LETTER
Synthesis of Aldehydes and Ketones from Thiol Esters
479
(2) For reviews, see: (a) O’Neill, B. T. Nucleophilic Addition to
Carboxylic Acid Derivatives, In Comprehensive Organic
Synthesis, Vol. 1; Trost, B. M.; Fleming, I., Eds.; Pergamon:
Oxford, 1991, Chap. 1.13, 397. (b) Jorgenson, M. J. Org.
React. 1970, 18, 1.
(3) Mukaiyama, T.; Araki, M.; Takei, H. J. Am. Chem. Soc.
1973, 95, 4763.
(4) Nagao, Y.; Kawabata, K.; Fujita, E. J. Chem. Soc., Chem.
Commun. 1978, 330.
Table 4 Coupling of Dodecanethiol Esters with 1-Hexyne
1-hexyne (2.0 equiv)
CuI (2.0 equiv)
O
PdCl2(dppf) (10 mol%)
O
P(2-furyl)3 (25 mol%)
R1
R1
SR2
DMF-Et3N, 50 °C
n-Bu
Entry Substrate
R2 = (CH2)11Me R2 = Eta,b
Time Yield
(min) (%)
Time Yield
(min) (%)
(5) (a) Liebeskind, L. S.; Srogl, J. J. Am. Chem. Soc. 2000, 122,
11260. (b) Wittenberg, R.; Srogl, J.; Egi, M.; Liebeskind, L.
S. Org. Lett. 2003, 5, 3033.
O
1
3.0
99
2.0
94
(6) (a) Fukuyama, T.; Lin, S.-C.; Li, L. J. Am. Chem. Soc. 1990,
112, 7050. (b) Tokuyama, H.; Yokoshima, S.; Lin, S.-C.; Li,
L.; Fukuyama, T. Synthesis 2002, 1121. (c) Tokuyama, H.;
Yokoshima, S.; Yamashita, T.; Lin, S.-C.; Fukuyama, T. J.
Braz. Chem. Soc. 1998, 9, 381.
SR2
MeO
2
1.5
82
1.0
81
O
SR2
(7) Tokuyama, H.; Yokoshima, S.; Yamashita, T.; Fukuyama,
T. Tetrahedron Lett. 1998, 39, 3189.
Br
(8) Tokuyama, H.; Miyazaki, T.; Yokoshima, S.; Fukuyama, T.
Synlett 2003, 1512.
3
1.0
17
85
83
0.6
5.0
74c
53d
O
Cl
SR2
(9) (a) Kanda, Y.; Fukuyama, T. J. Am. Chem. Soc. 1993, 115,
8451. (b) Fujiwara, A.; Kan, T.; Fukuyama, T. Synlett 2000,
1667. (c) Evans, D. A.; Black, W. C. J. Am. Chem. Soc.
1993, 115, 4497. (d) Evans, D. A.; Ng, H. P.; Rieger, D. L.
J. Am. Chem. Soc. 1993, 115, 11446. (e) Smith, A. B. III;
Chen, S.-Y.; Nelson, F. C.; Reichert, J. M.; Salvatore, B. A.
J. Am. Chem. Soc. 1997, 119, 10935. (f) Makino, K.;
Henmi, Y.; Hamada, Y. Synlett 2001, 613.
(10) (a) Hayashi, Y.; Itoh, T.; Fukuyama, T. Org. Lett. 2003, 5,
2235. (b) Mori, Y.; Seki, M. Heterocycles 2002, 58, 125.
(11) (a) Node, M.; Kumar, K.; Nishide, K.; Ohsugi, S.;
Miyamoto, T. Tetrahedron Lett. 2001, 42, 9207.
4
OAc
SR2
O
a Ref.8
b 1.7 Equiv of CuI was used.
c 12% of the by-product, i.e., the Michael adduct of ethyl thiolate to
the product, was obtained.
d 45% of starting material remained.
(b) Nishide, K.; Ohsugi, S.; Fudesaka, M.; Kodama, S.;
Node, M. Tetrahedron Lett. 2002, 43, 5177. (c) 1-
Dodecanethiol is available from Aldrich at $22.90 (500 mL).
(12) 3-(4-Methoxyphenyl)-thiopropionic Acid (S)-dodecyl
Ester (3). (a) Via mixed anhydride: To a solution of 3-(4-
methoxyphenyl)propionic acid (1; 1.02 g, 5.66 mmol) in
CH2Cl2 (23 mL) was added isobutyl chloroformate (0.880
mL, 6.79 mmol) and Et3N (0.780 mL, 5.66 mmol). After
stirring for 30 min at r.t., 1-dodecanethiol (1.60 mL, 6.79
mmol), Et3N (0.780 mL, 5.66 mmol), and DMAP (35.0 mg,
0.283 mmol) were added successively and the resulting
mixture was stirred for 70 min at r.t. The reaction was
quenched by addition of H2O (50 mL). The mixture was
partitioned, and the aqueous layer was extracted with EtOAc
twice. The combined organic extracts were washed with
brine, dried over MgSO4, and concentrated. Purification by
flash column chromatography on silica gel (66 g, 0–2%
EtOAc/hexanes) gave the thiol ester 3 (1.82 g, 4.99 mmol,
88%) as a white crystalline solid: mp: 31–32 °C. IR(film):
2925, 2853, 1693, 1612, 1514, 1465, 1248, 1178, 1040, 823
cm–1. 1H NMR (400 MHz, CDCl3): d = 7.10 (d, J = 8.8 Hz,
2 H), 6.82 (d, J = 8.8 Hz, 2 H), 3.78 (s, 3 H), 2.94–2.79 (m,
6 H), 1.58–1.51 (m, 2 H), 1.25 (br, 18 H), 0.88 (t, J = 6.8 Hz,
3 H). 13C NMR (100 MHz, CDCl3): d = 198.8, 158.2, 132.3,
132.3, 129.3, 129.3, 113.9, 55.2, 45.8, 31.9, 30.7, 29.6, 29.6,
29.5, 29.5, 29.3, 29.1, 28.9, 28.8, 22.7, 14.1. Anal. Calcd for
C22H36O2S: C, 72.48; H, 9.95. Found: C, 72.38; H, 9.67. (b)
With water-soluble carbodiimide (WSCD): To a solution of
acid (1; 1.05 g, 5.83 mmol), WSCD (1.34 g, 6.99 mmol), and
DMAP (36.0 mg, 0.292 mmol) in CH2Cl2 (23 mL) was
added 1-dodecanethiol (1.67 mL, 6.99 mmol). The solution
was stirred for 40 min at r.t., and the reaction was quenched
by addition of H2O (50 mL). A similar purification
procedure as above afforded the thiol ester 3 (2.01 g, 5.51
O
O
O
OH
O
Me
a
b
O
O
O
O
N
Ar
N
Me
Bn
Bn
Ar = p-(MeO)C6H4
O
TBSO
TBSO
11
Me
c
O
Ar
N
Ar
S
Me
Me
Bn
TBSO
O
d
Ar
H
Me
Scheme 2 Reagents and conditions: (a) Bu2BOTf, Et3N, CH2Cl2,
0 °C; p-MeOC6H4(CH2)2CHO, 83%; (b) TBSOTf, 2,6-lutidine,
CH2Cl2, 0 °C, 67%; (c) n-BuLi, dodecanethiol, THF, 0 °C, 87%;
(d) Et3SiH, 10% Pd/C, acetone, r.t., 77%.
References
(1) For representative examples, see: (a) Mosettig, E. Org.
React. 1954, 8, 218. (b) Cha, J. S.; Kim, J. E.; Yoon, M. S.;
Kim, Y. S. Tetrahedron Lett. 1987, 28, 6231. (c) Corriu, R.
J. P.; Lanneau, G. F.; Perrot, M. Tetrahedron Lett. 1987, 28,
3941. (d) Brown, H. C.; Cha, J. S.; Nazer, B.; Yoon, N. M.
J. Am. Chem. Soc. 1984, 106, 8001.
Synlett 2004, No. 3, 477–480 © Thieme Stuttgart · New York