), 1666

(m), 1602 (w), 1572 (w), 1477 (w), 1439 (w), 1346 (w), 1314 (m),

1247 (w), 1202 (m), 1146 (m), 1088 (m), 1013 cm^–1(w).

3

¹H NMR (250 MHz, CDCl₃): d = 0.82 (t, J = 7.3 Hz, 3 H, CH₃),

1.18–1.28 (m, 8 H, 4CH₂), 1.51–1.59 (m, 2 H, CH₂), 2.46 (s, 3 H,

3

PhCH₃), 2.62 (t, J = 7.5 Hz, 2 H, PhCH₂), 3.84 (s, 3 H, OCH₃),

HRMS (EI): m/z [M]⁺(³⁵Cl) calcd for C₂₁H₁₆O₅Cl₂S: 450.00900;

found: 450.008249.

7.37–7.40 (m, 2 H, 2CH_Ar), 7.65–7.68 (m, 2 H, 2CH_Ar), 8.15 (s, 1

H, CH_Ar), 11.38 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 13.0, 17.9 (CH₃), 21.6, 28.0, 28.1,

28.4, 28.9, 30.8 (CH₂), 51.8 (OCH₃), 113.6 (CCOOCH₃), 127.6

(2CH_Ar), 128.3 (2CH_Ar), 128.8, 129.0 (C_Ar), 133.8 (CH_Ar), 138.3,

138.7, 139.7 (C_Ar), 162.7 (COH), 170.5 (CO).

MS (EI, 70 eV): m/z (%) = 440 (18), 439 (11), 438 [M]⁺(46), 408

(14), 407 (14), 406 (31), 389 (13), 380 (13), 379 (10), 378 (35), 365

(11), 364 (10), 363 (27), 336 (11), 335 (14), 324 (37), 323 (31), 322

(100), 321 (33), 308 (12), 296 (14), 295 (12), 294 (31), 288 (11),

231 (10), 230 (11), 111 (11), 97 (13), 85 (12), 83 (13), 71 (17), 69

(17), 59 (15), 57 (24), 55 (16).

Methyl 5-(4-Chlorophenylsulfonyl)-2-hydroxy-4,4¢-dimethyl-

biphenyl-3-carboxylate (4aa)

Starting with 2c (0.433 g, 1.5 mmol) and 3m (0.578 g, 1.7 mmol),

4aa was isolated after chromatography (silica gel, heptanes–

EtOAc).

Yellow solid; yield: 0.342 g (53%); mp 186–189 °C.

IR (KBr): 3101 (w), 3007 (w), 2951 (w), 2919 (w), 2855 (w), 1738

(w), 1664 (m), 1631 (w), 1604 (w), 1573 (w), 1547 (w), 1514 (w),

1477 (w), 1441 (m), 1431 (m), 1394 (w), 1348 (w), 1308 (s), 1281

(m), 1206 (m), 1178 (m), 1148 (s), 1120 (w), 1090 (m), 1043 (w),

1021 (w), 1012 (w), 1000 cm^–1(w).

HRMS (EI): m/z [M]⁺calcd for C₂₂H₂₇ClO₅S: 438.12622; found:

438.126117.

¹H NMR (250 MHz, CDCl₃): d = 2.34 (s, 3 H, PhCH₃), 2.52 (s, 3 H,

PhCH₃), 3.89 (s, 3 H, OCH₃), 7.18–7.22 (m, 2 H, 2CH_Ar), 7.37–7.40

(m, 2 H, 2CH_Ar), 7.41–7.42 (m, 2 H, 2CH_Ar), 7.62–7.73 (m, 2 H,

2CH_Ar), 8.35 (s, 1 H, CH_Ar), 11.19 (s, 1 H, OH).

PAPER

Synthesis of Functionalized Diaryl Sulfones

2233

¹³C NMR (75 MHz, CDCl₃): d = 19.0, 21.3 (CH₃), 53.0 (OCH₃),

116.2 (CCOOCH₃), 128.7 (C_Ar), 128.9 (2CH_Ar), 129.2 (2CH_Ar),

129.3 (2CH_Ar), 129.4 (2CH_Ar), 130.9, 132.6 (C_Ar), 135.4 (CH_Ar),

138.1, 139.6, 140.4, 140.7 (C_Ar), 162.1 (COH), 171.2 (CO).

MS (EI, 70 eV): m/z (%) = 432 [M⁺] (³⁷Cl) (8), 430 [M⁺] (³⁵Cl) (20),

398 (100), 362 (4), 320 (19), 293 (4), 275 (6), 233 (26), 219 (10),

189 (10), 165 (14), 128 (57), 105 (37), 97 (6), 86 (73), 69 (16).

Methyl 4-Butyl-2-hydroxy-4¢-methyl-5-(phenylsulfonyl)biphe-

nyl-3-carboxylate (4ad)

Starting with 2d (0.445 g, 1.5 mmol) and 3m (0.578 g, 1.7 mmol),

4ad was isolated after chromatography (silica gel, heptanes–

EtOAc).

Yellowish oil; yield: 0.494 g (75%).

IR (KBr): 2956 (w), 2929 (w), 2872 (w), 2255 (w), 1736 (w), 1664

(m), 1601 (w), 1573 (w), 1551 (w), 1514 (w), 1446 (m), 1437 (m),

1399 (w), 1307 (m), 1202 (m), 1178 (m), 1147 (s), 1093 (m), 1023

cm^–1(w).

HRMS (EI): m/z [M]⁺(³⁵Cl) calcd for C₂₂H₁₉O₅ClS: 430.07145;

found: 430.07204.

Methyl 2-Butyl-6-hydroxy-3-(phenylsulfonyl)benzoate (4ab)

Starting with 2d (0.445 g, 1.5 mmol) and 3a (0.429 g, 1.7 mmol),

4ab was isolated after chromatography (silica gel, heptanes–

EtOAc).

3

¹H NMR (250 MHz, CDCl₃): d = 0.69 (t, J = 7.0 Hz, 3 H, CH₃),

0.91–1.04 (m, 2 H, CH₂), 1.09–1.18 (m, 2 H, CH₂), 2.28 (s, 3 H,

PhCH₃), 3.01 (t, ³J = 8.0 Hz, 2 H, PhCH₂), 3.82 (s, 3 H, OCH₃), 7.15

(d, ³J = 7.8 Hz, 2 H, 2CH_Ar), 7.34–7.44 (m, 5 H, 5CH_Ar), 7.70–7.74

(m, 2 H, 2CH_Ar), 8.35 (s, 1 H, CH_Ar), 10.93 (s, 1 H, OH).

Yellowish oil; yield: 0.403 g (77%).

IR (KBr): 3339 (w, br), 3065 (w), 2956 (w), 2931 (w), 2872 (w),

2256 (w), 1732 (m), 1665 (m), 1598 (m), 1576 (m), 1446 (m), 1396

(w), 1380 (w), 1347 (w), 1302 (s), 1225 (m), 1210 (m), 1143 (s),

1107 (s), 1076 (m), 1012 cm^–1(m).

¹³C NMR (75 MHz, CDCl₃): d = 13.72, 21.3 (CH₃), 23.4, 30.9, 33.9

(CH₂), 52.9 (OCH₃), 115.8 (CCOOCH₃), 127.2 (2CH_Ar), 128.6

(C_Ar), 129.1 (2CH_Ar), 129.2 (4CH_Ar), 131.1, 132.8 (C_Ar), 132.9,

135.8 (CH_Ar), 138.0, 142.7, 145.8 (C_Ar), 161.9 (COH), 171.2 (CO).

¹H NMR (250 MHz, CDCl₃): d = 0.68 (t, J = 7.4 Hz, 3 H, CH₃),

MS (EI, 70 eV): m/z (%) = 438 [M⁺] (60), 408 (21), 407 (73), 406

3

1.05–1.17 (m, 2 H, CH₂), 1.31–1.43 (m, 2 H, CH₂), 3.01 (t,

³J = 8.03 Hz, 2 H, PhCH₂), 3.82 (s, 3 H, OCH₃), 6.90 (d, ³J = 9.0 Hz,

1 H, CH_Ar), 7.35–7.47 (m, 3 H, 3CH_Ar), 7.68–7.72 (m, 2 H, 2CH_Ar),

8.28 (d, ³J = 9.0 Hz, 1 H, CH_Ar), 10.97 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 13.7 (CH₃), 23.3, 30.9, 33.9 (CH₂),

52.9 (OCH₃), 115.1 (CCOOCH₃), 115.9 (CH_Ar), 127.2 (2CH_Ar),

129.2 (2CH_Ar), 131.1 (C_Ar), 132.9 (CH_Ar), 135.6 (C_Ar), 142.5, 147.8

(C_Ar), 165.3 (COH), 170.9 (CO).

MS (EI, 70 eV): m/z (%) = 348 [M⁺] (9), 331 (6), 313 (18), 306 (6),

281 (22), 254 (8), 239 (50), 231 (14), 211 (100), 198 (12), 165 (55),

141 (82), 125 (54), 98 (18), 85 (29), 77 (97), 69 (28), 57 (38), 43

(28).

(100), 377 (8), 335 (3), 223 (15), 195 (62), 165 (14), 119 (10), 91

(7).

HRMS (EI): m/z [M]⁺calcd for C₂₅H₂₆O₅S: 438.15737; found:

438.15819.

Methyl 3-Hydroxy-4¢-nitro-6-tosylbiphenyl-2-carboxylate (4ae)

Starting with 2e (0.563 g, 1.5 mmol) and 3a (0.429 g, 1.7 mmol),

4ae was isolated after chromatography (silica gel, heptanes–

EtOAc).

White solid; yield: 0.289 g (45%); mp 196–198 °C.

IR (KBr): 3400 (w), 3106 (w), 3018 (w), 2924 (w), 2857 (w), 1703

(m), 1650 (w), 1593 (w), 1576 (m), 1515 (m), 1445 (w), 1433 (w),

1380 (w), 1347 (m), 1286 (m), 1183 (w), 1147 (m), 1119 (m), 1079

(m), 1017 cm^–1(w).

HRMS (EI): m/z [M]⁺calcd for C₁₈H₂₀O₅S: 348.11042; found:

348.11064.

¹H NMR (300 MHz, CDCl₃): d = 2.30 (s, 3 H, PhCH₃), 3.20 (s, 3 H,

OCH₃), 6.91–6.94 (m, 2 H, 2CH_Ar), 6.96–7.02 (m, 4 H, 4CH_Ar),

7.19 (d, ³J = 8.5 Hz, 1 H, CH_Ar), 7.89–7.92 (m, 2 H, 2CH_Ar), 8.47

(d, ³J = 8.5 Hz, 1 H, CH_Ar), 11.28 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 21.7 (CH₃), 52.9 (OCH₃), 113.9

(CCOOCH₃), 118.4 (CH_Ar), 121.5 (2CH_Ar), 127.2 (2CH_Ar), 129.2

(2CH_Ar), 130.8 (2CH_Ar), 132.2 (C_Ar), 135.0 (CH_Ar), 138.2., 142.4,

143.4, 144.1, 147.0 (C_Ar), 165.0 (COH), 169.7 (CO).

MS (EI, 70 eV): m/z (%) = 427 [M]⁺(36), 396 (19), 395 (100), 139

(12), 91 (8).

HRMS (EI): m/z [M]⁺calcd for C₂₁H₁₇O₇NS: 427.07202; found:

427.071814.

Methyl 2-Butyl-6-hydroxy-5-methyl-3-(phenylsulfonyl)ben-

zoate (4ac)

Starting with 2d (0.445 g, 1.5 mmol) and 3b (0.452 g, 1.7 mmol),

4ac was isolated after chromatography (silica gel, heptanes–

EtOAc).

Yellowish solid; yield: 0.430 g (79%); mp 113–115 °C.

IR (KBr): 3067 (w), 2957 (w), 2930 (w), 2872 (w), 1737 (w), 1664

(w), 1604 (w), 1568 (w), 1446 (w), 1439 (w), 1381 (w), 1347 (w),

1304 (m), 1250 (w), 1200 (w), 1163 (m), 1144 (m), 1087 (m), 1042

cm^–1(w).

3

¹H NMR (250 MHz, CDCl₃): d = 0.71 (t, J = 7.4 Hz, 3 H, CH₃),

0.91–0.99 (m, 2 H, CH₂), 1.10–1.18 (m, 2 H, CH₂), 2.25 (s, 3 H,

3

PhCH₃), 3.04 (t, J = 7.4 Hz, 2 H, PhCH₂), 3.86 (s, 3 H, OCH₃),

Methyl 3-Hydroxy-4-methyl-4¢-nitro-6-tosylbiphenyl-2-carbox-

ylate (4af)

Starting with 2e (0.563 g, 1.5 mmol) and 3b (0.452 g, 1.7 mmol),

4af was isolated after chromatography (silica gel, heptanes–

EtOAc).

7.39–7.52 (m, 3 H, 3CH_Ar), 7.72–7.75 (m, 2 H, 2CH_Ar), 8.23 (s, 1

H, CH_Ar), 11.41 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 13.7, 16.1 (CH₃), 23.4, 30.8, 34.0

(CH₂), 52.8 (OCH₃), 113.7 (CCOOCH₃), 125.3 (C_Ar), 127.1

(2CH_Ar), 129.1 (2CH_Ar), 130.1 (C_Ar), 132.8 (CH_Ar), 136.0 (CH_Ar),

142.9, 145.1(C_Ar), 164.2 (COH), 171.6 (CO).

MS (EI, 70 eV): m/z (%) = 362 [M⁺] (37), 345 (6), 330 (90), 313 (8),

295 (26), 260 (6), 239 (4), 211 (10), 189 (89), 179 (100), 161 (34),

147 (55), 125 (26), 119 (12), 91 (15), 69 (26), 57 (16), 43 (22).

Yellow solid; yield: 0.324 g (49%); mp 180–182 °C.

IR (KBr): 3078 (w), 2925 (w), 2854 (w), 2256 (w), 1668 (m), 1597

(w), 1564 (w), 1518 (m), 1440 (w), 1380 (w), 1346 (s), 1302 (m),

1251 (m), 1148 (s), 1117 (m), 1084 (w), 1017 cm^–1(w).

¹H NMR (250 MHz, CDCl₃): d = 2.30 (s, 3 H, PhCH₃), 2.35 (s, 3 H,

PhCH₃), 3.24 (s, 3 H, OCH₃), 6.87–7.02 (m, 6 H, 6CH_Ar), 7.86–7.91

(m, 2 H, 2CH_Ar), 8.35 (s, 1 H, CH_Ar), 11.53 (s, 1 H, OH).

HRMS (EI): m/z [M]⁺calcd for C₁₉H₂₂O₅S: 362.12607; found:

362.12619.

¹³C NMR (75 MHz, CDCl₃): d = 16.2, 21.6 (CH₃), 52.5 (OCH₃),

113.1 (CCOOCH₃), 121.5 (2CH_Ar), 127.1 (2CH_Ar), 128.2 (C_Ar),

2234

M. Shkoor et al.

PAPER

129.2 (2CH_Ar), 131.0 (CH_Ar), 131.2 (C_Ar), 135.1(2CH_Ar), 138.4,

139.8, 143.8, 143.9, 146.9 (C_Ar), 163.5 (COH), 170.3 (CO).

MS (EI, 70 eV): m/z (%) = 441 [M]⁺(37), 411 (10), 410 (23), 409

(100), 363 (20), 254 (22), 253 (19).

HRMS (EI): m/z [M]⁺calcd for C₂₂H₁₉NO₇S: 441.08767; found:

McCombie, S. W.; Steensma, R. W.; Lin, S.-I.; Nazareno,

D. V.; Baroudy, B.; Vantuno, N.; Xu, S.; Liu, J. Bioorg.

Med. Chem. Lett. 2001, 11, 2143.

(9) Stanton, J. L.; Cahill, E.; Dotson, R.; Tan, J.; Tomaselli,

H. C.; Wasvary, J. M.; Stephan, Z. F.; Steele, R. E. Bioorg.

Med. Chem. Lett. 2000, 10, 1661.

441.087563.

(10) (a) Kozlowski, J. A.; Zhou, G.; Tagat, J. R.; Lin, S.-I.;

McCombie, S. W.; Ruperto, V. B.; Duffy, R. A.; McQuade,

R. A.; Crosby, G.; Taylor, L. A.; Billard, W. Bioorg. Med.

Chem. Lett. 2002, 12, 791. (b) Wang, Y.; Chackalamannil,

S.; Hu, Z.; Clader, J. W.; Greenlee, W.; Billard, W.; Binch,

H.; Crosby, G.; Ruperto, V.; Duffy, R. A.; McQuade, R.;

Lachowicz, J. E. Bioorg. Med. Chem. Lett. 2000, 10, 2247.

(c) Boyle, C. D.; Chackalamannil, S.; Chen, L.-Y.; Dugar,

S.; Pushpavanam, P.; Billard, W.; Binch, H.; Crosby, G.;

Cohen-Williams, M.; Coffin, V. L.; Duffy, R. A. Bioorg.

Med. Chem. Lett. 2000, 10, 2727. (d) Wang, Y.;

Methyl 4-Butyl-3-hydroxy-4¢-nitro-6-tosylbiphenyl-2-carbox-

ylate (4ag)

Starting with 2e (0.563 g, 1.5 mmol) and 3d (0.522 g, 1.7 mmol),

4ag was isolated after chromatography (silica gel, heptanes–

EtOAc).

Yellowish solid; yield: 0.340 g (47%); mp 130–133 °C.

IR (KBr): 3115 (w), 3088 (w), 2917 (w), 2850 (w), 1731 (w), 1651

(m), 1596 (m), 1516 (m), 1493 (w), 1465 (w), 1398 (m), 1344 (m),

1288 (m), 1181 (m), 1149 (m), 1121 (m), 1081 (m), 1012 cm^–1(m).

Chackalamannil, S.; Chang, W.; Greenlee, W.; Ruperto, V.;

Duffy, R. A.; McQuade, R.; Lachowicz, J. E. Bioorg. Med.

Chem. Lett. 2001, 11, 891. (e) Boyle, C. D.;

Chackalamannil, S.; Clader, J. W.; Greenlee, W. J.; Josien,

H. B.; Kaminski, J. J.; Kozlowski, J. A.; McCombie, S. W.;

Nazareno, D. V.; Tagat, J. R.; Wang, Y. Bioorg. Med. Chem.

Lett. 2001, 11, 2311. (f) Boyle, C. D.; Vice, S. F.; Campion,

J.; Chackalamannil, S.; Lankin, C. M.; McCombie, S. W.;

Billard, W.; Binch, H.; Crosby, G.; Williams, M.-C.; Coffin,

V. L. Bioorg. Med. Chem. Lett. 2002, 12, 3479.

3

¹H NMR (250 MHz, CDCl₃): d = 0.60 (t, J = 6.3 Hz, 3 H, CH₃),

1.22–1.30 (m, 2 H, CH₂), 1.59–1.63 (m, 2 H, CH₂), 2.30 (s, 3 H,

3

PhCH₃), 2.75 (t, J = 6.9 Hz, 2 H, PhCH₂), 3.25 (s, 3 H, OCH₃),

6.90–6.93 (m, 2 H, 2CH_Ar), 6.95–7.02 (m, 4 H, 4CH_Ar), 7.83–7.91

(m, 2 H, 2CH_Ar), 8.36 (s, 1 H, CH_Ar), 11.70 (s, 1 H, OH).

¹³C NMR (75 MHz, CDCl₃): d = 12.2, 20.5 (CH₃), 22.2, 28.6, 32.3

(CH₂), 52.8 (OCH₃), 112.2 (CCOOCH₃), 120.5 (2CH_Ar), 126.1

(2CH_Ar), 126.9 (C_Ar), 128.2 (2CH_Ar), 130.2 (2CH_Ar), 132.5 (CH_Ar),

132.8, 137.5, 138.7, 142.9, 143.0, 146.0 (C_Ar), 163.7 (COH), 169.0

(CO).

MS (EI, 70 eV): m/z (%) = 483 [M]⁺(35), 424 (33), 406 (27), 395

(100), 165 (11), 139 (16), 91 (16).

(11) Sasse, A.; Ligneau, X.; Sadek, B.; Elz, S.; Pertz, H. H.;

Ganellin, C. R.; Arrang, J.-M.; Schwartz, J.-C.; Schunack,

W.; Stark, H. Arch. Pharm. (Weinheim, Ger.) 2001, 334, 45.

(12) Langler, R. F.; Paddock, R. L.; Thompson, D. B.; Crandall,

I.; Ciach, M.; Kain, K. C. Aust. J. Chem. 2003, 56, 1127.

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HRMS (EI): m/z [M]⁺calcd for C₂₅H₂₅O₇NS: 483.13485; found:

483.133950.

Acknowledgment

(14) Lavey, B. J.; Kozlowski, J. A.; Hipkin, R. W.; G onsiorek,

W.; Lundell, D. J.; Piwinski, J. J.; Narula, S.; Lunn, C. A.

Bioorg. Med. Chem. Lett. 2005, 15, 783.

(15) Lu, I.-L.; Mahindroo, N.; Liang, P.-H.; Peng, Y.-H.; Kuo,

C.-J.; Tsai, K.-C.; Hsieh, H.-P.; Chao, Y.-S.; Wu, S.-Y.

J. Med. Chem. 2006, 9, 5154.

Financial support by the State of Mecklenburg-Vorpommern (scho-

larship for M. S.) is gratefully acknowledged.

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Article Doi

Diversity-oriented synthesis of functionalized diaryl sulfones by regioselective [3+3] cyclizations of 1,3-bis(siloxy)buta-1,3-dienes with 2-(arylsulfonyl)-3-ethoxy-2-en-1-ones: Scope and limitations

DOI: 10.1055/s-0029-1216801

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Article abstract of DOI:10.1055/s-0029-1216801

Full text of DOI:10.1055/s-0029-1216801

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