N, N-di-boc-substituted thiourea as a novel and mild thioacylating agent applicable for the synthesis of thiocarbonyl compounds

Article abstract of DOI:10.1055/s-0029-1219273

Stable and readily available N,N-di-Boc-substituted thiourea, when activated with trifluoroacetic acid anhydride, was used as a novel thioacylating agent. Through the thioacylation of nucleophiles, such as amines, alcohols, thiols, sodium benzene-thiolate

Full text of DOI:10.1055/s-0029-1219273

PAPER
991
N,N¢-Di-Boc-Substituted Thiourea as a Novel and Mild Thioacylating Agent
Applicable for the Synthesis of Thiocarbonyl Compounds
N
a
,
N
¢
-Di-Boc-Sub
i
stituted
a
Thiourea
i
n the Synthe
-
sis of Th
L
iocarbonyl
C
om
i
pound
n
s
Yin,*a Zhao-Gui Liu,b Jian-Cun Zhang,b Zheng-Rong Lia
School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, 510640, P. R. of China
E-mail: blyin@scut.edu.cn
b
Guangzhou Institute of Biomedicine & Health, The Chinese Academy of Sciences, Guangzhou International Business Incubator A-3,
Guangzhou Science Park, Guangzhou, 510663, P. R. of China
Received 26 October 2009; revised 2 December 2009
tion conditions such as high temperature, long reaction
time, the use of a strong acid or base and noxious reagents
such as hydrogen sulfide and carbon disulfide. Therefore,
the development of novel, mild, environmentally benign,
Abstract: Stable and readily available N,N¢-di-Boc-substituted
thiourea, when activated with trifluoroacetic acid anhydride, was
used as a novel thioacylating agent. Through the thioacylation of
nucleophiles, such as amines, alcohols, thiols, sodium benzene-
thiolate, and sodium malonates with N,N¢-di-Boc-substituted thio- and especially functional-group-tolerant thioacylating
urea, a series of thiocarbonyl compounds were prepared under mild
agents is still needed.
conditions with good chemical selectivity and functional group tol-
erance.
N,N¢-Di-Boc-substituted thiourea 1 is a commonly used
reagent in the preparation of guanidine derivatives 2 when
its thiocarbonyl is selectively activated by mercury salt
and coupled with amines (Scheme 1).17 However, its syn-
thetic applications in other aspects are seldom reported,
especially in the selective activation of its carbonyl group.
The activation of the carbonyl group of an amide toward
nucleophilic attack has been well studied by adding some
activators such as triflic anhydride (Tf2O) and benzotriaz-
ol-1-yloxytris(dimethylamino)phosphonium hexafluoro-
phosphate (BOP). These methods have been used
extensively in the synthesis of esters, amidines, thiazo-
lines, thioamides, 18O-labeled amides and so on.18 Our in-
terest is focused in the selective activation of the carbonyl
groups of 1 and its further transformation with nucleo-
philes to prepare a series of novel, potentially bioactive ni-
trogen-containing compounds. Herein we report that
N,N¢-di-Boc-substituted thiourea 1 can be used as a novel
and mild thioacylating agent applicable for the synthesis
of thiocarbonyl compounds.19
Key words: N,N¢-di-Boc-substituted thiourea, thioacylating agent,
thiocarbonyl
Thiocarbonyl compounds such as thioureas, thiocarbam-
ates, dithiocarbamates, and thioamides, are important
compounds and have attracted much attention due to their
bioactivities as pesticides and pharmaceutics. For exam-
ple, a variety of thiourea derivatives and their metal com-
plexes
exhibit
analgesic,1
anti-inflammatory,2
antimicrobial,3 anticancer,4 and antifungal activities.5
Some O-alkyl thiocarbamate derivatives demonstrate in-
secticidal,6 antimycotic,7 antiviral8 and anti-HIV9 activi-
ties. Moreover, thiocarbonyl compounds are important
building blocks in the synthesis of heterocycles. For ex-
ample, 2-amino-1,3-thiazoles can be readily prepared
through the condensation of thioureas with a-halocarbon-
yl compounds.10 Likewise, arylthioureas can be trans-
formed into benzothiazoles upon treatment with
bromine.11 Other examples include the synthesis of thiaz-
oline from thioamide and dithiocarbamates. Therefore,
the synthesis of novel thiocarbonyl compounds and devel-
opment of new methods for their preparation are of great
importance in the search for bioactive molecules as well
as in synthetic chemistry.
O
NHR O
tBuO
N
N
OtBu
H
2
mercury salt thiocarbonyl
NH2R
activation
To date, one of the most common methods for the prepa-
ration of such thiocarbonyl compounds involves the reac-
tion of nucleophiles, such as amines, alcohols,
thiophenols, and carbanions, with diverse thioacylating
agents including thiophosgene,12 carbon disulfide,13 1,1-
thiocarbonyldiimidazole,14 thioacyl-N-phthalimide15 and
thiocarbonylbenzotriazoles.16 However, these thioacylat-
ing agents sometimes suffer from some drawbacks and
limitations: difficult preparation, instability or harsh reac-
carbonyl activation
and nucleophiles
O
S
O
?
tBuO
N
N
OtBu
H
H
1
Scheme 1 Preparation of guanidine derivatives 2 from N,N¢-di-Boc-
substituted thiourea 1
Similar to the activation of the carbonyl group of an
amide, we activated the carbonyl group of the carbamate
unit of 1 with Tf2O as an activator and pyridine as a base
in THF at 0 °C for one hour. The color of the reaction mix-
ture turned to yellow soon after the addition of Tf2O. TLC
SYNTHESIS 2010, No. 6, pp 0991–0999
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x
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0
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Advanced online publication: 25.01.2010
DOI: 10.1055/s-0029-1219273; Art ID: F20309SS
© Georg Thieme Verlag Stuttgart · New York

992
B.-L.Yin et al.
PAPER
Table 1 Optimization of the Reaction Conditions of 1 with BnNH2
Table 2 Synthesis of Thioureas via the Reaction of 1 with Amines
reaction conditions
1) NaH (1.2 equiv), TFAA (1.1 equiv)
THF, 0 °C
S
S
1
+
BnNH2
3a
Boc
Boc
THF, overnight
Boc
NR1R2
N
N
N
2) R1R2NH (1.1 equiv), r.t.
H
H
H
Entry
1
Reaction conditions
Yield (%)a
3b–l
1
BOP (1.1 equiv), pyridine (1.2 equiv), 0 °C; 52
then BnNH2 (1.1 equiv), r.t.
Entry R1R2NH
Product Yield (%)a
1
i-PrNH2
3b
94
2
3
4
5
6
7
MsCl (1.1 equiv), pyridine (1.2 equiv), 0 °C; 60
then BnNH2 (1.1 equiv), r.t.
O
AcO
Ac2O (1.1 equiv), pyridine (1.2 equiv), 0 °C; 58
then BnNH2 (1.1 equiv), r.t.
OEt
2
3c
78
AcHN
TFAA (1.1 equiv), pyridine (1.2 equiv), 0 °C; 78
then BnNH2 (1.1 equiv), r.t.
NH2
OAc
O
Tf2O (1.1 equiv), DIPEA (1.2 equiv), 0 °C; 25
then BnNH2 (1.1 equiv), r.t.
AcO
AcO
O
OMe
3
4
3d
3e
88
82
Tf2O (1.1 equiv), NMM (1.2 equiv), 0 °C;
then BnNH2 (1.1 equiv), r.t.
32
AcHN
NH2
Ph
TFAA (1.1 equiv), NaH (1.2 equiv), 0 °C;
then BnNH2 (1.1 equiv), r.t.
91
OH
H2N
O
a Isolated yield.
5
6
3f
90
92
NH
demonstrated that an intermediate was formed, but its iso-
lation by chromatography failed possibly due to its insta-
bility. This intermediate can be trapped with BnNH2 and
converted into the thiourea 3a in 64% yield, whose struc-
ture was determined by spectroscopic data. In contrast, the
coupling of 1 with benzylamine alone gives exclusively
the corresponding guanidine 4 in 75% yield (Scheme 2).
This unusual but useful result, to the best of our knowl-
edge, provides the first example of applying 1 as a thio-
acylating agent of amine and a novel access to
unsymmetrical thioureas. Further efforts were made to ad-
just the reaction variants such as activator, base, reaction
temperature, and the amount of amine to optimize the re-
action conditions. As shown in Table 1, when other acti-
vators such as BOP, MsCl, and Ac2O were used, the yields
were lower (entries 1–3), and TFAA (trifluoacetic acid
anhydride) as an activator afforded a little higher yield
(entry 4). Meanwhile, when other organic base such as
DIPEA (N,N-diisopropylethylamine) or NMM (N-meth-
ylmorpholine) was used, 3a was formed in lower yields
along with many other unidentified by-products. To our
3g
NH
7
8
(n-Bu)2NH
PhNH2
HO
3h
3i
0
91
9
3j
81
NH2
10
11
PhNHMe
3k
3l
0
PhNHNH2
85
a Isolated yield.
delight, when NaH was used as a base to deprotonate and
TFFA as an activator, the reaction yield was increased to
91% (entry 7). Based on the results, we concluded that
TFAA (1.1 equiv) and NaH (1.2 equiv) at 0 °C, then
BnNH2 (1.1 equiv) at room temperature in THF solvent
are suitable conditions for this conversion. The scope of
the reaction was then examined with different amines, and
the results are summarized in Table 2. As can be seen, the
steric hindrance of amines influenced the reaction obvi-
ously. The reaction of primary amines and cyclic five- or
six-membered-ring amines proceeded well with 1 afford-
ing the desired compounds 3b–g in good to excellent
yields (entries 1–6). In contrast, more hindered acyclic
secondary amines did not lead to the desired products un-
der these conditions (entries 7 and 10). Less nucleophilic
primary arylamines also afforded the desired products in
excellent yields (entries 8 and 9). With aminophenol, only
the thiourea product was isolated and no thiocarbamate
was observed (entry 9). Reaction of 1 with phenylhydra-
zine afforded exclusively the thiohydrozone product 3l
S
Boc
Bn
N
N
H
H
a
b
3a 64%
S
Boc
Boc
+
BnNH2
N
N
NHBn
H
H
Boc
Boc
1
N
N
H
4 75%
Scheme 2 The reaction of 1 with BnNH2 under different reaction
conditions. Reagents and conditions: (a) Tf2O (1.1 equiv), pyridine
(1.2 equiv), THF, 0 °C, then r.t. (b) THF, r.t.
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

PAPER
N,N¢-Di-Boc-Substituted Thiourea in the Synthesis of Thiocarbonyl Compounds
993
(entry 8), while 1-phenylethanol, a more sterically hin-
dered secondary alcohol, did not lead to the desired prod-
uct (entry 9).
Table 3 Optimization of the Reaction Conditions of 1 with BnOH
S
S
a) TFAA (1.1 equiv), NaH (1.2 equiv)
THF, 0 °C
Boc
Boc
Boc
N
OBn
N
N
then reaction conditions
H
The thioacylation of thiols was also investigated under the
same reaction conditions as used for the amines. Equimo-
lar amounts (1.1 equiv) of n-C4H9SH and n-C12H25SH re-
acted with 1 providing dithiocarbamate 6a and 6b in 78%
and 75% yield, respectively (Table 5, entries 1, 2). Possi-
bly owing to their lower nucleophilicity, thiophenols did
not react with 1 to provide the desired dithiocarbamates
under the same conditions, but their sodium salts reacted
well with 1 giving the corresponding dithiocarbamates
6c–e in excellent yield (entries 1–3). The substrate carry-
ing an electron-donating group on the phenyl ring gave
slightly higher yield than those with an electron-
withdrawing one (6d > 6c > 6e). Similarly, sodium salt of
dimethyl malonate and diethyl malonate as nucleophiles
gave the corresponding thioamides in moderate yield (en-
tries 6 and 7). Nevertheless, under the same conditions,
when the nucleophile was sodium ethyl acetoacetate, no
desired thioamide 7c was formed (entry 8). The real rea-
son is not clear at present, but may be attributable to the
nucleophilicity of sodium acetoacetate being lower than
that of sodium malonate.
H
H
1
5a
Entry Reaction conditions
Yield (%)a
1
2
3
4
5
6
BnOH (1.1 equiv), r.t.
40
53
55
60
63
75
BnOH (1.5 equiv), r.t.
BnOH (2.0 equiv), r.t.
BnOH (1.5 equiv), NMM (1.0 equiv), r.t.
BnOH (1.5 equiv), DIPEA (1.0 equiv), r.t.
BnOH (1.5 equiv), DMAP (1.0 equiv), r.t.
a Isolated yield.
(entry 11). It is worth noting that under these relatively
mild reaction conditions, functional groups such as amide,
ester, enol ether, and hydroxy are tolerated, which renders
the ready access of polyfunctionalized thioureas. Impor-
tantly, under these conditions, no epimerization of com-
1
pounds 3c and 3d was observed based on H NMR
Based on the above results, we propose a possible mecha-
nism for these reactions of thioacylation of nucleophiles
with 1 (Scheme 3). Upon deprotonation of 1 by NaH gives
rise to ambident ion A. TFAA is a hard acid, accordingly,
it attacks A preferentially at the oxygen or nitrogen termi-
nus, not at sulfur forming O-acylated intermediate 8 or N-
acylated intermediate 9, which was further converted into
intermediate 10. The addition of nucleophiles, such as
amines, alcohols, thiols, thiophenols, and activated meth-
ylenes, to the thiocarbonyl group of 8 and 10 provides
thiocarbonyl compounds 3, 5, 6, and 7.
spectroscopy (entries 2, 3).
Encouraged by the successful thioacylation of amines, we
studied the thioacylation of alcohols with 1 to synthesize
O-alkyl thiocarbamates. Under the same reaction condi-
tions as for BnNH2, BnOH (1.1 equiv) reacted with 1 pro-
viding O-alkyl thiocarbamate 5a in only 40% yield
(Table 3, entry 1). When the amount of BnOH was in-
creased to 1.5 equivalents, the yield was improved to 53%
(entry 2). More BnOH (2.0 equiv) did not lead to higher
yield (entry 3). Addition of organic base DIPEA or NMM
as an additive gave rise to higher yields (entries 4, 5). To
our delight, when 1.0 equivalent of DMAP [4-(dimethyl-
amino)pyridine] was added, the yield was improved re-
markably to 75% (entry 6). DMAP in this coupling might
act as a base to activate the alcohol and as a catalyst to ac-
tivate the thiocarbonyl group.
Nu
S
S
Boc
Boc
N
H
Nu
N
NBoc
H
COCF3
3,5–7
8
On the basis of the above results, we concluded that
TFAA (1.1 equiv) and NaH (1.2 equiv) at 0 °C, then
BnOH (1. 5 equiv) and DMAP (1.0 equiv) at room tem-
perature in THF are suitable conditions for the thioacyla-
tion of BnOH. The scope of the reaction was then
explored with various alcohols. As can be seen in Table 4,
all primary alcohols can be thioacylated to provide the
corresponding thiocarbamates in acceptable yields (en-
tries 1–6). Functional groups such as amide, ester, azide,
acetal, and nucleobase (uracil) were tolerated (entries 1–
6). It is worth noting that the primary alcohol can be selec-
tively thioacylated in the presence of secondary alcohol
and no dithioacylated product was observed (entry 6).
Due to the acidity of the phenolic hydroxy group, salicyl
alcohol was not converted into 5h (entry 7) under these
conditions. Propan-2-ol, a small, slightly sterically hin-
dered secondary alcohol, was thioacylated in lower yield
path b
S
TFAA
O
S
O
TFAA
path a
NaH
Boc
Boc
S
Boc
Boc
OtBu
N
N
H
OtBu
N
H
N
H
A
1
S
OtBu
S
OCOCF3
N
OtBu
Boc
N
N
N
Nu
H
H
N
H
10
Nu
3,5–7
9
Scheme 3 Proposed mechanism for the formation of thiocarbonyl
compounds
In summary, we have reported N,N¢-di-Boc-substituted
thiourea 1, when activated with TFAA, as a novel thio-
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

994
B.-L.Yin et al.
PAPER
Table 4 Synthesis of Thiocarbamates via the Reaction of 1 with Alcohols
1) NaH (1.2 equiv), TFAA (1.1 equiv)
S
S
THF, 0 °C
Boc
Boc
Boc
N
N
N
OR
H
H
H
2) ROH (1.5 equiv), DMAP (1.0 equiv)
r.t., 48 h
1
5b–j
Entry
1
ROH
Product
Yield (%)a
71
S
S
S
S
MeOH
EtOH
BocHN
OMe
OEt
OnBu
O
5b
2
3
68
76
BocHN
5c
n-BuOH
BocHN
5d
O
O
O
O
BocHN
5e
OMe
HO
OMe
4
5
66
62
AcHN
AcHN
N3
O
N3
H
N
O
H
O
N
S
O
O
N
O
N
BocHN
O
HO
O
O
O
O
Ph
Ph
5f
S
OMe
OMe
6
7
65
0
HO
BocHN
O
OH
O
OH
O
5g
S
OH
OH
O
NHBoc
OH
5h
S
8
9
i-PrOH
45
0
BocHN
O
O
5i
S
NHBoc
OH
5j
a Isolated yield.
acylating agent possessing the advantage of stability and good chemical selectivity and functional group tolerance.
ready availability. Through the thioacylation of nucleo- In addition, we have proposed a possible mechanism for
philes, such as amines, alcohols, thiols, sodium ben- this thioacylation which might be useful for further design
zenethiolate, and sodium malonates with 1, thiocarbonyl of other novel thioacylating agents. Further studies on the
compounds (thioureas, thiocarbamates, dithiocarbamates, selective activation of the carbonyl or thiocarbonyl group
and thioamide) were prepared under mild conditions with of 3, 5, and 6 to prepare novel nitrogen- or sulfur-contain-
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

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N,N¢-Di-Boc-Substituted Thiourea in the Synthesis of Thiocarbonyl Compounds
995
Reaction of N,N¢-Di-Boc-Substituted Thiourea 1 with Amines
and Thiols; General Procedure
Table 5 Synthesis of Dithiocarbamates and Thioamides
S
S
To a mixture of 1 (276 mg, 1 mmol) and THF (20 mL) was added
60% NaH (48 mg, 1.2 mmol) at 0 °C. The reaction mixture was
stirred at the same temperature for 1 h, then TFAA (185 mL, 1.1
mmol) was added and the stirring continued for an additional 1 h.
Then, amine or thiol (1.1 mmol) was added and the resulting reac-
tion was stirred at r.t. overnight. H2O (10 mL) was added to quench
the reaction and the mixture was extracted with EtOAc (3 × 15 mL).
The combined organic layers were dried (MgSO4) and the solvent
was removed under reduced pressure. The residue was purified by
flash column chromatography to afford 3, 6a, or 6b (Tables 2, 5).
1) NaH (1.2 equiv), TFAA (1.1 equiv)
Boc
Boc
THF, 0 °C
Boc
N
N
N
Nu
H
H
H
2) NuH (or NuNa) (1.1 equiv)
r.t., overnight
1
6a–e
7a–c
Entry NuH (or NuNa)
Product
Yield
(%)a
S
1
2
n-BuSH
78
BocHN
SnBu
6a
3a
S
S
Yield: 242 mg (91%); white solid; mp 147–148 °C.
n-C12H25SH
75
92
IR (film): 3446, 3172, 2971, 1668, 1534, 1250, 1206, 1150, 964,
918, 750 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.97 (s, 1 H), 7.94 (s, 1 H), 7.38–
7.29 (m, 5 H), 4.86 (d, J = 5.6 Hz, 2 H), 1.47 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 179.8, 151.8, 136.5, 128.8, 128.0,
127.9, 83.8, 49.5, 28.1.
BocHN
6b
SnC12H25
3
4
PhSNa
BocHN
SPh
6c
S
S
S
ESI-MS: m/z = 265 (M – H).
4-MeC6H4SNa
96
89
BocHN
S
S
Anal. Calcd for C13H18N2O2S: C, 58.62; H, 6.81; N, 10.52; S, 12.04.
Found: C, 58.44; H, 6.86; N, 10.64; S, 12.33.
6d
3b
5
6
4-MeC6H4SNa
NaCH(CO2Et)2
BocHN
NO2
Yield: 204.9 mg (94%); syrup.
IR (film): 3412, 3168, 2973, 1626, 1530, 1244, 1138, 953, 910, 747
cm–1.
1H NMR (400 MHz, CDCl3): d = 9.53 (s, 1 H), 7.84 (s, 1 H), 4.53–
4.48 (m, 1 H), 1.47 (s, 9 H), 1.28 (d, J = 6.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): d = 178.2, 151.9, 83.4, 47.4, 28.0,
21.8.
6e
CO2Et
CO2Et
64
67
0
BocHN
7a
S
S
ESI-MS: m/z = 219 (M + H).
CO2Me
CO2Me
7
8
NaCH(CO2Me)2
BocHN
Anal. Calcd for C13H18N2O2S: C, 49.51; H, 8.31; N, 12.83; S, 14.69.
Found: C, 49.64; H, 8.25; N, 12.95; S, 14.47.
7b
O
3c
Yield: 345.7 mg (78%); white solid; mp 104–105 °C; [a]D20 +17.6
(c 1.0, CHCl3).
NaCH(COMe)(CO2Et)
BocHN
CO2Et
IR (film): 3485, 2931, 1725, 1719, 1633, 1557, 1433, 1297, 1031,
774, 659 cm–1.
7c
a Isolated yield.
1H NMR (400 MHz, CDCl3): d = 9.89 (d, J = 8.4 Hz, 1 H), 7.94 (s,
1 H), 6.67 (s, 1 H), 6.32 (d, J = 8.4 Hz, 1 H), 5.60 (d, J = 8.8 Hz, 1
H), 4.87–4.84 (m, 1 H), 4.41–4.36 (m, 1 H), 4.24–4.18 (m, 2 H),
3.00 (dd, J = 6.0, 18.0 Hz, 1 H), 2.49–2.42 (m, 1 H), 2.09 (s, 3 H),
1.93 (s, 3 H), 1.48 (s, 9 H), 1.29 (t, J = 7.2 Hz, 3 H).
ing heterocyclic compounds are currently under way in
our laboratory and the results will be reported in due
course.
13C NMR (100 MHz, CDCl3): d = 181.1, 170.9, 170.8, 165.2, 151.3,
135.3, 130.7, 84.4, 71.9, 61.3, 53.9, 53.0, 30.4, 28.0, 23.3, 21.0,
20.9, 14.2.
IR spectra were recorded with a Perkin-Elmer1 983 or a Shimadzu
IR-440 spectrometer. 1H and 13C NMR spectra were recorded with
an AMX-300, DPX-300, Gemini-2000, or IN-OVA-600 spectrom-
eter with TMS as the internal standard. Mass spectra were taken
with a Mariner (PE, for ESI), HP5973N or HP5989A instrument.
HRMS (EI or ESI) spectra were obtained with a Kratos CONCEPT
1H or Bruker APEXIII 7.0 TESLA mass spectrometer. Optical ro-
tations were measured with a Perkin-Elmer 241 MC polarimeter.
Elemental analyses were carried out in a Heraeus CHN-O-RAPID
Elemental Analyzer. Melting points were determined on X-4 Mel-
Temp apparatus and were uncorrected. Flash column chromatogra-
phy was performed on silica gel H (1040 mm) with a PE–EtOAc or
EtOAc–EtOH system as eluent.
ESI-MS: m/z = 444 (M + H).
Anal. Calcd for C19H29N3O7S: C, 51.45; H, 6.59; N, 9.47; S, 7.23.
Found: C, 51.67; H, 6.33; N, 9.50; S, 7.10.
3d
Yield: 518.5 mg (88%); syrup; [a]D20 +23.4 (c 1.0, CHCl3).
IR (film): 3479, 2950, 1722, 1705, 1703, 1638, 1543, 1401, 1257,
1062, 783, 644 cm–1.
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

996
B.-L.Yin et al.
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1H NMR (400 MHz, CDCl3): d = 9.79 (d, J = 8.8 Hz, 1 H), 7.80 (s,
1 H), 6.06 (d, J = 8.8 Hz, 1 H), 5.96 (s, 1 H), 5.55 (t, J = 8.8 Hz, 1
H), 5.46 (d, J = 4.0 Hz, 1 H), 5.29 (m, 1 H), 4.65 (d, J = 12.4 Hz, 1
H), 4.40–4.33 (m, 2 H), 4.17–4.07 (m, 2 H), 3.77 (s, 3 H), 2.09 (s, 3
H), 2.05 (s, 3 H), 2.03 (s, 3 H), 1.90 (s, 3 H), 1.46 (s, 9 H).
Anal. Calcd for C12H16N2O2S: C, 57.12; H, 6.39; N, 11.10; S, 12.71.
Found: C, 57.07; H, 6.45; N, 11.24; S, 12.88.
3j
Yield: 217.2 mg (81%); white solid; mp 120–122 °C.
13C NMR (100 MHz, CDCl3): d = 181.2, 171.2, 171.1, 170.6, 170.2,
161.6, 151.3, 145.2, 109.0, 84.5, 71.4, 67.7, 62.2, 60.4, 54.0, 52.5,
47.4, 28.0, 23.2, 21.0, 20.9, 14.2.
IR (film): 3423, 2947, 1639, 1554, 1421, 1235, 1022, 748, 645 cm–1.
1H NMR (400 MHz, CDCl3): d = 11.50 (s, 1 H), 8.07 (s, 1 H), 7.35
(s, 1 H), 7.25–7.19 (m, 1 H), 7.05 (d, J = 8.0 Hz, 1 H), 6.72 (dd,
J = 8.4, 2.4 Hz, 1 H), 1.52 (s, 9 H).
ESI-MS: m/z = 590 (M + H).
Anal. Calcd for C24H35N3O12S: C, 48.89; H, 5.98; N, 7.13; S, 5.44.
Found: C, 48.76; H, 5.39; N, 7.24; S, 5.69.
13C NMR (100 MHz, CDCl3): d = 178.2, 156.0, 151.9, 138.7, 129.8,
116.4, 114.0, 111.5, 84.5, 28.0.
ESI-MS: m/z = 269 (M + H).
3e
Anal. Calcd for C12H17N3O2S: C, 53.71; H, 6.01; N, 10.44; S, 11.95.
Found: C, 53.94; H, 6.28; N, 10.27; S, 11.82.
Yield: 254.3 mg (82%); syrup.
IR (film): 3458, 2932, 1710, 1635, 1569, 1427, 1255, 1038, 771,
637 cm–1.
1H NMR (400 MHz, CDCl3): d = 10.00 (d, J = 7.6 Hz, 1 H), 8.17 (s,
1 H), 7.30–7.20 (m, 5 H), 4.74–4.69 (m, 1 H), 3.76 (dd, J = 11.2, 4.0
Hz, 1 H), 3.65 (dd, J = 11.2, 4.0 Hz, 1 H), 3.09 (dd, J = 13.2, 5.6 Hz,
1 H), 2.94 (dd, J = 13.2, 5.6 Hz, 1 H), 1.48 (s, 9 H).
3l
Yield: 227 mg (85%); white solid; mp 143–145 °C.
IR (film): 3417, 2938, 1647, 1558, 1432, 1222, 1054, 743, 649 cm–1.
1H NMR (400 MHz, CDCl3): d = 11.15 (s, 1 H), 8.00 (s, 1 H), 7.29–
7.25 (m, 2 H), 6.97 (t, J = 7.2 Hz, 1 H), 6.90 (d, J = 8.4 Hz, 2 H),
1.54 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 178.8, 151.7, 146.5, 129.3, 122.1,
114.5, 84.4, 28.0.
13C NMR (100 MHz, CDCl3): d = 179.5, 151.8, 137.5, 129.4, 128.6,
126.7, 83.7, 62.1, 58.1, 36.2, 28.0.
ESI-MS: m/z = 309 (M – H).
Anal. Calcd for C15H22N2O3S: C, 58.04; H, 7.14; N, 9.02; S, 10.33.
Found: C, 57.90; H, 7.29; N, 9.29; S, 10.18.
ESI-MS: m/z = 266 (M – H).
Anal. Calcd for C12H17N3O2S: C, 53.91; H, 6.41; N, 15.72; S, 11.99.
Found: C, 53.88; H, 6.65; N, 15.84; S, 11.84.
3f
Yield: 221.5 mg (90%); white solid; mp 104–105 °C.
IR (film): 3412, 2921, 1626, 1542, 1457, 1235, 1025, 777, 645 cm–1.
6a
Yield: 194.3 mg (78%); syrup.
IR (film): 3471, 3141, 2934, 1744, 1493, 1230, 845, 751 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.93 (s, 1 H), 3.25 (t, J = 7.8 Hz,
2 H), 1.75–1.70 (m, 2 H), 1.49 (s, 9H), 1.51–1.46 (m, 2 H), 0.95 (t,
J = 7.2 Hz, 3 H).
1H NMR (400 MHz, CDCl3): d = 7.32 (s, 1 H), 3.88 (m, 4 H), 3.79
(m, 4 H), 1.46 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 180.1, 149.2, 82.7, 66.2, 52.1,
28.2.
ESI-MS: m/z = 245 (M–H).
13C NMR (100 MHz, CDCl3): d = 203.9, 149.2, 83.7, 36.7, 29.3,
Anal. Calcd for C10H18N2O3S: C, 48.76; H, 7.37; N, 11.37; S, 13.02.
Found: C, 48.52; H, 7.39; N, 11.49; S, 13.28.
28.0, 22.2, 13.6.
ESI-MS: m/z = 248 (M – H).
Anal. Calcd for C6H10NO2S: C, 48.16; H, 7.68; N, 5.62; S, 25.71.
Found: C, 48.27; H, 7.59; N, 5.57; S, 25.69.
3g
Yield: 211.7 mg (92%); white solid; mp 117–118 °C.
IR (film): 3431, 2924, 1720, 1648, 1537, 1444, 1025, 783, 642 cm–1.
1H NMR (400 MHz, CDCl3): d = 7.26 (s, 1 H), 3.79 (t, J = 6.4 Hz,
2 H), 3.66 (t, J = 6.0 Hz, 2 H), 1.96 (m, 4 H), 1.46 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 176.6, 149.4, 82.2, 54.2, 52.4,
28.1.
6b
Yield: 270.9 mg (75%); syrup.
IR (film): 3465, 3138, 2951, 1746, 1466, 1242, 839, 746 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.09 (s, 1 H), 3.23 (t, J = 7.8 Hz,
2 H), 1.76–1.71 (m, 2 H), 1.52 (s, 9 H), 1.46–1.41 (m, 2 H), 1.37–
1.25 (m, 16 H), 0.88 (t, J = 7.2 Hz, 3 H).
ESI-MS: m/z = 229 (M – H).
Anal. Calcd for C10H18N2O2S: C, 52.15; H, 7.88; N, 12.16; S, 13.92.
Found: C, 52.24; H, 7.79; N, 12.33; S, 13.85.
13C NMR (100 MHz, CDCl3): d = 203.9, 149.2, 83.7, 37.0, 31.9,
29.7, 29.6, 29.5, 29.4, 29.3, 29.2, 29.1, 28.0, 27.3, 22.7, 14.1.
ESI-MS: m/z = 360 (M – H).
3i
Anal. Calcd for C6H10NO2S: C, 59.79; H, 9.76; N, 3.87; S, 17.73.
Found: C, 59.65; H, 9.54; N, 3.91; S, 17.88.
Yield: 229.4 mg (91%); white solid; mp 135–136 °C.
IR (film): 3422, 2926, 1635, 1564, 1459, 1217, 1060, 745, 641 cm–1.
1H NMR (400 MHz, CDCl3): d = 11.50 (s, 1 H), 8.04 (s, 1 H), 7.64
(d, J = 5.7 Hz, 2 H), 7.39 (t, J = 5.7 Hz, 2 H), 7.27–7.24 (m, 1 H),
1.54 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 178.4, 151.9, 137.8, 128.8, 126.7,
124.3, 84.3, 28.0.
Reaction of 1 with Alcohols; General Procedure
To a mixture of 1 (276 mg, 1 mmol) and THF (20 mL) was added
60% NaH (48 mg, 1.2 mmol) at 0 °C. The reaction mixture was
stirred at the same temperature for 1 h, then TFAA (185 mL, 1.1
mmol) was added and the stirring continued for an additional 1 h.
Then alcohol (162 mg, 1.5 mmol) and DMAP (122 mg, 1 mol) were
added and the resulting reaction was stirred at r.t. for 1 d. H2O (10
mL) was added to quench the reaction and the mixture was extract-
ed with EtOAc (3 × 15 mL). The combined organic layers were
ESI-MS: m/z = 253 (M + H).
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

PAPER
N,N¢-Di-Boc-Substituted Thiourea in the Synthesis of Thiocarbonyl Compounds
997
dried (MgSO4), and the solvent was removed under reduced pres-
sure. The residue was purified by flash column chromatography to
afford compound 5 (Table 4).
Anal. Calcd for C16H23N5O7S: C, 44.75; H, 5.40; N, 16.31; S, 7.47.
Found: C, 44.64; H, 5.29; N, 16.38; S, 7.57.
5f
5a
Yield: 304.5 mg (62%); syrup; [a]D20 +7.9 (c 1.0, CHCl3).
Yield: 200.3 mg (75%); white solid; mp 143–145 °C.
IR (film): 3480, 2935, 1726, 1718, 1635, 1559, 1430, 1289, 1034,
766 cm–1.
IR (film): 3442, 3168, 2974, 1674, 1541, 1251, 1066, 644 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.10 (s, 1 H), 7.45–7.34 (m, 5 H),
1H NMR (400 MHz, CDCl3): d = 8.13 (s, 1 H), 7.52–7.41 (m, 5 H),
7.35–7.33 (m, 1 H), 6.12 (s, 1/3 H), 6.04 (s, 2/3 H), 5.77–5.74 (m, 1
H), 5.66 (d, J = 3.0 Hz, 1 H), 5.22 (dd, J = 3.0, 7.2 Hz, 2/3 H), 5.16
(dd, J = 3.0, 7.2 Hz, 1/3 H), 5.14 (dd, J = 3.6, 6.6 Hz, 1/3 H), 5.10
(dd, J = 3.6, 6.6 Hz, 2/3 H), 4.47 (m, 2/3 H), 4.34 (m, 1/3 H), 4.02–
3.97 (m, 1 H), 3.95–3.82 (m, 1 H).
5.57 (s, 2 H), 1.48 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 188.3, 147.9, 134.8, 128.7, 128.6,
128.3, 83.1, 73.7, 28.1.
ESI-MS: m/z = 266 (M – H).
13C NMR (100 MHz, CDCl3): d = 163.2, 150.3, 142.1, 136.2, 129.7,
128.4, 128.3, 126.9, 126.8, 106.5 (2/3 C), 102.6 (1/3 C), 102.0 (1/3
C), 101.7 (2/3 C), 91.3 (2/3 C), 90.4 (1/3 C), 86.4 (2/3 C), 84.4 (2/3
C), 83.9 (1/3 C), 83.0 (1/3 C), 81.9 (2/3 C), 80.1 (1/3 C), 61.4 (1/3
C), 61.3 (2/3 C).
Anal. Calcd for C13H17NO3S: C, 58.40; H, 6.41; N, 5.24; S, 11.99.
Found: C, 58.30; H, 6.27; N, 5.48; S, 12.07.
5b
Yield: 135.7 mg (71%); syrup.
IR (film): 3421, 3155, 2969, 1633, 1518, 1233, 1120, 943, 767 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.22 (s, 1 H), 4.09 (s, 3 H), 1.45
(s, 9 H).
ESI-MS: m/z = 490 (M – H).
Anal. Calcd for C22H25N3O8S: C, 53.76, H, 5.13; N, 8.55; S, 6.52.
Found: C, 53.70; H, 5.24; N, 8.59; S, 6.48.
13C NMR (100 MHz, CDCl3): d = 189.9, 147.6, 83.0, 59.0, 27.9.
5g
ESI-MS: m/z = 190 (M – H).
Yield: 190.5 mg (65%); syrup.
Anal. Calcd for C7H13NO3S: C, 43.96; H, 6.85; N, 7.32; S, 16.77.
Found: C, 43.85; H, 6.69; N, 7.43; S, 16.84.
IR (film): 3443, 2924, 1730, 1642, 1520, 1428, 1126, 1044, 775 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.21 (s, 1 H), 4.44 (m, 2 H), 3.78
(t, J = 7.6 Hz, 1 H), 3.68 (s, 3 H), 2.62 (t, J = 5.6 Hz, 2 H), 1.49 (s,
9 H).
5c
Yield: 139.5 mg (68%); syrup.
13C NMR (100 MHz, CDCl3): d = 188.9, 172.2, 148.0, 83.0, 74.9,
IR (film): 3439, 3164, 2958, 1630, 1517, 1238, 1129, 953, 766 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.12 (s, 1 H), 4.61 (m, 2 H), 1.49
(s, 9 H), 1.42 (t, J = 4.8 Hz, 3 H).
66.2, 52.2, 37.9, 28.2.
ESI-MS: m/z = 292 (M – H).
13C NMR (100 MHz, CDCl3): d = 189.0, 147.6, 82.9, 68.9, 27.9,
13.7.
Anal. Calcd for C9H17NO3S: C, 45.04; H, 6.53; N, 4.77; S, 10.93.
Found: C, 45.27; H, 6.61; N, 4.60; S, 10.80.
ESI-MS: m/z = 204 (M – H).
5i
Anal. Calcd for C7H13NO3S: C, 46.81; H, 7.37; N, 6.82; S, 15.62.
Found: C, 46.96; H, 7.28; N, 6.91; S, 15.55.
Yield: 98.6 mg (45%); syrup.
IR (film): 3432, 3178, 2967, 1670, 1520, 1241, 1055, 659 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.11 (s, 1 H), 5.57 (t, J = 6.0 Hz,
1 H), 1.49 (s, 9 H).
5d
Yield: 177.1 mg (76%); syrup.
13C NMR (100 MHz, CDCl3): d = 188.2, 147.8, 82.6, 67.9, 27.9,
IR (film): 3441, 3173, 2966, 1642, 1518, 1240, 1131, 956, 764 cm–1.
21.2.
1H NMR (400 MHz, CDCl3): d = 8.11 (s, 1 H), 4.53 (t, J = 6.8 Hz,
2 H), 1.82–1.74 (m, 2 H), 1.49 (s, 9 H), 1.48–1.40 (m, 2 H), 0.96 (t,
J = 7.2 Hz, 3 H).
13C NMR (100 MHz, CDCl3): d = 188.9, 147.4, 82.6, 72.6, 30.0,
27.8, 18.8, 13.5.
ESI-MS: m/z = 218 (M – H).
Anal. Calcd for C9H17NO3S: C, 49.29; H, 7.81; N, 6.39; S, 14.62.
Found: C, 49.41; H, 7.74; N, 6.44; S, 14.81.
Reaction of 1 with Thiophenols and Activated Methylenes;
General Procedure
ESI-MS: m/z = 232 (M – H).
Anal. Calcd for C10H19NO3S: C, 51.48; H, 8.21; N, 6.00; S, 13.74.
Found: C, 51.31; H, 8.49; N, 6.21; S, 13.78.
To a mixture of 1 (276 mg, 1 mmol) and THF (20 mL) was added
60% NaH (48 mg, 1.2 mmol) at 0 °C. The reaction mixture was
stirred at the same temperature for 1 h, then TFAA (185 mL, 1.1
mmol) was added and the stirring continued for an additional 1 h.
Then, sodium benzenethiolate or sodium malonate (2 mmol) in an-
hyd THF (5 mL) was added and the resulting reaction was stirred at
r.t. overnight. H2O (10 mL) was added to quench the reaction and
the mixture was extracted with EtOAc (3 × 15 mL). The combined
organic layers were dried (MgSO4), and the solvent was removed
under reduced pressure. The residue was purified by flash column
chromatography to afford 6c–e and 7 (Table 5).
5e
Yield: 283.1 mg (66%); syrup; [a]D20 –10.8 (c 1.0, CHCl3).
IR (film): 3465, 2957, 1721, 1704, 1700, 1642, 1518, 1128, 949,
755 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.03 (s, 1 H), 7.15 (d, J = 8.4 Hz,
1 H), 5.69 (t, J = 8.0 Hz, 1 H), 4.19 (m, 1 H), 3.92 (d, J = 11.2 Hz,
2 H), 3.81 (s, 3 H), 3.76–3.70 (m, 2 H), 2.05 (s, 3 H), 1.51 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 188.8, 171.1, 170.2, 151.2, 147.5,
109.4, 82.9, 71.6, 67.5, 53.8, 52.4, 51.7, 27.9.
6c
Yield: 247.5 mg (92%); yellow solid; mp 127–129 °C.
ESI-MS: m/z = 428 (M – H).
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

998
B.-L.Yin et al.
PAPER
IR (film): 3466, 3137, 2941, 1740, 1488, 1226, 1145, 1003, 749 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.02 (s, 1 H), 7.51–7.46 (m, 5 H),
1.56 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 205.9, 149.3, 136.0, 131.1, 130.3,
129.4, 84.1, 28.0.
Acknowledgment
This work was supported by The Project Sponsored by the Scienti-
fic Research Foundation for the Returned Overseas Chinese Schol-
ars, State Education Ministry, and Doctoral Fund of Ministry of
Education of China (200805611041).
ESI-MS: m/z = 268 (M – H).
Anal. Calcd for C12H15NO2S2: C, 53.50; H, 5.61; N, 5.20; S, 23.81. References
Found: C, 53.67; H, 5.49; N, 4.99; S, 23.74.
(1) Lee, J.; Lee, J.; Kang, M.; Shin, M.; Kim, J.-M.; Kang,
S.-U.; Choi, H.-K.; Suh, Y.-G.; Park, H.-G.; Oh, U.; Kim,
H.-D.; Park, Y.-H.; Ha, H.-J.; Kim, Y.-H.; Toth, A.; Wang,
Y.; Tran, R.; Pearce, L. V.; Lundberg, D. J.; Blumberg, P. M.
J. Med. Chem. 2003, 46, 3116.
6d
Yield: 271.7 mg (96%); syrup.
IR (film): 3460, 3132, 2940, 1735, 1479, 1224, 1142, 1011, 755 cm–1.
1H NMR (400 MHz, CDCl3): d = 8.44 (s, 1 H), 7.42 (d, J = 8.0 Hz,
2 H), 7.32 (d, J = 8.0 Hz, 2 H), 2.46 (s, 3 H), 1.60 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 204.1, 149.1, 140.6, 135.6, 130.1,
127.5, 83.8, 27.8, 21.3.
(2) Ranise, A.; Spallarossa, A.; Bruno, O.; Schenone, S.; Fossa,
P.; Menozzi, G.; Bondavalli, F.; Mosti, L.; Capuano, A.;
Mazzeo, F.; Falcone, G.; Filippelli, W. Farmaco 2003, 58,
765.
(3) Cunha, S.; Macedo, F. C.; Costa, G. A. N.; Rodrigues, M. T.;
Verde, R. B. V.; De Souza Neta, L. C.; Vencato, I.; Lariucci,
C.; Sá, F. P. Monatsh. Chem. 2007, 138, 511.
(4) Omar, A.-M. M. E.; Farghaly, A. M.; Hazzai, A. A. B.;
Eshba, N. H.; Sharabi, F. M.; Daabees, T. T. J. Pharm. Sci.
1981, 70, 1075.
(5) Krishnamurthy, R.; Govindaraghavan, S.; Narayanasamy, J.
Pestic. Sci. 1999, 52, 145.
(6) Kochansky, J.; Cohen, C. F. J. Agric. Entomol. 1990, 7, 293.
(7) Vosatka, V.; Capek, A.; Budesinsky, Z. Collect. Czech.
Chem. Commun. 1977, 42, 3186.
(8) Hahn, H.-G.; Rhee, H. K.; Lee, C. K.; Whang, K. J. Korean
J. Med. Chem. 2000, 10, 66.
ESI-MS: m/z = 282 (M – H).
Anal. Calcd for C12H15NO2S2: C, 55.09; H, 6.05; N, 4.94; S, 22.63.
Found: C, 55.21; H, 6.17; N, 4.87; S, 22.55.
6e
Yield: 279.5 mg (89%); syrup.
IR (film): 3475, 3148, 2936, 1749, 1487, 1143, 1053, 774 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.12 (s, 1 H), 7.99 (d, J = 8.0 Hz,
2 H), 7.51 (d, J = 8.4 Hz, 2 H), 1.62 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 207.8, 151.2, 142.7, 137.9, 132.4,
128.5, 84.9, 28.6.
(9) Strickley, R. G.; Anderson, B. D. Pharm. Res. 1993, 10,
1076.
ESI-MS: m/z = 313 (M – H).
(10) Patil, D. G.; Chedekel, M. R. J. Org. Chem. 1984, 49, 997.
(11) Kasmi, S.; Hamelin, J.; Benhaoua, H. Tetrahedron Lett.
1998, 39, 8093.
Anal. Calcd for C12H14N2O4S2: C, 45.85; H, 4.49; N, 8.91; S, 20.40.
Found: C, 45.79; H, 4.38; N, 8.95; S, 20.28.
(12) (a) Satyavan, S. Synthesis 1978, 803. (b) Mayer, R. In
Organosulfur Chemistry; Janssen, M. J., Ed.; Wiley-
Interscience: New York, 1967, 219.
(13) Wang, C.; Chen, J.; Song, Q.; Li, Z.; Xi, Z. ARKIVOC 2003,
(ii), 155.
(14) Staab, H. A.; Walther, G. Liebigs Ann. Chem. 1962, 657, 98.
(15) (a) Brain, C. T.; Hallett, A.; Ko, S. Y. J. Org. Chem. 1997,
62, 3808. (b) Brain, C. T.; Hallett, A.; Ko, S. Y. Tetrahedron
Lett. 1998, 39, 127.
(16) Katritzky, A. R.; Witek, R. M.; Rodriguez-Garcia, V.;
Mohapatra, P. P.; Rogers, J. W.; Cusido, J.; Abdel-Fattah, A.
A. A.; Steel, P. J. J. Org. Chem. 2005, 70, 7866.
(17) Exposito, A.; Femandez-Suarez, M.; Iglesias, T.; Munoz, L.;
Riguera, R. J. Org. Chem. 2001, 66, 4206.
7a
Yield: 204.1 (64%); syrup.
IR (film): 3451, 2944, 1745, 1723, 1638, 1543, 1420, 1279, 1022,
756 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.30 (s, 1 H), 5.40 (s, 1 H), 4.25
(q, J = 7.2 Hz, 4 H), 1.49 (s, 9 H), 1.28 (t, J = 7.2 Hz, 6 H).
13C NMR (100 MHz, CDCl3): d = 164.9, 149.4, 149.0, 110.2, 84.1,
62.3, 28.0, 14.0.
ESI-MS: m/z = 320 (M + H, 10), 121 (11).
HRMS: m/z calcd for C13H21NO6S: 319.1090; found: 319.1077.
7b
(18) For examples concerning the activation of the carbonyl
group of an amide and its synthetic application, see:
(a) Falmagne, J. B.; Escudero, J.; Taleb-saharaoui, S.;
Ghosez, L. Angew. Chem., Int. Ed. Engl. 1981, 20, 879.
(b) Sisti, N. J.; Fowler, F. W.; Grierson, D. S. Synlett 1991,
816. (c) Thomas, E. W. Synthesis 1993, 767. (d) Barbaro,
G.; Battaglia, A.; Bruno, C.; Giorgianni, P.; Guerrini, A.
J. Org. Chem. 1996, 61, 8480. (e) Sisti, N. J.; Zeller, E.;
Grierson, D. S.; Fowler, F. W. J. Org. Chem. 1997, 62,
2093. (f) Charette, A. B.; Chua, P. J. Org. Chem. 1998, 63,
908. (g) Charette, A. B.; Chua, P. Tetrahedron Lett. 1997,
38, 8499. (h) Charette, A. B.; Chua, P. J. Org. Chem. 1998,
63, 908. (i) Charette, A. B.; Chua, P. Synlett 1998, 163.
(j) Charette, A. B.; Chua, P. Tetrahedron Lett. 1998, 39,
Yield: 195.2 mg (67%); syrup.
IR (film): 3455, 2947, 1746, 1720, 1633, 1540, 1413, 1274, 1016,
748 cm–1.
1H NMR (400 MHz, CDCl3): d = 9.15 (s, 1 H), 5.36 (s, 1 H), 3.88
(s, 3 H), 1.48 (s, 9 H).
13C NMR (100 MHz, CDCl3): d = 165.2, 149.9, 149.2, 109.5, 84.1,
61.7, 28.2.
ESI-MS: m/z = 292 (M + H).
Anal. Calcd for C11H17NO6S: C, 45.35; H, 5.88; N, 4.81; S, 11.01.
Found: C, 45.47; H, 5.76; N, 4.64; S, 11.14.
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York

PAPER
N,N¢-Di-Boc-Substituted Thiourea in the Synthesis of Thiocarbonyl Compounds
999
245. (k) Charette, A. B.; Grenon, M. Tetrahedron Lett. 2000,
41, 1677. (l) Wan, Z.-K.; Wacharasindhu, S.; Levins, C. G.;
Lin, M.; Tabei, K.; Mansour, T. S. J. Org. Chem. 2007, 72,
(19) Part of this work was published as a preliminary
communication: Yin, B.; Liu, Z.; Yi, M.; Zhang, J.
Tetrahedron Lett. 2008, 49, 3687.
10194.
Synthesis 2010, No. 6, 991–999 © Thieme Stuttgart · New York