Aryl(chloro)methyl 4-tolyl sulfoxides: Synthesis and application to the synthesis of α-aryl ketones

PAPER

3615

Aryl(chloro)methyl 4-Tolyl Sulfoxides: Synthesis and Application to the

Synthesis of a-Aryl Ketones

A

ryl(chloro)m

h

e

thyl 4-Toly

i

l

Sulfo

g

Graduate School of Chemical Sciences and Technology, Tokyo University of Science, Ichigaya-Funagawara-machi 12, Shinjuku-ku,

Tokyo 162-0826, Japan

Fax 81(3)52614631; E-mail: tsatoh@rs.kagu.tus.ac.jp

Received 21 July 2011; revised 25 August 2011

mologation and elongation of carbonyl compounds

Abstract: Aryl(chloro)methyl 4-tolyl sulfoxides were synthesized

through the magnesium b-oxido carbenoid rearrange-

from arylmethyl 4-tolyl sulfoxides in moderate-to-good yields by

sequential treatment with lithium diisopropylamide and tosyl chlo-

ride at low temperatures. Treatment of the lithium a-sulfinyl car-

ment, we recently began to study the synthesis of ar-

yl(chloro)methyl 4-tolyl sulfoxides 2b and their use in the

banion of the aryl(chloro)methyl 4-tolyl sulfoxides with aldehydes synthesis of a-aryl carbonyl compounds 6b from carbonyl

or ketones resulted in the formation of adducts in good-to-high

compounds by a one-carbon homologation or elongation

yields. Treatment of these adducts with tert-butylmagnesium chlo-

process (Scheme 1). Here, we wish to report a general

ride gave the corresponding magnesium alkoxides. On treatment

method for the synthesis of aryl(chloro)methyl 4-tolyl sul-

with isopropylmagnesium chloride, the alkoxides gave the corre-

foxides 2b and for the elongation and homologation of al-

sponding magnesium b-oxido carbenoids, which rearranged to give

dehydes and ketones, respectively, to give a-aryl ketones

6b (R = Ar) by using sulfoxides 2b as the one-carbon ho-

mologating agents.

a-aryl ketones in good-to-high yields. The magnesium enolate in-

termediates generated by rearrangement of the b-oxido carbenoids

could also be trapped with electrophiles to give a-aryl a-substituted

ketones. These procedures offer a good method for the synthesis of

a variety of a-aryl ketones from aldehydes and ketones.

Cl

Key words: sulfoxides, a-aryl ketones, homologations, aldehydes

RCHS(O)Tol

R¹

R²

R¹

R²

2

1) base

OH

O

LDA

Cl

2) t-BuLi

or R³MgCl

The b-oxido carbenoid rearrangement is one of the most

useful reactions for the homologation or elongation of car-

bonyl compounds.¹Several methods for the homologation

of carbonyl compounds by using the b-oxido carbenoid

rearrangement as the key reaction have been reported.^2–6

We have been interested for long time in the homologa-

tion and elongation of carbonyl compounds by the b-oxi-

do carbenoid rearrangement as the key reaction. Our

previous method⁷was based on the rearrangement of lith-

ium b-oxido carbenoids 4a (M = Li) derived from adducts

of carbonyl compounds 1 with the lithium a-sulfinyl car-

banion of 1-chloroalkyl 4-tolyl sulfoxides 2a (Scheme 1).

The rearrangement gives enolates 5a as the intermediates,

and one-carbon homologated carbonyl compounds 6a are

obtained on treating enolates 5a with a range of electro-

philes.⁷Later, we found that magnesium b-oxido car-

benoids (4a, M = MgCl) are better for our homologation

reaction, and we established a versatile procedure for ho-

mologation of ketones and aldehydes.⁸In all our investi-

gations mentioned above, we used 1-chloroalkyl 4-tolyl

sulfoxides 2a as the one-carbon homologating agents.

S(O)Tol

2a R= H, alkyl (Lit. 7, 8)

2b R= Ar (this work)

R

1

3

R

β-oxido carbenoid

R¹

rearrangement

E⁺

R¹

E

O^–

R

O^–

O

E⁺= H⁺,

Cl

M

R²

electrophile

4

5

6

β-oxido carbenoid

M = Li or MgCl

Scheme 1

In our previous studies, we synthesized 1-chloroalkyl 4-

tolyl sulfoxides 2a by treating the corresponding alkyl 4-

tolyl sulfoxides with N-chlorosuccinimide (NCS) in car-

bon tetrachloride.¹⁰On the basis of this experience and a

report on the chlorination of benzyl phenyl sulfoxide,^9d

we treated benzyl 4-tolyl sulfoxide (7) with NCS in car-

bon tetrachloride at room temperature overnight. This

reaction worked well and gave the desired chloro(phen-

yl)methyl 4-tolyl sulfoxide (8) cleanly as a mixture of two

diastereomers in 86% yield (Scheme 2).

If the procedures could be carried out with aryl(chlo-

ro)methyl 4-tolyl sulfoxides 2b (R = Ar), a-aryl carbonyl

compounds 6b (R = Ar) should be obtained. However, no

general method for the synthesis of sulfoxides 2b has been

reported so far.⁹In a continuation of our interest in the ho-

Next, to synthesize aryl(chloro)methyl 4-tolyl sulfoxides

other than 8, we treated 4-methoxybenzyl 4-tolyl sulfox-

ide (9) with NCS under the same conditions as described

above. Somewhat surprisingly, the chlorination did not

proceed at all, and prolonging the reaction time resulted

only in decomposition of 9 to give a complex mixture. We

SYNTHESIS 2011, No. 22, pp 3615–3626

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Advanced online publication: 05.10.2011

DOI: 10.1055/s-0031-1260251; Art ID: F71511SS

3616

S. Fukuda et al.

PAPER

Investigations to find the best conditions for the reaction

resulted in an improvement of the yield of 11 to 73%

(Scheme 2). Thus, treatment of 4-methoxybenzyl 4-tolyl

sulfoxide (9) with 1.2 equivalents of LDA in tetrahydro-

furan at –78 °C gave the lithium a-sulfinyl carbanion 10.

A solution of tosyl chloride (3 equivalents) in tetrahydro-

furan was then added to the reaction mixture, which was

stirred at –78 °C for one hour and then slowly warmed to

–30 °C for two hours. These optimal conditions gave 11

in 73% yield, together with recovered starting material 9

(13%). Chloro(4-fluorophenyl)methyl 4-tolyl sulfoxide

(12) and chloro(2-naphthyl)methyl 4-tolyl sulfoxide (13)

were similarly obtained in moderate yields from the cor-

responding arylmethyl 4-tolyl sulfoxides under the condi-

tions described above.

O

Cl

NCS (1.2 equiv)

CCl₄, r.t., overnight

STol

S(O)Tol

86%

7

8

LDA

(1.2 equiv)

THF

Li

S(O)Tol

–78 °C

MeO

9

10

ClSO₂Tol (3 equiv)

THF, –78 °C

1 h, then

–78 to –30 °C, 2 h

Cl

S(O)Tol

+

9 (13%)

MeO

11 (73%)

Having obtained the desired aryl(chloro)methyl 4-tolyl

sulfoxides, we next investigated the properties of these

compounds and their synthetic uses (Scheme 3). First,

chloro(phenyl)methyl 4-tolyl sulfoxide (8) was treated

with 2.5 equivalents of LDA in tetrahydrofuran at –78 °C

for 20 minutes. The colorless reaction mixture became

yellow and the lithium a-sulfinyl carbanion of 8 was gen-

erated instantaneously. To this reaction mixture we added

a solution of 3-phenylpropanal (3 equivalents) in tetrahy-

drofuran to give adduct 14L [the less polar adduct on sil-

ica gel thin-layer chromatography (TLC)] and 14P (the

more polar adduct on silica gel TLC) in 68% and 31%

yields, respectively. On the basis of our previous study^8d

and a report by García-Martínez and co-workers,^9dwe as-

sumed that the configuration of these two products are

those shown in Scheme 3.

Cl

S(O)Tol

F

12 (64%)

13 (49%)

Scheme 2 Synthesis of aryl(chloro)methyl 4-tolyl sulfoxides by the

chlorination of lithium a-sulfinyl carbanions with tosyl chloride

tried other chlorinating reagents, such as (dichloro-

iodo)benzene,¹¹but none gave any promising results.

Next, we attempted to chlorinate of lithium a-sulfinyl car-

banion 10 with an electrophilic chlorinating agent. After

searching for a suitable chlorinating agent, we found that

sequential treatment of sulfoxide 9 with lithium diisopro-

pylamide (LDA) and tosyl chloride at –78 °C gave the de-

sired chlorinated sulfoxide 11 in moderate yield.

Table 1 Synthesis of a-Aryl Ketones from Aldehydes with Aryl(chloro)methyl 4-Tolyl Sulfoxides as One-Carbon Elongating Agents

Cl

1) t-BuMgCl (1.2 equiv)

OH

Ar

S(O)Tol

2) i-PrMgCl (5 equiv)

Ar

H

R

H

+

RCOCH₂Ar

+

RCHO

17

RCHCHO

S(O)Tol

LDA (2.5 equiv)

THF, –45 ºC to r.t.

Cl

17L

Cl

17P

Ar

18

19

Entry

Aldehyde

Ar(Cl)CHS(O)Tol

Ar

a-Aryl carbonyl compounds

R

Product 17 [yield (%)]

Product 18 [yield (%)]

Product 19 [yield (%)]

1

2

(CH₂)₂Ph

2-naphthyl (13)

17aL (78)

17aP (22)

18a (70)

18a (63)

19a (0)

19a (9)

3

4

(CH₂)₂Ph

4-MeOC₆H₄(11)

17bL (63)

17bP (35)

18b (82)

19b (0)

5

(CH₂)₂Ph

Ph

4-FC₆H₄(12)

Ph (8)

17c (99)^a

18c (75)

19c (5)

6

7

17dL (72)

17dP (27)

18d (95)

18d (30)

19d (0)

19d (9)

8

9

Ph

4-MeOC₆H₄(11)

4-FC₆H₄(12)

17eL (71)

17eP (28)

18e (85)

18e (75)

19e (0)

19e (14)

10

11

17fL (73)

17fP (27)

18f (86)

18f (31)

19f (0)

19f (16)

^a~3:1 mixture of two inseparable diastereomers.

Synthesis 2011, No. 22, 3615–3626 © Thieme Stuttgart · New York

PAPER

Aryl(chloro)methyl 4-Tolyl Sulfoxides

3617

Cl

enolate intermediate. However, the alkyl group is known

to have a poor migratory ability so that rearrangement of

the hydrogen is the main reaction, giving 15 as a major

product.

Ph

S(O)Tol

8

Ph

HO

H

CH₂CH₂CHO

S(O)Tol

PhH₂CH₂C

LDA (2.5 equiv)

The scope of the elongation of aldehydes to a-aryl ke-

tones, as described above, was investigated by using var-

ious aryl(chloro)methyl 4-tolyl sulfoxides 8 and 11–13

with 3-phenylpropanal and benzaldehyde as representa-

tive examples of an alkyl aldehyde and an aryl aldehyde,

respectively. The results are summarized in Table 1.

Cl

14L (68%)

Ph

HO

PhH₂CH₂C

S(O)Tol

+

H

Cl

14P (31%)

As shown in Table 1, the addition of the lithium a-sulfinyl

carbanion of aryl(chloro)methyl 4-tolyl sulfoxides with

either the alkylaldehyde or the arylaldehyde gave an al-

most quantitative yield of the corresponding adducts 17.

In all cases, the less-polar adduct 17L was the major prod-

uct. Treatment of 17L with Grignard reagents as de-

scribed above gave the expected a-aryl ketones 18 in

good-to-high yields, without any a-aryl aldehydes 19. The

same reaction of the minor adducts 17P with Grignard re-

agents gave the a-aryl ketones 18 in somewhat variable

yields and, in some cases, the corresponding a-aryl alde-

hydes 19 were also obtained in less than 16% yield. These

CH₂CH₂COCH₂

1) t-BuMgCl (1.2 equiv)

14L

14P

2) i-PrMgCl (5 equiv),

THF, –45 ºC to r.t.

15 (84%)

CH₂CH₂CHCHO

1) t-BuMgCl (1.2 equiv)

15 (61%)

+

2) i-PrMgCl (5 equiv)

THF, –45 ºC to r.t.

16 (5%)

rotation of

C–C bond

Ph

MgCl

ClMgO

H

ClMgO

H

MgCl

Ph

14L

14P

15

16

PhH₂CH₂C

Cl

A

C

B

ClMgO

PhH₂CH₂C

MgCl

Ph

ClMgO

PhH₂CH₂C

Table 2 Synthesis of a-Phenyl a-Substituted Ketones 21 from 14L

by Trapping the Enolate Intermediate 20 with Electrophiles

MgCl

H

Cl

rotation of

C–C bond

1) t-BuMgCl (1.2 equiv)

OH

OMgCl

D

2) i-PrMgCl (5 equiv)

Ph

H

R

S(O)Tol

PhH₂CH₂C

MgCl

Scheme 3 Synthesis of a-phenyl ketone 15 from 3-phenylpropanal

and sulfoxide 8 with the b-oxido carbenoid rearrangement as the key

reaction

THF, –45 ºC to r.t.

Cl

14L

A

β-oxido carbenoid

electrophile

(7 equiv)

OMgCl

O

rearrangement

The major adduct 14L was treated sequentially with 1.2

equivalents of tert-butylmagnesium chloride, to form the

magnesium alkoxide, and then with 5 equivalents of iso-

propylmagnesium chloride at –45 °C, to generate the

magnesium b-oxido carbenoid A by means of a sulfox-

ide–magnesium exchange reaction.¹²The mixture was

then allowed to warm slowly to room temperature to give

1,4-diphenylbutan-2-one (15) in 84% yield. Interestingly,

the same treatment of 14P gave the a-phenyl ketone 15 in

a somewhat lower yield (61%), together with the a-phenyl

aldehyde 16 in 5% yield.

Ph

R

PhH₂CH₂C

r.t., 1.5 h

H

E

20

21

Entry

1

Electrophile

MeOD

Additive

none

Product 21 [Yield (%)]

O

Ph

PhH₂CH₂C

D

21a (84)^b

O

Ph

The difference in the reactivity of 14L and 14P with iso-

propylmagnesium chloride can be explained as follows

(see Scheme 3). As the sulfoxide–magnesium exchange

reaction¹²is known to occur with retention of the config-

uration at the carbon bearing a sulfinyl group,¹³the sulf-

oxide–magnesium exchange reaction of the magnesium

alkoxide of 14L gives magnesium b-oxido carbenoid A.

The conformation of A must be fixed to give B by forma-

tion of a chelate ring. The hydrogen at the rear of the chlo-

rine in the b-oxido carbenoid B rearranges smoothly to

give ketone 15 via a magnesium enolate. On the other

hand, the sulfoxide–magnesium exchange reaction of the

magnesium alkoxide of 14P gives b-oxido carbenoid D

via the initially generated intermediate C. From D, the 2-

phenylethyl group rearranges to give aldehyde 16 via an

2

3

MeI

HMPA^a

PhH₂CH₂C

21b (66)

O

Ph

CH₂=CHCH₂I

PhH₂CH₂C

21c (69)

O

Ph

HMPA^a

PhH₂CH₂C

4

BnBr

Ph

21d (43)

^aHMPA (5 equiv) was added.

^bDeuterium content 94%.

Synthesis 2011, No. 22, 3615–3626 © Thieme Stuttgart · New York

3618

S. Fukuda et al.

PAPER

results confirmed that the procedure for the elongation of chloride gave the magnesium enolate intermediate, which

aldehydes to a-aryl ketones has general applicability.

was trapped with iodomethane or allyl iodide to give the

expected a-alkyl a-aryl ketones 22a and 22b, respective-

ly, in moderate yields (Table 3, entries 1 and 2). The reac-

tion with benzoyl chloride gave the expected b-diketone

22c in 45% yield (entry 3). Interestingly, the reaction with

ethyl chloroformate gave the enol carbonate 22d in a low

yield (entry 4). The reaction starting from 17eL and 17fL

with allyl iodide gave relatively good yields of the desired

products 22e and 22f, respectively (entries 5 and 6).

As reported previously, the product of the b-oxido car-

benoid rearrangement has been shown to be a magnesium

enolate.⁸We hoped that if such enolate intermediates

could be trapped with electrophiles, we might realize a

synthesis of an a-aryl a-substituted ketones. We prepared

the enolate intermediate 20 from adduct 14L by treatment

with Grignard reagents, via the b-oxido carbenoid inter-

mediate A, and we attempted to trap the enolate 20 with

some haloalkanes. This procedure did indeed work well Next, we investigated the reaction of the lithium a-sulfi-

and gave a-phenyl a-substituted ketones 21 in moderate- nyl carbanion of aryl(chloro)methyl 4-tolyl sulfoxides

to-good yields (Table 2).

with ketones, and our results are summarized in Table 4.

The addition reaction of the lithium a-sulfinyl carbanion

of chloro(phenyl)methyl 4-tolyl sulfoxide (8) with cy-

clobutanone, cyclopentanone, or cyclohexanone gave the

desired adducts 23a–c, respectively, in almost quantita-

tive yields (Table 4, entries 1 to 3). The same reaction of

the lithium a-sulfinyl carbanions of 8, 13, 11, and 12 with

cyclohexane-1,4-dione monoethylene ketal (1,4-dioxa-

spiro[4.5]decan-8-one) gave adducts 23d–g, respectively,

in high-to-quantitative yields (entries 4 to 7).

When adduct 14L was treated sequentially with tert-bu-

tylmagnesium chloride and isopropylmagnesium chlo-

ride, and the reaction was quenched with an excess of

methanol-d₁, we obtained the a-deuterio a-phenyl ketone

21a with a 94% deuterium content in 84% yield (Table 2,

entry 1). When alkyl halides were used as the electro-

philes, hexamethylphosphoramide (HMPA) was found to

be useful additive in the alkylation reaction, giving a-

alkyl a-phenyl ketones 21b–d in moderate yields (entries

2 to 4, respectively). Disappointingly, attempt to trap the Interestingly, the lithium a-sulfinyl carbanion of chlo-

enolate intermediate 20 with benzaldehyde, benzoyl ro(phenyl)methyl 4-tolyl sulfoxide (8) did not react at all

chloride, or ethyl chloroformate resulted in the formation with cycloalkanones larger than cyclohexanone (entries 8

of complex mixtures.

and 9) or with acyclic ketones other than acetone (entries

10 to 12). The results are in sharp contrast to those for the

lithium a-sulfinyl carbanions of 1-chloroalkyl 4-tolyl sul-

foxides, the carbanions of which reacted with large cyclic

ketones and acyclic ketones larger than acetone to give

adducts in good yields.^7bThis can be rationalized in terms

Next, we applied the procedure to the adducts 17L, de-

rived from an aryl aldehyde (benzaldehyde) and an ar-

yl(chloro)methyl 4-tolyl sulfoxide; the results are

summarized in Table 3. Thus, treatment of 17dL with

tert-butylmagnesium chloride and isopropylmagnesium

Table 3 Synthesis of a-Aryl a-Substituted Ketones from Adduct 17L by Trapping the Enolate Intermediates

OH

OMgCl

Ar

electrophile

(7 equiv)

1) t-BuMgCl (1.2 equiv)

2) i-PrMgCl (5 equiv)

O

Ar

H

Ar

Ph

S(O)Tol

THF, –45 ºC to r.t.

r.t., 1.5 h

H

Cl

17L

E

22

Entry

Adduct 17

Electrophile

Product 22 [Yield (%)]

Ar

E

1

2

3

4

5

6

17dL

Ph

MeI^a

Me

22a (41)

22b (71)

22c (45)

22d (30)^b

22e (67)

22f (52)

17dL

17eL

17fL

Ph

CH₂=CHCH₂I^a

BzCl

CH₂CH=CH₂

Bz

Ph

ClCO₂Et

CO₂Et

4-MeOC₆H₄

4-FC₆H₄

CH₂=CHCH₂I^a

CH₂CH=CH₂

^aHMPA (5 equiv) was present as an additive.

^bThe product 22d was found to be an enol carbonate (single isomer, E/Z not determined).

OCO₂Et

Ph

H

22d

Synthesis 2011, No. 22, 3615–3626 © Thieme Stuttgart · New York

PAPER

Aryl(chloro)methyl 4-Tolyl Sulfoxides

3619

of the bulk of the lithium a-sulfinyl carbanion of ar- Benzoyl chloride also reacted with the magnesium enolate

yl(chloro)methyl 4-tolyl sulfoxides and the highly acidic intermediate to give the b-diketone 25e in 51% yield (en-

nature of the hydrogen atoms on the carbon atoms bearing try 5).

the sulfinyl group in comparison with those of the corre-

sponding 1-chloroalkyl 4-tolyl sulfoxides. The formation

of the magnesium b-oxido carbenoids from the adducts 23

and their rearrangement reaction proceeded without any

problem to give the desired one-carbon ring-expanded a-

aryl ketones 24 in up to 94% yield.

Table 5 Synthesis of 9-Substituted 9-Phenyl-1,4-dioxa-

spiro[4.6]undecan-8-ones 25

1) t-BuMgCl (1.2 equiv)

2) i-PrMgCl (5 equiv)

THF, –45 ºC to r.t.

O

OH

Cl

S(O)Tol

E

O

Ph

O

Ph

3) additive (5 equiv)

electrophile (7 equiv)

r.t., 1.5 h

O

Table 4 Synthesis of a-Aryl Ketones from Ketones with Aryl(chlo-

ro)methyl 4-Tolyl Sulfoxides as One-Carbon Homologating Agents

23d

25

Cl

entry

Electrophile

MeOD

Additive

none

25 [Yield (%)]

25a (91)^a

25b (72)

OH

Ar

S(O)Tol

R

1

2

3

4

5

S(O)Tol

Ar

O

R

LDA (2.5 equiv)

R

MeI

HMPA

none

R

Cl

23

CH₂=CHCH₂I

BnBr

25c (85)

O

1) t-BuMgCl (1.2 equiv)

2) i-PrMgCl (5 equiv)

25d (58)

Ar

R

BzCl

25e (51)

THF, –45 ºC to r.t.

R

^aDegree of deuteration = 99%.

24

Entry Ketone^a

Ar(Cl)CHS(O)Tol 23 [Yield 24 [Yield

(%)] (%)]

Finally, we examined the reactions with the a,b-unsatur-

ated aldehyde methacrolein, and the results are shown in

Scheme 4. Thus, the addition reaction of the lithium a-

sulfinyl carbanion of 8 with methacrolein gave adducts

26L and 26P in 72% and 28% yields, respectively. The re-

action of the major adduct 26L with Grignard reagents un-

der the conditions discussed above gave the expected a-

phenyl ketone 27 in 83% yield. In contrast, the reaction of

26P with the Grignard reagents gave a trace of ketone 27

together with the cyclopropanecarbaldehyde 28 as a sin-

gle diastereomer in 43% yield.

Ar

1

2

3

cyclobutanone

cyclopentanone

cyclohexanone

Ph (8)

23a (99) 24a (94)

23b (95) 24b (92)

23c (98)

24c (85)

4

5

6

7

Ph (8)

2-naphthyl (13)

4-MeOC₆H₄(11) 23f (99)

23d (99) 24d (91)

O

23e (98)

24e (80)

24f (44)

O

4-FC₆H₄(12)

23g (88) 24g (86)

Cl

8

9

cycloheptanone

cyclooctanone

Ph (8)

nr^b

S(O)Tol

Ph (8)

nr

O

OH

10 acetone

Ph (8)

23h (90) 24h (73)

Cl

S(O)Tol

8

H

11 pentan-3-one

12 heptan-4-one

Ph (8)

nr

LDA (2.5 equiv)

Ph

26L (72%)

26P (28%)

Ph (8)

^aThe ketone (3 equiv) was treated with the lithium a-sulfinyl carban-

ion of the aryl(chloro)methyl 4-tolyl sulfoxide.

^bnr = no reaction.

O

1) t-BuMgCl (1.2 equiv)

Ph

26L

2) i-PrMgCl (5.0 equiv)

THF, –45 ºC to r.t.

27 (83%)

Next, we examined the synthesis of a-aryl a-substituted

ketones from ketones with one-carbon homologation by

using 23d as a representative example, and the results are

summarized in Table 5. Adduct 23d (see Table 4, entry 4)

was treated sequentially with tert-butylmagnesium chlo-

ride and isopropylmagnesium chloride in tetrahydrofuran

at –45 °C and the mixture was slowly allowed to warm to

room temperature. Seven equivalents of electrophile were

added and the mixture was stirred at room temperature for

1.5 hours. a-Alkyl a-phenyl cycloheptanone derivatives

25b–d were obtained in up to 85% yield (entries 2 to 4).

CHO

26P

27 (trace)

+

Ph

28 (43%)

ClMg

O

OMgCl

Cl

MgCl

Ph

29

30

Scheme 4

Synthesis 2011, No. 22, 3615–3626 © Thieme Stuttgart · New York

3620

S. Fukuda et al.

PAPER

IR (KBr): 2945, 1593, 1493, 1453, 1087 (SO), 1056, 807, 697, 514

cm^–1.

The mechanism responsible for this interesting result is as

follows. Initially, the reaction of 26P with the Grignard

reagents gives the b-oxido carbenoid intermediate 29. As ¹H NMR (500 MHz, CDCl₃): d = 2.37 (s, 3 H), 5.46 (s, 1 H), 7.06

(d, J = 8.3 Hz, 2 H), 7.10–7.15 (m, 4 H), 7.26 (t, J = 7.7 Hz, 2 H),

mentioned above, the rearrangement of the alkenyl group

in this intermediate must be slow and, instead, addition of

7.35 (t, J = 7.4 Hz, 1 H).

Anal. Calcd for C₁₄H₁₃ClOS: C, 63.51; H, 4.95; Cl, 13.39; S, 12.11.

Found: C, 63.50; H, 4.81; Cl, 13.11; S, 11.99.

the magnesium carbenoid to the double bond must occur

to give highly strained intermediate 30. Carbon–carbon

bond cleavage between the carbon bearing the alkoxide

and the carbon bearing the phenyl group occurs next to

give a cyclopropyl anion with a negative charge on the

carbon bearing the phenyl group. This anion is protonated

by water during the workup to afford aldehyde 28. Actu-

ally, when this reaction was quenched with methanol-d₁,

the hydrogen on the carbon bearing the phenyl group was

almost completely replaced by deuterium.

4-Methoxybenzyl 4-Tolyl Sulfoxide (9)

A soln of 4-TolSH (1.98 g; 16.0 mmol) in EtOH (5 mL) was added

dropwise to a soln of NaOEt (1.20 g; 17.6 mmol) in EtOH (5 mL)

at 0 °C with stirring, and the soln was stirred for 15 min. 4-Meth-

oxybenzyl chloride (1.1 mL, 8.0 mmol) was then added dropwise

with stirring and the mixture was stirred for 15 min. The reaction

was quenched with 5% aq NaOH (20 mL) and the mixture was ex-

tracted with benzene (2 × 20 mL). The organic layer was dried

(MgSO₄) and concentrated to give the crude sulfide.

In conclusion, we have developed a method for the syn-

thesis of aryl(chloro)methyl 4-tolyl sulfoxides from aryl-

methyl 4-tolyl sulfoxides by sequential treatment with

LDA and 4-tosyl chloride. The lithium a-sulfinyl carban-

ions generated from the aryl(chloro)methyl 4-tolyl sulfox-

ides and LDA reacted with either alkyl or aryl aldehydes

to afford the corresponding adducts in high-to-quantita-

tive yields, whereas the scope of the corresponding addi-

tion reaction with ketones was quite limited. Sequential

treatment of the adducts with tert-butylmagnesium chlo-

ride and isopropylmagnesium chloride gave the corre-

sponding one-carbon homologated or elongated a-aryl

ketones in good-to-high yields via magnesium enolate in-

termediates. a-Substituted a-aryl ketones were obtained

by trapping the magnesium enolate intermediates with

electrophiles. As the synthesis of a-aryl carbonyl com-

pounds is still recognized as being relatively difficult,¹⁴

our results contribute to the synthesis of a-aryl ketones

from aldehydes and ketones by one-carbon homologation

and/or elongation.

A stirred soln of the crude sulfide in CHCl₃(16 mL) was treated

with MCPBA (2.39 g; 10.4 mmol) at 0 °C, and the mixture was

stirred for 30 min. The reaction was quenched with sat. aq Na₂SO₃

(10 mL) and NaHCO₃(10 mL), and the mixture was extracted with

CHCl₃(2 × 20 mL). The product was purified by column chroma-

tography (silica gel, hexane–EtOAc) to give the sulfoxide 9 as col-

orless crystals; yield: 1.75 g (84%, two steps); mp 128.0–129.0 °C

(hexane–EtOAc).

IR (KBr): 2960, 1610, 1514, 1253, 1037 (SO), 811, 519 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.40 (s, 3 H), 3.79 (s, 3 H), 3.92

(d, J = 12.6 Hz, 1 H), 4.03 (d, J = 12.6 Hz, 1 H), 6.78 (d, J = 8.7 Hz,

2 H), 6.91 (d, J = 8.7 Hz, 2 H), 7.23 (d, J = 8.3 Hz, 2 H), 7.28 (d,

J = 8.3 Hz, 2 H).

Chloro(4-methoxyphenyl)methyl 4-Tolyl Sulfoxide (11); Typi-

cal Procedure

A soln of sulfoxide 9 (1.04 g; 4.0 mmol) in anhyd THF (50 mL) was

added dropwise with stirring to a soln of LDA (4.8 mmol) in anhyd

THF (6.6 mL) in a flame-dried flask at –78 °C under argon, and the

soln was stirred at –78 °C for 20 min. A soln of TsCl (2.29 g; 12.0

mmol) in anhyd THF (10 mL) was then added dropwise with stir-

ring. The mixture was stirred at –78 °C for 1 h and then slowly al-

lowed to warm to –30 °C for 1.5 h. The reaction was quenched with

sat. aq NH₄Cl (60 mL), and the mixture was extracted with CHCl₃

(2 × 60 mL). The organic layer was dried (MgSO₄) and the product

was purified by column chromatography (silica gel, hexane–

EtOAc) to give a white solid; yield 859 mg (73%; ~2:1 mixture of

two diastereomers).

All melting points were measured on a Yanaco MP-S3 apparatus

and are uncorrected. ¹H NMR spectra were recorded in CDCl₃soln

by using a JEOL JNM-LA 500, a Bruker DPX 300 or a Bruker

UltraShield 400 spectrometer. IR spectra were recorded on a

Perkin-Elmer Spectrum One FT-IR instrument. Electron-impact

mass spectra were recorded at 70 eV by direct insertion into a JEOL

JMS-SX102A spectrometer. Silica gel 60N containing 0.5% fluo-

rescence reagent 254 (Kanto Chemical) and a quartz column were

used for column chromatography, and products showing a UV ab-

sorption were detected by UV irradiation. In experiments requiring

dry solvents and reagents, THF was distilled from sodium diphe-

nylketyl, and i-Pr₂NH was distilled from CaH₂. Acetone and HMPA

were dried over CaSO₄and distilled before use. Allyl iodide, MeI,

BnBr, PhCHO, BzCl, and EtO₂CCl were distilled before use. Com-

pounds 7,¹⁵18d,¹⁶18e,¹⁶18f,¹⁷22a,¹⁸24a,¹⁶24b,¹⁶24c,¹⁶24h,¹⁹and

27²⁰are known in the literature.

IR (KBr): 2948, 1609, 1512, 1256, 1176, 1087, 1056 (SO), 811, 515

cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.38 (s, 2 H), 2.42 (s, 1 H), 3.81

(s, 2 H), 3.83 (s, 1 H), 5.38 (s, 0.33 H), 5.42 (s, 0.67 H), 6.77 (d,

J = 8.8 Hz, 1.33 H), 6.87 (d, J = 8.8 Hz, 0.67 H), 6.98 (d, J = 8.8 Hz,

1.33 H), 7.10–7.28 (m, 4 H), 7.36 (d, J = 8.2 Hz, 0.67 H).

MS (FAB): m/z (%) = 295 (4) [M + 1]⁺, 155 (100).

HRMS (FAB): m/z [M + H]⁺calcd for C₁₅H₁₆ClO₂S: 295.0560;

found: 295.0556.

Chloro(4-fluorophenyl)methyl 4-Tolyl Sulfoxide (12)

White solid (~ 3:2 mixture of two diastereomers).

Chloro(phenyl)methyl 4-Tolyl Sulfoxide (8)

NCS (1.39 g; 10.4 mmol) was added to a soln of 4-TolS(O)Bn (7;

2.00 g; 8.7 mmol) in CCl₄(21 mL) and the suspension was stirred

at r.t. for 15 h. The precipitate was filtered off and the solvent was

evaporated. The residue was purified by column chromatography

(silica gel, hexane–EtOAc) to give a white solid; yield: 1.97 g (86%,

~3:2 mixture of two diastereomers). The major isomer was isolated

by crystallization; mp 153.0–153.5 °C (hexane–EtOAc).

IR (KBr): 2958, 1596, 1508, 1229, 1058 (SO), 814, 746, 522, 462

cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.39 (s, 1.2 H), 2.42 (s, 1.8 H),

5.39 (s, 0.6 H), 5.48 (s, 0.4 H), 6.92–7.35 (m, 8 H).

Anal. Calcd for C₁₄H₁₂ClFOS: C, 59.47; H, 4.28; Cl, 12.54; F, 6.72;

S, 11.34. Found: C, 59.50; H, 4.08; Cl, 12.20; F, 6.48, S, 11.26.

Synthesis 2011, No. 22, 3615–3626 © Thieme Stuttgart · New York

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Aryl(chloro)methyl 4-Tolyl Sulfoxides

3621

Chloro(2-naphthyl)methyl 4-Tolyl Sulfoxide (13)

IR (neat): 3028, 1710 (CO), 1603, 1498, 1455, 1412, 702 cm^–1.

White solid (~ 2:1 mixture of two diastereomers).

IR (KBr): 2947, 1508, 1087 (SO), 1059, 809, 755, 626, 478 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.72–2.81 (m, 2 H), 2.81–2.92 (m,

2 H), 3.66 (s, 2 H), 7.09–7.21 (m, 5 H), 7.21–7.36 (m, 5 H).

¹H NMR (300 MHz, CDCl₃): d 2.34 (s, 1 H), 2.41 (s, 2 H), 5.60 (s,

0.67 H), 5.62 (s, 0.33 H), 7.05–7.59 (m, 7 H), 7.69–7.89 (m, 4 H).

MS: m/z (%) = 224 (24) [M]⁺, 133 (48), 105 (87), 91 (100), 65 (14).

HRMS: m/z [M]⁺calcd for C₁₆H₁₆O: 224.1201; found: 224.1200.

Anal. Calcd for C₁₈H₁₅ClOS: C, 68.67; H, 4.80; Cl, 11.26; S, 10.18.

Found: C, 68.67; H, 4.69; Cl, 11.07; S, 10.18.

2,4-Diphenylbutanal (16)

Colorless oil.

1-Chloro-1,4-diphenyl-1-[(4-tolyl)sulfinyl]butan-2-ol (14L and

14P)

IR (neat): 1722 (CHO), 1603, 1454, 699 cm^–1.

¹H NMR (500 MHz, CDCl₃): d = 2.02–2.11 (m, 1 H), 2.37–2.47 (m,

1 H), 2.51–2.67 (m, 2 H), 3.51 (ddd, J = 1.8, 6.3, 8.2 Hz, 1 H), 7.13–

7.16 (m, 2 H), 7.19–7.35 (m, 6 H), 7.40 (t, J = 7.4 Hz, 2 H), 9.67 (d,

J = 1.7 Hz, 1 H).

MS: m/z (%) = 224 (6) [M]⁺, 133 (23), 120 (46), 105 (45), 91 (100),

77 (12), 65 (13).

A soln of sulfoxide 8 (212 mg, 0.80 mmol) in anhyd THF (6 mL)

was added dropwise to a stirred soln of LDA (2.00 mmol) in anhyd

THF (2 mL) at –78 °C under argon. The resulting mixture was

stirred at –78 °C for 20 min and then 3-phenylpropanal (0.32 mL,

2.40 mmol) was added dropwise with stirring. The mixture was

stirred at –78 °C for 10 min before the reaction was quenched by se-

quential addition of MeOH (5 mL) and sat. aq NH₄Cl (10 mL). The

mixture was extracted with CHCl₃(2 × 10 mL) and the organic layer

was dried (MgSO₄). The product was purified by column chroma-

tography (silica gel, hexane–EtOAc) to give the less-polar isomer

14L as a colorless oil [yield: 217 mg (68%] and the more-polar iso-

mer 14P as colorless crystals [yield: 99 mg (31%)].

HRMS: m/z [M]⁺calcd for C₁₆H₁₆O: 224.1201; found: 224.1200.

1-Chloro-1-(2-naphthyl)-4-phenyl-1-[(4-tolyl)sulfinyl]butan-2-

ol (17aL and 17aP)

17aL

Colorless amorphous.

IR (KBr): 3379 (OH), 1596, 1494, 1455, 1081 (SO), 1040, 812, 756

cm^–1.

14L

IR (neat): 3402 (OH), 1597, 1494, 1454, 1081 (SO), 1042, 811, 750,

700 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.41 (td, J = 8.5, 15.5 Hz, 1 H),

1.78–1.95 (m, 1 H), 2.28 (s, 3 H), 2.69 (td, J = 8.4, 13.5 Hz, 1 H),

2.85 (ddd, J = 4.5, 8.1, 13.5 Hz, 1 H), 4.72 (br s, 1 H), 4.98 (d,

J = 10.3 Hz, 1 H), 6.72 (d, J = 8.2 Hz, 2 H), 6.94 (d, J = 8.2 Hz, 2

H), 7.01–7.08 (m, 2 H), 7.12–7.26 (m, 4 H), 7.47–7.61 (m, 3 H),

7.63–7.71 (m, 1 H), 7.75 (d, J = 8.7 Hz, 1 H), 7.85 (d, J = 8.2 Hz, 1

H).

¹H NMR (500 MHz, CDCl₃): d = 1.40 (td, J = 8.6, 13.9 Hz, 1 H),

1.76–1.88 (m, 1 H), 2.33 (s, 3 H), 2.66 (td, J = 8.3, 13.7 Hz, 1 H),

2.87 (ddd, J = 4.5, 8.6, 13.7 Hz, 1 H), 4.68 (br s, 1 H), 4.88 (d,

J = 10.1 Hz, 1 H), 6.76 (d, J = 8.1 Hz, 2 H), 7.03 (d, J = 8.1 Hz, 2

H), 7.08 (d, J = 7.3 Hz, 2 H), 7.11 (d, J = 7.7 Hz, 2 H), 7.17 (t,

J = 7.3 Hz, 1 H), 7.20–7.32 (m, 4 H), 7.36 (t, J = 7.3 Hz, 1 H).

MS (FAB) m/z (%) = 449 (13) [M + 1]⁺, 391 (23), 291 (58), 273

MS (FAB): m/z (%) = 399 (74) [M + 1]⁺, 241 (100), 223 (97), 205

(50), 167 (21), 149 (100), 91 (20).

(38), 154 (18), 140 (16), 91 (42).

HRMS (FAB): m/z [M + H]⁺Calcd for C₂₇H₂₆ClO₂S: 449.1342;

HRMS (FAB): m/z [M + H]⁺calcd for C₂₃H₂₄ClO₂S: 399.1186;

found: 449.1341.

found: 399.1185.

17aP

14P

Colorless crystals; mp 140.0–141.0 °C (hexane–EtOAc).

Mp 153.5–154.0 °C (hexane–EtOAc).

IR (KBr): 3279 (OH), 1597, 1493, 1083, 1048 (SO), 807, 758, 699,

511 cm^–1.

IR (KBr): 3305 (OH), 1597, 1492, 1446, 1082 (SO), 1044, 750, 698,

507 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.37–1.54 (m, 1 H), 1.92–2.06 (m,

1 H), 2.28 (s, 3 H), 2.63–2.76 (m, 1 H), 2.89 (ddd, J = 4.9, 10.0, 14.3

Hz, 1 H), 3.85 (br s, 1 H), 4.64 (ddd, J = 1.7, 6.3, 10.6 Hz, 1 H), 6.79

(d, J = 8.3 Hz, 2 H), 6.96 (d, J = 8.3 Hz, 2 H), 7.08–7.16 (m, 3 H),

7.16–7.24 (m, 2 H), 7.47–7.60 (m, 2 H), 7.78–7.91 (m, 4 H), 8.05

(d, J = 1.7 Hz, 1 H).

¹H NMR (500 MHz, CDCl₃): d = 1.40–1.52 (m, 1 H), 1.96 (td,

J = 8.4, 13.9 Hz, 1 H), 2.32 (s, 3 H), 2.69 (ddd, J = 7.3, 9.3, 14.1 Hz,

1 H), 2.89 (ddd, J = 4.8, 10.1, 14.1 Hz, 1 H), 3.90 (d, J = 6.3 Hz, 1

H), 4.56 (dd, J = 6.2, 9.0 Hz, 1 H), 6.81 (d, J = 8.0 Hz, 2 H), 7.03

(d, J = 8.0 Hz, 2 H), 7.14 (d, J = 7.7 Hz, 2 H), 7.15 (d, J = 5.0 Hz, 1

H), 7.23 (t, J = 7.6 Hz, 2 H), 7.34 (t, J = 7.4 Hz, 2 H), 7.38 (t, J = 7.2

Hz, 1 H), 7.66 (d, J = 7.6 Hz, 2 H).

MS (FAB) m/z (%) = 449 (27) [M + 1]⁺, 291 (100), 273 (85), 246

(24), 185 (53), 154 (80), 137 (64), 93 (82).

HRMS (FAB): m/z [M + H]⁺Calcd for C₂₇H₂₆ClO₂S: 449.1342;

Anal. Calcd for C₂₃H₂₃ClO₂S: C, 69.24; H, 5.81; Cl, 8.89; S, 8.04.

Found: C, 69.14; H, 5.81; Cl, 8.85; S, 8.09.

found: 449.1347.

1,4-Diphenylbutan-2-one (15); Typical Procedure

A soln of adduct 14L (40.0 mg, 0.1 mmol) in anhyd THF (1.8 mL)

was added dropwise with stirring to a soln of t-BuMgCl (0.12

mmol) in anhyd THF (0.2 mL) in a flame-dried flask at –45 °C un-

der argon, and the mixture was stirred at –45 °C for 10 min. The re-

sulting soln of magnesium alkoxide was stirred and treated by

dropwise addition of i-PrMgCl (0.5 mmol). The mixture was then

slowly warmed to r.t. for 1.7 h before the reaction was quenched

with sat. aq NH₄Cl (10 mL). The mixture was extracted with CHCl₃

(2 × 10 mL), and the organic layer was washed with sat. aq NH₄Cl

then dried (MgSO₄). The product was purified by column chroma-

tography (silica gel) to give a colorless oil; yield: 18.8 mg (84%).

1-Chloro-1-(4-methoxyphenyl)-4-phenyl-1-[(4-tolyl)sulfi-

nyl]butan-2-ol (17bL and 17bP)

17bL

Colorless crystals; mp 105.0–106.0 °C (hexane–EtOAc).

IR (KBr): 3284 (OH), 1610, 1511, 1259, 1081, 1033 (SO), 815, 753,

540 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.42 (m, 1 H), 1.81 (m, 1 H), 2.34

(s, 3 H), 2.65 (td, J = 8.4, 13.6 Hz, 1 H), 2.87 (ddd, J = 4.7, 8.6, 13.6

Hz, 1 H), 3.83 (s, 3 H), 4.63 (t, J = 2.2 Hz, 1 H), 4.80 (td, J = 2.2,

10.1 Hz, 1 H), 6.79 (d, J = 9.0 Hz, 2 H), 6.80 (d, J = 8.2 Hz, 2 H),

Synthesis 2011, No. 22, 3615–3626 © Thieme Stuttgart · New York

3622

S. Fukuda et al.

PAPER

7.00 (d, J = 9.0 Hz, 2 H), 7.06 (d, J = 8.2 Hz, 2 H), 7.09 (d, J = 7.7

HRMS (FAB): m/z [M + H]⁺calcd for C₂₁H₂₀ClO₂S: 371.0873;

Hz, 2 H), 7.13–7.27 (m, 3 H).

found: 371.0874.

MS (FAB): m/z (%) = 429 (10) [M + 1]⁺, 393 (27), 289 (59), 271

(49), 253 (100), 121 (87), 91 (34).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₄H₂₆ClO₃S: 429.1291;

found: 429.1292.

2-Chloro-2-(4-methoxyphenyl)-1-phenyl-2-[(4-tolyl)sulfi-

nyl]ethanol (17eL and 17eP)

17eL

Colorless amorphous.

IR (KBr): 3343 (OH), 1607, 1510, 1261, 1180, 1063 (SO), 1024,

829, 705 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.32 (s, 3 H), 3.81 (s, 3 H), 5.50

(s, 1 H), 6.09 (s, 1 H), 6.80 (d, J = 9.0 Hz, 2 H), 6.88 (d, J = 8.3 Hz,

2 H), 7.03–7.25 (m, 9 H).

MS (FAB): m/z (%) = 401 (10) [M + 1]⁺, 365 (8), 261 (100), 225

(90), 197 (32), 154 (23), 137 (22), 93 (37).

17bP

Colorless crystals; mp 119.0–120.0 °C (hexane–EtOAc).

IR (KBr): 3326 (OH), 1610, 1510, 1260, 1045 (SO), 1032, 810, 704,

512 cm^–1.

¹H NMR (500 MHz, CDCl₃): d = 1.46 (m, 1 H), 1.94 (td, J = 8.5,

15.6 Hz, 1 H), 2.33 (s, 3 H), 2.68 (ddd, J = 7.0, 9.4, 14.1 Hz, 1 H),

2.89 (ddd, J = 4.8, 10.1, 14.1 Hz, 1 H), 3.83 (s, 3 H), 4.04 (d, J = 5.6

Hz, 1 H), 4.54 (dd, J = 6.8, 9.9 Hz, 1 H), 6.85 (d, J = 8.3 Hz, 4 H),

7.06 (d, J = 8.2 Hz, 2 H), 7.10–7.18 (m, 3 H), 7.22 (t, J = 7.5 Hz, 2

H), 7.57 (d, J = 8.9 Hz, 2 H).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₂H₂₂ClO₃S: 401.0978;

found: 401.0975.

17eP

Anal. Calcd for C₂₄H₂₅ClO₃S: C, 67.20; H, 5.87; Cl, 8.26; S, 7.47.

Found: C, 67.05; H, 5.77; Cl, 8.31; S, 7.50.

Colorless crystals; mp 127.0–128.0 °C (hexane–EtOAc).

IR (KBr): 3244 (OH), 1609, 1509, 1256, 1181, 1083 (SO), 1043,

702, 509 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.31 (s, 3 H), 3.49 (d, J = 4.8 Hz,

1 H), 3.85 (s, 3 H), 5.60 (d, J = 4.8 Hz, 1 H), 6.84 (d, J = 9.0 Hz, 2

H), 6.93 (d, J = 8.3 Hz, 2 H), 6.98–7.23 (m, 7 H), 7.54 (d, J = 9.0

Hz, 2 H).

1-Chloro-1-(4-fluorophenyl)-4-phenyl-1-[(4-tolyl)sulfinyl]bu-

tan-2-ol (17c)

Colorless amorphous (~3:1 mixture of two diastereomers).

IR (KBr): 3295 (OH), 1596, 1509, 1239, 1081, 1039 (SO), 1017,

806, 703, 536 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.32–1.50 (m, 1 H), 1.77–1.95 (m,

1 H), 2.33 (s, 0.75 H), 2.34 (s, 2.25 H), 2.62–2.74 (m, 1 H), 2.82–

2.94 (m, 1 H), 4.13 (br s, 0.25 H), 4.46 (dd, J = 1.7, 3.3 Hz, 0.75 H),

4.55 (ddd, J = 1.7, 6.1, 10.5 Hz, 0.25 H), 4.75 (ddd, J = 1.9, 3.3,

10.5 Hz, 0.75 H), 6.79–6.87 (m, 2 H), 6.78–6.88 (m, 2 H), 6.92–7.32

(m, 8.5 H), 7.62–7.69 (m, 0.5 H).

MS (FAB): m/z (%) = 401 (12) [M + 1]⁺, 261 (100), 246 (23), 225

(80), 197 (28), 185 (72), 154 (52), 137 (56), 107 (15), 93 (93).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₂H₂₂ClO₃S: 401.0978;

found: 401.0977.

2-Chloro-2-(4-fluorophenyl)-1-phenyl-2-[(4-tolyl)sulfinyl]eth-

anol (17fL and 17fP)

17fL

MS (FAB) m/z (%) = 417 (42) [M + 1]⁺, 259 (100), 242 (69), 223

(20), 140 (14), 91 (45).

Colorless amorphous.

HRMS (FAB): m/z [M + H]⁺calcd for C₂₃H₂₃ClFO₂S: 417.1091;

found: 417.1092.

IR (KBr): 3392 (OH), 1596, 1507, 1232, 1095, 1082 (SO), 805, 696,

514 cm^–1.

2-Chloro-1,2-diphenyl-2-[(4-tolyl)sulfinyl]ethanol (17dL and

17dP)

17dL

¹H NMR (400 MHz, CDCl₃): d = 2.33 (s, 3 H), 5.39 (d, J = 1.1 Hz,

1 H), 6.07 (br s, 1 H), 6.90 (d, J = 8.3 Hz, 2 H), 6.95–7.03 (m, 2 H),

7.06–7.18 (m, 7 H), 7.25–7.34 (m, 1 H), 7.38 (d, J = 4.3 Hz, 1 H).

MS (FAB): m/z (%) = 389 (43) [M + 1]⁺, 249 (46), 213 (100), 185

(36), 154 (9).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₁H₁₉ClFO₂S: 389.0778;

found: 389.0783.

Colorless crystals; mp 137.5–138.5 °C (hexane–CHCl₃).

IR (KBr): 3349 (OH), 1595, 1492, 1447, 1078, 1064, 1048 (SO),

815, 699, 519 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.31 (s, 3 H), 5.50 (d, J = 1.0 Hz,

1 H), 6.14 (s, 1 H), 6.85 (d, J = 8.2 Hz, 2 H), 7.04 (d, J = 8.2 Hz, 2

H), 7.06–7.17 (m, 5 H), 7.23–7.41 (m, 5 H).

17fP

MS (FAB) m/z (%) = 371 (65) [M + 1]⁺, 246 (19), 231 (33), 195

Colorless crystals; mp 168.0–169.0 °C (hexane–EtOAc).

(100), 154 (48), 137 (45), 93 (68), 75 (11).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₁H₂₀ClO₂S: 371.0873;

IR (KBr): 3254 (OH), 1595, 1507, 1237, 1083 (SO), 1057, 700

cm^–1.

found: 371.0874.

¹H NMR (400 MHz, CDCl₃): d = 2.32 (s, 3 H), 3.45 (d, J = 4.8 Hz,

1 H), 5.61 (d, J = 4.8 Hz, 1 H), 6.94 (d, J = 8.3 Hz, 2 H), 6.98–8.28

(m, 4 H), 7.07 (d, J = 8.3 Hz, 2 H), 7.13 (t, J = 7.5 Hz, 2 H), 7.17–

7.23 (m, 1 H), 7.59–7.65 (m, 2 H).

17dP

Colorless crystals; mp 165.0–165.5 °C (hexane–CHCl₃).

IR (KBr): 3267 (OH), 1596, 1492, 1445, 1084, 1050 (SO), 699, 509

cm^–1.

¹H NMR (500 MHz, CDCl₃): d = 2.30 (s, 3 H), 3.75 (br s, 1 H), 5.64

(d, J = 5.0Hz, 1 H), 6.90 (d, J = 8.0 Hz, 2 H), 7.02 (d, J = 8.0 Hz, 4

H), 7.11 (t, J = 7.6 Hz, 2 H), 7.18 (t, J = 7.2 Hz, 1 H), 7.31 (t, J = 7.7

Hz, 2 H), 7.39 (t, J = 7.3 Hz, 1 H), 7.63 (d, J = 7.8 Hz, 2 H).

MS (FAB): m/z (%) = 389 (34) [M + 1]⁺, 249 (35), 213 (80), 185

(74), 154 (79), 137 (71), 107 (22), 93 (100), 75 (16).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₁H₁₉ClFO₂S: 389.0778;

found: 389.0782.

1-(2-Naphthyl)-4-phenylbutan-2-one (18a)

White solid; mp 83.5–84.5 °C.

MS (FAB) m/z (%) = 371 (42) [M + 1]⁺, 246 (23), 231 (24), 195

(83), 154 (66), 137 (64), 93 (100), 75 (16).

IR (KBr): 1712 (CO), 745, 699 cm^–1.

PAPER

Aryl(chloro)methyl 4-Tolyl Sulfoxides

3623

¹H NMR (300 MHz, CDCl₃): d = 2.75–2.93 (m, 4 H), 3.82 (s, 2 H),

7.06–7.31 (m, 6 H), 7.41–7.52 (m, 2 H), 7.61 (s, 1 H), 7.71–7.85 (m,

3 H).

MS: m/z (%) = 238 (19) [M]⁺, 133 (44), 105 (100), 91 (45), 77 (13).

HRMS: m/z [M]⁺calcd for C₁₇H₁₈O: 238.1358; found: 238.1357.

MS: m/z (%) = 274 (90) [M]⁺, 141 (82), 133 (40), 115 (37), 105

1,4-Diphenylhept-6-en-3-one (21c)

(100), 91 (72).

Colorless oil.

HRMS: m/z [M]⁺calcd for C₂₀H₁₈O: 274.1358; found: 274.1355.

IR (neat): 1714 (CO), 1495, 1454, 752, 700 cm^–1.

¹H NMR (500 MHz, CDCl₃): d = 2.43 (td, J = 7.2, 14.3 Hz, 1 H),

2.60–2.89 (m, 5 H), 3.66 (t, J = 7.5 Hz, 1 H), 4.94 (dd, J = 1.3, 10.2

Hz, 1 H), 4.98 (dd, J = 1.3, 17.1 Hz, 1 H), 5.63 (tdd, J = 6.9, 10.2,

17.1 Hz, 1 H), 7.05 (d, J = 7.2 Hz, 2 H), 7.12–7.18 (m, 3 H), 7.18–

7.27 (m, 3 H), 7.29 (t, J = 7.2 Hz, 2 H).

MS: m/z (%) = 264 (12) [M]⁺, 133 (64), 105 (100), 91 (94).

HRMS: m/z [M]⁺calcd for C₁₉H₂₀O: 264.1514; found: 264.1512.

1-(4-Methoxyphenyl)-4-phenylbutan-2-one (18b)

Colorless crystals; mp 64.0–65.0 °C (hexane–EtOAc).

IR (KBr): 1710 (CO), 1518, 1251, 1035, 747, 700 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.75 (dt, J = 1.7, 7.7 Hz, 2 H),

2.80–2.91 (m, 2 H), 3.60 (s, 2 H), 3.79 (s, 3 H), 6.85 (d, J = 8.7 Hz,

2 H), 7.04–7.21 (m, 5 H), 7.21–7.31 (m, 2 H).

MS: m/z (%) = 254 (40) [M]⁺, 121 (100), 105 (19), 91 (22).

1,2,5-Triphenylpentan-3-one (21d)

White solid; mp 49.0–50.0 °C.

HRMS: m/z [M]⁺calcd for C₁₇H₁₈O₂: 254.1307; found: 254.1307.

1-(4-Fluorophenyl)-4-phenylbutan-2-one (18c)

Colorless crystals; mp 38.0–38.5 °C (hexane).

IR (KBr): 3026, 1709 (CO), 1699 (CO), 1495, 1453, 1069, 726, 698

cm^–1.

IR (KBr): 1714 (CO), 1509, 1218, 747, 699 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.47–2.61 (m, 1 H), 2.61–2.85 (m,

3 H), 2.89 (dd, J = 7.1, 13.7 Hz, 1 H), 3.41 (dd, J = 7.7, 13.7 Hz, 1

H), 3.87 (t, J = 7.4 Hz, 1 H), 6.95–7.05 (m, 4 H), 7.08–7.35 (m, 11

H).

MS: m/z (%) = 314 (49) [M]⁺, 209 (22), 181 (77), 165 (21), 133 (74),

105 (100), 91 (88), 77 (18).

¹H NMR (300 MHz, CDCl₃): d = 2.77 (dt, J = 1.7, 7.7 Hz, 2 H),

2.82–2.93 (m, 2 H), 3.63 (s, 2 H), 6.99 (t, J = 8.7 Hz, 2 H), 7.06–

7.31 (m, 7 H).

MS: m/z (%) = 242 (26) [M]⁺, 133 (60), 105 (100), 91 (85), 77 (13).

HRMS: m/z [M]⁺calcd for C₁₆H₁₅FO: 242.1107; found: 242.1106.

HRMS: m/z [M]⁺calcd for C₂₃H₂₂O: 314.1671; found: 314.1671.

Aldehydes 19a, 19c, 19d, 19e, and 19f

These aldehydes were not completely isolated; only the NMR data

for the protons on the aldehyde carbon are reported.

19a: ¹H NMR (300 MHz, CDCl₃): d = 9.74 (d, J = 1.7 Hz, 1 H).

19c: ¹H NMR (300 MHz, CDCl₃): d = 9.64 (d, J = 1.7 Hz, 1 H).

19d: ¹H NMR (500 MHz, CDCl₃): d = 9.96 (d, J = 2.4 Hz, 1 H).

19e: ¹H NMR (400 MHz, CDCl₃): d = 9.92 (d, J = 2.3 Hz, 1 H).

19f: ¹H NMR (300 MHz, CDCl₃): d = 9.93 (d, J = 2.3 Hz, 1 H).

1,2-Diphenylpent-4-en-1-one (22b)

Colorless oil.

IR (neat): 3064, 1682 (CO), 1448, 918, 759, 699 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.57 (td, J = 7.1, 14.2 Hz, 1 H),

2.95 (td, J = 7.1, 14.2 Hz, 1 H), 4.63 (t, J = 7.1 Hz, 1 H), 4.97 (d,

J = 10.2 Hz, 1 H), 5.04 (dd, J = 1.5, 17.1 Hz, 1 H), 5.75 (tdd,

J = 7.1, 10.2, 17.1 Hz, 1 H), 7.15–7.24 (m, 1 H), 7.26–7.34 (m, 4 H),

7.38 (t, J = 7.5 Hz, 2 H), 7.48 (t, J = 7.3 Hz, 1 H), 7.96 (d, J = 7.4

Hz, 2 H).

MS: m/z (%) = 236 (8) [M]⁺, 105 (100), 77 (25).

HRMS: m/z [M]⁺calcd for C₁₇H₁₆O: 236.1201; found: 236.1200.

1,4-Diphenylbutan-2-one-d₁(21a)

Colorless oil.

IR (neat): 3029, 1709 (CO), 1604, 1498, 1454, 702 cm^–1.

1,2,3-Triphenylpropane-1,3-dione (22c); Typical Procedure

A soln of sulfoxide 17dL (37.0 mg, 0.1 mmol) in anhyd THF (1.8

mL) was added dropwise with stirring to a soln of t-BuMgCl (0.12

mmol) in dry THF (0.2 mL) in a flame-dried flask at –45 °C under

argon, and the mixture was stirred at –45 °C for 10 min. i-PrMgCl

(0.5 mmol) was added dropwise with stirring, and the mixture was

slowly allowed to warm to r.t. for 1.7 h. BzCl (0.7 mmol) was added

dropwise with stirring, and the mixture was stirred at r.t. for 1.5 h.

The reaction was quenched by adding sat. aq NH₄Cl (10 mL) and

the mixture was extracted with CHCl₃(2 × 10 mL). The product was

purified by column chromatography (silica gel) to give colorless

crystals; 13.5 mg (45%); mp 152.5–153.5 °C (hexane–EtOAc).

¹H NMR (300 MHz, CDCl₃): d = 2.72–2.81 (m, 2 H), 2.81–2.92 (m,

2 H), 3.64 (t, J = 1.9 Hz, 1 H), 7.08–7.21 (m, 5 H), 7.21–7.35 (m, 5

H).

MS: m/z (%) = 225 (27) [M]⁺, 133 (57), 105 (100), 91 (88), 77 (12).

HRMS: m/z [M]⁺calcd for C₁₆H₁₅DO: 225.1264; found: 225.1263.

1,4-Diphenylpentan-3-one (21b); Typical Procedure

A soln of 14L (40.0 mg, 0.1 mmol) in anhyd THF (1.8 mL) was add-

ed dropwise with stirring to a soln of t-BuMgCl (0.12 mmol) in an-

hyd THF (0.2 mL) in a flame-dried flask at –45 °C under argon. The

mixture was stirred at –45 °C for 10 min to give the magnesium

alkoxide. i-PrMgCl (0.5 mmol) was then added to the mixture,

which was slowly allowed to warm to r.t. for 1.7 h. HMPA (0.5

mmol) and MeI (0.7 mmol) were added sequentially and the mix-

ture was stirred at r.t. for 1.5 h. The reaction was quenched with sat.

aq NH₄Cl (10 mL). The mixture was extracted with CHCl₃(2 × 10

mL) and the product was purified by column chromatography (sili-

ca gel) to give a colorless oil; yield: 15.8 mg (66%).

IR (KBr): 1697 (CO), 1670 (CO), 1594, 1448, 693 cm^–1.

¹H NMR (400 MHz, CDCl₃): d = 6.57 (s, 1 H), 7.27–7.35 (m, 1 H),

7.35–7.40 (m, 4 H), 7.43 (t, J = 7.7 Hz, 4 H), 7.55 (t, J = 7.4 Hz, 2

H), 7.97 (d, J = 7.5 Hz, 4 H).

MS: m/z (%) = 300 (36) [M]⁺, 105 (100), 77 (31).

HRMS: m/z [M]⁺calcd for C₂₁H₁₆O₂: 300.1150; found: 300.1150.

IR (neat): 3028, 1713 (CO), 1495, 1453, 752, 700 cm^–1.

Enol Carbonate (22d)

This compound was not isolated in a pure form, and only the carbo-

nyl absorption in the IR is reported.

¹H NMR (300 MHz, CDCl₃): d = 1.37 (d, J = 7.0 Hz, 3 H), 2.60–

2.70 (m, 2 H), 2.70–2.92 (m, 2 H), 3.70 (q, J = 7.0 Hz, 1 H), 7.02–

7.10 (m, 2 H), 7.11–7.18 (m, 3 H), 7.18–7.34 (m, 5 H).

3624

S. Fukuda et al.

PAPER

IR (neat): 1759 cm^–1.

8-{Chloro(phenyl)[(4-tolyl)sulfinyl]methyl}-1,4-dioxa-

spiro[4.5]decan-8-ol (23d)

2-(4-Methoxyphenyl)-1-phenylpent-4-en-1-one (22e)

Colorless crystals; mp 143.5–144.0 °C (hexane–EtOAc).

Colorless oil.

IR (KBr): 1682 (CO), 1511, 1251, 1035 cm^–1.

IR (KBr): 3337 (OH), 2965, 1597, 1377, 1103, 1079 (SO), 1033,

996, 718, 512 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.54 (td, J = 7.1, 14.2 Hz, 1 H),

2.91 (td, J = 7.1, 14.2 Hz, 1 H), 3.75 (s, 3 H), 4.57 (t, J = 7.1 Hz, 1

H), 4.92–5.10 (m, 2 H), 5.75 (tdd, J = 7.1, 10.2, 17.1 Hz, 1 H), 6.82

(d, J = 9.0 Hz, 2 H), 7.21 (d, J = 9.0 Hz, 2 H), 7.38 (t, J = 7.4 Hz, 2

H), 7.48 (t, J = 7.3 Hz, 1 H), 7.91–7.98 (m, 2 H).

¹H NMR (300 MHz, CDCl₃): d = 1.36–1.55 (m, 2 H), 1.63–1.74 (m,

1 H), 1.99 (dt, J = 4.2, 13.9 Hz, 1 H), 2.11–2.26 (m, 4 H), 2.30 (s, 3

H), 3.75–3.95 (m, 4 H), 4.47 (d, J = 1.6 Hz, 1 H), 6.93 (d, J = 8.3

Hz, 2 H), 7.03 (d, J = 8.3 Hz, 2 H), 7.32–7.45 (m, 3 H), 7.72 (br s,

2 H).

MS: m/z (%) = 266 (10) [M]⁺, 161 (100), 105 (17), 77 (15).

MS (FAB): m/z (%) = 421 (44) [M + 1]⁺, 281 (50), 245 (100), 185

(38), 154 (31), 137 (29), 93 (46).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₂H₂₅ClO₄S: 421.1240;

HRMS: m/z [M]⁺calcd for C₁₈H₁₈O₂: 266.1307; found: 266.1307.

2-(4-Fluorophenyl)-1-phenylpent-4-en-1-one (22f)

found: 421.1240.

Colorless oil.

8-{Chloro(2-naphthyl)[(4-tolyl)sulfinyl]methyl}-1,4-dioxa-

spiro[4.5]decan-8-ol (23e)

Colorless crystals; mp 145.0–146.0 °C (hexane–EtOAc).

IR (KBr): 1685 (CO), 1508, 1225, 691 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 2.55 (ttd, J = 1.2, 7.1, 14.2 Hz, 1

H), 2.92 (m, 1 H), 4.61 (t, J = 7.1 Hz, 1 H), 4.92–5.09 (m, 2 H), 5.73

(tdd, J = 7.1, 10.2, 17.1 Hz, 1 H), 6.98 (t, J = 8.7 Hz, 2 H), 7.21–

7.32 (m, 2 H), 7.40 (t, J = 7.4 Hz, 2 H), 7.50 (t, J = 7.3 Hz, 1 H),

7.90–7.98 (m, 2 H).

MS: m/z (%) = 254 (8) [M]⁺, 105 (100), 77 (22).

HRMS: m/z [M]⁺calcd for C₁₇H₁₅FO: 254.1107; found: 254.1108.

IR (KBr): 3381 (OH), 1596, 1416, 1160, 1106, 1078, 1045 (SO),

760 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.35–1.51 (m, 2 H), 1.65–1.72 (m,

1 H), 2.00 (dt, J = 4.4, 14.3 Hz, 1 H), 2.16–2.24 (m, 5 H), 2.34–2.39

(m, 2 H), 3.70–3.83 (m, 2 H), 3.86–3.90 (m, 2 H), 4.59 (d, J = 1.6

Hz, 1 H), 6.91–6.98 (m, 4 H), 7.52–7.63 (m, 2 H), 7.76–7.97 (m, 4

H), 8.18 (br s, 1 H).

MS (FAB): m/z (%) = 471 (10) [M + 1]⁺, 331 (27), 295 (44), 246

(25), 185 (68), 154 (77), 137 (70), 93 (100), 75 (17).

1-{Chloro(phenyl)[(4-tolyl)sulfinyl]methyl}cyclobutanol (23a)

Colorless crystals; mp 140.0–141.0 °C (hexane–EtOAc).

IR (KBr): 3269 (OH), 1594, 1489, 1444, 1154, 1080 (SO), 1034,

809, 698 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.56–1.72 (m, 1 H), 1.96–2.13 (m,

2 H), 2.14–2.28 (m, 1 H), 2.32 (s, 3 H), 2.70–2.85 (m, 1 H), 2.92–

3.05 (m, 1 H), 3.57 (br s, 1 H), 6.93 (d, J = 8.3 Hz, 2 H), 7.04 (d,

J = 8.3 Hz, 2 H), 7.30–7.43 (m, 3 H), 7.61–7.70 (m, 2 H).

MS (FAB): m/z (%) = 335 (63) [M + 1]⁺, 281 (22), 246 (24), 185

(65), 159 (100), 137 (66), 123 (17), 117 (75), 107 (20), 93 (99).

HRMS (FAB): m/z [M + H]⁺calcd for C₁₈H₂₀ClO₂S: 335.0873;

found: 335.0874.

HRMS (FAB): m/z [M + H]⁺calcd for C₂₆H₂₈ClO₄S: 471.1397;

found: 471.1399.

8-{Chloro(4-methoxyphenyl)[(4-tolyl)sulfinyl]methyl}-1,4-di-

oxaspiro[4.5]decan-8-ol (23f)

Colorless crystals; mp 120.0–121.0 °C (hexane–EtOAc).

IR (KBr): 3382 (OH), 1605, 1509, 1256, 1106, 1034 (SO), 815

cm^–1.

¹H NMR (500 MHz, CDCl₃): d = 1.34–1.44 (m, 1 H), 1.44–1.54 (m,

1 H), 1.66–1.72 (m, 1 H), 1.99 (dt, J = 4.4, 13.5 Hz, 1 H), 2.07–2.22

(m, 2 H), 2.23–2.33 (m, 5 H), 3.77–3.94 (m, 7 H), 4.49 (s, 1 H), 6.90

(d, J = 8.5 Hz, 2 H), 6.96 (d, J = 8.3 Hz, 2 H), 7.06 (d, J = 8.3 Hz, 2

H), 7.62 (br s, 2 H).

1-{Chloro(phenyl)[(4-tolyl)sulfinyl]methyl}cyclopentanol (23b)

Colorless crystals; mp 146.5–147.0 °C (hexane–EtOAc).

MS (FAB): m/z (%) = 451 (10) [M + 1]⁺, 311 (88), 275 (100), 246

(22), 185 (58), 154 (65), 137 (60), 93 (86).

IR (KBr): 3312 (OH), 2956, 1595, 1492, 1446, 1080, 1043 (SO),

809, 698, 512 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.48–2.12 (m, 7 H), 2.24–2.41 (m,

4 H), 3.55 (br s, 1 H), 6.90 (d, J = 8.2 Hz, 2 H), 7.02 (d, J = 8.2 Hz,

2 H), 7.30–7.43 (m, 3 H), 7.73–7.84 (m, 2 H).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₃H₂₈ClO₅S: 451.1346;

found: 451.1347.

8-{Chloro(4-fluorophenyl)[(4-tolyl)sulfinyl]methyl}-1,4-dioxa-

spiro[4.5]decan-8-ol (23g)

Colorless crystals; mp 150.0–151.0 °C (hexane–EtOAc).

Anal. Calcd for C₁₉H₂₁ClO₂S: C, 65.41; H, 6.07; Cl, 10.16; S, 9.19.

Found: C, 65.39; H, 6.1; Cl, 10.15; S, 9.17.

1-{Chloro(phenyl)[(4-tolyl)sulfinyl]methyl}cyclohexanol (23c)

Colorless crystals; mp 138.5–139.0 °C (hexane–EtOAc).

IR (KBr): 3302 (OH), 1601, 1504, 1374, 1227, 1108, 1040 (SO),

1001, 844, 792, 510 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.40–1.56 (m, 2 H), 1.61–1.75 (m,

1 H), 1.98 (dt, J = 4.4, 13.5 Hz, 1 H), 2.07–2.26 (m, 4 H), 2.31 (s, 3

H), 3.77–3.97 (m, 4 H), 4.35 (s, 1 H), 6.95 (d, J = 8.3 Hz, 2 H),

7.02–7.14 (m, 4 H), 7.71 (br s, 2 H).

MS (FAB): m/z (%) = 439 (26) [M + 1]⁺, 299 (40), 263 (100), 219

(13), 185 (45), 154 (47), 137 (44), 93 (68), 75 (12).

IR (KBr): 3288 (OH), 2937, 1596, 1491, 1444, 1080, 1047 (SO),

805, 697, 512 cm^–1.

¹H NMR (500 MHz, CDCl₃): d = 0.88–1.15 (m, 2 H), 1.45 (d,

J = 13.2 Hz, 1 H), 1.51–1.74 (m, 3 H), 1.76–1.89 (m, 1 H), 1.93 (dt,

J = 3.7, 12.7 Hz, 1 H), 2.09–2.26 (m, 2 H), 2.29 (s, 3 H), 4.31 (s, 1

H), 6.95 (d, J = 8.1 Hz, 2 H), 7.02 (d, J = 8.1 Hz, 2 H), 7.38 (br s, 3

H), 7.72 (br s, 2 H).

HRMS (FAB): m/z [M + H]⁺calcd for C₂₂H₂₅ClFO₄S: 439.1146;

found: 439.1146.

Anal. Calcd for C₂₀H₂₃ClO₂S: C, 66.19; H, 6.39; Cl, 9.77; S, 8.83.

Found: C, 66.13; H, 6.44; Cl, 9.71; S, 8.88.

PAPER

Aryl(chloro)methyl 4-Tolyl Sulfoxides

3625

1-Chloro-2-methyl-1-phenyl-1-[(4-tolyl)sulfinyl]propan-2-ol

(23h)

Colorless crystals; mp 143.0–144.0 °C (hexane–EtOAc).

¹H NMR (300 MHz, CDCl₃): d = 1.71–1.86 (m, 1 H), 1.93–2.10 (m,

4 H), 2.30–2.46 (m, 2 H), 2.94 (ddd, J = 4.7, 10.9, 13.6 Hz, 1 H),

3.97–4.04 (m, 4 H), 7.19–7.28 (m, 3 H), 7.28–7.36 (m, 2 H).

IR (KBr): 3280 (OH), 1595, 1141, 1080 (SO), 1040, 728, 698, 513

cm^–1.

MS: m/z (%) = 247 (28) [M]⁺, 219 (15), 142 (12), 113 (12), 105

(100), 99 (50), 86 (36), 28 (32).

¹H NMR (300 MHz, CDCl₃): d = 1.31 (s, 3 H), 1.76 (s, 3 H), 2.30

(s, 3 H), 4.55 (s, 1 H), 6.94 (d, J = 8.3 Hz, 2 H), 7.04 (d, J = 8.3 Hz,

2 H), 7.34–7.42 (m, 3 H), 7.69–7.78 (m, 2 H).

HRMS: m/z [M]⁺calcd for C₁₅H₁₇DO₃: 247.1319; found: 247.1317.

9-Methyl-9-phenyl-1,4-dioxaspiro[4.6]undecan-8-one (25b)

Colorless oil.

IR (neat): 2965, 1705 (CO), 1443, 1110, 701 cm^–1.

MS (FAB): m/z (%) = 323 (100) [M + 1]⁺, 246 (25), 219 (12), 183

(74), 147 (91), 137 (58), 93 (62), 77 (12).

HRMS (FAB): m/z [M + H]⁺calcd for C₁₇H₂₀ClO₂S: 323.0873;

found: 323.0877.

¹H NMR (500 MHz, CDCl₃): d = 1.38 (s, 3 H), 1.67 (dd, J = 10.9,

14.4 Hz, 1 H), 1.77–1.86 (m, 1 H), 1.86–1.96 (m, 2 H), 2.04 (dd,

J = 9.5, 14.8 Hz, 1 H), 2.26 (ddd, J = 2.8, 7.1, 11.9 Hz, 1 H), 2.67

(dd, J = 10.8, 14.7 Hz, 1 H), 2.71 (dt, J = 2.6, 12.2 Hz, 1 H), 3.86–

4.03 (m, 4 H), 7.17–7.26 (m, 3 H), 7.32 (t, J = 7.7 Hz, 2 H).

9-Phenyl-1,4-dioxaspiro[4.6]undecan-8-one (24d)

Colorless oil.

IR (neat): 2948, 2884, 1704 (CO), 1450, 1111, 699, 454 cm^–1.

MS: m/z (%) = 260 (5) [M]⁺, 232 (7), 118 (100), 99 (29), 86 (24).

HRMS: m/z [M]⁺calcd for C₁₆H₂₀O₃: 260.1412; found: 260.1411.

¹H NMR (300 MHz, CDCl₃): d = 1.79 (t, J = 12.2 Hz, 1 H), 1.90–

2.11 (m, 4 H), 2.30–2.46 (m, 2 H), 2.94 (ddd, J = 4.7, 10.9, 13.6 Hz,

1 H), 3.70 (dd, J = 3.8, 11.6 Hz, 1 H), 3.97–4.04 (m, 4 H), 7.19–7.28

(m, 3 H), 7.28–7.36 (m, 2 H).

9-Allyl-9-phenyl-1,4-dioxaspiro[4.6]undecan-8-one (25c)

Colorless oil.

MS: m/z (%) = 246 (35) [M]⁺, 218 (14), 142 (12), 113 (12), 104

IR (neat): 2952, 1704 (CO), 1444, 1112 cm^–1.

(100), 99 (49), 86 (36), 28 (26).

HRMS: m/z [M]⁺calcd for C₁₅H₁₈O₃: 246.1256; found: 246.1253.

¹H NMR (500 MHz, CDCl₃): d = 1.56–1.69 (m, 1 H), 1.75–1.94 (m,

3 H), 2.10–2.26 (m, 2 H), 2.39 (dd, J = 8.8, 14.2 Hz, 1 H), 2.52 (dd,

J = 10.8, 14.9 Hz, 1 H), 2.63 (dt, J = 2.8, 12.3 Hz, 1 H), 2.77 (dd,

J = 5.4, 14.2 Hz, 1 H), 3.85–4.02 (m, 4 H), 4.92 (d, J = 17.2 Hz, 1

H), 4.94 (d, J = 9.5 Hz, 1 H), 5.35 (m, 1 H), 7.19 (d, J = 7.6 Hz, 2

H), 7.24 (t, J = 7.4 Hz, 1 H), 7.32 (t, J = 7.6 Hz, 2 H).

MS: m/z (%) = 286 (22) [M]⁺, 245 (18), 144 (100), 129 (73), 115

(32), 99 (48), 86 (36).

HRMS: m/z [M]⁺calcd for C₁₈H₂₂O₃: 286.1569; found: 286.1571.

9-(2-Naphthyl)-1,4-dioxaspiro[4.6]undecan-8-one (24e)

Colorless crystals; mp 109.0–110.0 °C (hexane–EtOAc).

IR (KBr): 2944, 1697 (CO), 1105, 826, 753, 477 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.77–1.95 (m, 1 H), 1.96–2.06 (m,

2 H), 2.06–2.19 (m, 2 H), 2.37–2.59 (m, 2 H), 3.00 (ddd, J = 5.5,

10.0, 13.8 Hz, 1 H), 3.86 (dd, J = 3.7, 11.4 Hz, 1 H), 3.97–4.06 (m,

4 H), 7.36 (dd, J = 8.6, 1.7 Hz, 1 H), 7.40–7.53 (m, 2 H), 7.67 (s, 1

H), 7.74–7.87 (m, 3 H).

9-Benzyl-9-phenyl-1,4-dioxaspiro[4.6]undecan-8-one (25d)

Colorless crystals; mp 120.0–120.5 °C (hexane–EtOAc).

IR (KBr): 2953, 1709 (CO), 1450, 1139, 1094, 704 cm^–1.

MS: m/z (%) = 296 (10) [M]⁺, 154 (100).

HRMS: m/z [M]⁺calcd for C₁₉H₂₀O₃: 296.1412; found: 296.1414.

¹H NMR (500 MHz, CDCl₃): d = 1.69 (dd, J = 10.5, 14.7 Hz, 1 H),

1.81–1.95 (m, 3 H), 2.05 (dd, J = 9.5, 15.2 Hz, 1 H), 2.19 (ddd,

J = 2.9, 6.3, 11.8 Hz, 1 H), 2.41 (dd, J = 10.7, 15.1 Hz, 1 H), 2.65

(dt, J = 3.4, 12.1 Hz, 1 H), 2.99 (d, J = 13.9 Hz, 1 H), 3.27 (d,

J = 13.9 Hz, 1 H), 3.85–4.01 (m, 4 H), 6.53 (d, J = 7.2 Hz, 2 H),

6.99–7.13 (m, 5 H), 7.21–7.30 (m, 3 H).

9-(4-Methoxyphenyl)-1,4-dioxaspiro[4.6]undecan-8-one (24f)

Colorless oil.

IR (neat): 2951, 1704 (CO), 1610, 1512, 1250, 833 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.70–1.85 (m, 1 H), 1.87–2.09 (m,

4 H), 2.25–2.43 (m, 2 H), 2.92 (ddd, J = 4.5, 11.0, 13.5 Hz, 1 H),

3.65 (dd, J = 3.7, 11.6 Hz, 1 H), 3.79 (s, 3 H), 3.95–4.04 (m, 4 H),

6.86 (d, J = 8.8 Hz, 2 H), 7.15 (d, J = 8.8 Hz, 2 H).

Anal. Calcd for C₂₂H₂₄O₃: C, 78.54; H, 7.19. Found: C, 78.54; H,

7.16.

MS: m/z (%) = 276 (13) [M]⁺, 134 (100), 99 (23).

HRMS: m/z [M]⁺calcd for C₁₆H₂₀O₄: 276.1362; found: 276.1358.

9-Benzoyl-9-phenyl-1,4-dioxaspiro[4.6]undecan-8-one (25e)

Colorless oil.

IR (neat): 2956, 1722 (CO), 1664 (CO), 1447, 1239, 1113, 700

cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.78–2.04 (m, 4 H), 2.55–2.73 (m,

2 H), 2.77–2.90 (m, 2 H), 3.87–4.00 (m, 4 H), 7.19–7.28 (m, 4 H),

7.28–7.43 (m, 4 H), 7.47–7.55 (m, 2 H).

MS: m/z (%) = 350 (23) [M]⁺, 149 (22), 105 (100), 77 (18).

HRMS: m/z [M]⁺calcd for C₂₂H₂₂O₄: 350.1518; found: 350.1519.

9-(4-Fluorophenyl)-1,4-dioxaspiro[4.6]undecan-8-one (24g)

Colorless crystals; mp 109.0–110.0 °C (hexane–EtOAc).

IR (KBr): 2884, 1701 (CO), 1602, 1512, 1223, 844 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.72–1.88 (m, 1 H), 1.92–2.09 (m,

4 H), 2.24–2.36 (m, 1 H), 2.36–2.47 (m, 1 H), 2.82–2.98 (m, 1 H),

3.69 (dd, J = 3.5, 11.4 Hz, 1 H), 3.99 (s, 4 H), 7.00 (t, J = 8.7 Hz, 2

H), 7.18 (dd, J = 5.4, 8.7 Hz, 2 H).

Anal. Calcd for C₁₅H₁₇FO₃: C, 68.17; H, 6.48; F, 7.19. Found: C,

68.22; H, 6.5; F, 7.17.

1-Chloro-3-methyl-1-phenyl-1-[(4-tolyl)sulfinyl]but-3-en-2-ol

(26L and 26P)

26L

Colorless oil.

9-Deuterio-9-Phenyl-1,4-dioxaspiro[4.6]undecan-8-one (25a)

Colorless oil.

IR (neat): 2948, 2884, 1702 (CO), 1447, 1116, 699 cm^–1.

IR (neat): 3394 (OH), 1647, 1596, 1446, 1085 (SO), 911, 809 cm^–1.

3626

S. Fukuda et al.

PAPER

(4) (a) Taguchi, H.; Yamamoto, H.; Nozaki, H. Tetrahedron

¹H NMR (500 MHz, CDCl₃): d = 1.48 (s, 3 H), 2.32 (s, 3 H), 4.84

(s, 1 H), 4.97 (s, 2 H), 5.54 (s, 1 H), 6.80 (d, J = 8.0 Hz, 2 H), 7.04

(d, J = 8.0 Hz, 2 H), 7.30–7.45 (m, 5 H).

MS: m/z (%) = 334 (4) [M]⁺, 298 (3), 246 (10), 193 (12), 158 (14),

123 (27), 105 (100), 91 (18), 77 (36).

HRMS: m/z [M]⁺calcd for C₁₈H₁₉ClO₂S: 334.0794; found:

334.0793.

Lett. 1972, 13, 4661. (b) Taguchi, H.; Yamamoto, H.;

Nozaki, H. J. Am. Chem. Soc. 1974, 96, 6510. (c) Taguchi,

H.; Yamamoto, H.; Nozaki, H. Tetrahedron Lett. 1976, 17,

2617. (d) Taguchi, H.; Yamamoto, H.; Nozaki, H. Bull.

Chem. Soc. Jpn. 1977, 50, 1592.

(5) Hiyama, T.; Shinoda, M.; Nozaki, H. Tetrahedron Lett.

1979, 20, 3529.

(6) Abraham, W. D.; Bhupathy, M.; Cohen, T. Tetrahedron

26P

Lett. 1987, 28, 2203.

Colorless crystals; mp 140.0–141.0 °C (hexane–EtOAc).

(7) (a) Satoh, T.; Itoh, N.; Gengyo, K.; Yamakawa, K.

Tetrahedron Lett. 1992, 33, 7543. (b) Satoh, T.; Itoh, N.;

Gengyo, K.; Takada, S.; Asakawa, N.; Yamani, Y.;

Yamakawa, K. Tetrahedron 1994, 50, 11839.

(8) (a) Satoh, T.; Miyashita, K. Tetrahedron Lett. 2004, 45,

4859. (b) Miyashita, K.; Satoh, T. Tetrahedron 2005, 61,

5067. (c) Satoh, T.; Tanaka, S.; Asakawa, N. Tetrahedron

Lett. 2006, 47, 6769. (d) Tanaka, S.; Anai, T.; Tadokoro,

M.; Satoh, T. Tetrahedron 2008, 64, 7199.

(9) Only the synthesis of a-chlorobenzyl phenyl sulfoxide and

some of its applications in organic synthesis have been

reported: (a) Tsuchihashi, G.; Ogura, K.; Iriuchijima, S.;

Tomisawa, S. Synthesis 1971, 89. (b) More, K. M.;

Wemple, J. J. Org. Chem. 1978, 43, 2713. (c)Makosza, M.;

Golinski, J. Synthesis 1983, 40. (d) García-Martínez, C.;

Pérez-Espino, M. A.; Cervantes-Cuevas, H.; Escalante-

García, J. J. Mex. Chem. Soc. 2006, 50, 130.

IR (KBr): 3269 (OH), 1645, 1596, 1492, 1445, 1081 (SO), 1036,

913, 807, 697, 510 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 1.37 (s, 3 H), 2.31 (s, 3 H), 3.44

(br s, 1 H), 4.93 (t, J = 1.5 Hz, 1 H), 4.99 (br s, 1 H), 5.08 (d, J = 5.3

Hz, 1 H), 6.82 (d, J = 8.2 Hz, 2 H), 7.02 (d, J = 8.2 Hz, 2 H), 7.30–

7.44 (m, 3 H), 7.69–7.77 (m, 2 H).

MS (FAB): m/z (%) = 335 (54) [M + 1]⁺, 177 (20), 159 (100), 131

(18), 93 (12).

HRMS (FAB): m/z [M + H]⁺calcd for C₁₈H₂₀ClO₂S: 335.0873;

found: 335.0873.

1-Methyl-2-phenylcyclopropanecarbaldehyde (28)

Colorless oil.

IR (neat): 1708 (CHO), 1603, 903, 699 cm^–1.

¹H NMR (300 MHz, CDCl₃): d = 0.98 (s, 3 H), 1.44 (dd, J = 5.3, 7.1

Hz, 1 H), 1.68 (dd, J = 5.3, 9.3 Hz, 1 H), 2.73 (dd, J = 7.1, 9.3 Hz,

1 H), 7.12–7.41 (m, 5 H), 8.95 (s, 1 H).

MS: m/z (%) = 160 (100) [M]⁺, 145 (73), 131 (72), 115 (39), 103

(15), 91 (85), 77 (19), 69 (22), 51 (13).

(10) Satoh, T.; Kondo, A.; Musashi, J. Tetrahedron 2004, 60,

5453.

(11) Krassowska-Řwiebocka, B.; Prokopienko, G.; Skulski, L.

Synlett 1999, 1409.

(12) (a) Satoh, T. Chem. Soc. Rev. 2007, 36, 1561. (b) Satoh, T.

In The Chemistry of Organomagnesium Compounds;

Rappoport, Z.; Marek, I., Eds.; John Wiley and Sons:

Chichester, 2008, 717. (c) Satoh, T. Yakugaku Zasshi 2009,

129, 1013; Chem. Abstr. 2009, 152, 261972.

(13) (a) Satoh, T.; Kobayashi, S.; Nakanishi, S.; Horiguch, K.;

Irisa, S. Tetrahedron 1999, 55, 2515. (b) Hoffmann, R. W.;

Holzer, B.; Knopff, O.; Harms, K. Angew. Chem. Int. Ed.

2000, 39, 3072. (c) Satoh, T.; Matsue, R.; Fujii, T.;

Morikawa, S. Tetrahedron 2001, 57, 3891. (d) Hoffmann,

R. W. Chem. Soc. Rev. 2003, 32, 225.

(14) For some recent reviews and papers on the synthesis of a-

aryl ketones, see: (a) Johansson, C. C. C.; Colacot, T. J.

Angew. Chem. Int. Ed. 2010, 49, 676. (b) Burtoloso, A. C.

B. Synlett 2009, 320. (c) Lundin, P. M.; Esquivias, J.; Fu, G.

C. Angew. Chem. Int. Ed. 2009, 48, 154.

(15) Choudary, B. M.; Bharathi, B.; Reddy, C. V.; Kantam, M. L.

J. Chem. Soc., Perkin Trans. 2002, 1, 2069.

(16) Li, L.; Cai, P.; Guo, Q.; Xue, S. J. Org. Chem. 2008, 73,

3516.

(17) Pfefferkorn, J. A.; Bowles, D. M.; Kissel, W.; Boyles, D. C.;

Choi, C.; Larsen, S. D.; Song, Y.; Sun, K.-L.; Miller, S. R.;

Trivedi, B. K. Tetrahedron 2007, 63, 8124.

(18) Landers, B.; Berini, C.; Wang, C.; Navarro, O. J. Org. Chem.

2011, 76, 1390.

HRMS: m/z [M]⁺calcd for C₁₁H₁₂O: 160.0888; found: 160.0889.

Acknowledgment

This work was supported by a Grant-in-Aid for Scientific Research

No. 19590018 and 22590021 from the Ministry of Education, Cul-

ture, Sports, Science and Technology, Japan, and a TUS Grant for

Research Promotion from Tokyo University of Science, which is

gratefully acknowledged.

References

(1) For a monograph and some reviews on homologation and/or

elongation of carbonyl compounds, see: (a) Hase, T. A.

Umpoled Synthons: A Survey of Sources and Uses in

Synthesis; John Wiley and Sons: New York, 1987.

(b) Martin, S. F. Synthesis 1979, 633. (c) Hase, T. A.;

Koskimies, J. K. Aldrichimica Acta 1981, 14, 73.

(d) Stowell, J. C. Chem. Rev. 1984, 84, 409. (e) Badham, N.

F. Tetrahedron 2004, 60, 11. (f) Satoh, T. J. Synth. Org.

Chem., Jpn. 2009, 67, 381.

(2) (a) Villieras, J.; Bacquet, C.; Normant, J. F. J. Organomet.

Chem. 1972, 40, C1. (b) Villieras, J.; Bacquet, C.; Masure,

D.; Normant, J. F. J. Organomet. Chem. 1973, 50, C7.

(3) (a) Kobrich, G.; Grosser, J. Tetrahedron Lett. 1972, 13,

4117. (b) Kobrich, G.; Grosser, J. Chem. Ber. 1973, 106,

2626.

(19) McIntosh, M. L.; Moore, C. M.; Clark, T. B. Org. Lett. 2010,

12, 1996.

(20) Satoh, T.; Itoh, M.; Ohara, T.; Yamakawa, K. Bull. Chem.

Soc. Jpn. 1987, 60, 1839.

Article Doi

Aryl(chloro)methyl 4-tolyl sulfoxides: Synthesis and application to the synthesis of α-aryl ketones

DOI: 10.1055/s-0031-1260251

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Article abstract of DOI:10.1055/s-0031-1260251

Full text of DOI:10.1055/s-0031-1260251

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