Direct organocatalytic -sulfenylation of aldehydes and ketones with tetramethylthiuram disulfide

Article abstract of DOI:10.1055/s-0030-1258359

The direct pyrrolidine-catalyzed -sulfenylation of aldehydes and ketones with the commercially available, very cheap chemical tetramethylthiuram disulfide (thiram) is described. The dithiocarbamoyl derivatives are obtained in good to excellent yields (47-

Full text of DOI:10.1055/s-0030-1258359

PAPER
281
Direct Organocatalytic a-Sulfenylation of Aldehydes and Ketones with
Tetramethylthiuram Disulfide
Dieter Enders,* Andreas Rembiak, Jens X. Liebich
Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany
Fax +49(241)8092127; E-mail: enders@rwth-aachen.de
Received 10 November 2010
per-catalyzed reaction of 2-haloanilines for the synthesis
of 2-aminobenzothiazoles.10 While thiram has been used
in metal- and base-mediated reactions, to the best of our
knowledge, no application in organocatalysis has been
Abstract: The direct pyrrolidine-catalyzed a-sulfenylation of alde-
hydes and ketones with the commercially available, very cheap
chemical tetramethylthiuram disulfide (thiram) is described. The
dithiocarbamoyl derivatives are obtained in good to excellent yields
(47–98%). In the case of a-substituted aldehydes the protocol al- published so far.
lows the generation of quaternary stereocenters. The sensibility of
the a-sulfenylated carbonyl compounds for racemization has been
investigated.
We now wish to report a secondary amine catalyzed a-
sulfenylation of aldehydes and ketones with thiram. Earli-
er work by Fanghänel already showed the reactivity of
thiram towards preformed enamines under stoichiometric
conditions.11 With this in mind a catalytic version of this
reaction was envisaged, in which an in situ generated
enamine attacks the disulfide moiety of thiram with the
dithiocarbamic acid anion acting as a leaving group. After
hydrolytic regeneration of the catalyst, the desired a-
sulfenylated aldehydes and ketones 3 should be obtained
along with dithiocarbamic acid (Scheme 1).
Key words: organocatalysis, thiram, sulfenylation, dithiocarbam-
ate, enamine
The formation of C–S bonds is a significant task in organ-
ic synthesis, since sulfur-containing compounds are
known to be important structural motifs in many biologi-
cally active substances such as pharmaceuticals and agro-
chemicals. Especially the synthesis of a-sulfenylated
carbonyl compounds from simple and readily available
starting materials is an important field as they are com-
monly used as building blocks in a variety of organic
transformations.1 Besides the broad use of nucleophilic
sulfur derivatives in metal-catalyzed cross-coupling
reactions2 or sulfa-Michael additions,3 electrophilic sulfe-
nylating reagents, which allow a direct a-sulfenylation of
aldehydes and ketones, are found frequently in the litera-
ture.1c Besides the preparation of a-sulfenylated carbonyl
compounds via SN2 displacement of a-halogenated carbo-
nyl compounds with sulfide anions, methods based on the
reaction of the parent carbonyl compounds or preformed
enolates and enamines with sulfenylating agents such as
sulfur, disulfides, N-(phenylsulfanyl)succinimide, and
sulfenyl chlorides are used.4 While asymmetric electro-
philic a-sulfenylations under stoichiometric conditions
are known for quite some time,5 the catalytic asymmetric
protocols employing organocatalysts6 and enantiopure ti-
tanium(IV) or nickel(II) complexes7 have only been re-
cently reported.
S
O
S
NMe2
R3
+
Me2N
S
R1
S
R2
1
2
S
cat.
–
R4R5NH
Me2N
NMe2
SH
O
S
R1
R2 R3
S
3
Scheme 1 Organocatalytic electrophilic a-sulfenylation of alde-
hydes and ketones
Our initial investigations started with a screening of fre-
quently used secondary amine catalysts under solvent-
free conditions using pentan-3-one (1a) as a model sub-
strate (Scheme 2, Table 1). It was expected that an enam-
ine formation is essential for the C–S bond forming step,
thus without the addition of any catalyst it came as no sur-
prise that no conversion was observed (Table 1, entry 1).
With the addition of a catalytic amount of a cyclic second-
The very cheap, commercially available tetramethylthi-
uram disulfide (TMTD, thiram, 2) exhibits broad applica-
tions as a fungicide, an animal repellant, in the treatment
of human scabies, and as a vulcanization accelerator. Re-
cently thiram has been used in the metal-mediated thiola-
tion of aliphatic and aromatic compounds,8 the synthesis
of sulfur containing heteroaromatics9 as well as in a cop-
O
O
catalyst
thiram (2)
S
NMe2
neat
S
SYNTHESIS 2011, No. 2, pp 0281–0286
Advanced online publication: 10.12.2010
x
x
.
x
x
.2
0
1
1
1a
3a
Scheme 2 a-Sulfenylation of pentan-3-one (1a) with thiram (2)
DOI: 10.1055/s-0030-1258359; Art ID: Z27010SS
© Georg Thieme Verlag Stuttgart · New York

282
D. Enders et al.
PAPER
ary amine the desired product 3a was formed, albeit only ene dissolved the reagents only insufficiently and the re-
in low to moderate yields. Piperidine and its sterically hin- action yield decreased to 20% (Table 2, entry 8).
dered analogue tetramethylpiperidine provided poor and
no conversion respectively (Table 1, entries 2 and 3). Fur-
Next the effects of additives on the catalytic thiram a-
sulfenylation reaction were examined (Table 3). Several
thermore morpholine and piperazine showed only low
basic, acidic, oxidizing, and thiophilic additives were
conversions at room temperature or a slightly elevated
screened. Although methanol seemed to be the best sol-
temperature. A yield of 59% was obtained by employing
vent in this reaction, further optimization was performed
pyrrolidine as the catalyst. However, (S)-proline as an
in acetonitrile as no significant increase of yield was
achieved in methanol. Additionally the temperature was
lowered to suppress a possible reaction in which the
enantiopure pyrrolidine derivative was ineffective in this
transformation (Table 1, entry 8).
dithiocarbamate moiety in thiram is attacked by the cata-
Table 1 Catalyst Screening for the Synthesis of Dithiocarbamate 3a
(Scheme 2)
lyst.12 The addition of trimethylsilyl chloride as thiophile
to scavenge the dithiocarbamic acid side product proved
Entrya
Catalyst (0.3 equiv)
Temp (°C) Time (h) Yield (%)b
to be unsuccessful and resulted in no conversion, most
probably resulting from the silylation of the catalyst. The
acidic additive trifluoroacetic acid was found to inhibit the
catalytic activity completely. Compared to the reaction
performed without additive the use of an inorganic base or
oxidizing agents gave similar conversion (Table 3, entries
3 and 4). The addition of 1.0 equivalent of triethylamine
to the reaction mixture showed no improvement. However
the addition of 2.0 equivalents resulted in an increased
yield (Table 3, entries 6 and 7).
1
2
3
4
5
6
7
8
–
50
50
18
24
17
24
68
48
18
24
–
piperidine
19
–
tetramethylpiperidine r.t.
morpholine
piperazine
piperazine
pyrrolidine
(S)-proline
50
r.t.
45
50
50
7
10
25
59
16
Table 3 Additive Screening for the Synthesis of Dithiocarbamate
3a (Scheme 2)
Entrya
Additive (equiv)
TMSCl (0.1)
TFA (0.3)
Temp (°C) Time (d) Yield (%)b
a All reactions were performed on a 2.0 mmol scale.
b Yield of isolated product 3a.
1
2
3
4
5
6
7
8c
-22
50
0.3
1.0
1.0
7.0
1.0
1.0
3.0
6.0
–
–
Since a reaction under solvent-free conditions could result
in insufficient solubility of thiram and would prove im-
practical for high-boiling carbonyl compounds, a solvent
screening was undertaken (Table 2). Polar aprotic sol-
vents proved unsuitable in this reaction and gave no con-
version. The best results were achieved in methanol and
acetonitrile (Table 2, entries 4 and 6). Attempts to per-
form the reaction in slightly basic aqueous solution gave
only poor yields. Highly nonpolar solvents such as tolu-
K2CO3 (0.1)
NaIO4 (0.3)
Et3N (1.0)
50
42
37
42
51
54
84
-22
50
Et3N (2.0)
50
Et3N (2.0)
-22
-22
Et3N (2.0)
a All reactions were performed on a 2.0 mmol scale in MeCN.
b Yield of isolated product 3a.
Table 2 Solvent Screening for the Synthesis of Dithiocarbamate 3a
(Scheme 2)
c Reaction was performed in a mixture of MeCN–CH2Cl2 (3:1).
Entrya
Solvent
DMSO
DMF
Temp (°C)
Time (h) Yield (%)b
1
2
3
4
5
6
7
8
r.t.
20
20
20
24
24
24
20
24
–
After several test reactions two equivalents of triethyl-
amine were found to be optimal. Lowering the reaction
temperature to –22 °C significantly improved the yields
up to 84% (Table 3, entry 8) even though longer reaction
times were necessary for the reactions to go to comple-
tion. Substrates that showed poor solubility in pure aceto-
nitrile could be reacted using mixtures of acetonitrile and
dichloromethane without a significant change in yield.
r.t.
–
NMP
r.t. to 50
50
–
MeOH
THF
53
15
40
12
20
50
MeCN
50
Once the reaction conditions had been optimized, we in-
vestigated the substrate scope of the organocatalyzed a-
sulfenylation of carbonyl compounds with thiram
(Table 4). Ketones with various substitution patterns were
successfully converted to the desired dithiocarbamates in
good to excellent yields. Unfortunately methyl ketones
c
K2CO3
r.t.
toluene
50
a All reactions were performed on a 2.0 mmol scale.
b Yield of isolated product 3a.
c 1 M solution of K2CO3 in H2O.
Synthesis 2011, No. 2, 281–286 © Thieme Stuttgart · New York

PAPER
a-Sulfenylation of Aldehydes and Ketones with Thiram
283
were found to be unsuitable substrates and gave only low over a period of several hours and the half-life for racemi-
yields of product even when the reactions were performed zation can be estimated to be greater than three days
under solvent-free conditions. Additionally, aldehydes (Table 5). Slightly elevated temperatures, however, led to
can be employed in this reaction, with a,a-disubstituted complete racemization within minutes.
aldehydes allowing the creation of quaternary stereo-
centers in good yields.13
Table 5 Evaluation of the Optical Stability of Dithiocarbamate 3k
Entry
Temp
r.t.
Time (h)
ee (%)a
96
Table 4 Scope of the Organocatalyzed a-Sulfenylation of Alde-
hydes and Ketones with Thiram
1
2
3
4
5
0
r.t.
16
90
N
H
r.t.
23
86
(0.3 equiv)
O
O
thiram (2)
R3
S
NMe2
r.t.
41
82
R1
R1
Et3N, MeCN
–22 °C
R2 R3
R2
S
40 °C
0.05
0
1
3
a Determined by HPLC analysis on a chiral stationary phase (n-hep-
tane–i-PrOH, 8:2, 1.0 mL/min, Daicel Chiralpak AD column):
tR = 6.7 min (major), tR = 7.7 min (minor).
Producta
3a
R1
R2
R3
H
Yield (%)b
Et
Me
84
90
75
37
98
72
71
75
49
47
73
83
3b
n-Pr
Et
H
In summary, we have developed a direct pyrrolidine-cata-
lyzed a-dithiocarbamoylation of aldehydes and ketones
employing the very cheap, commercially available tet-
ramethylthiuram disulfide (thiram) as electrophilic sulfe-
nylation reagent. Besides acyclic and cyclic ketones,
aldehydes can be sulfenylated in this way allowing the
generation of quaternary stereocenters with good to excel-
lent yields.
3c
CF3
Ph
H
3d
Ph
Ph
H
3e
H
i-Pr
Me
Me
Me
Me
H
3f
H
Me
Et
n-Pr
Ph
H
3g
H
3h
H
Unless otherwise noted, all commercially available compounds
were used without further purification. For preparative column
chromatography SIL G-25 UV254 from Macherey-Nagel, particle
size 0.040–0.063 mm (230–240 mesh, flash) was used. Visualiza-
tion of the developed TLC plates was performed with ultraviolet ir-
radiation (254 nm) or by staining with a KMnO4 solution.
Microanalyses were performed with a Vario EL element analyzer.
Mass spectra were measured on a Finnigan SSQ7000 (EI 70 eV)
spectrometer and high-resolution mass spectra on a Thermo Fisher
Scientific Orbitrap XL. IR spectra were recorded on a PerkinElmer
FT-IR Spectrum 100 instrument. 1H and 13C NMR spectra were re-
corded at ambient temperature with Varian Mercury 300 or Inova
400 spectrometers with TMS as an internal standard.
3i
H
3jc
3kc
3lc
-(CH2)3-
-(CH2)4-
H
-(CH2)2OCH2-
H
a All reactions were performed on a 2.0 mmol scale at – 22 °C for 6 d
in a mixture of MeCN–CH2Cl2 (3:1).
b Yield of isolated product 3.
c Reactions were performed under neat conditions with 10 equiv of
ketone at 50 °C for 1 d.
a-Sulfenylation of Aliphatic Aldehydes and Ketones; General
Procedure 1 (GP 1)
Interestingly it was discovered that the reaction of cyclic
ketones with thiram (2) occurs without the addition of a A screw-capped vial was charged with thiram (2; 480 mg, 2.0
mmol, 1 equiv) and MeCN–CH2Cl2 (3:1; 4 mL, 0.5 M), and the re-
sulting suspension was cooled to –40 °C. Et3N (405 mg, 4 mmol, 2
catalyst or an additive (Table 4, 3j–l,). It was assumed that
in this case the reaction proceeds via an enol-type inter-
equiv), ketone (4.0 mmol, 2 equiv), and pyrrolidine (0.43 mg, 0.6
mediate. To demonstrate the practicability of our proto-
mmol, 0.3 equiv) were added sequentially. The reaction was stirred
col, the synthesis of 3a was performed on a one mole scale
at –22 °C for 6 d. The solvent was removed in vacuo and the result-
to give 172 g of the a-dithiocarbamoylated ketone.
ing crude product was purified by flash column chromatography us-
ing n-pentane–Et2O as eluent (Table 4).
Towards the development of an asymmetric version of
this reaction the optical stability of the dithiocarbamates 3
has to be considered as it is conceivable that the product
with R3 = H may racemize by enolization. Therefore, both
enantiomers of the cyclohexanone derivative 3k were sep-
arated by preparative chiral HPLC. The enantiomeric ex-
cess of a virtually enantiopure sample in a solution of
heptane–i-PrOH at room temperature slowly diminished
a-Sulfenylation of Cyclic Ketones; General Procedure 2 (GP 2)
A screw-capped vial was charged with thiram (2; 480 mg, 2.0
mmol, 1 equiv) and ketone (20.0 mmol, 10 equiv). The reaction was
stirred at 50 °C until a clear solution was obtained. Removal of the
unreacted ketone in vacuo and purification of the resulting crude
product by flash column chromatography (silica gel, n-pentane–
Et2O) afforded the pure product (Table 4).
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284
D. Enders et al.
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2-(Dimethylaminothiocarbonylthio)pentan-3-one (3a)
Compound 3a was synthesized according to GP 1 to yield 349 mg
(84%) of a yellowish oil; Rf = 0.69 (n-pentane–Et2O, 1:1).
1H NMR (400 MHz, CDCl3): d = 3.37 (s, 3 H, NCH3), 3.48 (s, 3 H,
NCH3), 6.95 (s, 1 H, CH), 7.23–7.51 (m, 8 H, CHarom), 8.08 (d,
J = 7.8 Hz, 2 H, CHarom).
IR (film): 3408, 2974, 2926, 1713, 1576, 1499, 1450, 1377, 1252,
1149, 1054, 971, 869, 799, 574 cm–1.
1H NMR (400 MHz, CDCl3): d = 1.08 (t, J = 7.4 Hz, 3 H, CH2CH3),
1.48 (d, J = 7.4 Hz, 3 H, CHCH3), 2.60 (dq, J = 7.2, 7.4 Hz, 1 H,
CH3CHH), 2.80 (dq, J = 7.2, 7.4 Hz, 1 H, CH3CHH), 3.40 (s, 3 H,
NCH3), 3.55 (s, 3 H, NCH3), 4.90 (q, J = 7.4 Hz, 1 H, CH3CH).
13C NMR (100 MHz, CDCl3): d = 8.2 (CH3), 16.1 (CH3), 34.1
(CH2), 41.8 (NCH3), 45.8 (NCH3), 55.1 (CH), 195.2 (C=S), 208.6
(C=O).
13C NMR (100 MHz, CDCl3): d = 41.8 (NCH3), 45.8 (NCH3), 62.6
(CH), 128.5 (CHarom), 128.5 (CHarom, 2 C), 129.1 (CHarom, 2 C),
129.1 (CHarom, 2 C), 129.3 (CHarom, 2 C), 133.0 (CHarom), 133.7
(Carom), 136.2 (Carom), 194.3 (C=S), 195.1 (C=O).
2-(Dimethylaminothiocarbonylthio)isovaleraldehyde (3e)14
The synthesis of 3e following GP 1 yielded 3.36 g (98%) of a lightly
yellow oil; Rf = 0.39 (n-pentane–Et2O, 1:1).
1H NMR (300 MHz, CDCl3): d = 0.99 [d, J = 6.8 Hz, 3 H,
CH(CH3)2], 1.05 [d, J = 6.8 Hz, 3 H, CH(CH3)2], 2.47 [d sept,
J = 6.8, 4.9 Hz, 1 H, CH(CH3)2], 3.42 (s, 3 H, NCH3), 3.50 (s, 3 H,
NCH3), 4.80 (dd, J = 4.9, 1.3 Hz, 1 H, CH), 9.52 (d, J = 1.3 Hz, 1
H, CHO).
MS (EI): m/z = 205 (8, [M]+), 172 (32), 120 (7), 88 (100), 77 (5), 73
(6), 57 (10).
Anal. Calcd for C8H15NOS2: C, 46.79; H, 7.36; N, 6.82. Found: C,
46.89; H, 7.56; N, 7.17.
13C NMR (75 MHz, CDCl3): d = 19.9 (CH3), 20.2 (CH3), 28.0
[CH(CH3)2], 41.6 (NCH3), 45.7 (NCH3), 67.1 (CH), 194.7 (C=S),
198.0 (CHO).
3-(Dimethylaminothiocarbonylthio)heptan-4-one (3b)
The synthesis of 3b following GP 1 yielded 419 mg (90%) of a yel-
low oil; Rf = 0.79 (n-pentane–Et2O, 1:1).
2-(Dimethylaminothiocarbonylthio)isobutyraldehyde (3f)
The synthesis of 3f following GP 1 yielded 275 mg (72%) of a col-
orless solid; mp 63 °C; Rf = 0.51 (n-pentane–Et2O, 1:1).
IR (film): 3406, 2963, 2924, 2874, 1710, 1578, 1539, 1499, 1458,
1377, 1252, 1148, 1051, 980, 869, 805, 574 cm–1.
1H NMR (400 MHz, CDCl3): d = 0.93 (t, J = 7.4 Hz, 3 H,
CH2CH2CH3), 1.02 (t, J = 7.4 Hz, 3 H, CHCH2CH3), 1.64 (sext,
J = 7.4 Hz, 2 H, CH3CH2CH2), 1.75–1.90 (m, 1 H, CH2CHH), 1.95–
2.09 (m, 1 H, CH2CHH), 2.51–2.61 (dt, J = 6.6, 6.9 Hz, 1 H,
CH3CHHCH), 2.67–2.78 (dt, J = 7.1, 7.4 Hz, 1 H, CH3CHHCH),
3.42 (s, 3 H, NCH3), 3.56 (s, 3 H, NCH3), 4.89 (t, J = 7.4 Hz, 1 H,
CH2CH).
13C NMR (100 MHz, CDCl3): d = 11.9 (CH3), 13.8 (CH3), 17.3
(CH2), 23.7 (CH2), 41.7 (NCH3), 43.5 (CH2), 45.9 (NCH3), 62.0
(CH), 195.4 (C=S), 207.4 (C=O).
IR (ATR): 2969, 2927, 2874, 2703, 2106, 1705, 1501, 1450, 1376,
1248, 1156, 1131, 1053, 1013, 983, 902, 813, 711 cm–1.
1H NMR (400 MHz, C6D6): d = 1.58 [s, 6 H, C(CH3)2], 3.38 (s, 3 H,
NCH3), 3.47 (s, 3 H, NCH3), 9.64 (s, 1 H, CHO).
13C NMR (100 MHz, C6D6): d = 22.8 (CH3, 2 C), 40.9 (NCH3), 43.7
(NCH3), 58.6 (C), 192.8 (C=S), 196.5 (CHO).
MS (EI): m/z = 191 (11, [M]+), 163 (6), 153 (6), 121 (21), 120 (9),
89 (9), 88 (100), 85 (6), 83 (16), 77 (6), 73 (10), 71 (20), 56 (9), 47
(6).
HRMS (ESI): m/z calcd for C7H13NOS2: 192.0517 ([M + H]+);
MS (EI): m/z = 234 (27, [M + H]+), 233 (20, [M]+), 200 (39), 121
(20), 113 (72), 89 (8), 88 (100), 72 (6), 71 (7).
found: 192.0511 ([M + H]+).
Anal. Calcd for C10H19NOS2: C, 51.46; H, 8.21; N, 6.00. Found: C,
51.92; H, 8.24; N, 6.45.
2-(Dimethylaminothiocarbonylthio)-2-methylbutyraldehyde
(3g)
The synthesis of 3g following GP 1 yielded 290 mg (71%) of a yel-
low oil; Rf = 0.60 (n-pentane–Et2O, 1:1).
3-(Dimethylaminothiocarbonylthio)-1,1,1-trifluoro-3-phenyl-
propan-2-one (3c)
The synthesis of 3c following GP 1 yielded 290 mg (75%) of a col-
orless solid; mp 106 °C; Rf = 0.80 (n-pentane–Et2O, 1:1).
IR (film): 3403, 2970, 2924, 2851, 2707, 1708, 1576, 1500, 1457,
1377, 1252, 1147, 1052, 991, 898, 782, 578 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.00 (t, J = 7.4 Hz, 3 H, CH3),
1.63 (s, 3 H, CCH3), 1.79–1.90 (m, 1 H, CH3CHH), 2.00–2.15 (m,
1 H, CH3CHH), 3.40 (s, 3 H, NCH3), 3.46 (s, 3 H, NCH3), 9.69 (s,
1 H, CHO).
13C NMR (75 MHz, CDCl3): d = 8.5 (CH3), 19.7 (CH3), 28.3 (CH2),
42.2 (NCH3), 44.6 (NCH3), 63.3 (C), 193.3 (C=S), 198.5 (CHO).
MS (EI): m/z = 205 (7, [M]+), 122 (5), 121 (23), 120 (7), 90 (5), 89
(8), 88 (100), 85 (24), 77 (6), 73 (8), 72 (6), 71 (5), 57 (13), 56 (6),
55 (10), 45 (5).
IR (ATR): 3075, 2948, 2325, 2101, 1744, 1591, 1500, 1455, 1384,
1316, 1248, 1196, 1138, 1024, 980, 872, 842, 822, 743, 721, 690
cm–1.
1H NMR (300 MHz, CDCl3): d = 3.35 (s, 3 H, NCH3), 3.47 (s, 3 H,
NCH3), 6.20 (s, 1 H, CH), 7.38 (s, 5 H, CHarom).
13C NMR (75 MHz, CDCl3): d = 42.2 (NCH3), 45.2 (NCH3), 60.6
(CH), 115.7 (q, J = 292.2 Hz, CF3), 128.3 (Carom), 129.4 (CHarom, 2
C), 129.6 (CHarom, 2 C), 129.6 (CHarom), 186.2 (q, J = 34.4 Hz,
C=O), 193.9 (C=S).
Anal. Calcd for C8H15NOS2: C, 46.79; H, 7.36; N, 6.82. Found: C,
46.95; H, 7.11; N, 6.49.
19F NMR (376 MHz, CDCl3): d = 73.95 (s, CF3).
MS (EI): m/z = 308 (12, [M + H]+), 307 (36, [M]+), 121 (13), 120
(100), 109 (12), 90 (12), 89 (14), 88 (79), 77 (16).
2-(Dimethylaminothiocarbonylthio)-2-methylvaleraldehyde
(3h)
The synthesis of 3h following GP 1 yielded 327 mg (75%) of a yel-
low oil; Rf = 0.61 (n-pentane–Et2O, 1:1).
Anal. Calcd for C12H12F3NOS2: C, 46.89; H, 3.94; N, 4.56. Found:
C, 46.73; H, 3.92; N, 4.52.
2-(Dimethylaminothiocarbonylthio)desoxybenzoin (3d)11b
The synthesis of 3d following GP 1 yielded 235 mg (37%) of a
lightly red solid; mp 129 °C; Rf = 0.54 (n-pentane–Et2O, 1:1).
IR (film): 2960, 2928, 2872, 2850, 2703, 1708, 1576, 1499, 1464,
1376, 1252, 1149, 1051, 990, 938, 911, 868, 745, 707, 579, 480
cm–1.
1H NMR (400 MHz, CDCl3): d = 0.93 (t, J = 7.3 Hz, 3 H, CH3),
1.36–1.48 (m, 2 H, CH3CH2), 1.66 (s, 3 H, CCH3), 1.71–1.79 (m, 1
Synthesis 2011, No. 2, 281–286 © Thieme Stuttgart · New York

PAPER
a-Sulfenylation of Aldehydes and Ketones with Thiram
285
H, CH2CHH), 1.90–1.98 (m, 1 H, CH2CHH), 3.40 (s, 3 H, NCH3),
MS (EI): m/z = 220 (2, [M + H]+), 121 (8), 99 (38), 90 (6), 88 (100),
3.46 (s, 3 H, NCH3), 9.67 (s, 1 H, CHO).
77 (5), 73 (11), 72 (8), 59 (7), 56 (6), 55 (5), 45 (10).
13C NMR (100 MHz, CDCl3): d = 14.5 (CH3), 17.5 (CH2), 20.4
(CH3), 37.8 (CH2), 42.2 (NCH3), 44.6 (NCH3), 63.0 (C), 193.2
(C=S), 198.3 (CHO).
Anal. Calcd for C8H13NO2S2: C, 43.81; H, 5.97; N, 6.39. Found: C,
43.63; H, 5.82; N, 6.64.
MS (EI): m/z = 220 (23, [M + H]+), 219 (7, [M]+), 122 (10), 121
(35), 120 (12), 99 (28), 90 (6), 89 (11), 88 (100), 77 (5), 73 (5).
Acknowledgment
This work was supported by the Fonds der Chemischen Industrie.
We thank BASF AG and the former Degussa AG for the donation
of chemicals.
Anal. Calcd for C9H17NOS2: C, 49.28; H, 7.81; N, 6.39. Found: C,
49.78; H, 7.85; N, 6.27.
2-(Dimethylaminothiocarbonylthio)hydratropaldehyde (3i)
The synthesis of 3i following GP 1 yielded 246 mg (49%) of a red
oil; Rf = 0.73 (n-pentane–Et2O, 2:1).
References
(1) (a) Trost, B. M. Chem. Rev. 1978, 78, 363. (b) Trost, B. M.
Acc. Chem. Res. 1978, 11, 453. (c) Wladislaw, B.;
Marzorati, L.; Di Vitta, C. Org. Prep. Proced. Int. 2007, 39,
447.
(2) (a) Kondo, T.; Mitsudo, T. Chem. Rev. 2000, 100, 3205.
(b) Bichler, P.; Love, J. A. Top. Organomet. Chem. 2010, 31,
39.
IR (ATR): 3059, 2983, 2930, 2825, 2701, 2324, 2084, 1989, 1950,
1705, 1596, 1494, 1445, 1374, 1250, 1144, 1063, 987, 914, 888,
756, 698 cm–1.
1H NMR (400 MHz, CDCl3): d = 2.18 (s, 3 H, CCH3), 3.38 (s, 3 H,
NCH3), 3.46 (s, 3 H, NCH3), 7.32–7.40 (m, 3 H, CHarom), 7.53 (dd,
J = 6.9, 1.5 Hz, 2 H, CHarom), 10.03 (s, 1 H, CHO).
13C NMR (100 MHz, CDCl3): d = 22.0 (CH3), 42.2 (NCH3), 44.6
(NCH3), 64.8 (C), 127.5 (CHarom), 128.3 (CHarom, 2 C), 128.9
(CHarom, 2 C), 136.9 (Carom), 192.9 (C=S), 195.9 (CHO).
MS (EI): m/z = 253 (13, [M]+), 225 (9), 133 (13), 132 (67), 122 (8),
121 (37), 120 (53), 105 (100),104 (12), 103 (25), 88 (95), 79 (16),
78 (14), 77 (55), 73 (11), 59 (7), 56 (6), 51 (16).
(3) Review: Enders, D.; Lüttgen, K.; Narine, A. A. Synthesis
2007, 959.
(4) For selected examples, see: (a) Asinger, F.; Thiel, M.;
Kalzendorf, I. Justus Liebigs Ann. Chem. 1957, 610, 25.
(b) Kuehne, M. E. J. Org. Chem. 1963, 28, 2124.
(c) Asinger, F.; Schaefer, W.; Triem, H. Monatsh. Chem.
1966, 97, 1510. (d) Murai, S.; Kuroki, Y.; Hasegawa, K.;
Tsutsumi, S. Chem. Commun. 1972, 946. (e) Kumamoto,
T.; Kobayashi, S.; Mukaiyama, T. Bull. Chem. Soc. Jpn.
1972, 45, 866. (f) Seebach, D.; Teschner, M. Chem. Ber.
1976, 109, 1601. (g) Huang, C.-H.; Liao, K.-S.; De S, K.;
Tsai, Y.-M. Tetrahedron Lett. 2000, 41, 3911. (h) Yadav, J.
S.; Reddy, B. V. S.; Jain, R.; Baishya, G. Tetrahedron Lett.
2008, 49, 3015. (i) Okragla, E.; Demkowicz, S.; Rachon, J.;
Witt, D. Synthesis 2009, 1720.
(5) (a) Hiroi, K.; Nishida, M.; Nakayama, A.; Nakazawa, K.;
Fujii, E.; Sato, S. Chem. Lett. 1979, 969. (b) Yura, T.;
Iwasawa, N.; Clark, R.; Mukaiyama, T. Chem. Lett. 1986,
1809. (c) Youn, J.-H.; Herrmann, R.; Ugi, I. Synthesis 1987,
159. (d) Poli, G.; Belvisi, L.; Manzoni, L.; Scolastico, C.
J. Org. Chem. 1993, 58, 3165. (e) Enders, D.; Schäfer, T.;
Piva, O.; Zamponi, A. Tetrahedron 1994, 50, 3349.
(f) Chibale, K.; Warren, S. Tetrahedron Lett. 1994, 35,
3991. (g) Enders, D.; Zamponi, A.; Schäfer, T.; Nübling, C.;
Eichenauer, H.; Demir, A. S.; Raabe, G. Chem. Ber. 1994,
127, 1707. (h) Enders, D.; Schäfer, T.; Mies, W.
Tetrahedron 1998, 54, 10239. (i) Evans, D. A.; Campos, K.
R.; Tedrow, J. S.; Michael, F. E.; Gagné, M. R. J. Am. Chem.
Soc. 2000, 122, 7905. (j) Enders, D.; Schaadt, A. Synlett
2002, 498.
(6) (a) Wang, W.; Li, H.; Wang, J.; Liao, L. Tetrahedron Lett.
2004, 45, 8229. (b) Marigo, M.; Wabnitz, T. C.; Fielenbach,
D.; Jørgensen, K. A. Angew. Chem. Int. Ed. 2005, 44, 794.
(c) Sobhani, S.; Fielenbach, D.; Marigo, M.; Wabnitz, T. C.;
Jørgensen, K. A. Chem. Eur. J. 2005, 11, 5689. (d) Zhao,
G.-L.; Rios, R.; Vesely, J.; Eriksson, L.; Córdova, A. Angew.
Chem. Int. Ed. 2008, 47, 8468. (e) Fang, L.; Lin, A. J.; Hu,
H. W.; Zhu, C. J. Chem. Eur. J. 2009, 15, 7039.
(7) (a) Jereb, M.; Togni, A. Org. Lett. 2005, 7, 4041.
(b) Srisailam, S. K.; Togni, A. Tetrahedron: Asymmetry
2006, 17, 2603. (c) Jereb, M.; Togni, A. Chem. Eur. J. 2007,
13, 9384. (d) Ishimaru, T.; Ogawa, S.; Tokunaga, E.;
Nakamura, S.; Shibata, N. J. Fluorine Chem. 2009, 130,
1049.
2-(Dimethylaminothiocarbonylthio)cyclopentanone (3j)11b
The synthesis of 3j following GP 2 yielded 189 mg (47%) of a
brownish solid; mp 94 °C; Rf = 0.42 (n-pentane–Et2O, 1:1).
1H NMR (400 MHz, CDCl3): d = 1.92–2.36 (m, 4 H, CH2), 2.42–
2.54 (m, 1 H, CHH), 2.62–2.73 (m, 1 H, CHH), 3.40 (s, 3 H, NCH3),
3.56 (s, 3 H, NCH3), 4.74–4.81 (m, 1 H, CH).
13C NMR (100 MHz, CDCl3): d = 20.6 (CH2), 31.0 (CH2), 37.1
(CH2), 41.7 (NCH3), 46.1 (NCH3), 57.7 (CH), 195.2 (C=S), 213.6
(C=O).
2-(Dimethylaminothiocarbonylthio)cyclohexanone (3k)11b
The synthesis of 3k following GP 2 yielded 316 mg (73%) of a col-
orless solid; mp 111 °C; Rf = 0.50 (n-pentane–Et2O, 1:1).
1H NMR (400 MHz, CDCl3): d = 1.65–2.00 (m, 4 H, CH2), 2.10–
2.20 (m, 1 H, CHH), 2.50–2.62 (m, 3 H, CHH, CH2), 3.41 (s, 3 H,
NCH3), 3.53 (s, 3 H, NCH3), 4.97 (m, 1 H, CH).
13C NMR (100 MHz, CDCl3): d = 25.9 (CH2), 27.7 (CH2), 35.4
(CH2), 41.7 (NCH3), 42.4 (CH2), 45.6 (NCH3), 62.4 (CH), 195.1
(C=S), 205.8 (C=O).
3-(Dimethylaminothiocarbonylthio)tetrahydro-4H-pyran-4-
one (3l)
The synthesis of 3l following GP 2 yielded 364 mg (83%) of a col-
orless solid; mp 75 °C; Rf = 0.42 (n-pentane–Et2O, 1:2).
IR (ATR): 2971, 2913, 2871, 2753, 2069, 1709, 1500, 1376, 1245,
1205, 1147, 1091, 1051, 967, 920, 860, 819, 714, 671 cm–1.
1H NMR (300 MHz, C6D6): d = 2.59 (dt, J = 9.6, 2.5 Hz, 1 H, CHH-
CO), 2.83–2.94 (m, 1 H, CHHCO), 3.43 (s, 3 H, NCH3), 3.54 (s, 3
H, NCH3), 3.60 (t, J = 10.6 Hz, 1 H, CH), 3.81 (dt, J = 11.6, 3.0 Hz,
1 H, CHCHHO), 4.32 (m, 1 H, CH2CHHO), 4.34 (m, 1 H,
CH2CHHO), 5.14 (td, J = 10.6, 6.9, 1.0 Hz, 1 H, CHCHHO).
13C NMR (75 MHz, C6D6): d = 41.7 (NCH3), 43.3 (CH2), 45.8
(NCH3), 60.4 (CH), 68.2 (CH2), 72.2 (CH2), 193.3 (C=S), 201.5
(C=O).
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PAPER
(8) (a) Schnell, B.; Kappe, T. J. Heterocycl. Chem. 2000, 37,
911. (b) Krasovskiy, A.; Gavryushin, A.; Knochel, P. Synlett
2005, 2691. (c) Krasovskiy, A.; Gavryushin, A.; Knochel, P.
Synlett 2006, 792. (d) Rauhut, C. B.; Cervino, C.;
(10) Pi, S. S.; Zhang, X. G.; Tang, R. Y.; Li, J. H. Synlett 2009,
3032.
(11) (a) Fanghänel, E. Z. Chem. 1964, 4, 70. (b) Fanghänel, E.
J. Prakt. Chem. 1975, 317, 123.
(12) Van Boi, L. Russ. Chem. Bull. 1999, 48, 2319.
(13) Recent review: Bella, M.; Gasperi, T. Synthesis 2009, 1583.
(14) Tsuboi, S.; Kohara, N.; Doi, K.; Utaka, M.; Takeda, A. Bull.
Chem. Soc. Jpn. 1988, 61, 3205.
Krasovskiy, A.; Knochel, P. Synlett 2009, 67.
(9) (a) Kienle, M.; Unsinn, A.; Knochel, P. Angew. Chem. Int.
Ed. 2010, 49, 4751. (b) Tang, R.-Y.; Luo, P.-S.; Zhang,
X.-G.; Zhong, P.; Li, J.-H. Synlett 2010, 1345.
Synthesis 2011, No. 2, 281–286 © Thieme Stuttgart · New York