Cleavage of oxygen-sulfur double bonds and carbon-sulfur bonds: Unusual highly selective electrophilic addition of allenylic sulfoxides

Article abstract of DOI:10.1039/c2sc21920d

Selective cleavage and formation of covalent bonds is an everlasting topic in the science of synthesis. Recently, much attention has been paid to the activation and functionalization of inert covalent chemical bonds such as C-H, C-O, C-Cl bonds, etc. In this edge article, we report that hydrogen bonding may mediate efficient and highly selective cleavage of OS and C-S bonds in 1,2-allenyl sulfoxides with I₂ and BnSH, which transfer the oxygen to the adjacent allenylic carbon atom forming a ketone or aldehyde carbonyl functionality with one CC bond in the allene moiety remaining in a highly stereoselective manner. This method provides a general and highly stereoselective route to the synthetically important yet difficult to prepare polysubstituted enals or enones.

Full text of DOI:10.1039/c2sc21920d

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Cleavage of Oxygen-Sulfur Double Bond and Carbon-Sulfur Bond:
Unusual Highly Selective Electrophilic Addition of Allenylic Sulfoxides
Minyan Wang, Chunling Fu, and Shengming Ma*
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
Selective cleavage and formation of covalent bonds is an everlasting topic in science of synthesis.
Recently, much attention has been paid to the activation and functionalization of inert covalent
chemical bonds such as CꢀH, CꢀO, CꢀCl bonds, etc. In this article, we would like to report that
hydrogen bonding may mediate an efficient and highly selective cleavage of the O=S bond and Cꢀ
10 S bond in 1,2ꢀallenyl sulfoxides with I2 and BnSH, which transfer the oxygen to the adjacent
allenylic carbon atom forming the ketone or aldehyde carbonyl functionality with one C=C bond in
the allene moiety remained in a highly stereoselective manner. This method provides a general and
highly stereoselective entry to the synthetically important yet difficult to prepare polyꢀsubstituted
enals or enones.
electron-deficient C=C bond
1. E+
R3
R2
FG
R1
E
FG
R1
2. Nu-
15 Introduction
Nu
ref. 3
Allenes have been continuously catching the attention from the
R2
R3
general rule
reaction occurred to electron-rich C=C bond:
FG = SOPh, SO2Ph, P(O)R2 SR, SeR, etc.
scientists due to its broad existence in biologically active natural
products as well as pharmaceuticals.1,2 In addition, the chemistry
of allenes has also become more and more important due to the
20 versatile reactivities observed with these unique two cumulated
C=C bonds.3ꢀ5 However, due to the presence of two C=C bonds,
control of selectivity with the reaction to each of the two C=C
bonds is still challenging. For example, in all the known
electrophilic addition reactions, the relatively electronꢀrich C=C
25 bonds are reacted as usual by following the general principle:
these is no report that in the presence of two cumulated C=C
bonds with different electronic properties, the electronꢀdeficient
C=C bonds are electrophilically reacted (Scheme 1).6,7 On the
other hand, although polysubstituted stereodefined α,βꢀ
30 unsaturated enones or enals are important building blocks in
organic synthesis,8 however, there is no general methods for their
synthesis due to the limited success on control the
stereoselectivity of the C=C bond,9ꢀ15 difficulty to introduce the
desired substituent to the specific location(s) of these types of
35 compounds,16ꢀ18 the issue of regioselectivity,19 and the limited
access to the corresponding sterodefined allylic alcohols (See SI
for detailed literature information).20ꢀ30 Herein we show the
realization of such a highly selective electrophilic addition
reaction with the electronꢀdeficient C=C bond in the readily
40 available 1,2ꢀallenylic sulfoxides from propargylic alcohols,31ꢀ34
which provides a straightforward route to the notꢀreadilyꢀ
available αꢀiodoꢀα,βꢀunsaturated carbonyl compounds35ꢀ37 with an
excellent stereoselectivity. Because of the existence of CꢀI bond,
different substituents may be easily incorporated by transition
45 metalꢀcatalyzed crossꢀcoupling reactions.38
18O
18O
R3
R2
SPh
R1
R3
R2
R1
E+ = I+
This report
I
1
3
unuaual
reaction occurred to electron-deficient C=C bond:
Scheme 1. Electrophilic addition reactions of allenes.
Results and discussion
The current study was started with our previous observation on
50 the reaction of nonaꢀ3,4ꢀdienꢀ5ꢀylphenyl sulfoxide 1a with I2 in
the presence of BnSH (Scheme 2).39 When the reaction was
conducted with 1.5 equiv of I2 in MeCN in the presence of 1
equiv of BnSH at a higher temperature (40 oC), surprisingly,
instead of the reported reductive iodohydroxylation product 2,39
55 an unknown product 3a was formed, albeit in rather low yield.
Through careful analysis of the 1H NMR, 13C NMR, and IR
spectra, we noticed that there is a carbonyl functionality in this
unknown compound. Thus, we attempted the reaction of this
unknown compound 3 with 2,4ꢀdinitrophenylhydrazine, which
60 afforded a solid product 4. The Xꢀray single crystal diffraction
study of 4 clearly showed that this new product is 4ꢀiodononꢀ3ꢀ
enꢀ5ꢀone in Zꢀconfiguration (Scheme 2),10 indicating that the
electronꢀdeficient C=C in 1a was surprisingly reacted formally
here. When Et2O was used as the solvent (entry 1, Table 1), only
65 2% of Zꢀ3a was formed with 56% of the normal reductive
iodohydroxylation product Eꢀ2a. The reaction in other solvents,
such as CH2Cl2, DMF, CH3NO2, and 1,4ꢀdioxane etc., afforded
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O
Zꢀ3a in low yields (entries 2ꢀ12, Table 1). To our surprise, the
reaction in commercially available CHCl3 without any treatment
afforded Zꢀ3a in 52% yield, exclusively (entry 13, Table 1).
CHCl3a/H2O or EtOH
30 min, 40 o
C
PhOS
H
n-C4H9
H
+
I2
+
BnSH
n-C4H9
Et
I
Et
1.5 equiv 1.0 equiv
1a
Z-3a
R3
I2 (1.5 equiv), H2O (2.0 equiv)
HO
MeCN, -20 o
C
PhS
R2
ref. 39
b
O
S
3a
H2O or EtOH
0
yield of Z- (%)
or I2 (1.2 equiv), H2O (10.0 equiv)
MeCN, -40 o
R1
I
Ph
R3
R2
C
E-2
0
0
+
BnSH
R1
O
1.0 equiv
µ
27 L H2O (5.0 equiv)
R1 = n-Bu, R2 = Et, R3 = H
1
n-Bu
H
µ
120 L EtOH (7.1 equiv)
53
I2 (1.5 equiv)
MeCN, 30 min, 40 oC, 20%
I
Et
a CHCl3 was dried over P2O5 under reflux for 5 hours and distilled before use.
b The yields were determined by 1H NMR analysis with CH2Br2 as the internal standard.
3a
Z-
25
NO2
H2SO4, H2O
EtOH
rt, 5 h
NHNH2
Scheme 3. Effect of H2O or EtOH.
71%
O2N
Furthermore, we examined the effect of temperature, loading
of I2, and concentration on the reaction (Scheme 4). Firstly, the
reaction of 1a with I2 in the presence of BnSH at 40 oC gave Zꢀ3a
Bu-n
NO2
H
N
I
N
30 in the highest yield (53%) (entry 5, Table S2 in SI); better result
was achieved by increasing the loading of I2 (Table S3 in SI).
When 3.5 equiv of I2 were employed, Zꢀ3a was formed in 81%
yield (entry 5, Table S3 in SI). Further improving the loading of
I2 did not affect the yield (entries 6ꢀ7, Table S3 in SI); when the
35 reaction was conducted in 0.1 M, 85% of Zꢀ3a was afforded
(entry 3, Table S4 in SI). Finally the optimized conditions for the
formation of Zꢀ3a were defined as follows: 3.5 equiv of I2 and 1
equiv of BnSH in the mixture of CHCl3 and anhydrous EtOH
(50/1) at 40 oC.
Et
H
NO2
4a
4a
ORTEP presentation of
5
Scheme 2. Unnatural electrophilic addition product Zꢀ3a and ORTEP
presentation of 4a.
Table 1. Effect of solvent on the reaction of nonaꢀ3,4ꢀdienꢀ5ꢀylphenyl
sulfoxide 1a with I2 in the presence of BnSH a
40
O
PhOS
H
n-C4H9
H
CHCl3/EtOH = 50/1
Et
O
+
I2
+
BnSH
PhOS
H
15 min, 40 o
C
PhS
OH
solvent
time, 40 oC
n-C4H9
H
n-C4H9
Et
I
Et
+
I2
+
BnSH
+
1.0 equiv
Z-3a
1a
n-C4H9
Et
n-C4H9
I
I
Et
1.5 equiv 1.0 equiv
E-2a
3a
Z-
1a
time (min) temp (oC)
loading of I2 (equiv)
M (mmol/L)
yield (%)a
10
30
15
15
40
40
40
1.5
3.5
3.5
0.05
0.05
0.2
53
time
(min)
60
30
30
yield of
yield of
entry
solvent
Eꢀ2a (%)b
Zꢀ3a (%)b
81
1
2
3
Et2O
CH2Cl2
DMF
56
0
62
0
2
5
ꢀꢀ
2
89 (82)b
a The yields were determined by 1H NMR analysis with CH2Br2 as the internal standard.
b Isolated yields were presented.
4
CH3NO2
60
5
6
7
1,4ꢀdioxane
ClCH2CH2Cl
MeOH
30
30
30
39
4
15
0
Scheme 4. The influence of temperature, loading of I2, and concentration
on the reaction.
0
89 (87c)
8
9
10
11
12
13
THF
Acetone
DMSO
CH3COOH
EtOH
CHCl3
30
60
120
120
30
26
0
0
0
90
0
16
42
0
3
0
Then, we studied the scope of this unique iodohydroxylation of
45 3ꢀdisubstitutedꢀ1,2ꢀallenyl sulfoxides 1 with 3.5 equiv of I2 at 40
oC (Table 2). In all these cases, differently substituted Zꢀ1ꢀiodoꢀ1ꢀ
alkenyl ketones 3 were afforded in good to excellent yields with a
very high selectivity.
d
30
52
a Reaction conditions: 1a (0.3 mmol), I2 (0.45 mmol), BnSH (0.3 mmol),
40 oC. b The yields were determined by 1H NMR analysis with CH2Br2 as
the internal standard. c Isolated yields. d commercial CHCl3 was used.
50
15
However, neither 2a nor 3a was formed when the commercial
CHCl3 was purified by drying over P2O5 under reflux for 5 h and
distilled before use (Scheme. 3). Then, water was added to the
freshly distilled CHCl3, however, it failed to promote the
formation of Zꢀ3a significantly. Considering the solubility of
55 Table 2. Preparation of Zꢀ1ꢀiodoꢀ1ꢀalkenyl ketonesa
20 water in CHCl3, we tried to add EtOH to in place of water. It is
exciting to observe that with the addition of 5 equiv of
EtOHafforded Zꢀ3a in 46% yield (Scheme 3) and observed that
53% yield of Zꢀ3a was realized when the ratio of CHCl3 and
anhydrous EtOH was 50/1 (See Table S1 in SI for details).
O
PhOS
R2
H
R2
H
CHCl3/EtOH = 50/1
+
BnSH
+
I2
40 o
C
R1
I
R1
3.5 equiv
1
3
Z-
2
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Table 3. Preparation of 2ꢀiodoꢀ2ꢀenalsa
entry
R1
R2
time
(min)
yield of Zꢀ3
(%)b
O
ArOS
H
R1
R2
1
2
3
4
5
6
Et
Bn
iꢀPr
nꢀBu (1a)
nꢀBu (1b)
nꢀBu (1c)
nꢀBu (1d)
nꢀC5H11 (1e)
CH2CH2Ph (1f)
15
30
20
30
60
60
82 (Zꢀ3a)
65 (Zꢀ3b)
83 (Zꢀ3c)c
63 (Zꢀ3d)d
73 (Zꢀ3e)
68 (Zꢀ3f)
CHCl3/EtOH = 50/1
time, Temp
H
R1
R2
+
I2 + BnSH
I
3.5 equiv
1
1.0 equiv
3
Cyclohexyl
Et
3
T (oC)/t
(min
CH3
entry
R1
Et
R2
a Reaction conditions: 1a (0.3 mmol), CHCl3 (1 mL, dried under reflux
over P2O5 for 5 hours and distilled), anhydrous EtOH (30 ꢁL), I2 (1.05
mmol), BnSH in CHCl3 (0.6 M, 0.5 mL, dried under reflux over P2O5 for
5 hours and distilled), 40 oC. b Isolated yields were presented. c 99.3%
purity. d 96.8% purity.
yield (%)b
Z/E
1
2
ꢀ(CH2)5ꢀ (1h)
Et (1i)
ꢀ10/30
0/30
0/45
ꢀ10/60
15/60
15/30
15/45
20/30
ꢀ15/60
ꢀ10/45
67 (3h)
67 (3i)
ꢀꢀ
ꢀꢀ
5
3
nꢀC4H9
nꢀC4H9 (1j)
75 (3j)
ꢀꢀ
4c
5
ꢀ(CH2)5ꢀ (1k)
63 (3h)
ꢀꢀ
H
H
H
CH2CH2Ph (1l)
nꢀC5H11 (1m)
nꢀC7H15 (1n)
Bn (1o)
91 (Zꢀ3l)
83 (Zꢀ3m)
78 (Zꢀ3n)
37 (Zꢀ3o)
72 (3p)
100/0
100/0
100/0
100/0
4/96d
4/96d
To show the practicality, the reaction of 30 mmol of 1a
afforded the corresponding ketone Zꢀ3a in 77% yield (eq. 1).
6
7
8
H
O
PhOS
H
CHCl3/EtOH = 50/1
40 oC, 30 min
n-Bu
H
9
10
CH3
Et
Phꢀ
Phꢀ
+ BnSH
1.0 equiv
+ I2
(eq. 1)
26 (3q)
n-Bu
Et
I
Et
3.5 equiv
1a
7.4418 g (30 mmol)
a Reaction conditions: 1a (0.3 mmol), CHCl3 (1 mL, dried under reflux
35 over P2O5 for 5 hours and distilled), anhydrous EtOH (30 ꢁL), I2 (1.05
mmol), BnSH in CHCl3 (0.6 M, 0.5 mL, dried under reflux over P2O5 for
5 hours and distilled), Ar = Phꢀ. b Isolated yields were presented. c Ar =
4ꢀBrPhꢀ. d The ratio of E/Z was determined by the 1H NMR analysis.
Z-3a
6.1528 g, 77%
10
However, the current reaction conditions are not yet suitable
for the formation of αꢀiodoꢀα,βꢀunsaturated aldehydes. Further
optimization showed that the temperature affects the reaction to
some extent. Because of the impact of different substituents on
the reactivity, 2ꢀiodoꢀ2ꢀenals 3hꢀ3q were then successfully
15 prepared at different temperature (Table 3). Interestingly, even
the reaction of the 3ꢀmonosubstituted 1,2ꢀallenyl sulfoxides
afforded the enals 3lꢀ3o in single Zꢀconfiguration with good
yields, showing the high stereoselective nature of this reaction
(Table 3, entries 5ꢀ8). The reaction at the scale of 20 mmol of 1l
20 afforded 4.7854 g (85%) of Zꢀ3l (Scheme 5). The Zꢀconfiguration
in these aldehydes was confirmed by the Xꢀray single crystal
diffraction study of hydrazone 4l prepared from Zꢀ3l (Scheme
5).41 Even for 3ꢀalkylsubstitutedꢀ3ꢀphenylꢀ1,2ꢀdienyl sulfoxides,
the stereoselectivity was practical affording the Eꢀ3p and Eꢀ3q
25 with high selectivity (Table 3, entries 9ꢀ10).
40
Thus, αꢀiodoꢀα,βꢀunsaturated enones or enals may now be
conveniently prepared from 1,2ꢀallenyl sulfoxides, which are
readily available from proparglic alcohols.31ꢀ34 Polysubstituents
α,βꢀunsaturated aldehydes or ketones with high stereopurity may
then be prepared by the wellꢀestablished coupling reactions due
45 to the the presence of the CꢀI bond: The Suzuki coupling of Zꢀ3a
with phenylboronic acid using Na2CO3 as base in DME and H2O
(1:1) afforded enone 5 in 84% yield; the Sonogashira coupling of
Zꢀ3a with a terminal alkyne was carried out in THF under the
catalysis of Pd(PPh3)2Cl2 and CuI to afford alkynenone 6 in 94%
50 yield after 2 h (Scheme 6).
O
PhB(OH)2
Pd(OAc)2, Na2CO3
n-Bu
H
O
H2O, DME
rt, 13 h, 84%
Ph
Et
n-Bu
H
5
O
I
Et
Ph
C CH
n-Bu
H
Pd(PPh3)2Cl2, CuI
Z-3a
Et
i-Pr2NH, THF
0 oC, 2 h, 94%
Ph
6
Scheme 6. The synthetic application of the Zꢀ3a.
As we have mentioned before, neither Eꢀ2a nor Zꢀ3a was
55 formed when CHCl3 was purified by drying over P2O5 under
reflux for 5 hours and distilled before use. However, adding
anhydrous EtOH to the solvent could promote the formation of Zꢀ
3a significantly (Scheme 3). In order to trace the source of the
carbonyl oxygen in the final products, αꢀiodoꢀα,βꢀunsaturated
60 ketones or aldehydes 3, we ran the reaction of 1a with Me18OH
instead of ethanol. To our surprise, the normal product Zꢀ3a with
no 18O incorporation was afforded (eq. 2).
Scheme 5. The 20 mmol scale reaction of 1l and 4l.
30
O
O
S
H
CH318OH/CHCl3 = 1/50
40 oC, 20 min
n-C4H9
H
+
I2
+ BnSH
(eq. 2)
n-C4H9
Et
I
Et
3.5 equiv 1.0 equiv
1a
Z-3a
90%
(no 18O incorporation)
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When Eꢀ2a was subjected to the standard conditions, Zꢀ3a was
not formed (Scheme 7). But when 45 wt.% HI in H2O was used,
the product Zꢀ3a can be formed from Eꢀ2a in very low yield
(36%), indicating the inꢀsitu generated HI may transform Eꢀ2a to
Zꢀ3a.
nucleophilicity of the sulfoxide oxygen stopping the formation of
cyclic intermediate M5 42 and weakens the sulfurꢀoxygen double
bond to facilitate the electrophilic addition with this C=C bond.
This C=C bond reacts with I+ to form the threeꢀmembered
40 iodonium intermediate M1, which may be easily transformed into
the intermediate M2 via the 1,3ꢀrearrangement to release the ringꢀ
strain. Different from the known reactions,43 the intermediate M2
undergoes 1,3ꢀrearrangement to form the intermediate M3. Next,
the intermediate M3 would afford the aldehyde or ketone 3 upon
45 releasing PhS+. The PhS+ can be captured by BnSH to afford 1ꢀ
benzylꢀ2ꢀphenyldisulfane 8, which would react with the excessive
I2 affording 1,2ꢀdiphenyldisulfane 9, and 1,2ꢀdibenzyldisulfane
5
2.0 equiv I2
Complicated
Et
CHCl3/EtOH = 50/1
40 oC, 18 h
PhS
OH
O
n-C4H9
I
45 wt.% HI in H2O (2.0 equiv) n-Bu
H
2a
E-
CHCl3/EtOH = 50/1
40 oC, 3 h
I
Et
Z-3a
36%
Scheme 7. The possible formation of Zꢀ3a from Eꢀ2a.
10.
O
R
H
Then 4.0 equiv of K2CO3 were applied to quench the inꢀsitu
18O
18O
O18
10 generated HI, the product Zꢀ3a was still formed in 20% yield,
indicating there should be another major pathway for the
R3
R2
Ph
S
R3
R2
Ph
S
R3
Ph
S
ROH
+
I2
minor
major
R1 I+
R1
R1
R2
formation of Zꢀ3a (eq. 3).
I
M4
1
M1
O
PhOS
H
I+ react with
CHCl3/EtOH = 50/1
40 oC, 1.5 h
K2CO3 (4.0 equiv)
n-Bu
H
BnSH
Ph
+
I2
+
BnSH
(eq. 3)
electron-deficient C=C bond
n-Bu
Et
R3
R2
18O
I
Et
3.5 equiv
1.0 equiv
1a
S
Z-3a
20%
R1
I
Finally, the sulfoxide 1aꢀ18O was prepared via the sequential
15 reactions shown in Scheme 9: the reaction of 3ꢀbromononꢀ4ꢀyne
with Na18OH afforded nonꢀ4ꢀynꢀ3ꢀol (18O) 7ꢀ18O, which was
treated with sulfenyl chloride and Et3N in THF at ꢀ78 oC to afford
nonaꢀ3,4ꢀdienꢀ5ꢀyl phenyl sulfoxide 1aꢀ18O in 17% yield in two
steps with 64% 18O. We are happy to observe that the reaction of
20 1aꢀ18O under the standard reaction conditions did afford Zꢀ3aꢀ18O
M5
H
O
Ph
I
PhSSPh
R
S
O
9
R1
R3
SBn18OH
R3
R2
PhS
R1
R2
BnSSBn
M2
PhSSBn
10
I
8
M6
BnSH
BnSH
PhS+
BnSSBn
R1 R3
18O
H18
PhS
O
R3
R2
R1
R3
S
in 81% yield with 41% of 18O incorporation, showing that the 18
O
Ph
R2
18O
HI
in the sulfoxide 1aꢀ18O has indeed been incorporated into the
carbonyl oxygen in Zꢀ3aꢀ18O (Scheme 8). Furthermore, Eꢀ2aꢀ18O
with ~ 69% 18O was synthesized from the reported reductive
25 iodohydroxylation39 of 1,2ꢀallenylic sulfoxides 1aꢀ18O (~ 69%
18O) in the presence of BnSH in 84% yield. The reaction of this
Eꢀ2aꢀ18O (~ 69% 18O) under 45 wt.% HI in H2O did afford Zꢀ3aꢀ
I
R1
I
I
R2
M3
3
E-2
50
Scheme 9. Mechanism for the reaction.
This was confirmed by applying 4ꢀbromophenthyl alcohol,
which was indeed recovered in 95% yield after the reaction,
instead of ethanol, indicating that this alcohol has not been
18O in 35% yield, however with only 1% 18O incorporation.
Et
55 incorporated into the product. All the byproducts 1ꢀbenzylꢀ2ꢀ
phenyldisulfane 8, diphenyldisulfane 9, and 1,2ꢀdibenzyldisulfane
10 have also been isolated from this reaction (eq. 4).
n-C4H9
PhSCl
Et3N, THF
Et
Br
Na
H218O
Na18OH
n-C4H9
18OH -78 oC, 60 min
reflux, 19 h
(86% 18O)
7 18
-
O
non-4-yn-3-ol-18
O18
O
O
O18
O
S
2-(4-bromophenyl)enthanol
n-C4H9
H
n-C4H9
H
H
S
H
I2, BnSH
(1.7 equiv)
+
I2
+
BnSH
CHCl3, 40 o
60 min
C
CHCl3/EtOH = 50/1
40 oC, 60 min
I
I
n-C4H9
1a-18
n-C4H9
Et
1.0 equiv
3.5 equiv
3a
Z-
1a
3a 18
Z-
-
O
O
39%
81% (41% 18O)
17% in two steps
(64% 18O)
(Z)-4-iodonon-3-en-5-one-18
O
S
S
S
S
S
(eq. 4)
nona-3,4-dien-5-yl
phenyl sulfoxide-18
+
+
+
S
O
8
9
10
O18
31%
32%
Et
O
I2 (1.5 equiv)
BnSH (1.5 equiv)
MeOH, 40 o
60 min
26%
18OH
45 wt.% HI in H2O
S
H
PhS
n-Bu
H
4-BrPhCH2CH2OH (95% recovered)
C
n-C4H9
CHCl3/EtOH = 50/1
40 oC, 12 h
n-Bu
E-2a-18
84% (69% 18O)
I
I
Et
O
60
Z-3a-18
1a 18
O
-
O
35% (1% 18O)
After the isolatation of unsymmetrical disulfide 8, control
experiment showed that under the standard conditions PhSSBn 8
may indeed be converted to disulfides 9 and 10 which were
isolated in 32% and 26% yields, respectively (Scheme 10).
19% in two steps
(69% 18O)
30
Scheme 8. The isotopic 18O distribution experiments.
With these evidences in hand, we reasoned that there are two
pathways for this reaction, which are shown in Scheme 9. The
major pathway is as follows: EtOH in the solvent may form a
35 hydrogen bonding with the sulfinyl oxygen, which decreases the
4
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2
3
a) P. Blake, The Chemistry of Ketenes, Allenes and Related
Compounds (Wiley, New York, 1980), pp. 342. b) H. F. Schuster
and G. M. Coppola, Allenes in Organic Synthesis (Wiley, New
York, 1984).
S
I2
S
S
S
CHCl3/EtOH = 50/1
S
S
+
45
50
55
60
65
70
75
40 o
C
8
10
9
a) S. Yu, S. Ma Angew. Chem. Int. Ed. 2012, 51, 3074. b) For a
review, see: S. Ma Ionic Addition to Allenes. In Modern Allene
Chemistry; N. Krause, A. S. K. Hashmi, Eds.; WileyꢀVCH:
Weinheim, Germany, 2004. c) S. Ma, Pure Appl. Chem. 2007, 79,
261ꢀ267. d) S. Ma Acc. Chem. Res. 2003, 36, 701. e) Ma, S. Chem.
Rev. 2005, 105, 2829. f) S. Ma, Aldrichimica Acta 2007, 40, 91.
a) R. Zimmer, C. U. Dinesh, E. Nandanan, F. A. Khan Chem. Rev.
2000, 100, 3067. b) A. S. K. Hashmi Angew. Chem., Int. Ed. 2000,
39, 3590. c) M. Brasholz, H.ꢀU. Reissig, R. Zimmer Acc. Chem.
Res. 2009, 42, 45. d) L. K. Sydnes Chem. Rev. 2003, 103, 1133. e)
X. Lu, C. Zhang, Z. Xu Acc. Chem. Res. 2001, 34, 535. f) L.
Brandsma, N. A. Nedolya Synthesis 2004, 735. g) L.ꢀW. Ye, J.
Zhou, Y. Tang Chem. Soc. Rev. 2008, 37, 1140. h) R. W. Bates, V.
Satcharoen Chem. Soc. Rev. 2002, 31, 12. i) F. López, J. L.
Mascareñas Chem. Eur. J. 2011, 17, 418. j) B. Alcaide, P.
Almendros, C. Aragoncillo Chem. Soc. Rev. 2010, 39, 783. k) N.
Krause, C. Winter Chem. Rev. 2011, 111, 1994. l) M. Bandini
Chem. Soc. Rev. 2011, 40, 1358.
yielda
I2 (equiv)
time (h)
8
9
10
0
28
24
17
24
100
0
0
0.2
1.0
1.5
66
34
34
4
47 (46)b
46
53 (52)
54
53 (54)
54
a The yields were determined by 1H NMR analysis with CH2Br2 as the internal standard.
b Isolated yields.
Scheme 10. The reaction of 1ꢀbenzylꢀ2ꢀphenyldisulfane 8 with I2.
The minor pathway is the formation of Eꢀ2 via the
intermediates M4, M5, and M6 (Scheme 9).39,42 The final
products 3 would be formed via the reaction of the inꢀsitu
generated HI with Eꢀ2 with essentially no 18O incorporation with
a rather low yield (Scheme 8). Because of the existence of this
minor pathway, the 18O incorporation of Zꢀ3a dropped from 64%
(1a) to 41% (Zꢀ3a).
5
5
a) W. Smadja, Chem. Rev. 1983, 83, 263. b) William L. Waters,
William S. Linn, and Marjorie C. Caserio J. Am. Chem. Soc. 1968,
90, 6741. c) C. Georgoulis, W. Smadja, J. M. Valery synthesis 1981,
572. d) J. Barluenga, E. CamposꢀGómez, A. Minatti, D. Rodríguez,
J. M. González Chem. Eur. J. 2009, 15, 8946.
6
7
a) S. Ma, Acc. Chem. Res. 2009, 42, 1679. b) S. Ma,; H. Ren, Q. Wei
J. Am. Chem. Soc. 2003, 125, 4817.
10 Conclusions
a) V. C. Christov, B. Prodanov Phosphorus, Sulfur and Silicon 2002,
177, 2445. b) V. C. Christov, I. K. Ivanov, Sulfur Lett. 2002, 25,
191; c) V. C. Christov, B. Prodanov Synth. Commun. 2004, 34,
1577. d) S. Braverman, D. Reisman J. Am. Chem. Soc. 1977, 99,
605. e) S. Braverman, Y. Duar J. Am. Chem. Soc. 1983, 105, 1061.
D. R. Buckle, I. L. Pinto In Comprehensive Organic Synthesis; B. M.
Trost Ed.; Pergamon: Oxford, 1991; Vol. 7, pp 119.
In conclusion, we have developed a unique iodohydroxylation
of readily available 1,2ꢀallenylic sulfoxides in the presence of
BnSH forming αꢀiodoꢀα,βꢀunsaturated ketones or aldehydes in
good to excellent yields highly stereoselectively. Based on the
15 mechanistic study, we believe that the hydrogenꢀbonding between
the sulfoxide and EtOH may be responsible for the reversed
regioselectivity of the two C=C bonds in allenes. The reaction
may easily be carried in 20 mmol or 30 mmol. The CꢀI bonds
provides opportunities for further synthetic elaboration. This
20 reaction will be of high interest in the scientific community due
to the potentials of the notꢀreadilyꢀavailable products and the
interesting mechanism. Further studies including the new
reactivity of the sulfoxide functionality in this area are being
pursued in our laboratory.
8
9
T. Tsuda, T. Kiyoi, T. Saegusa J. Org. Chem. 1990, 55, 2554.
80 10 a) K. Kokubo, K. Matsumasa, M. Miura, M. Nomura J. Org. Chem.
1997, 62, 4564. b) C.ꢀH. Jun, H. Lee, J.ꢀB. Hong, B.ꢀI. Kwon
Angew. Chem., Int. Ed. 2002, 41, 2146.
11 V. M. Williams, J. C. Leung, R. L. Patman, M. J. Krische
Tetrahedron 2009, 65, 5024.
85 12 S. Hatanaka, Y. Obora, Y. Ishii Chem. Eur. J. 2010, 16, 1883.
13 a) G. S. Viswanathan, C.ꢀJ. Li Tetrahedron Lett. 2002, 43, 1613. b)
A. Hayashi, M. Yamaguchi, M. Hirama Synlett 1995, 195. c) M.
Curini, F. Epifano, F. Maltese; O. Rosati Synlett 2003, 552. d) M.
F. A. Adamo, G. Bellini, S. Suresh Tetrahedron 2011, 67, 5784.
90 14 A. ElꢀBatta, C. Jiang, W. Zhao, R. Anness, A. L. Cooksy, M.
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25 Acknowledgments
15 a) B. E. Maryanoff, A. B. Reitz Chem. Rev. 1989, 89, 863. b) G.
Sabitha, P. Gopal, J. S. Yadav Tetrahedron: Asymmetry 2009, 20,
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95 16 Y. Sugawara, W. Yamada, S. Yoshida, T. Ikeno, T. Yamada J. Am.
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17 a) M. Egi, Y. Yamaguchi, N. Fujiwara, S. Akai Org. Lett. 2008, 10,
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J. Org. Chem. 2011, 76, 1479.
Financial support from the National Basic Research Program of
China (2011CB808700) and National Natural Science Foundation
of China (No. 20972135) is greatly appreciated. Shengming Ma
is a Qiu Shi Adjunct Professor at Zhejiang University. We thank
30 Mr. C. Zhu and B. Guo in this group for reproducing the
preparation of Zꢀ3b in Table 6, 3i in Table 7, and Zꢀ3l in Table 8.
100 18 a) M. Picquet, C. Bruneau, P. H. Dixneuf Chem. Commun. 1997,
1201. b) V. Cadierno, S. E. GarcíaꢀGarrido, J. Gimeno Adv. Synth.
Catal. 2006, 348, 101.
Notes and references
Laboratory of Molecular Recognition and Synthesis, Department of
Chemistry, Zhejiang University, 310027 Hangzhou, Zhejiang, P. R. China
35 Address, Address, Town, Country. Fax: (+86) 21ꢀ62609305; Eꢀmail:
masm@sioc.ac.cn
† Electronic Supplementary Information (ESI) available: detail Tables
S1ꢀS4, spectral data of NMR (1H, 13C), MS data of 18Oꢀ1a and 18OꢀZꢀ3a.
See DOI: 10.1039/b000000x/
19 a) C. P. Mehnert, N. C. Dispenziere, R. A. Cook Chem. Commun.
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Z. Luo, W.ꢀG. Song Chem. Commun. 2010, 46, 1109. d) S. Abelló,
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Tichit, B. Coq Chem. Commun. 2004, 1096. e) A. Arnold, M.
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1
a) A. Arnold, M. Markert, R. Mahrwald Synthesis 2006, 7, 1099. b)
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41 4l: C17H15N4O4I, MW = 466.23, triclinic, space group Pꢀ1, final R
indices [I > 2σ(I)], R1 = 0.0310, wR2 = 0.0770; Rindices (all data),
R1 = 0.0355, wR2 = 0.0799; a = 7.1296 (10) Å, b = 7.4865 (10) Å, c
= 17.896 (3) Å, α= 87.393 (2)°, β= 84.501 (2)°, γ= 71.105 (2)°, V =
899.5 (2) Å3, T = 293 (2) K, Z = 2, reflections collected/unique
4891/3458 (Rint = 0.0171), number of observations [> 2σ(I)] 3458,
parameters: 239. Supplementary crystallographic data have been
deposited at the Cambridge Crystallographic Data Centre, CCDC
877901.
75
80
85
90
5
10
15
20
25
30
42 For isolation of the fiveꢀmembered intermediates, see: a) C. Zhou, C.
Fu, S. Ma, Angew. Chem. Int. Ed. 2007, 46, 4379; b) C. Zhou, C.
Fu, S. Ma, Tetrahedron 2007, 63, 7612. For a similar effect of
sulfoxide on such electrophilic addition reactions, see: c) J. L. G.
Ruano, V. Marcos, J. Alemén, Angew. Chem. Int. Ed. 2009, 48,
3155.
43 Reviews on sulfoxide rearrangements see: a) E. Schaumann Sulfurꢀ
Mediated Rearrangements II. Topics in Current Chemistry. Springer,
Vol. 275, 2007. b) S. Braverman, M. Cherkinsky Top. Curr. Chem.
2007, 275, 67. c) R. Fernández de la Pradilla, M. Tortosa, A. Viso
Top. Curr. Chem. 2007, 275, 103.
25 D. Zhang, J. M. Ready J. Am. Chem. Soc. 2007, 129, 12088.
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T. Yamazaki, T. Yamamoto, R. Ichihara J. Org. Chem. 2006, 71,
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Prod. Res. 2010, 24, 1274.
27 a) M. Slodowicz, S. BarataꢀVallejo, A. Vázquez, N. S. Nudelman, A.
Postigo J. Fluorine Chem. 2012, 135, 137. b) J. F. Chesa, D.
Velasco, F. LópezꢀCalahorra Synth. Commun. 2010, 40, 1822. c) X.ꢀ
Q. Tang. C.ꢀM. Hu J. Chem. Soc., Chem. Commun. 1994, 631. d)
H.ꢀP. Guan, X.ꢀQ. Tang, B.ꢀH. Luo, C.ꢀM. Hu Synthesis 1997, 1489.
28 a) X. Fang, X. Yang, X. Yang, S Mao, Z. Wang, G. Chen, F. Wu
Tetrahedron 2007, 63, 10684. b) Z.ꢀY. Long, Q.ꢀY. Chen
Tetrahedron Lett. 1998, 39, 8487. c) A.ꢀR. Li, Q.ꢀY. Chen Synthesis
1997, 333. d) Y. Li, H. Li, J. Hu Tetrahedron 2009, 65, 478.
35 29 a) S. Ma, Z. Lu Adv. Synth. Catal. 2006, 348, 1894. b) Z. Lu, S. Ma
J. Org. Chem. 2006, 71, 2655.
30 a) S. Ma, Acc. Chem. Res. 2009, 42, 1679. b) J. Luis G. Ruano, V.
Marcos, J. Alemén Angew. Chem. Int. Ed. 2009, 48, 3155. c) R. W.
Friesen, C. Vanderwal J. Org. Chem. 1996, 61, 9103.
40 31 S. Ma, Q. Wei, H. Wang Org. Lett. 2000, 2, 3893.
32 J. Baudin, S. A. Julia, Y. Wang Tetrahedron Lett. 1989, 30, 4965.
33 J. Baudin, I. BkoucheꢀWaksman, S.A. Julia, C. Pascard, Y. Wang
Tetrahedron 1991, 47, 3353.
34 S. Braverman, Y. Stabinsky Isr. J. Chem. 1967, 5, 125.
45 35 For Auꢀcatalyzed synthesis of αꢀiodoꢀβꢀmonsubstituted enones with
6/1~36/1 Z/E ratio or (Z)ꢀ2ꢀiodooctꢀ2ꢀenal with >50/1 Z/E ratio from
proparylic alcohols or proparylic acetates see: a). L. Ye, L. Zhang
Org. Lett. 2009, 11, 3646. b) M. Yu, G. Zhang, L. Zhang
Tetrahedron 2009, 65, 1846. In these references, the reaction
50
afforded αꢀiodoꢀβ,βꢀdialkylsubstituted enones ignoring the issue of
selectivity.
36 For αꢀiodination of cyclic enals or enones and their derivatives
leading to αꢀiodoꢀenals or enones see: a) C. Sha, S. Huang
Tetrahedron Lett. 1995, 36, 6927. b) M. E. Krafft, J. W. Cran
Synlett, 2005, 8, 1263. c) J. P. Whang, S. G. Yang, Y. H. Kim
Chem. Commun., 1997, 1355. d) E. Djuardi, P. Bovonsornbat, E. M.
Nelis Synth. Commun., 1997, 27, 2497. e) A. Alimardanov, E.
Negishi Tetrahedron Lett. 1999, 40, 3839.
55
37 D. Wang, X. Ye, X. Shi Ort. Lett. 2010, 12, 2088.
60 38 E. Negishi J. Organomet. Chem. 1999, 576, 179.
39 a) C. Fu, X. Huang, S. Ma Tetrahedron Lett. 2004, 45, 6063. b) M.
Wang, C. Fu, S. Ma Adv. Synth. Catal. 2011, 353, 1775.
40 4a:C15H19N4O4I, MW = 446.24, monoclinic, space group P 21/n, final
R indices [I > 2σ(I)], R1 = 0.0336, wR2 = 0.0752; Rindices (all
65
70
data), R1 = 0.0482, wR2 = 0.0829; a = 12.5720 (7) Å, b = 9.3235
(5) Å, c = 15.1484 (6) Å, α= 90.00°, β= 90.258 (4)°, γ= 90.00°, V =
1775.61 (16) Å3, T = 293 (2) K, Z = 4, reflections collected/unique
9033/3241 (Rint = 0.0325), number of observations [> 2σ(I)] 2579,
parameters: 219. Supplementary crystallographic data have been
deposited at the Cambridge Crystallographic Data Centre, CCDC
877900.
6
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This journal is © The Royal Society of Chemistry [year]