An asymmetric synthesis of esters and γ-lactones with simultaneous construction of vicinal stereogenic carbons at the α- and β-position starting from optically active 1-chlorovinyl p-tolyl sulfoxides

Article abstract of DOI:10.1016/j.tetasy.2008.01.040

Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides with two different substituents at the 2-position, which were synthesized from aldehydes or unsymmetrical ketones and (R)-(-)-chloromethyl p-tolyl sulfoxide in two or three steps, with the lithium enolate of carboxylic acid tert-butyl esters gave the adducts with substituents at the α- and β-position with high 1,3- and 1,4-chiral induction from the stereogenic sulfur center in high yields. The adducts were converted to optically active esters and γ-lactones having stereogenic centers at the α- and β-position in good to high yields. This procedure offers a new method for a synthesis of optically active carboxylic acid derivatives with stereogenic centers at the α- and β-position.

Full text of DOI:10.1016/j.tetasy.2008.01.040

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 401–406
An asymmetric synthesis of esters and c-lactones with simultaneous
construction of vicinal stereogenic carbons at the a- and b-position
starting from optically active 1-chlorovinyl p-tolyl sulfoxides
Shimpei Sugiyama, Nobuhito Nakaya and Tsuyoshi Satoh*
Department of Chemistry, Faculty of Science, Tokyo University of Science, Ichigaya-funagawara-machi,
Shinjuku-ku, Tokyo 162-0826, Japan
Received 8 January 2008; accepted 29 January 2008
Abstract—Treatment of optically active 1-chlorovinyl p-tolyl sulfoxides with two different substituents at the 2-position, which were syn-
thesized from aldehydes or unsymmetrical ketones and (R)-(ꢀ)-chloromethyl p-tolyl sulfoxide in two or three steps, with the lithium eno-
late of carboxylic acid tert-butyl esters gave the adducts with substituents at the a- and b-position with high 1,3- and 1,4-chiral induction
from the stereogenic sulfur center in high yields. The adducts were converted to optically active esters and c-lactones having stereogenic
centers at the a- and b-position in good to high yields. This procedure offers a new method for a synthesis of optically active carboxylic
acid derivatives with stereogenic centers at the a- and b-position.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
Recently, we reported a novel method for the asymmetric
synthesis of esters and lactones with either a tertiary or a
quaternary carbon at the b-position, from optically active
1-chlorovinyl p-tolyl sulfoxides, which were derived from
aldehydes or unsymmetrical ketones in two or three steps,7
and the lithium enolate of tert-butyl acetate.8 We have also
found that various lithium enolate of tert-butyl esters, such
as tert-butyl propionate, reacted with the optically active
1-chlorovinyl p-tolyl sulfoxides, which were synthesized
from symmetrical ketones, to afford various optically
active adducts having a stereogenic center at the a-position
in high enantiomeric excess (ee).9
Carboxylic acids and their derivatives are among the most
important and fundamental compounds in organic and
synthetic organic chemistry; innumerable studies with re-
gard to the chemistry and synthesis of them have already
been reported.1 However, due to the importance of these
compounds in organic chemistry, the development of new
and practical synthetic methods is still eagerly sought.
The synthesis of optically active carboxylic acids and their
derivatives is also one of the most important targets in syn-
thetic organic chemistry.2 Recently, highly enantio- and
diastereoselective reactions for the construction of vicinal
chiral carbon centers in one step have emerged as the most
challenging topics. For example, asymmetric aldol-type
reactions,3 asymmetric Michael reactions,4 and asymmetric
Diels–Alder reactions5 have been widely investigated. In
addition, Uenishi et al.6 reported a palladium-catalyzed
asymmetric synthesis of esters or amino acid derivatives
possessing vicinal stereogenic centers at the a- and b-
position.
Based on these results, it was expected that if the substi-
tuted tert-butyl acetate (R3 = alkyl group; see Scheme 1)
and optically active 1-chlorovinyl p-tolyl sulfoxides 3 hav-
ing two different substituents at the 2-position, which were
synthesized from aldehydes or unsymmetrical ketones 1
and optically active 2, were used in this reaction, various
optically active adducts 4 with 1,3- and 1,4-chiral induction
from the stereogenic sulfur center could be synthesized.
Furthermore, we anticipated that optically active adducts
4 could be converted to optically active c-lactones 5 or
esters 6 with vicinal stereogenic carbon centers at the a-
and b-position (Scheme 1). Herein, we report the feasibility
of this expectation as well as our results.
*
Corresponding author. Tel.: +81 3 5228 8272; fax: +81 3 5261 4631;
e-mail: tsatoh@rs.kagu.trus.ac.jp
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.01.040

402
S. Sugiyama et al. / Tetrahedron: Asymmetry 19 (2008) 401–406
with triethylamine (TEA) in CH2Cl2 at room temperature
for 5 h to afford a 2:1 mixture of 3a and 3b in 86% overall
yield from 2 (Scheme 2).
O
S
ClH2C
Tol
R3CH2COOC(CH3)3
R1
R2
Cl
S
R1
(R)-(-)-2
LDA
O
O
R2
LDA / THF
R3 = Alkyl
Ph OH
PhCHO
MsCl / TEA
CH2Cl2
Tol
S
1
ClH2C
(R)-(-)-2
Tol
O
THF, -78 ºC
H
S
3
Tol
R1 > R2
Cl
86%; 2-steps
3a : 3b = 2 : 1
O
R3
H
7
R1
R2
O
R3
H
Cl
Ph
H
Cl
R1
R2
COOC(CH3)3
S(O)Tol
O
+
Ph
S
O
S
5
Tol
Tol
R3
H
Cl
O
R1
COOC(CH3)3
3a
Scheme 2.
3b
4
R2
H3C
6
At first, 5 equiv of the lithium ester enolate of tert-butyl
propionate was generated from tert-butyl propionate with
LDA in THF at ꢀ78 °C (Scheme 3). To this solution was
added 1-chlorovinyl p-tolyl sulfoxide (Z)-3a. The desired
addition reaction took place within 5 min to afford adduct
4a in a quantitative yield. Adduct 4a has four stereogenic
centers meaning that eight diastereomers could theoreti-
cally be produced. Interestingly, adduct 4a was obtained
as a single isomer. No other diastereomer was observed
Scheme 1.
2. Results and discussion
For the substrates in this investigation, we synthesized
optically active vinyl sulfoxides 3a and 3b from enantio-
merically pure (R)-(ꢀ)-chloromethyl p-tolyl sulfoxide 2
and benzaldehyde.10 Thus, 2 was treated with LDA in
THF at ꢀ78 °C followed by benzaldehyde to give alcohol
7 as a mixture of two diastereomers in quantitative yield.
Alcohol 7 was then treated with methanesulfonyl chloride
1
from a detailed inspection of the H NMR spectra. This
result implied that the addition reaction took place with
high 1,2- 1,3-, and 1,4-asymmetric induction from the
stereogenic sulfur center.
H
CH3
TFAA
NaI
Ph
H
Ph
H
Cl
S
COOC(CH3)3
CH3CH2COOC(CH3)3
CH3CN
LDA / THF
-78 ºC, 99%
S
Tol
Tol
H
-40 ˚C, 80%
Cl
O
O
3a
4a
CH3
H
NOE
CH3
1) mCPBA / CH2Cl2, 0 ºC , 93%
2) i-PrMgCl / THF, -78 ºC, 85%
Ph
H
O
H
O
O
Ph
O
STol
8a
5a
98% de, 99% ee (main diastereomer)
CH3
1) n-Bu3SnH, AIBN / benzene, reflux, 92%
Ph
4a
COOC(CH3)3
2) Raney-Ni / ethanol, 50 ºC, 99%
CH3
6a
H3C CH3
COOH
1) CH3I, LDA / THF, 0 ºC, 97%
Ph
2) TFA / CH2Cl2, r.t., 82%
CH3
9a
[α]D24= +29.4 (c 1.09, ethanol)
{lit.15, [α]D22= +45.3 (c 1.0, ethanol)}
Scheme 3.

S. Sugiyama et al. / Tetrahedron: Asymmetry 19 (2008) 401–406
403
In order to determine the absolute stereochemistry of ad-
duct 4a, we first determined the relative stereochemistry
of the two substituents at the a- and b-position (methyl
and phenyl groups), as shown in Scheme 3. Thus, adduct
4a was treated with trifluoroacetic anhydride (TFAA) in
the presence of NaI in acetonitrile at ꢀ40 °C to give a mix-
ture of two c-lactones with a p-tolylsulfanyl group at the
c-position 8a in 80% yield.11 The sulfanyl group was
oxidized, with m-chloroperbenzoic acid (m-CPBA) at 0 °C,
to a sulfinyl group, and the sulfinylated lactone was treated
with i-PrMgCl to give c-lactone 5a via a sulfoxide-magne-
sium exchange reaction12 in 79% overall yield from 8a.
that an (S)-configuration is induced by the addition reac-
tion of the lithium enolates of tert-butyl esters to 1-chloro-
vinyl p-tolyl sulfoxides having an (R)-sulfinyl group.16
Based on the results mentioned above, adduct 4a was deter-
mined to be (2R,3R,4S,SR)-4-chloro-2-methyl-3-phenyl-4-
(p-tolylsulfinyl)butylic acid tert-butyl ester, as shown in
Scheme 3.
Previously, we reported a plausible transition state model
for the addition reaction of the lithium enolate of tert-butyl
acetate or its homologues to optically active 1-chlorovinyl
p-tolyl sulfoxides 3 with 1,3-8 or 1,4-9 chiral induction from
the stereogenic sulfur center. A plausible mechanism for
the simultaneous construction of the vicinal stereogenic
carbons mentioned above is proposed as shown in Figure 1.
Thus, the lithium cation forms a five-membered chelate
between the oxygen atom of the sulfoxide and the chlorine
atom. In this event, the enolates were introduced to vinyl
sulfoxide 3a from the less hindered si face (Fig. 1). Treat-
ment of the carboxylic acid esters with LDA in THF at
low temperature was reported to give the Z-enolate.17
While the real reason remains unknown at present, the
Z-enolate of tert-butyl propionate could be placed, as
shown in Figure 1, by chelation with the lithium cation
and is introduced from the si face to afford adduct 4a with
1,2-, 1,3-, and 1,4-chiral induction from the stereogenic sul-
fur center.
The diastereomeric excess (de) of 5a was confirmed to be
98% while the enantiomeric excess of the main diastereo-
mer was measured to be 99% (ee) by using Chiralcel OD
as a chiral stationary column. In order to determine the rel-
ative stereochemistry of the two substituents, the NOESY
spectrum of 5a was measured. From a detailed inspection
of the spectra, we were able to determine that the relative
stereochemistry of the two substituents was trans, as shown
in Scheme 3.
Next, in order to determine the absolute configuration of
the carbon bearing the phenyl group of 4a, adduct 4a
was converted to the known carboxylic acid 9a (see Scheme
3). Thus, the reduction of the chlorine atom in 4a with
Bu3SnH13 followed by reduction of the sulfinyl group with
Raney-Ni14 at 50 °C gave optically active ester 6a in 91%
overall yield from 4a. The optically active ester 6a was trea-
ted with excess LDA, followed by the addition of iodo-
methane in THF at 0 °C to give a dimethylated ester in
quantitative yield. Finally, the dimethylated ester was
treated with trifluoroacetic acid (TFA) in CH2Cl2 at room
temperature to afford (3R)-2,2-dimethyl-3-phenylbutyric
acid 9a in good yield. Comparing the sign of the spe-
cific rotation of the product with that of the reported
optically active 9a [the sign of the specific rotation of
(R)-9a was reported to be positive15], the absolute configu-
ration of 9a synthesized was unambiguously determined to
be (R).
In a similar way, the addition reaction of tert-butyl propi-
onate with vinyl sulfoxide 3b gave the adduct 4b in a quan-
titative yield as an inseparable mixture of two
diastereomers with a ratio of 95:5 as judged from their
1H NMR spectra. Adduct 4b was converted to c-lactones
5b in the same way as described above in moderate overall
yield. Again, the diastereomeric excess and enantiomeric
excess of 5b were confirmed to be 89% (de), and 99% (ee)
of the main diastereomer by using Chiralcel OD as a chiral
stationary column. In order to determine the stereochemis-
try of the main product, the NOSEY spectrum of 5b was
measured. From a detailed inspection of the spectrum,
we were able to determine that the relative stereochemistry
of the two substituents was cis to each other, as shown in
Scheme 4. The minor isomer was expected to be the epimer
with respect to the a-position.
With regard to the absolute stereochemistry of the carbon
bearing the chlorine atom of 4a, we have already reported
H3C
(R)S(O)Tol
re
H
(S)
H
O
H
H
S
(R)
Cl
O
Ph
H
(R)
Ph
H3C
O
Ph
Cl
Li
CH3
3a
H3C
H
(H3C)3COOC
4a
5a
si
OC(CH3)3
H
O
H
Z-enolate
CH3
H
Ph
(H3C)3COOC CH3
6a
Figure 1.

404
S. Sugiyama et al. / Tetrahedron: Asymmetry 19 (2008) 401–406
CH3
COOC(CH3)3
H
TFAA
NaI
H
H
Cl
S
CH3CH2COOC(CH3)3
CH3CN
Ph
LDA / THF
-78 ºC, 99%
Ph
S
Tol
Tol
O
H
-40 ºC, 81%
Cl
O
O
3b
4b
NOE
H
CH3
O
CH3
H
1) mCPBA / CH2Cl2, 0 ºC, 78%
2) i-PrMgCl / THF, -78 ºC, 77%
Ph
O
Ph
O
STol
5b
89% de, 99% ee (main diastereomer)
8b
CH3
1) n-Bu3SnH, AIBN / benzene, reflux, 89%
Ph
4b
COOC(CH3)3
2) Raney-Ni / ethanol, 50 ºC, 93%
CH3
6b
H3C CH3
1) CH3I, LDA / THF, 0 ºC, 97%
2) TFA / CH2Cl2, r.t., 90%
Ph
COOH
CH3
9b
[α]D25= -34.5 (c 1.98, ethanol)
Scheme 4.
Table 1. Asymmetric synthesis of c-lactones having stereogenic centers at the a- and b-position of 5 from optically active 1-chlorovinyl p-tolyl sulfoxides 3
R3
H
1) TFAA, NaI / CH3CN, -40 ºC
R3
H
R1
R2
Cl
S
R3CH2COOC(CH3)3 R1
COOC(CH3)3
R1
R2
2) mCPBA / CH2Cl2, 0 ºC
O
R2
S
LDA / THF
3) i-PrMgCl / THF, -78 ºC
Tol
O
Tol
-78 ºC
4
Cl
3
5
O
O
Entry
Vinyl sulfoxide 3
Adduct 4
c-Lactone 5a
R1
R2
R3
Yield (%)
Yield (%) de (%)
eeb (%)
1
2
3
4
5
6
7
8
9
3a
3b
3c
3d
3c
3d
3e
3f
Ph
H
H
Ph
H
4c
nBu
nBu
CH3
CH3
nBu
nBu
CH3
CH3
nBu
nBu
99
99
99
99
99
99
90
93
86
83
5c
5d
5e
5f
5g
5h
5i
70
58
67
48
50
48
93
87
65
56
99
84
61
98
47
99
98
95
97
83
99
99
99
99
99
99
98
99
99
99
4d
4e
4f
4g
4h
4i
PhCH2CH2
H
PhCH2CH2
H
PhCH2CH2
CH3
PhCH2CH2
CH3
PhCH2CH2
H
PhCH2CH2
CH3
PhCH2CH2
CH3
PhCH2CH2
4j
5j
3e
3f
4k
4l
5k
5l
10
a Diastereomeric excess and enantiomeric excess were determined by HPLC using chiral stationary columns.
b Enantiomeric excess of the main diastereomer.
Furthermore, in order to determine the absolute configura-
tion of the carbon bearing the phenyl group of c-lactone
5b, compound 4b was converted to carboxylic acid 9b in
the same way as described above. As the sign of the specific
rotation of the derived 9b was negative, the absolute
configuration of 9b was unambiguously determined to be
(S). Based on the results mentioned above, the absolute
configuration of the adduct 4b was determined to be
(2R,3S,4S,SR)-4-chloro-2-methyl-3-phenyl-4-(p-tolylsulfinyl)-
butylic acid tert-butyl ester, as shown in Scheme 4.
Next, the generality of this reaction was examined and the
results are summarized in Table 1. Benzaldehyde, 3-phenyl-
propanal, and 4-phenyl-2-butanone were selected as the
starting aldehyde or ketone, and tert-butyl propionate and
tert-butyl hexanoate were selected as the esters. As shown
in Table 1, the conjugate addition reaction of the lithium
enolate (generated from the ester with LDA in THF at
ꢀ78 °C) to vinyl sulfoxides 3 gave adducts of esters 4 in high
to quantitative yields. Adducts 4d, 4e, 4g, and 4l were
obtained as an inseparable mixture of two diastereomers.

S. Sugiyama et al. / Tetrahedron: Asymmetry 19 (2008) 401–406
405
(c) Nerz-Stormes, M.; Thornton, E. R. J. Org. Chem. 1991,
56, 2489; (d) Walker, M. A.; Heathcock, C. H. J. Org. Chem.
1991, 56, 5747; (e) Denmark, S. E.; Stavenger, R. A. Acc.
Chem. Res. 2000, 33, 432; (f) Shirokawa, S.; Kamiyama, M.;
Nakamura, T.; Okada, M.; Nakazaki, A.; Hosokawa, S.;
Kobayashi, S. J. Am. Chem. Soc. 2004, 126, 13604; (g) Kong,
K.; Romo, D. Org. Lett. 2006, 8, 2909.
Adducts 4 were converted to c-lactones 5 in the same
manner as described above in moderate to good overall
yields. The diastereomeric excess of all the c-lactones 5
was determined to be 83–99% by using HPLC with Chiralcel
OD, except for 5e and 5g. At present, the low diastereoselec-
tivities of 5e and 5g are still unexplained. However, all of the
enantiomeric excess of the c-lactones 5 from both the main
diastereomers and minor diastereomers was found to be
excellent. From these results, it can be concluded that in
these reactions, the facial selection of the 1-chlorovinyl
p-tolyl sulfoxides is perfect; however, facial selection of the
enolate of the esters is not good in some cases. It is also
worthwhile noting (as shown in the entries 7–10) that the
vicinal quaternary and tertiary carbon centers were con-
structed with high diastereo- and enantioselectivity by this
method.18
4. Some recent papers concerning this chemistry: (a) List, B.;
Pojarliev, P.; Martin, H. J. Org. Lett. 2001, 3, 2423; (b)
Berner, O. M.; Tebeschi, L.; Enders, D. Eur. J. Org. Chem.
2002, 1877; (c) Mase, N.; Thayumanavan, R.; Tanaka, F.;
Barbas, C. F., III Org. Lett. 2004, 6, 2527; (d) Cobb, A. J. A.;
Longbottom, D. A.; Shaw, D. M.; Ley, S. V. Chem. Commun.
2004, 1808; (e) Notz, W.; Tanaka, F.; Barbas, C. F., III Acc.
Chem. Res. 2004, 37, 580; (f) Mase, N.; Watanabe, K.; Yoda,
H.; Takabe, K.; Tanaka, F.; Barbas, C. F., III J. Am. Chem.
Soc. 2006, 128, 4966; (g) Cao, C-L.; Ye, M-C.; Sun, X-L.;
Tang, Y. Org. Lett. 2006, 8, 2901; (h) Zu, L.; Wang, J.; Li, H.;
Wang, W. Org. Lett. 2006, 8, 3077; (i) Majima, K.; Tosaki, S.;
Ohshima, T.; Shibasaki, M. Tetrahedron Lett. 2005, 46, 5377.
5. Some recent papers concerning this chemistry: (a) Ahrendt,
K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc.
2000, 122, 4243; (b) Jorgensen, K. A. Angew. Chem., Int. Ed.
2000, 39, 3558; (c) Motoyama, Y.; Koga, Y.; Nishiyama, H.
Tetrahedron 2001, 57, 853; (d) Corey, E. J. Angew. Chem., Int.
Ed. 2002, 41, 1651; (e) Gotoh, H.; Hayashi, Y. Org. Lett.
2007, 9, 2859.
3. Conclusion
In conclusion, we have reported an asymmetric synthesis of
optically active carboxylic acid derivatives with simulta-
neous construction of vicinal stereogenic centers at the a-
and b-position from (R)-(ꢀ)-chloromethyl p-tolyl sulfoxide
as a source of chirality. Unfortunately, in some cases (5e
and 5g), the diastereoselectivity was not satisfactory; how-
ever, the method described above contributes to the synthe-
sis of optically active esters having tertiary and/or
quaternary carbon stereogenic centers at the a- and b-
position.
6. (a) Ikeda, D.; Kawatsura, M.; Uenishi, J. Tetrahedron Lett.
2005, 46, 6663; (b) Kawatsura, M.; Ikeda, D.; Komatsu, Y.;
Mitani, K.; Tanaka, T.; Uenishi, J. Tetrahedron 2007, 63,
8815.
7. (a) Satoh, T.; Hayashi, Y.; Yamakawa, K. Bull. Chem. Soc.
Jpn. 1993, 66, 1866; (b) Satoh, T.; Kawashima, T.; Takahashi,
S.; Sakai, K. Tetrahedron 2003, 59, 9599.
8. Sugiyama, S.; Satoh, T. Tetrahedron: Asymmetry 2005, 16,
665.
9. Sugiyama, S.; Kido, M.; Satoh, T. Tetrahedron Lett. 2005, 46,
6771.
10. Satoh, T.; Ota, H. Tetrahedron 2000, 56, 5113.
11. (a) Satoh, T.; Sugiyama, S.; Ota, H. Tetrahedron Lett. 2002,
43, 3033; (b) Satoh, T.; Sugiyama, S.; Kamide, Y.; Ota, H.
Tetrahedron 2003, 59, 4327.
Acknowledgment
This work was supported by a Grant-in-Aid for Scientific
Research No. 19590018 from the Ministry of Education,
Culture, Sports, Science and Technology, Japan, which is
gratefully acknowledged.
12. Sugiyama, S.; Shimizu, H.; Satoh, T. Tetrahedron Lett. 2006,
47, 8771.
13. (a) Ramaiah, M. Tetrahedron 1987, 43, 3541; (b) Satoh, T.;
Sato, T.; Oohara, T.; Yamakawa, K. J. Org. Chem. 1989, 54,
3973.
14. Mozingo, R. Org. Synth. 1965, Coll. Vol. 3, 181.
15. Brienne, par M. J.; Ouannes, C.; Jacques, J. Bull. Soc. Chim.
Fr. 1967, 2, 613.
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18. The synthesis of 5i is reported as a representative example for
this method. tert-Butyl 3-[chloro(p-tolylsulfinyl)methyl]-2,3-
dimethyl-5-phenylpentanoate 4i: tert-Butyl propionate
(0.12 mL; 0.80 mmol) was added to a solution of LDA
(0.80 mmol) in 2.5 mL of dry THF at ꢀ78 °C with stirring
under an argon atmosphere. The solution was stirred for
10 min, and a solution of 3e8 (50 mg; 0.16 mmol) in THF
(0.6 mL) was added. The reaction mixture was stirred for
10 min, and the reaction was quenched by adding saturated
aq NH4Cl. The whole was extracted with CHCl3 and the
organic layer was dried over MgSO4. The solvent was

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S. Sugiyama et al. / Tetrahedron: Asymmetry 19 (2008) 401–406
evaporated and the residue was purified by silica gel column
(49.5 mg; 0.22 mmol) was added to a solution of the sulfanyl-
lactone in 3.6 mL of CH2Cl2 at 0 °C with stirring. The
solution was stirred for 20 min, and the reaction was
quenched by adding saturated aq Na2SO3 and saturated aq
NaHCO3. The whole was extracted with CH2Cl2. The organic
layer was washed with saturated aq NaHCO3 and dried over
MgSO4. The solvent was evaporated and the residue was
purified by silica gel column chromatography (hexane/
AcOEt = 2:1) to give a c-tolylsulfinyl c-lactone as a colorless
oil; IR (neat) 2927, 1791 (CO), 1598, 1495, 1455, 1390, 1330,
chromatography (hexane/AcOEt = 3:1) to give adduct 4i
(63.5 mg; 90%) as a colorless oil; IR (neat) 2979, 1728 (CO),
1598, 1495, 1456, 1368, 1256, 1217, 1160, 1058 (SO) cmꢀ1; 1H
NMR d 1.29 (3H, d, J = 7.2 Hz), 1.43 (9H, s), 1.53 (3H, s),
1.96–2.07 (1H, m), 2.17–2.28 (1H, m), 2.44 (3H, s), 2.85 (2H,
double quintet, J = 13.1, 5.0 Hz), 3.16 (1H, q, J = 7.2 Hz),
4.91 (1H, s), 7.19–7.35 (7H, m), 7.75 (2H, d, J = 8.3 Hz). MS
m/z (%) 448 (M+, trace), 431 (6), 375 (17), 255 (3), 253 (11),
217 (23), 199 (8), 171 (13), 143 (57), 140 (100), 139 (24), 91
(91). Calcd for C25H33O3ClS: M, 448.1839. Found; m/z
i
1152, 1084, 1041 (SO), 1015 cmꢀ1. PrMgCl (2.0 mol/L in
27
448.1825. ½aꢁD ¼ ꢀ50:9 (c 1.77, EtOH). 3,4-Dimethyl-4-(2-
THF; 0.27 mL, 0.54 mmol) was added dropwise to a solution
of the resultant sulfinyl-lactone in 3.6 mL of dry THF at
ꢀ78 °C with stirring under an argon atmosphere. The
solution was stirred for 15 min at ꢀ78 °C, and the reaction
was quenched by adding saturated aq NH4Cl. The whole was
extracted with CHCl3. The solvent was removed in vacuo and
the residue was purified by silica gel column chromatography
(hexane/AcOEt = 3:1) to afford 5i (37.3 mg; 93% in three
steps) as a colorless oil; IR (neat) 3062, 3027, 2977, 1773
(CO), 1603, 1497, 1455, 1390, 1368, 1289, 1124, 1096, 1042,
1009 cmꢀ1; 1H NMR d 1.09 (3H, s), 1.14 (3H, d, J = 7.3 Hz),
1.67–1.78 (1H, m), 1.83–1.93 (1H, m), 2.40 (1H, q,
J = 7.2 Hz), 2.48–2.58 (1H, m), 2.65–2.75 (1H, m), 3.95
(2H, s), 7.16–7.33 (5H, m). MS m/z (%) 218 (M+, 72) 187 (31),
171 (7), 157 (7), 143 (7), 131 (9), 113 (47), 104 (55), 91 (100).
Calcd for C14H18O2: M, 218.1306. Found; m/z 218.1309.
phenylethyl)tetrahydrofuran-2-one 5i: A suspension of NaI
(137.4 mg; 0.92 mmol) in 3.2 mL of acetonitrile was stirred
for 10 min at ꢀ40 °C. TFAA (0.13 mL; 0.92 mmol) was
added dropwise to the suspension of NaI with stirring at
ꢀ40 °C and the suspension was stirred for 10 min. Adduct 4i
(82.3 mg; 0.18 mmol) in 0.5 mL of acetonitrile was added
dropwise to the suspension of NaI and TFAA at ꢀ40 °C with
stirring for 10 min. The reaction was quenched by adding
saturated aq NaHCO3 followed by saturated aq Na2SO3. The
whole was extracted with CHCl3. The organic layer was
washed with saturated aq NaHCO3 and dried over MgSO4.
The solvent was removed in vacuo and the residue was
purified by silica gel column chromatography (hexane/
AcOEt = 3:1) to give c-tolylsulfanyl c-lactone as a colorless
oil; IR (neat) 3026, 2978, 2923, 1771 (CO), 1602, 1495, 1455,
1388, 1334, 1254, 1184, 1165, 1117, 964 cmꢀ1. m-CPBA
26
½aꢁD ¼ ꢀ11:0 (c 0.93, EtOH).