Diastereoselective Synthesis of Z-Alkenyl Disulfides from α-Thiophosphorylated Ketones and Thiosulfonates

Article abstract of DOI:10.1002/adsc.201901208

We developed a simple and efficient method for the synthesis of functionalized unsymmetrical Z-alkenyl disulfides under mild conditions in moderate to good yields. The designed method is based on the reaction of α-thiophosphorylated carbonyl compounds with thiotosylates in the presence of a base. The developed method allows the preparation of unsymmetrical Z-alkenyl disulfides bearing additional hydroxy, carboxy, or ester functionalities. (Figure presented.).

Full text of DOI:10.1002/adsc.201901208

Title: Diastereoselective synthesis of Z-alkenyl disulfides from α-
thiophosphorylated ketones and thiosulfonates
Authors: Mateusz Musiejuk, Justyna Doroszuk, Bartosz Jędrzejewski,
Gregory Ortiz Nieto, Marisol Marin Navarro, and Dariusz Witt
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901208
Link to VoR: http://dx.doi.org/10.1002/adsc.201901208

10.1002/adsc.201901208
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Diastereoselective Synthesis of Z-Alkenyl Disulfides from α-
Thiophosphorylated Ketones and Thiosulfonates
Mateusz Musiejuka, Justyna Doroszuka, Bartosz Jędrzejewskia, Gregory Ortiz Nietob,
Marisol Marin Navarrob, Dariusz Witta*
a
Department of Organic Chemistry, Faculty of Chemistry, Gdansk University of Technology, Narutowicza 11/12, 80-
233 Gdansk, Poland, phone +48(58)3471851; fax +48(58)3472694; e-mail: dariusz.witt@pg.edu.pl
CEU San Pablo University, Calle de Julián Romea 18, 28003 Madrid, Spain
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. We developed a simple and efficient method for
the synthesis of functionalized unsymmetrical Z-alkenyl
disulfides under mild conditions in moderate to good yields.
The designed method is based on the reaction of α-
thiophosphorylated carbonyl compounds with thiotosylates
in the presence of a base. The developed method allows the
preparation of unsymmetrical Z-alkenyl disulfides bearing
additional hydroxy, carboxy, or ester functionalities.
Keywords: disulfides; alkenes; thiotosylates;
diastereoselectivity; phosphorodithioic acid
with a sulfinylbenzimidazole,[23] a rhodium-catalyzed
disulfide exchange,[24] an electrochemical method,[25]
the ring opening of an aziridine using
tetrathiomolybdate in the presence of a symmetrical
disulfide,[26] or the use of diethyl azodicarboxylate
(DEAD)[27] or a solid support[28] in a sequential
coupling of two different thiol groups. Recently, the
oxidation of a mixture of two different thiols by 2,3-
dichloro-5,6-dicyanobenzoquinone (DDQ)[29] or
iridium (III) photoredox catalysis[30] to produce an
unsymmetrical disulfide have also been reported.
Earlier studies demonstrated the preparation of
functionalized unsymmetrical molecules, such as
Introduction
Organosulfur compounds have been widely
investigated for their importance in many chemical
and biochemical processes. In this field, oligosulfides,
such as disulfides,[1] represent important and versatile
molecules for their applications in food chemistry and
material science. The formation of unsymmetrical
disulfides is an important transformation in organic
synthesis and medicinal chemistry[2] as well. Recent
developments in disulfide bond formation reactions
have been reviewed.[3] Although many different
methods exist for the preparation of unsymmetrical
disulfides, the most common approach involves
substitution of a sulfenyl derivative with a thiol or
thiol derivative. To date, the most commonly utilized
sulfenyl derivatives are sulfenyl chlorides,[4] S-alkyl
thiosulfates and S-aryl thiosulfates (Bunte salts),[5] S-
dialkyl
disulfides,[31]
alkyl-aryl
disulfides,[32]
‘bioresistant’ disulfides,[33] unsymmetrical disulfides
of L-cysteine and L-cystine,[34] and diaryl
disulfides[35] based on the readily available 5,5-
dimethyl-2-thioxo-1,3,2-dioxaphosphorinane-2-
disulfanyl derivatives. These disulfanyl derivatives of
phosphorodithioic acid are convenient for the
alkylsulfanylisothioureas,[6]
benzothiazol-2-yl
disulfides,[7]
benzotriazolyl
sulfanes,[8]
preparation
of
-sulfenylated
carbonyl
dithioperoxyesters,[9] (alkylsulfanyl)dialkylsulfonium
compounds,[36] functionalized phosphorothioates,[37]
and unsymmetrical alkynyl sulfides[38] as well as
symmetrical[39] and unsymmetrical trisulfides.[40]
Ajoene was first isolated by Block[41] in 1984 as an
E/Z-mixture of a rearrangement product of allicin
produced from freshly crushed garlic. It was
established to be an allyl sulfoxide containing an
unusual vinyl disulfide functionality, which is rarely
seen in the structures of natural products. Z-Ajoene is
salts,[10] 2-pyridyl disulfides and derivatives,[11] N-
alkyltetrazolyl
disulfides,[12]
sulfonamides,[13]
sulfenyldimesylamines,[14] sulfenyl thiocyanates,[15] 4-
nitroarenesulfenanilides,[16]
thiosulfonates,[17]
thiolsulfinates
and
sulfanylsulfinamidines,[18]
thionitrites,[19]
sulfenyl
thiocarbonates,[20]
thioimides,[21] and thiophosphonium salts.[22] Other
practical procedures involve the reaction of a thiol
1
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10.1002/adsc.201901208
Advanced Synthesis & Catalysis
Results and Discussion
more active than its E-isomer as an anti-thrombotic
agent,[42] and some studies on anticancer treatments
have focused primarily on the Z-isomer.[43]
Although many different synthetic methods exist for
the preparation of unsymmetrical disulfides, the
preparation of unsymmetrical alkenyl disulfides can
be achieved by only three methods (Scheme 1).
The corresponding α-thiophosphorylated carbonyl
compounds 1a-j were obtained by the reaction of α-
bromo carbonyl compounds with the sodium salt of
phosphorodithioic acid in THF. As shown in Table 1,
compounds 1a-j bear R1 groups: aliphatic or aromatic
with electron donating or electron withdrawing
groups. The transformation seems to be convenient,
and the presence of additional functional groups, such
as nitro, cyano or ester, did not disturb the progress of
the reaction. Compounds 1a-j were obtained in good
yields of 52-95%.
Table 1. Synthesis of α-thiophosphorylated carbonyl
compounds 1a-ja)
Scheme 1. Previously reported methods for the synthesis
of alkenyl disulfides (A, B, C) and our new approach (D).
The first method is based on the reaction of sulfenyl
bromide with trityl-alkenyl sulfide[44] (Scheme 1A).
The second method involves the low temperature
hydroxide-promoted cleavage of an alkenyl
thioacetate followed by sulfenylation with an
appropriate S-alkyl p-toluenethiosulfonate to afford
the vinyl disulfide in high yield after
chromatography[45] (Scheme 1B). Unfortunately, the
above methods exclusively provide the E isomer or a
mixture of Z/E alkenyl disulfides, respectively. The
third method is diastereoselective and allows the
preparation of functionalized unsymmetrical Z-
alkenyl disulfides exclusively under mild conditions
in moderate to good yields (Scheme 1C). The
designed method is based on the reaction of Z-
alkenyl thiotosylates with thiols in the presence of
base.[46] The presence of additional hydroxy, carboxy,
or amino functionalities did not disturb the progress
of the reaction. In this context, we investigated the
feasibility of a convenient and experimentally
practical diastereoselective method to access
functionalized Z-alkenyl disulfides from readily
a)
Conditions: bromoketone (10 mmol), phosphorodithioic
b)
acid sodium salt (11 mmol), THF (25 mL), rt, 3-4h
Isolated yield.
available
α-thiophosphorylated
ketones
and
thiosulfonates (Scheme 1D).
2
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10.1002/adsc.201901208
Advanced Synthesis & Catalysis
We
selected
α-thiophosphorylated
carbonyl
constants were in the range 1-3 Hz. However, E-
isomers were obtained for disulfides 3ja’, 3jb’, 3jd’
and 3jf’, respectively (Table 3, entries 81, 82, 84, and
86). Although, these compounds are allylic - type
compounds 1a-c to determine the optimal conditions
for their conversion to the appropriate vinyl-type
disulfides 3aa, 3ba and 3ca, respectively. S-dodec-1-
yl thiotosylate 2a was used as the thioalkylating agent. disulfides in contrast to the major products alkenyl
Reactions were performed in anhydrous THF or
dichloromethane (DCM) at room temperature in the
presence of NEt3, DBU, K2CO3, Cs2CO3, or NaOH
(Table 2).
disulfides 3ja, 3jb, 3jd and 3jf, their E-
stereochemistry was assigned on the observed JH-P
4
coupling constants 0.5 Hz (data included in the
supporting information). Indeed, the long distance
4JH-P coupling constant is very helpful in the
assignment of Z/E-stereochemistry of the alkene
functionality included in the compounds 3.
Table 2. Determination of the optimal conditions for the
preparation of alkenyl disulfides 3a)
THF and NEt3 were selected for further studies. We
selected a wide range of thiotosylates 2a-j to verify
the scope and limitations of the developed
transformation. Compounds 2 included alkyl and aryl
groups with additional nitro, ester, hydroxy or
carbon-carbon double bond functionalities. The
results are summarized in Table 3.
Table 3. Synthesis of alkenyl disulfides 3a)
Entry R1
Solvent Base
Time
Yieldb)
of 3 [%]
1
2
3
4
5
6
7
8
Ph
Ph
THF
CH2Cl2 NEt3
NEt3
1 h
1 h
1 h
1 h
3aa 90
3aa 77
3ba 40
3ba 45
t-Bu CH2Cl2 NEt3
t-Bu THF
t-Bu THF
t-Bu THF
t-Bu THF
i-Pr THF
i-Pr THF
i-Pr THF
Ph
Ph
Ph
NEt3
NEt3
NEt3
DBU
NEt3
DBU
NEt3
K2CO3 1 h
Cs2CO3 1 h
NaOH
1 day 3ba 65
3 days 3ba 77
3 h
1 h
3 h
3ba 67
3ca 61
3ca 69
Entry R1
R2
Yieldc) of 3
9
10
11
12
3 days 3ca 84
1
2
3
4
Ph
Ph
Ph
Ph
n-C12H25-
90 3aa
80 3ab
49 3ac
95 3ad
THF
THF
THF
3aa 57
3aa 65
3aa 53
CH2=CHCH2-
p-MeC6H4-
PhCH2-
13
1h
a)
Conditions: -thiophosphorylated ketone 1a-c (1.0
5
6
Ph
Ph
p-NO2C6H4CH2- 38 3ae
p-MeOC6H4CH2- 61 3af
mmol), thiotosylate 2a (0.91 mmol), base (1.0 mmol), THF
(5 mL), rt, 1 h under Ar. b) Isolated yield
7
8
9
Ph
Ph
Ph
MeO2CC10H20-
HOC11H22-
HOC2H4-
87 3ag
99 3ah
75 3ai
Reactions were effective with THF and DCM as the
solvent. The use of DBU, K2CO3, Cs2CO3, or NaOH
instead of TEA did not improve the conversion.
However, the presence of the t-Bu or i-Pr group,
probably due to steric reasons, required a prolonged
reaction time. All the transformations provided the Z
isomer exclusively. E/Z-Stereochemistry was
assigned on the basis of the vinyl proton chemical
shift and 4JH-P coupling constants as 1-3 Hz for the Z-
isomer and 0.5-0.7 Hz for the E-isomer. All
compounds 3aa, 3ba, and 3ca were obtained with Z-
10
11
12
13
14
15
16
17
18
19
20
21
22
Ph
2-furanylmethyl- 66 3aj
t-Bub)
t-Bub)
t-Bub)
t-Bub)
t-Bub)
t-Bub)
t-Bub)
t-Bub)
i-Prb)
i-Prb)
i-Prb)
i-Prb)
n-C12H25-
77 3ba
79 3bb
30 3bc
673bd
CH2=CHCH2-
p-MeC6H4-
PhCH2-
p-NO2C6H4CH2- 19 3be
p-MeOC6H4CH2- 39 3bf
MeO2CC10H20-
HOC11H22-
n-C12H25-
CH2=CHCH2-
p-MeC6H4-
PhCH2-
87 3bg
78 3bh
85 3ca
80 3cb
75 3cc
75 3cd
4
stereochemistry and the observed JH-P coupling
3
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10.1002/adsc.201901208
Advanced Synthesis & Catalysis
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
80
81
i-Prb)
p-NO2C6H4CH2- 20 3ce
p-MeOC6H4CH2- 44 3cf
83
84
p-MeC6H4-
PhCH2-
27 3jc
58 3jd
19 3jd‘
EtO2CCH2COCH2
EtO2CCH2COCH2
i-Prb)
i-Prb)
MeO2CC10H20-
HOC11H22-
87 3cg
78 3ch
i-Prb)
85
86
p-NO2C6H4CH2- 24 3je
p-MeOC6H4CH2- 35 3jf
10 3jf‘
MeO2CC10H20-
HOC11H22-
HOC2H4-
EtO2CCH2COCH2
EtO2CCH2COCH2
i-Prb)
2-furanylmethyl- 23 3cj
Me
Me
Me
Me
Me
Me
Me
Me
n-C12H25-
79 3da
75 3db
45 3dc
73 3dd
CH2=CHCH2-
p-MeC6H4-
PhCH2-
87
88
89
50 3jg
60 3jh
39 3ji
EtO2CCH2COCH2
EtO2CCH2COCH2
EtO2CCH2COCH2
EtO2CCH2COCH2
p-NO2C6H4CH2- 26 3de
p-MeOC6H4CH2- 54 3df
90
2-furanylmethyl- 25 3jj
a)
Conditions: -thiophosphorylated ketone 1 (1.0 mmol),
thiotosylate 2 (0.91 mmol), NEt3 (1.0 mmol), THF (5 mL),
rt, 1 h under Ar. b) Reaction time 3 days. c) Isolated yield.
MeO2CC10H20-
HOC11H22-
HOC2H4-
67 3dg
87 3dh
94 3di
Me
Me
2-furanylmethyl- 65 3dj
p-ClC6H4-
p-ClC6H4-
p-ClC6H4-
p-ClC6H4-
p-ClC6H4-
p-ClC6H4-
p-ClC6H4-
p-ClC6H4-
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
2-naphthyl
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-NO2C6H4-
p-MeOC6H4-
p-MeOC6H4-
p-MeOC6H4-
p-MeOC6H4-
p-MeOC6H4-
p-MeOC6H4-
p-MeOC6H4-
p-MeOC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
p-CNC6H4-
EtO2CCH2COCH2
n-C12H25-
88 3ea
85 3eb
41 3ec
88 3ed
Generally, all reactions were successful. However,
when the R1 group of starting materials 1 were
secondary or tertiary alkyl groups 1b-d, prolonged
reaction time (3 days) was required for substantial
conversion to disulfides 3ba-dj respectively. We also
observed a low reaction yield when S-4-nitrobenzyl
thiotosylate 2e was used as the thioalkylating agent.
However, S-alkyl thiotosylates 2a-b and 2g-j with
additional functionalities provided very good yields.
The presence of hydroxy, ester or carbon-carbon
double bonds did not disturb the progress of the
reaction. However, when S-4-tolyl thiotosylate 2c
was used, the desired product 3 was formed in
moderate yield (Table 4 entries 2 and 3).
CH2=CHCH2-
p-MeC6H4-
PhCH2-
p-NO2C6H4CH2- 45 3ee
p-MeOC6H4CH2- 54 3ef
MeO2CC10H20-
HOC11H22-
n-C12H25-
CH2=CHCH2-
p-MeC6H4-
PhCH2-
79 3eg
88 3eh
96 3fa
75 3fb
33 3fc
88 3fd
p-NO2C6H4CH2- 45 3fe
p-MeOC6H4CH2- 63 3ff
MeO2CC10H20-
HOC11H22-
HOC2H4-
99 3fg
94 3fh
85 3fi
Table 4. Formation of side productsa)
n-C12H25-
80 3ga
87 3gb
43 3gc
23 3gd
CH2=CHCH2-
p-MeC6H4-
PhCH2-
p-NO2C6H4CH2- 20 3ge
p-MeOC6H4CH2- 45 3gf
MeO2CC10H20-
HOC11H22-
87 3gg
100 3gh
2-furanylmethyl- 93 3gj
n-C12H25-
93 3ha
87 3hb
44 3hc
87 3hd
CH2=CHCH2-
p-MeC6H4-
PhCH2-
p-NO2C6H4CH2- 24 3he
p-MeOC6H4CH2- 69 3hf
MeO2CC10H20-
HOC11H22-
n-C12H25-
CH2=CHCH2-
p-MeC6H4-
PhCH2-
91 3hg
90 3hh
92 3ia
100 3ib
50 3ic
Entry R1
Yieldb) of Yieldb) of Yieldb) of
3 [%]
3’ [%]
4 [%]
20 3id
1
2
3
i-Pr
Me
75 3cc
45 3dc
2-naphthyl 33 3fc
15 3cc’
9 3dc’
20 3fc‘
12
10
23
p-NO2C6H4CH2- 14 3ie
p-MeOC6H4CH2- 54 3if
MeO2CC10H20-
HOC11H22-
HOC2H4-
95 3ig
99 3ih
74 3ii
a)
Conditions: -thiophosphorylated ketone 1 (1.0 mmol),
thiotosylate 2c (0.91 mmol), NEt3 (1.0 mmol), THF (5 mL),
rt, 1 h under Ar. b)Isolated yield
n-C12H25-
77 3ja
10 3ja‘
49 3jb
2 3jb‘
82
CH2=CHCH2-
EtO2CCH2COCH2
4
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10.1002/adsc.201901208
Advanced Synthesis & Catalysis
Although starting materials 1 and 2c were consumed
to produce the expected product 3, we were also able
to isolate side products 3’ and 4, respectively. It
appeared as if product 3, under the developed
conditions, underwent a disulfide exchange reaction
to produce symmetrical disulfides 3’ and 4. It is well
known35 that unsymmetrical aryl disulfides can
readily undergo disulfide exchange reactions to form
the
corresponding
symmetrical
disulfides.
Nevertheless, the developed method allows for the
formation of aryl-alkenyl disulfides 3 at least in
moderate yield.
Based on the obtained results, the following
mechanism can be proposed (Scheme 2). The first
step of the reaction is abstraction of the proton from
the  position of starting material 1. Triethylamine is
a general weak base that abstracts protons from
methyl ketones, but the presence of the sulfur atom at
the  position makes these hydrogens more acidic,
and the equilibrium can be shifted to form the
appropriate anion. An enolate anion is therefore
produced with a negative charge localized on the
oxygen atom. Although the E isomer is probably
formed in larger quantities, only the Z isomer can
undergo the intramolecular rearrangement to form the
corresponding Z isomer of the thioenolate anion.
Most likely, the formation of the P-O bond is a
driving force for that rearrangement. Subsequent
thioalkylation with thiotosylate 2 provides alkenyl
disulfide 3 with the same Z geometry. The Z-
thioenolate anion may be in equilibrium with its more
stable E isomer. This is why the formation of both Z
and E isomers of product 3 can be expected. However,
when NEt3 is added to the mixture of 1 and 2, the Z-
thioenolate anion will react with thiotosylate 2 before
it can be converted to the E-thioenolate. As a result,
the exclusive formation of Z-alkenyl disulfide 3 is
observed in the transformation.
Scheme 2. Proposed mechanism for formation of
disulfides 3.
The formation of alkenyl disulfides 3 is more
complex when the derivative of ethyl acetoacetate 1j
is used as the starting material (Scheme 3).
Compound 1j can react with NEt3 in two different
ways. First, a proton can be abstracted from either
carbon C4 (upper part of Scheme 3) or C2 (lower part
of Scheme 3). We estimated the pKa of both positions,
and it appears that the hydrogens from carbon C4 are
more acidic than the hydrogens from carbon C2.
Although the difference is not large, in the case of a
weak base such as NEt3, the difference is large
enough to promote the formation of alkenyl disulfides
3 as the major products. When a proton is abstracted
from carbon C2, the appropriate enolate anion can be
produced. Both the E and Z isomers can undergo
rearrangement to produce the corresponding thiolate
anion, but the E isomer is more stable and can be
formed in larger quantities. Subsequent thioalkylation
provided disulfides 3ja’, 3jb’, 3jd’ and 3jf’,
respectively. These compounds are allylic - type
disulfides in contrast to the major products alkenyl
disulfides 3ja, 3jb, 3jd and 3jf.
5
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10.1002/adsc.201901208
Advanced Synthesis & Catalysis
To a suspension of NaH (0.44 g, 60% in mineral oil, 11
mmol) in dry THF (10 mL) was added slowly a solution of
phosphorodithioic acid (2.18 g, 11 mmol) in dry THF (10
mL). When evolution of hydrogen was complete, a
solution of α-bromoketone (10 mmol) in dry THF (5 mL)
was added. The reaction mixture was stirred at rt for 3-4h
and evaporated under vacuum. Then water (30 mL) was
added and the mixture was extracted with Et2O (3 × 50
mL). The combined organic layers were dried with anh
MgSO4, filtered and evaporated. The residue was purified
by column chromatography (SiO2) to yield pure 1.
2-((5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yl)thio)-1-phenylethanone 1a
Chromatography: Petroleum ether / CH2Cl2 9/1 Yield: 2.53
g (80%); mp 83-85 °C
IR: 921 (w), 1639 (m), 1447 (w), 1201 (w), 1042 (m), 982
(s), 813 (m), 682 (s), 604 (m) cm-1
1H NMR (400 MHz, CDCl3) δ 8.08-8.00 (m, 2H), 7.67–
7.62 (m, 1H), 7.55-7.50 (m, 2H), 4.57 (d, J = 13.9 Hz, 2H),
4.38-4.28 (m, 2H), 4.05-3.90 (m, 2H), 1.30 (s, 3H), 0.96 (s,
3H).
13C NMR (101 MHz, CDCl3) δ 192.7 (d, J = 6.7 Hz), 135.2,
134.0, 128.9, 128.6 , 77.8 (d, J = 9.0 Hz), 40.7 (d, J = 0.8
Hz), 32.5 (d, J = 7.0 Hz), 22.2 , 20.9 .
31P NMR (162 MHz, CDCl3) δ 87.76.
HRMS (ESI): m/z [M + H]+calcd for C13H18O3PS2:
317.0429; found: 317.0432.
Synthesis of Unsymmetrical Alkenyl Disulfides 3;
General Procedure
To a solution of thiophosphorylated ketone (1; 1.0 mmol)
and S-alkylthiotosylate (2; 0.91mmol) in dry THF (5 mL),
NEt3 (0.101 g, 0.140 mL, 1.0 mmol) was added at rt under
an argon atmosphere. The reaction mixture was stirred at rt
for 1h and evaporated under vacuum. The residue was
purified by column chromatography (SiO2) to yield pure 3.
(Z)-1-(5,5-dimethyl-2-thioxo-1,3,2-dioxaphosphorinan-2-
yloxy)-1-phenyl-2-dodec-1-yldisulfanylethene 3aa
Chromatography: Petroleum ether : CH2Cl2, 4 : 1 Yield:
0.423 g (90%); mp 58-59 °C
IR: 2920 (m), 1593 (w), 1470 (w), 1277 (m), 1002 (s), 754
Scheme 3. Formation of alkenyl disulfides 3 and allylic
disulfides 3’ from starting material 1j.
(s), 694 (m) cm-1
1H NMR (400 MHz, CDCl3) δ 7.56–7.31 (m, 5H), 6.47 (d,
J = 2.7 Hz, 1H), 4.45-4.35 (m, 2H), 4.15-4.05 (m, 2H),
2.84 (t, J = 7.4 Hz, 2H), 1.70-1.80 (m, 2H), 1.50–1.15 (m,
21H), 1.02 (s, 3H), 0.90 (t, J = 6.9 Hz, 3H).
Conclusion
13C NMR (126 MHz, CDCl3) δ 146.3 (d, J = 9.2 Hz),
134.5 , 129.0, 128.8 , 125.2 , 119.2 (d, J = 7.9 Hz), 77.9 (d,
J = 8.4 Hz), 39.8 , 32.6 (d, J = 6.3 Hz), 32.2, 30.0, 29.9 ,
29.9 , 29.8 , 29.6, 29.50 , 29.2 , 28.7 , 23.0 , 22.1 , 21.3 ,
14.4.
We developed a convenient and efficient method for
preparing Z-alkenyl disulfides under mild conditions
based on readily available starting materials. The
mild conditions used herein are tolerant of additional
functional groups, including esters, ethers, carbon–
carbon double bonds, hydroxy, nitro, and cyano
groups. The reaction of α-thiophosphorylated
carbonyl compounds 1 with thiotosylates 2 in the
presence of NEt3 afforded Z-alkenyl disulfides 3 with
excellent diastereoselectivity.
31P NMR (202 MHz, CDCl3) δ 56.94.
HRMS (ESI): m/z [M + H]+calcd for C25H42O3PS3:
517.2028; found: 517.2031.
Acknowledgements
We gratefully acknowledge the National Science Centre
Experimental Section
(NCN)
for
financial
support
(grant
no.
2015/19/B/ST5/03359)
Synthesis of -Thiophosphorylated Ketones 1;
General Procedure
6
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10.1002/adsc.201901208
Advanced Synthesis & Catalysis
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Advanced Synthesis & Catalysis
FULL PAPER
Diastereoselective synthesis of Z-alkenyl disulfides
from α-thiophosphorylated ketones and
thiosulfonates
Adv. Synth. Catal. Year, Volume, Page – Page
Mateusz Musiejuk, Justyna Doroszuk, Gregory
Ortiz Nieto, Marisol Marin Navarro, Dariusz Witt*
9
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