A novel synthesis of carboxylic acid derivatives having a quaternary carbon at 3-position and functional groups at 4-position from 1-chlorovinyl p-tolyl sulfoxides and acetic acid esters

Article abstract of DOI:10.1016/S0040-4039(02)00414-8

Addition of the lithium enolate of acetic acid esters to 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones and chloromethyl p-tolyl sulfoxide in three steps in good yields, gave carboxylic acid esters having a quaternary carbon at the 3-po

Full text of DOI:10.1016/S0040-4039(02)00414-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 3033–3036
A novel synthesis of carboxylic acid derivatives having
a quaternary carbon at 3-position and functional groups
at 4-position from 1-chlorovinyl p-tolyl sulfoxides and acetic
acid esters
Tsuyoshi Satoh,* Shimpei Sugiyama and Hiroyuki Ota
Department of Chemistry, Faculty of Science, Science University of Tokyo, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan
Received 25 January 2002; revised 15 February 2002; accepted 22 February 2002
Abstract—Addition of the lithium enolate of acetic acid esters to 1-chlorovinyl p-tolyl sulfoxides, which were derived from ketones
and chloromethyl p-tolyl sulfoxide in three steps in good yields, gave carboxylic acid esters having a quaternary carbon at the
3-position, and chlorine and sulfinyl groups at the 4-position in high yields. Various kinds of functionalized carboxylic acid
derivatives, including spiro-lactones, were derived from the adducts in good to high yields. © 2002 Elsevier Science Ltd. All rights
reserved.
Carboxylic acids and their derivatives are obviously
among the most important and fundamental com-
pounds in organic and synthetic organic chemistry.
Innumerable studies on the chemistry and synthesis of
carboxylic acids and their derivatives have already been
reported; however, in view of the importance of these
compounds in organic chemistry, new synthetic meth-
ods are still eagerly sought.1 On the other hand, con-
struction of the quaternary carbon center has been a
formidable task and a quite interesting challenge in
synthetic organic chemistry.2
Recently, we reported several new synthetic methods
starting from 1-chlorovinyl p-tolyl sulfoxides 2 derived
from ketones 1 and chloromethyl p-tolyl sulfoxide.3 In
continuation of our studies for the development of a
Scheme 1.
Keywords: carboxylic acid; spiro-lactone; quaternary carbon; sulfoxide; 1-chlorovinyl aryl sulfoxide.
* Corresponding author.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)00414-8

3034
T. Satoh et al. / Tetrahedron Letters 43 (2002) 3033–3036
new synthetic method by using 1-chlorovinyl p-tolyl
sulfoxides, herein we report a novel method for the
synthesis of carboxylic acid derivatives having a quater-
nary carbon at the 3-position 4 and lactones 5 via the
adduct of the vinyl sulfoxide 2 with acetic acid esters
(Scheme 1).
highly functionalized carbon at the 4-position. By
chemical modification of the carbon, the adducts 3
would be converted to various kinds of carboxylic acid
derivatives. Based on this expectation, we investigated
the chemistry of 3, and quite interesting results were
obtained (Scheme 2).
In previous studies, we have found that cyanomethyl-
lithium (lithium carbanion of acetonitrile) added to the
1-chlorovinyl p-tolyl sulfoxides 2 in high yields.3b–d We
further investigated the reaction of 2 with nucleophiles,
and the lithium enolate of acetic acid esters was found
to work excellently. The results are summarized in
Table 1.
At first, transformation of the carbon having a chlorine
atom and a sulfinyl group to a methyl group was
investigated. Reduction of the chlorine atom of 3a was
successfully carried out under radical dehalogenation
conditions5 to give a sulfoxide 6 in high yield. Reduc-
tion of the sulfinyl group of 6 was easily carried out
with Raney nickel W-26 in refluxing ethanol to afford
the desired product 7 having the methyl group in
quantitative yield.
The reaction was conducted simply by adding a solu-
tion of 2 to a solution of the lithium enolate of tert-
butyl acetate derived from the acetate with LDA at
−75°C.4 The addition reaction was quite fast and found
to be completed within 5 min (entries 1, 3, and 4). The
yields of 3 were quantitative in all three cases. The
result of the reaction with the lithium enolate of ethyl
acetate was quite interesting (entry 2). In this case, the
reaction with vinyl sulfoxide at −75°C did not take
place at all. However, using 3 equivalents of the carb-
anion and allowing the temperature of the reaction to
warm to 0°C, the desired adduct 3b was obtained in
80% yield. We have no idea for the difference in
reactivity of ethyl acetate and tert-butyl acetate at
present. The adducts 3a–d have two chiral centers and
theoretically two diastereomers should be produced. In
these reactions, only one case (entry 3) gave a mixture
of the diastereomers.
Next, we investigated the transformation of the carbon
having the sulfinyl group to aldehyde. As we have
recognized that a-chlorinated sulfoxides are quite stable
to an acid or a base, we tried to reduce the sulfoxide to
sulfide. In some known reactions for the reduction of
sulfoxide,7 we tried to reduce 3a with trifluoroacetic
anhydride (TFAA) in the presence of NaI in acetone.7c
Quite a clean reaction took place to afford the unex-
pected spiro-g-lactone 8, having a tolylthio group at the
4-position, in high yield.
The presumed mechanism of this quite interesting reac-
tion is shown in Scheme 3. First, the reaction of the
sulfoxide 3a gives an acyloxysulfonium ion.8 At the
same time, the tert-butyl ester is eliminated by tri-
fluoroacetic acid to give carboxylic acid 14. The iodide
anion then attacks the chlorine atom to give thionium
ion 15. The oxygen of the carboxylic acid attacks
intramolecularly the thionium ion to afford the spiro-
lactone 8.
The adducts 3 are very interesting compounds in
organic chemistry. First, the adducts 3 have a quater-
nary carbon at the 3-position. Second, they have a
Table 1. Addition of lithium enolate of acetic acid esters to 1-chlorovinyl p-tolyl sulfoxides 2

T. Satoh et al. / Tetrahedron Letters 43 (2002) 3033–3036
3035
Scheme 2. Synthesis of various carboxylic acid derivatives from the adducts 3a and 3b.
Scheme 3. A plausible mechanism for the formation of lactone 8 and aldehyde 12 by treatment of 3a and 3b with TFAA.
Desulfurizaion of the tolylthio group of 8 was success-
fully carried out with Bu3SnH in the presence of 2,2%-
azobisisobutyronitrile (AIBN)9 to give the spiro-lactone
9 in quantitative yield. The spiro-lactone of the higher
oxidation state (11) than 9 was synthesized from 8 via
the sulfoxide 10. Thus, the sulfide 8 was oxidized with
m-chloroperbenzoic acid at −40°C to give the sulfoxide
10 in good yield. Treatment of the sulfoxide with
TFAA in acetone gave the desired lactone having an
hydroxyl group at the 4-position 11 through the Pum-
merer rearrangement.
ethyl ester 3b. Treatment of the ethyl ester 3b with
TFAA–NaI in the absence of a base gave the desired 12
in 60% yield; however, about 20% of the lactone 8 was
still present. We further investigated this reaction and
found that excess organic base worked to give the
desired aldehyde 12 in 85% yield without the lactone 8.
The mechanism of this reaction was presumed as shown
in Scheme 3. By the same reaction as above, 3b gave
thionium ion 17 through 16. As this reaction was
carried out in the presence of excess organic base, and
the ethyl ester was used, the ester remained intact by
TFAA. Trifluoroacetic acid was added to the thionium
ion 17 to afford the sulfide having a trifluoroacetoxy
group on the same carbon, which was hydrolyzed in the
work-up process to give the aldehyde 12. Oxidation of
Finally, we investigated conversion of the carbon bear-
ing the chlorine and the sulfinyl group to an aldehyde
group (Scheme 2). As mentioned above, as the tert-
butyl ester is easily eliminated by TFAA, we used the

3036
T. Satoh et al. / Tetrahedron Letters 43 (2002) 3033–3036
this aldehyde 12 to carboxylic acid was carried out with
2. (a) Martin, S. F. Tetrahedron 1980, 36, 419; (b) Fuji, K.
Chem. Rev. 1993, 93, 2037; (c) Corey, E. J.; Guzman-
Perez, A. Angew. Chem., Int. Ed. 1998, 37, 388.
3. (a) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Mat-
suda, K.; Koyama, M. Tetrahedron 1998, 54, 5557; (b)
Satoh, T.; Ota, H. Tetrahedron Lett. 1999, 40, 2977; (c)
Satoh, T.; Ota, H. Tetrahedron 2000, 56, 5113; (d) Satoh,
T.; Yoshida, M.; Ota, H. Tetrahedron Lett. 2001, 42,
9241.
4. Two equivalents of lithium enolate of tert-butyl acetate
was used. When this reaction was carried out with 1.5
equivalents of the enolate, significant amount of 2
remained.
10
NaClO2 to give the desired carboxylic acid 13 in
quantitative yield.
In conclusion, we have developed a novel and versatile
procedure for a synthesis of carboxylic acid derivatives
having a quaternary carbon on the 3-position from
1-chlorovinyl p-tolyl sulfoxides. These carboxylic acid
derivatives, in addition, have various kinds of func-
tional groups with a different oxidation state at the
4-position.
5. (a) Ramaiah, M. Tetrahedron 1987, 47, 3541; (b) Satoh,
T.; Sato, T.; Oohara, T.; Yamakawa, K. J. Org. Chem.
1989, 54, 3973.
Acknowledgements
6. Mozingo, R. Org. Syn. Coll. Vol. 3 1965, 181.
7. (a) Olah, G. A.; Husain, A.; Singh, B. P.; Mehrotra, A.
K. J. Org. Chem. 1983, 48, 3667; (b) Arai, Y.;
Yamamoto, M.; Koizumi, T. Bull. Chem. Soc. Jpn. 1988,
61, 467; (c) Bravo, P.; Piovosi, E.; Resnati, G. J. Chem.
Soc., Perkin Trans. 1 1989, 1201.
This work was supported by a Grant-in-Aid for Scien-
tific Research No. 11640545 from the Ministry of Edu-
cation, Culture, Sports, Science and Technology, Japan,
which is gratefully acknowledged.
8. (a) Block, E. Reaction of Organosulfur Compounds; Aca-
demic Press: New York, 1978; pp. 154–162; (b) DeLuc-
chi, O.; Miotti, U.; Modena, G. Org. React. 1991, 40,
157; (c) Padwa, A.; Bunn, D. E.; Osterhout, M. H.
Synthesis 1997, 1353; (d) Solladie, G.; Wilb, N.; Bauder,
C. Tetrahedron Lett. 2000, 41, 4189.
9. (a) Gutierrez, C. G.; Stringham, R. A.; Nitasaka, T.;
Glasscock, K. G. J. Org. Chem. 1980, 45, 3393; (b)
Gutierrez, C. G.; Summerhays, L. R. J. Org. Chem. 1984,
49, 5206; (c) Watanabe, Y.; Araki, T.; Ueno, Y.; Endo,
T. Tetrahedron Lett. 1986, 27, 5385; (d) Satoh, T.; Kub-
ota, K. Tetrahedron Lett. 2000, 41, 2121.
References
1. Some monographs for the chemistry of carboxylic acids
and their derivatives: (a) Patai, S. The Chemistry of
Carboxylic Acids and Esters; John Wiley and Sons: Lon-
don, 1969; (b) Zabicky, J. The Chemistry of Amides; John
Wiley and Sons: London, 1970; (c) Patai, S. The Chem-
istry of Acid Derivatives; John Wiley and Sons:
Chichester, Parts 1 and 2, 1979; (d) Sutherland, I. O.,
Ed.; Comprehensive Organic Chemistry; Pergamon Press:
Oxford, 1979; Vol. 2, Part 9; (e) Patai, S. The Chemistry
of Acid Derivatives; John Wiley and Sons: Chichester,
1992; Parts 1 and 2.
10. Dalcanale, E.; Montanari, F. J. Org. Chem. 1986, 51,
567.