A convenient and efficient α-sulfenylation of carbonyl compounds

Article abstract of DOI:10.1055/s-0029-1216641

A method for the α-sulfenylation of carbonyl compounds by 5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinanane-2-disulfanyl derivatives has been developed. Readily available reagents, mild reaction conditions, and excellent yields with high selectivity make t

Full text of DOI:10.1055/s-0029-1216641

1720
PAPER
A Convenient and Efficient a-Sulfenylation of Carbonyl Compounds
a
-Sulfenylation
m
of Carbonyl Compo
i
unds lia Okragla, Sebastian Demkowicz, Janusz Rachon, Dariusz Witt*
Department of Organic Chemistry, Chemical Faculty, Gdansk University of Technology, Narutowicza 11/12, 80-952 Gdansk, Poland
Fax +48(58)3472694; E-mail: dwitt@chem.pg.gda.pl
Received 4 December 2008; revised 22 January 2009
The presence of enolizable C–H bonds in aldehydes, ke-
Abstract: A method for the a-sulfenylation of carbonyl compounds
tones, and a-acidic hydrogens in b-keto esters allows the
possibility for reactions with different classes of electro-
by 5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinanane-2-disulfa-
nyl derivatives has been developed. Readily available reagents,
philic sulfenylating reagents leading to the formation of
C–S bonds. Herein, we report a convenient and efficient
method for the preparation of a-oxo sulfides from enoliz-
able carbonyl compounds and 5,5-dimethyl-2-thioxo-
1,3,2-dioxaphosphorinane-2-disulfanyl derivatives.
mild reaction conditions, and excellent yields with high selectivity
make this method quite simple, convenient and practical.
Key words: thioethers, sulfides, sulfenylation, thiols, carbonyl
compounds
Treatment of the stable and readily available bis(5,5-di-
The development of new reactions that produce conve-
nient and versatile building blocks from simple and readi-
ly available reagents is currently one of the most
important tasks for contemporary organic synthesis. a-
Sulfenylated carbonyl compounds are particularly inter-
esting synthetic intermediates since they have been used
for a variety of organic transformations.1 Preparation of
these compounds very often involves SN2 displacement of
a-halogenated carbonyl compounds with sulfides anions.2
Other methods are based on the reaction of enolates or
enamines with various electrophilic sulfenylating re-
agents such as commercially available dimethyl disulfide,
diphenyl disulfide, N-(phenylsulfanyl)phthalimide 3 or S-
methyl methanethiosulfonate, N-(phenylsulfanyl)capro-
lactam, N-(phenylsulfanyl)succinimide,4 and sulfenyl
chlorides (e.g., PhSCl).5 In recent years, some attention
has been paid to the enantioselective a-sulfenylation of
carbonyl compounds (aldehydes, ketones, lactones, lac-
tams, and 1,3-dicarbonyl compounds) using chiral
organocatalysts6 and also titanium(IV) catalysts.7 Al-
though a wide range of sulfenylating reagents is available,
many of them required multistep sequences for their prep-
aration. Moreover, their reactivity is often compromised
by their stability6b or the presence of additional functional
groups.
methyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl)
disul-
fide (1) (method A) or 5,5-dimethyl-2-sulfanyl-2-thioxo-
1,3,2-dioxaphosphorinane 2 (method B) with bromine at
–30 °C quantitatively affords 5,5-dimethyl-2-thioxo-
1,3,2-dioxaphosphorinane-2-sulfenyl
bromide
(3)
(Scheme 1). Subsequent treatment, without prior isola-
tion, of sulfenyl bromide 3 with dodecane-1-thiol, 11-sul-
fanylundecan-1-ol, or 11-sulfanylundecanoic acid
provides the corresponding 5,5-dimethyl-2-thioxo-1,3,2-
dioxaphosphorinane-2-disulfanyl derivatives 4a–c, which
can be isolated in very good yields12 (92–100%,
Scheme 1).
O
O
O
O
S
S
S
S
S
P
P
P
SH
O
O
1
2
method B
method A
O
S
S
Br2
CH2Cl2, –30 °C
Br2
CH2Cl2, –30 °C
P
Br
O
3
R3 SH
O
O
S
P
S
R3
S
We have previously prepared functionalized unsymmetri-
cal dialkyl disulfides, alkyl aryl disulfides,8 ‘bioresistant’
disulfides,9 unsymmetrical disulfides based on L-cysteine
and L-cystine derivatives,10 and diaryl disulfides11 using
of 5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinane-2-
disulfanyl derivatives in reactions with aliphatic, aromatic
thiols and thiol groups from cysteine derivatives. The
presence of additional functional groups such as amino,
hydroxy, or carboxy did not disturb the unsymmetrical
disulfide bond formation.
4a R3 = -(CH2)11Me
4b R3 = -(CH2)11OH
4c R3 = -(CH2)10COOH
Scheme 1 The synthesis of 5,5-dimethyl-2-thioxo-1,3,2-dioxaphos-
phorinane-2-disulfanyl derivatives 4a–c
These compounds are stable at room temperature for sev-
eral months; decomposition by moisture or formation of
symmetrical disulfides was not observed.
Initially, we attempted the sulfenylation of diethyl mal-
onate (5a) with disulfide 4a using stoichiometric amounts
of reagents. After three hours at room temperature, prod-
uct 6a was isolated only in 42% yield (54% of starting ma-
terial 4a was recovered) (Table 1, entry 1). When the
SYNTHESIS 2009, No. 10, pp 1720–1724
Advanced online publication: 14.04.2009
DOI: 10.1055/s-0029-1216641; Art ID: P13908SS
© Georg Thieme Verlag Stuttgart · New York
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PAPER
a-Sulfenylation of Carbonyl Compounds
1721
reaction of disulfide 4a was performed with a three-fold um hydride and sodium ethoxide were the most conve-
excess of diethyl malonate (5a), diethyl (dodecylsulfa- nient.
nyl)malonate (6a) was obtained in 81% yield (Table 1, en-
try 3) after 30 minutes at room temperature.
To demonstrate the scope of this new a-sulfenylation re-
action, we reacted compounds 5a–e with sulfenylating re-
agents 4a–c. Three equivalents of the enolate anion were
generated in tetrahydrofuran or ethanol by means of sodi-
um hydride or sodium ethoxide, respectively. Then treat-
ment with disulfides 4a–c at room temperature for 30
minutes afforded products 6a–o. The results are summa-
rized in Table 2.
Table 1 The Reactions of Disulfide 4a with Diethyl Malonate (5a)
O
O
S
S
base
–
P
+
CH(CO2Et)2
CH(CO2Et)2
CH2(CO2Et)2
S-(CH2)11Me
4a
5a
O
O
S
Generally, high yields (64–98%) were obtained for reac-
tions of carbonyl compounds 5a–e with sulfenylating re-
agents 4a–c (Table 2). Interestingly, in the case of
acetophenone (5b), the a,a-disulfenylated products were
also isolated in ca. 30% yield for reactions with 4a–c.
Probably, the smaller steric hindrance of the enolates ob-
tained from a-sulfenylated acetophenones 6b, 6g, and 6l
is responsible for a,a-disulfenylated product formation.
Diethyl malonate (5a), acetylacetone (5c), ethyl 3-oxobu-
tanoate (5d), and triethyl phosphonoacetate (5e) did not
show formation of a,a-disulfenylated products under the
same conditions.
Me(CH2)11
S
P
+
S–
6a
Entry
Ratio 5a/4a Base
Solvent
Yield (%)
1
2
3
4
5
6
7
8
9
1:1
3:2
3:1
1:1
3:1
1:1
3:1
1:1
3:1
NaH
THF
42
64
81
54
71
47
83
41
85
NaH
THF
NaH
THF
DBU
DBU
LDA
LDA
NaOEt
NaOEt
toluene
toluene
THF
To our knowledge, the reactions of disulfides 4b and 4c
with enolates anions are the first examples of sulfenyla-
tion of carbonyl compounds with reagents possessing ad-
ditional functional groups such as hydroxy or carboxy
(Table 2). The reported methods in the literature for the
a-sulfenylation of carbonyl compounds are based on the
introduction of arylsulfanyl,3–5 alkylsulfanyl6,7 or
phthalimidosulfanyl7b groups without additional function-
alities.
THF
EtOH
EtOH
As the data in Table 1 demonstrates, the reaction medium
did not show a great impact on the a-sulfenylation pro-
cess. Reactions in tetrahydrofuran and ethanol proceeded
in high yields, while toluene was only slightly less effi-
cient. The generation of an enolate anion from diethyl ma-
lonate was achieved by several bases, such as NaH, DBU,
LDA, and NaOEt, but from a practical point of view sodi-
In summary, a simple, efficient, and selective method for
a-sulfenylation of carbonyl compounds has been devel-
oped. Moreover, the presence of additional functional
groups such as hydroxy or carboxy did not disturb the
course of reaction and allowed preparation of more elab-
orate structures.
Table 2 a-Sulfenylation of Carbonyl Compounds 5a–e
O
O–
O
O
O
S
O
S
S
R2
R3
base
R2
R2
P
+
P
R1
+
R1
R1
S
R3
30 min, r.t.
S–
O
S
5a–e
4a–c
6a–o
R1
R2
Producta [isolated yield (%)]
4a R3 = (CH2)11Mea
4b R3 = (CH2)11OHa
6f [77]
4c R3 = (CH2)10CO2Hb
6k [90]
5a
5b
5c
5d
5e
OEt
CO2Et
H
6a [81]
6b [66]
6c [97]
6d [76]
6e [98]
Ph
6g [64]
6l [65]
Me
Me
OEt
Ac
6h [92]
6m [87]
CO2Et
PO(OEt)2
6i [81]
6n [90]
6j [69]
6o [80]
a NaH as a base in THF.
b NaOEt as a base in EtOH.
Synthesis 2009, No. 10, 1720–1724 © Thieme Stuttgart · New York

1722
E. Okragla et al.
PAPER
13C NMR (50 MHz, CDCl3): d = 197.4, 104.7, 36.9, 31.9, 29.6,
29.5, 29.3, 29.3, 29.2, 28.9, 24.5, 22.7, 14.1. Signals: expected, 15;
observed, 13.
HRMS (ESI): m/z [M + Na]+ calcd for C17H32NaO2S: 323.2021;
found: 323.2027.
Dodecane-1-thiol, 11-sulfanylundecan-1-ol, 11-sulfanylundecano-
ic acid, and NaH (60% in mineral oil) are commercially available
from Aldrich. Bis(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphori-
nan-2-yl) disulfide (1),13 5,5-dimethyl-2-sulfanyl-2-thioxo-1,3,2-
dioxaphosphorinane (2),13 1-[(5,5-dimethyl-2-thioxo-1,3,2-dioxa-
phosphorinan-2-yl)disulfanyl]dodecane (4a), 11-[(5,5-dimethyl-2-
thioxo-1,3,2-dioxaphosphorinan-2-yl)disulfanyl]undecan-1-ol (4b),
and 11-[(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-yl)di-
sulfanyl]undecanoic acid (4c)12 were synthesized by described pro-
cedures. THF and EtOH were dried and distilled by standard
procedures. Melting points are uncorrected. NMR spectra were re-
corded on a Varian Gemini 500 MHz or 200 MHz spectrometer.
The residual solvent peak was used as internal reference (CDCl3:
d = 7.26 for 1H, d = 77.0 for 13C); 31P NMR used an external stan-
dard as reference (85% H3PO4: d = 0). ESI-MS spectra were record-
ed on a Mariner PerSeptve Biosystem. Column chromatography
was performed with silica gel 60 (230–400 mesh, Merck). Prepara-
tive TLC chromatography was performed with silica gel Polygram
SIL G/UV254 (Macherey-Nagel). Petroleum ether = PE.
Ethyl 2-(Dodecylsulfanyl)-3-oxobutanoate (6d)
Chromatography (PE–CH2Cl2, 1:1); oil; yield: 76%; both enol and
keto isomers were observed with ratio 1:1.
1H NMR (500 MHz, CDCl3): d = 0.89 (t, J = 7.0 Hz, 3 H, CH3),
1.20–1.45 (m, 21 H, CH2, OCCH3), 1.57–1.65 (m, 2 H, CH2), 2.367
and 2.373 (s, 3 H, COCH3, C=CCH3), 2.54 (t, J = 7.3 Hz, 2 H,
SCH2), 4.11 (s, 0.56 H, SCH), 4.23–4.38 (m, 2 H, OCH2), 13.54 (s,
0.44 H, C=COH).
13C NMR (50 MHz, CDCl3): d = 197.3, 182.1, 173.3, 167.5, 94.1,
62.1, 61.4, 58.1, 35.6, 31.9, 31.6, 29.6, 29.5, 29.4, 29.3, 29.3, 29.1,
29.1, 28.9, 28.8, 28.7, 26.7, 22.7, 21.0, 14.2, 14.1, 14.0. Signals
from both isomers: expected, 27; observed, 27.
HRMS (ESI): m/z [M + Na]+ calcd for C18H34NaO3S: 353.2126;
found: 353.2131.
a-Sulfenylation of Carbonyl Compounds 5a–e with 4a or 4b;
General Procedure
A soln of carbonyl compound 5a–e (3.0 mmol) in anhyd THF (5
mL) was added dropwise to a suspension of NaH (0.12 g, 3.0 mmol)
in anhyd THF (15 mL) at r.t. under an N2 atmosphere. When the
evolution of H2 had ceased, a soln of 4a (0.398 g, 1.0 mmol) or 4b
(0.400 g, 1.0 mmol) in anhyd THF (5 mL) was added. The mixture
was stirred at r.t. for 3 h and evaporated under vacuum. The residue
was dissolved in EtOAc (50 mL), washed with sat. aq NH4Cl, dried
(MgSO4), filtered, and concentrated. The products were purified by
column chromatography (Table 2).
Ethyl 2-(Diethoxyphosphoryl)-2-(dodecylsulfanyl)acetate (6e)
Chromatography (PE–CH2Cl2, 1:1); oil; yield: 98%.
1H NMR (500 MHz, CDCl3): d = 0.88 (t, J = 6.8 Hz, 3 H, CH3),
1.20–1.35 (m, 18 H, CH2), 1.31 (t, J = 7.3 Hz, 3 H, COOCH2CH3),
1.36 (t, J = 7.3 Hz, 6 H, POCH2CH3), 1.55–1.63 (m, 2 H, CH2),
2
2.68–2.80 (m, 2 H, SCH2), 3.67 (d, JP-C = 20.0 Hz, 1 H, PCH),
4.20–4.30 (m, 6 H, OCH2).
2
13C NMR (125 MHz, CDCl3): d = 167.7, 63.8 (d, JP-C = 7.6 Hz),
2
63.7 (d, JP-C = 7.6 Hz), 62.1, 44.7 (d, JP-C = 141.0 Hz), 33.4 (d,
3JP-C = 5.5 Hz), 31.9, 29.6, 29.5, 29.4, 29.3, 29.1, 28.9, 28.6, 22.6,
Diethyl (Dodecylsulfanyl)malonate (6a)
Chromatography (PE–CH2Cl2, 2:1); oil; yield: 81%.
16.3 (d, 3JP-C = 5.9 Hz), 14.1, 14.0. Signals: expected, 20; observed,
1H NMR (500 MHz, CDCl3): d = 0.89 (t, J = 7.1 Hz, 3 H, CH3),
1.20–1.35 (m, 16 H, CH2), 1.31 (t, J = 7.3 Hz, 6 H, OCH2CH3),
1.35–1.45 (m, 2 H, CH2), 1.55–1.65 (m, 2 H, CH2), 2.74 (t, J = 7.3
Hz, 2 H, SCH2), 4.17 (s, 1 H, SCH), 4.27 (q, J = 7.3 Hz, 4 H, OCH2).
13C NMR (50 MHz, CDCl3): d = 167.0, 62.2, 53.0, 31.9, 31.8, 29.6,
29.5, 29.4, 29.3, 29.1, 28.9, 28.7, 22.7, 14.1, 14.0. Signals: expect-
ed, 16; observed, 15.
18.
31P NMR (202 MHz, CDCl3): d = 18.10.
HRMS (ESI): m/z [M + Na]+ calcd for C20H41NaO5PS: 447.2310;
found: 447.2315.
Diethyl [11-Hydroxyundecyl)sulfanyl]malonate (6f)
Chromatography (EtOAc–CH2Cl2, 1:6); oil; yield: 77%.
HRMS (ESI): m/z [M + Na]+ calcd for C19H36NaO4S: 383.2232;
found: 383.2237.
1H NMR (500 MHz, CDCl3): d = 1.20–1.45 (m, 20 H, CH2,
OCH2CH3), 1.52–1.74 (m, 4 H, CH2), 2.74 (t, J = 7.3 Hz, 2 H,
SCH2), 3.38 (s, 1 H, OH), 3.65 (t, J = 6.6 Hz, 2 H, OCH2), 4.17 (s,
1 H, SCH), 4.27 (q, J = 7.3 Hz, 4 H, OCH2).
13C NMR (50 MHz, CDCl3): d = 167.0, 63.0, 62.2, 51.0, 32.7, 31.7,
29.5, 29.4, 29.1, 28.9, 28.7, 28.4, 25.7, 14.0. Signals: expected, 15;
observed, 14.
2-(Dodecylsulfanyl)-1-phenylethanone (6b)
Chromatography (PE–CH2Cl2, 2:1); white solid; yield: 66%; mp
31–32 °C (Lit.14 31–32 °C).
1H NMR (200 MHz, CDCl3): d = 0.89 (t, J = 6.5 Hz, 3 H, CH3),
1.15–1.45 (m, 18 H, CH2), 1.50–1.70 (m, 2 H, CH2), 2.57 (t, J = 7.3
Hz, 2 H, SCH2), 3.79 (s, 2 H, COCH2S), 7.40–7.65 (m, 3 H, Ar),
7.90–8.05 (m, 2 H, Ar).
HRMS (ESI): m/z [M + Na]+ calcd for C18H34NaO5S: 385.2025;
found: 385.2028.
13C NMR (50 MHz, CDCl3): d = 194.6, 135.3, 133.2, 128.8, 128.6,
37.1, 32.4, 31.9, 29.6, 29.6, 29.5, 29.3, 29.2, 29.0, 28.7, 22.7, 14.1.
Signals: expected, 18; observed, 17.
HRMS (ESI): m/z [M + Na]+ calcd for C20H32NaOS: 343.2072;
found: 343.2081.
2-[(11-Hydroxyundecyl)sulfanyl]-1-phenylethanone (6g)
Chromatography (CHCl3); white solid; yield: 64%; mp 47–49 °C.
1H NMR (500 MHz, CDCl3): d = 1.20–1.42 (m, 14 H, CH2), 1.52–
1.66 (m, 5 H, CH2, OH), 2.58 (t, J = 7.3 Hz, 2 H, SCH2), 3.66 (t,
J = 6.8 Hz, 2 H, OCH2), 3.81 (s, 2 H, COCH2S), 7.50 (t, J = 7.8 Hz,
2 H, m-H), 7.60 (t, J = 7.8 Hz, 1 H, p-H), 8.00 (d, J = 7.8 Hz, 2 H,
o-H).
13C NMR (125 MHz, CDCl3): d = 194.6, 135.2, 133.3, 128.8, 128.7,
63.0, 37.1, 32.7, 32.3, 29.5, 29.4, 29.4, 29.4, 29.1, 28.9, 28.7, 25.7.
Signals: expected, 17; observed, 17.
3-(Dodecylsulfanyl)pentane-2,4-dione (6c)
Chromatography (PE–CH2Cl2, 2:1); oil; yield: 97%; only enol iso-
mer is observed.
1H NMR (500 MHz, CDCl3): d = 0.90 (t, J = 6.8 Hz, 3 H, CH3),
1.24–1.34 (m, 16 H, CH2), 1.35–1.44 (m, 2 H, CH2), 1.51–1.59 (m,
2 H, CH2), 2.45 (s, 6 H, CH3), 2.50 (t, J = 7.3 Hz, 2 H, SCH2), 17.09
(s, 1 H, C=COH).
HRMS (ESI): m/z [M + Na]+ calcd for C19H30NaO2S: 345.1864;
found: 345.1871.
Synthesis 2009, No. 10, 1720–1724 © Thieme Stuttgart · New York

PAPER
a-Sulfenylation of Carbonyl Compounds
1723
3-[(11-Hydroxyundecyl)sulfanyl]pentane-2,4-dione (6h)
Chromatography (EtOAc–CH2Cl2, 1:6); oil; yield: 92%; only enol
isomer is observed.
13C NMR (50 MHz, CDCl3): d = 179.7, 167.0, 62.2, 51.0, 34.0,
31.7, 29.3, 29.3, 29.1, 29.0, 29.0, 28.9, 28.7, 24.6, 14.0. Signals: ex-
pected, 15; observed, 15.
1H NMR (500 MHz, CDCl3): d = 1.20–1.43 (m, 14 H, CH2), 1.48–
1.62 (m, 4 H, CH2), 1.90 (br s, 1 H, OH), 2.42 (s, 6 H, CH3), 2.48 (t,
J = 7.3 Hz, 2 H, SCH2), 3.62 (t, J = 6.8 Hz, 2 H, OCH2), 17.10 (s, 1
H, C=COH).
HRMS (ESI): m/z [M + Na]+ calcd for C18H32NaO6S: 399.1817;
found: 399.1821.
2-[(10-Carboxydecyl)sulfanyl]-1-phenylethanone (6l)
Chromatography (CHCl3); yield: 65%
13C NMR (125 MHz, CDCl3): d = 197.5, 104.6, 62.9, 36.8, 32.7,
29.5, 29.4, 29.3, 29.2, 29.1, 28.8, 25.6, 24.5. Signals: expected, 14;
observed, 13.
HRMS (ESI): m/z [M + Na]+ calcd for C16H30NaO3S: 325.1813;
found: 325.1817.
1H NMR (500 MHz, CDCl3): d = 1.20–1.42 (m, 12 H, CH2), 1.53–
1.66 (m, 4 H, CH2), 2.35 (t, J = 7.4 Hz, 2 H, OOCCH2), 2.58 (t,
J = 7.3 Hz, 2 H, SCH2), 3.80 (s, 2 H, COCH2S), 6.70 (br s, 1 H,
COOH), 7.50 (t, J = 7.8 Hz, 2 H, m-H), 7.60 (t, J = 7.8 Hz, 1 H, p-
H), 8.00 (d, J = 7.8 Hz, 2 H, o-H).
Ethyl 2-[(11-Hydroxyundecyl)sulfanyl]-3-oxobutanoate (6i)
Chromatography (EtOAc–CH2Cl2, 1:6); oil; yield: 81%; both enol
and keto isomers were observed with ratio 1:1.
13C NMR (125 MHz, CDCl3): d = 194.6, 179.6, 135.2, 133.3, 128.8,
128.7, 37.1, 32.7, 32.3, 29.5, 29.4, 29.4, 29.3, 29.1, 28.9, 28.7, 24.7.
Signals: expected, 17; observed, 17.
1H NMR (500 MHz, CDCl3): d = 1.20–1.45 (m, 18 H, CH2, OH,
OCCH3), 1.47–1.62 (m, 4 H, CH2), 2.366 and 2.373 (s, 3 H, COCH3,
C=CCH3), 2.54 (t, J = 7.3 Hz, 2 H, SCH2), 3.66 (t, J = 6.8 Hz, 2 H,
OCH2), 4.12 (s, 0.55 H, SCH), 4.23–4.38 (m, 2 H, OCH2), 13.54 (s,
0.45 H, C=COH).
13C NMR (50 MHz, CDCl3): d = 197.2, 182.0, 173.2, 167.4, 94.0,
63.0, 62.1, 61.4, 58.1, 35.6, 31.9, 31.6, 29.6, 29.5, 29.4, 29.3, 29.1,
29.1, 28.9, 28.8, 28.7, 26.7, 22.7, 21.0, 14.2, 14.0. Signals from both
isomers: expected, 26; observed, 26.
HRMS (ESI): m/z [M + Na]+ calcd for C19H28NaO3S: 359.1657;
found: 359.1653.
3-[(10-Carboxydecyl)sulfanyl]pentane-2,4-dione (6m)
Chromatography (EtOAc–CH2Cl2, 1:10); white solid; yield: 87%;
mp 42–44 °C; only enol isomer is observed.
1H NMR (200 MHz, CDCl3): d = 1.20–1.45 (m, 12 H, CH2), 1.46–
1.74 (m, 4 H, CH2), 2.36 (t, J = 7.4 Hz, 2 H, OOCCH2), 2.44 (s, 6
H, CH3), 2.49 (t, J = 7.3 Hz, 2 H, SCH2), 7.60 (br s, 1 H, COOH),
17.08 (s, 1 H, C=COH).
13C NMR (50 MHz, CDCl3): d = 197.4, 179.9, 104.7, 36.9, 34.0,
29.4, 29.3, 29.2, 29.1, 29.0, 28.9, 24.6, 24.5. Signals: expected, 14;
observed, 13.
HRMS (ESI): m/z [M + Na]+ calcd for C17H32NaO4S: 355.1919;
found: 355.1925.
Ethyl 2-(Diethoxyphosphoryl)-2-[(11-hydroxyundecyl)sulfa-
nyl]acetate (6j)
Chromatography (EtOAc–CH2Cl2, 1:3); oil; yield: 69%.
1H NMR (200 MHz, CDCl3): d = 1.20–1.46 (m, 23 H, CH2,
COOCH2CH3, POCH2CH3), 1.50–1.70 (m, 5 H, CH2, OH), 2.74
(t, J = 7.3 Hz, 2 H, SCH2), 3.64 (t, J = 6.8 Hz, 2 H, OCH2), 3.66 (d,
2JP-C = 19.9 Hz, 1 H, PCH), 4.10–4.35 (m, 6 H, OCH2).
HRMS (ESI): m/z [M + Na]+ calcd for C16H28NaO4S: 339.1606;
found: 339.1616.
Ethyl 2-[(10-Carboxydecyl)sulfanyl]-3-oxobutanoate (6n)
Chromatography (EtOAc–CH2Cl2, 1:10); oil; yield: 90%; both enol
and keto isomers were observed with ratio 1:1.
2
13C NMR (125 MHz, CDCl3): d = 167.8, 63.8 (d, JP-C = 7.6 Hz),
1H NMR (200 MHz, CDCl3): d = 1.20–1.45 (m, 15 H, CH2,
OCCH3), 1.45–1.62 (m, 4 H, CH2), 2.35 and 2.36 (s, 3 H, COCH3,
C=CCH3), 2.36 (t, J = 7.4 Hz, 2 H, OOCCH2), 2.45–2.70 (m, 2 H,
SCH2), 4.11 (s, 0.55 H, SCH), 4.20–4.38 (m, 2 H, OCH2), 8.10 (br
s, 1 H, COOH), 13.52 (s, 0.45 H, C=COH).
13C NMR (50 MHz, CDCl3): d = 199.2, 182.8, 179.6, 173.2, 167.5,
94.0, 62.2, 61.4, 58.0, 35.6, 33.9, 31.6, 29.4, 29.3, 29.2, 29.1, 29.0,
28.9, 28.8, 28.7, 26.7, 24.6, 21.0, 14.2, 14.0. Signals from both iso-
mers: expected, 26; observed, 25.
2
63.7 (d, JP-C = 7.6 Hz), 63.0, 62.1, 44.7 (d, JP-C = 141.0 Hz), 33.4
(d, 3JP-C = 5.5 Hz), 31.9, 29.6, 29.5, 29.3, 29.1, 28.9, 28.6, 22.6, 16.3
(d, 3JP-C = 5.9 Hz), 14.0. Signals: expected, 19; observed, 17.
31P NMR (202 MHz, CDCl3): d = 18.09.
HRMS (ESI): m/z [M + Na]+ calcd for C19H39NaO6PS: 449.2103;
found: 449.2197.
a-Sulfenylation of Carbonyl Compounds 5a–e with 4c; General
Procedure
HRMS (ESI): m/z [M + Na]+ calcd for C17H30NaO5S: 369.1712;
A soln of carbonyl compound 5a–e (3.0 mmol) in anhyd EtOH (5
mL) was added dropwise to a soln of NaOEt [NaH (0.16 g, 4.0
mmol) was dissolved in EtOH] in anhyd EtOH (15 mL) at r.t. under
N2 atmosphere. Then a soln of 4c (0.414 g, 1.0 mmol) in anhyd
EtOH (5 mL) was added. The mixture was stirred at r.t. for 3 h and
evaporated under vacuum. The residue was dissolved in EtOAc (50
mL), washed with sat. aq NH4Cl, dried (MgSO4), filtered, and con-
centrated. The products were purified by column chromatography
(Table 2).
found: 369.1719.
Ethyl 2-[(10-Carboxydecyl)sulfanyl]-2-(diethoxyphosphor-
yl)acetate (6o)
Chromatography (EtOAc–CH2Cl2, 1:3); oil; yield: 80%.
1H NMR (200 MHz, CDCl3): d = 1.20–1.46 (m, 21 H, CH2,
COOCH2CH3, POCH2CH3), 1.50–1.70 (m, 4 H, CH2), 2.35 (t,
J = 6.8 Hz, 2 H, CH2COOH), 2.73 (t, J = 7.3 Hz, 2 H, SCH2), 3.65
2
(d, JP-C = 19.9 Hz, 1 H, PCH), 4.10–4.35 (m, 6 H, OCH2), 6.90
(br s, 1 H, COOH).
Diethyl [(10-Carboxydecyl)sulfanyl]malonate (6k)
Chromatography (EtOAc–CH2Cl2, 1:10); oil; yield: 90%.
1H NMR (200 MHz, CDCl3): d = 1.20–1.45 (m, 18 H, CH2,
OCH2CH3), 1.50–1.75 (m, 4 H, CH2), 2.36 (t, J = 7.4 Hz, 2 H,
OOCCH2), 2.73 (t, J = 7.3 Hz, 2 H, SCH2), 4.16 (s, 1 H, SCH), 4.26
(q, J = 7.1 Hz, 4 H, OCH2), 6.65 (br s, 1 H, COOH).
13C NMR (50 MHz, CDCl3): d = 179.6, 167.9, 63.7 (d, JP-C = 7.6
2
Hz), 63.6 (d, 2JP-C = 7.6 Hz), 62.1, 44.6 (d, JP-C = 141.0 Hz), 33.3 (d,
3JP-C = 5.5 Hz), 31.9, 29.6, 29.5, 29.3, 29.1, 28.9, 28.6, 22.6, 16.2 (d,
3JP-C = 5.9 Hz), 14.0. Signals: expected, 19; observed, 17.
31P NMR (202 MHz, CDCl3): d = 18.11.
HRMS (ESI): m/z [M + Na]+ calcd for C19H37NaO7PS: 463.1895;
found: 463.1883.
Synthesis 2009, No. 10, 1720–1724 © Thieme Stuttgart · New York

1724
E. Okragla et al.
PAPER
(5) (a) Yadav, J. S.; Subba Reddy, B. V.; Jain, R.; Baishya, G.
Tetrahedron Lett. 2008, 49, 3015. (b) Tan, J.; Liang, F.;
Wang, Y.; Cheng, X.; Liu, Q.; Yuan, H. Org. Lett. 2008, 10,
2485.
Acknowledgment
We gratefully acknowledge the Polish Ministry of Science and
Higher Education for financial support (grant no. N N204 4511 33).
(6) (a) Sobhani, S.; Fielenbach, D.; Marigo, M.; Wabnitz, T. C.;
Jørgensen, K. A. Chem. Eur. J. 2005, 11, 5689. (b) Marigo,
M.; Wabnitz, T. C.; Fielenbach, D.; Jørgensen, K. A. Angew.
Chem. 2005, 117, 804.
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(b) Srisailam, S. K.; Togni, A. Tetrahedron Asymmetry
2006, 17, 2603. (c) Jereb, M.; Togni, A. Org. Lett. 2005, 7,
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Synthesis 2009, No. 10, 1720–1724 © Thieme Stuttgart · New York