Nickel(II) chloride-catalyzed regioselective hydrothiolation of alkynes

Article abstract of DOI:10.1002/adsc.200505168

Regioselective Markovnikov-type addition of PhSH to alkynes (HC≡C-R) has been performed using easily available nickel complexes. The non-catalytic side reaction leading to anti-Markovnikov products was suppressed by addition of γ-terpinene to the catalyti

Full text of DOI:10.1002/adsc.200505168

FULL PAPERS
DOI: 10.1002/adsc.200505168
Nickel(II) Chloride-Catalyzed Regioselective Hydrothiolation of
Alkynes
Valentine P. Ananikov,a,* Denis A. Malyshev,a Irina P. Beletskaya,b,*
Grigory G. Aleksandrov,c Igor L. Eremenkoc
a
Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, Leninsky Prospect 47, Moscow 119991, Russia
Fax: (þ7)-095-135-5328, e-mail: val@ioc.ac.ru
b
Lomonosov Moscow State University, Chemistry Department, Vorobꢀevy gory, Moscow 119899, Russia
Fax: (þ7)-095-939-3618, e-mail: beletska@org.chem.msu.ru
c
Kurnakov Institute of General and Inorganic Chemistry, Russian Academy of Sciences, Leninsky Prospect 31, Moscow
117907, Russia
Received: April 22, 2005; Accepted: September 12, 2005
Supporting Information for this article is available on the WWW under http://asc.wiley-vch.de/home/.
Abstract: Regioselective Markovnikov-type addition significantly increased the yield and selectivity of
of PhSH to alkynes (HCꢀC-R) has been performed the catalytic reaction. Under optimized conditions
using easily available nickel complexes. The non-cata- high product yields of 60–85% were obtained for var-
lytic side reaction leading to anti-Markovnikov prod- ious alkynes [R¼n-C5H11, CH2NMe2, CH2OMe,
ucts was suppressed by addition of g-terpinene to the CH2SPh, C6H11(OH), (CH2)3CN]. The X-ray structure
catalytic system. The other side reaction leading to of one of the synthesized products is reported.
the bis(phenylthio)alkene was avoided by excluding
phosphine and phosphite ligands from the catalytic Keywords: alkynes; catalytic reaction; nickel; regiose-
system. It was found that catalytic amounts of Et3N lectivity; g-terpinene; vinyl sulphides
ꢁ
Introduction
5 (Scheme 2).[12] Selective addition of the Se H bond
was achieved using Pt(PPh3)4 as the catalyst
Addition of the S H bond to alkynes is an important (Scheme 2).[12]
ꢁ
method in the synthesis of vinyl sulphides.[1–3] It was
A mechanistic study has shown that hydride complex
ꢁ
shown that Pd(OAc)2 catalyzes the selective synthesis 6, formed after oxidative addition of the Se H bond,
of (phenylthio)alkenes 1,[4] while the chloride complex can react with the second PhSeH molecule leading to
of palladium PdCl2(PhCN)2 catalyzes Markovnikov- the complex 7 (Scheme 3). The formation of complex
type addition of PhSH to the CꢀC bond (Scheme 1) fol- 6 (M¼Pt) and evolution of molecular hydrogen were
lowed by isomerization of 1 to internal alkenes 1a and 1b detected by NMR.[12] The structure of complex 7
(for R groups with a-H atom).[5,6] Wilkinsonꢀs complex (M¼Pd, Pt) was established by independent synthesis
RhCl(PPh3)3 catalyzes the regio- and stereoselective ad- using the oxidative addition reaction of PhSe-SePh to
dition of benzenethiol to alkynes leading to the anti- Pd(PPh3)4 and Pt(PPh3)4.[12] Alkyne insertion into the
Markovnikov product 2a with trans-stereochemistry.[6] M Se bond of 7 followed by C Se reductive elimina-
A mixture of compounds 1, 2a, 2b and 3 was obtained tion gave the bis(phenylseleno)alkene 5. Alkyne inser-
ꢁ
ꢁ
ꢁ
ꢁ
when a phosphine complex of Pd(0) was used as the cat- tion into the M Se bond of 6 followed by C H reduc-
alyst (Scheme 1).[6] The non-catalytic free radical addi- tive elimination led to the Markovnikov product 4
tion of benzenethiol to alkynes gave a mixture of anti- (Scheme 3). Another pathway leading to 4 involves
Markovnikov isomers 2a and 2b.[7–9] Under nucleophilic protonolysis of the s-vinyl complex (obtained after al-
ꢁ
conditions the reaction proceeds in a more selective kyne insertion to the M E bond of 7; E¼S, Se) as pro-
manner leading to the cis- isomer 2b.[10,11] posed for the PhSeH[12] and PhSH[4–6] addition reac-
It is interesting to note that the Pd(PPh3)4-catalyzed tions.
reaction led to the formation of bis(phenylthio)alkene
The aim of the present study was to develop a conven-
3 as a by-product (Scheme 1).[6] A similar process involv- ient practical method for synthesis of the Markovnikov
ing PhSeH addition to alkynes gave the mixture of 4 and product (1) by addition of benzenethiol to terminal
Adv. Synth. Catal. 2005, 347, 1993 – 2001
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1993

Valentine P. Ananikov et al.
FULL PAPERS
Scheme 1.
the case of the palladium complex the mixture of 1,
2aþ2b and 3 with the yields of 20, 25 and 30%, respec-
tively, was formed. These results are in agreement with
those of a previous study performed for another al-
kyne.[6] NMR monitoring of the reaction of PhSH with
Pd(PPh3)4 detected the formation of molecular hydro-
gen (see Experimental Section for details). Therefore,
the Pd(PPh3)4-catalyzed PhSH addition reaction pro-
ceeds in the same manner as the reaction involving
PhSeH studied earlier (Scheme 3).[12] The platinum
complex Pt(PPh3)4 was not an efficient catalyst of alkyne
hydrothiolation. In the studied model reaction of PhSH
addition to 1-heptyne the non-catalytic products 2aþ2b
were mainly formed with 40% yield, and the yield of the
Markovnikov product 1 was <40%. These results are
also in agreement with the literature data, where poor
Scheme 2.
¼
catalytic activity of Pt(PPh3)2(CH2 CH2) has been re-
ported.[6] Since complete separation of product 1 from
compounds 2a, 2b and 3 is not possible with convention-
al purification techniques, Pd(PPh3)4 and Pt(PPh3)4 can
hardly be used for the selective synthesis of 1.
Next, we have studied the catalytic activity of chloride
complexes of different transition metals (Table 1). In
the model reaction of addition of PhSH to 1-heptyne
the yield of the Markovnikov product 1 was rather
Scheme 3.
alkynes, as well as to study the effect of the phosphine li- poor for all studied metal complexes. In the case of
gand in this reaction.
K2PtCl4 the catalytic product 1 was not formed at all (Ta-
ble 1, entry 3). For PdCl2 and NiCl2 the non-catalytic
pathway leading to 2a and 2b made the major contribu-
tion to the reaction (Table 1, entries 1, 4), the selectivity
was 3/10 and 1/5, respectively (the ratio of 1þ1aþ
Results and Discussion
At first we have studied the catalytic activity of 1b:2aþ2b will be considered as selectivity throughout
Pd(PPh3)4 and Pt(PPh3)4 in the model reaction of this article). Only for the RuCl3 catalytic and non-cata-
PhSH addition to 1-heptyne. We have found that in lytic products were formed with comparable yields of
1994
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Nickel(II) Chloride-Catalyzed Regioselective Hydrothiolation of Alkynes
Table 1. The addition of PhSH to 1-heptyne catalyzed by different transition metal chloride complexes.[a]
FULL PAPERS
Entry
Complex
Yield [%][b]
Without Et3N
1þ1aþ1b
With Et3N[c]
2aþ2b
1þ1aþ1b
2aþ2b
1
2
3
4
PdCl2
RuCl3
K2PtCl4
NiCl2
20
29
0
65
41
90
75
73
83
75
84
4
10
12
11
15
[a]
1.0 mmol of PhSH, 0.5 mmol of alkyne, 3 mol % of metal complex in 1 mL of toluene at 1208C for 3 h in a sealed tube with
stirring.
Total yield of vinyl sulphides 1–2 determined by NMR and calculated based on alkyne.
One equivalent of Et3N was added for each chloride atom of the metal complex (6 mol % for PdCl2 and NiCl2, 9 mol % for
RuCl3, 12 mol % for K2PtCl4).
[b]
[c]
29% and 41%, which corresponds to a 7/10 selectivity Table 2. The influence of g-terpinene on the non-catalytic ad-
dition of PhSH to alkynes.[a]
(Table 1, entry 2). In spite of the poor yield and selectiv-
ity, there is an important advantage of the chloride com-
plexes, namely the absence of the side reaction leading
to bis(phenylthio)alkene 3 [cf. Pd(PPh3)4 and PdCl2].
The direction of the addition reaction was dramatical-
ly changed upon addition of catalytic amounts of Et3N.
The Markovnikov product 1 was formed with high yields
of 75–86%. The biggest effect was observed for PdCl2
and the selectivity was changed from 3/10 to 18/1 (Ta-
ble 1, entry 1). In the presence of catalytic amounts of
triethylamine the Markovnikov product was the major
one for all studied complexes (Table 1, entries 1–4).
For the nickel-catalyzed reaction the selectivity changed
from 1/5 to 8/1 (Table 1, entry 4).
Entry
Alkyne
Yield of 2aþ2b [%][b]
Without
g-terpinene
With
g-terpinene[c]
1
2
3
4
HCꢀC-n-C5H11
HCꢀC-CH2OMe
HCꢀC-Ph
13
20
99
90
3
<2
56
HCꢀC-COOMe
20
[a]
Although the selectivity of the NiCl2-catalyzed reac-
tion was not the highest one we have decided to study
it in detail for two reasons: 1) Ni complexes are cheap
and easily available; and 2) the application of Ni com-
1 mmol of PhSH, 0.5 mmol of alkyne, in 1 mL of toluene at
1208C for 3 h in a sealed tube.
Determined by NMR and calculated based on initial
amount of alkyne.
[b]
[c]
1 equivalent to alkyne.
ꢁ
plexes in the catalytic E H bond addition to unsaturat-
ed compounds is scarcely studied.[13] Particularly, recent
studies have proven a great potential of Ni complexes in Markovnikov products 2a and 2b (2–3%) were obtained
[13c–e]
and S H[13b] to alkynes.
(Table 2, entries 1 and 2). For the activated alkynes the
ꢁ
ꢁ
selective addition of P H
We made an attempt to suppress the non-catalytic side yields of the radical reaction were significantly de-
reaction (Scheme 1). For this reason we have studied the creased from 99% and 90% to 56% and 20%, respec-
reaction between benzenethiol and alkynes without a tively (Table 2, entries 3 and 4). The remaining part of
catalyst (Table 2). Heating PhSH and alkyne in toluene the anti-Markovnikov products may be connected with
at 1208C for 3 h resulted in the mixture of 2aþ2b in 13% a Michael-type addition.
and 20% yields for 1-heptyne and methyl propargyl
The radical side reaction was efficiently suppressed by
ether, respectively (Table 2, entries 1 and 2). Activated g-terpinene under the catalytic conditions as well. Even
alkynes (phenylacetylene and methyl propiolate) react- a small amount of the radical trap (0.05 equivalents to al-
ed with PhSH with quantitative yields (Table 2, entries 3 kyne) increased the selectivity of the PhSH addition to
and 4). However, the side-reaction can be suppressed by 1-heptyne from 7.9/1 to 10.9/1 towards the Markovnikov
addition of a radical trap – g-terpinene (1-isopropyl-4- product (Table 3, entries 1 and 2). Increasing the
methylcyclohexa-1,4-diene). In the cases of 1-heptyne amount of g-terpinene further improved the selectivity
and methyl propargyl ether only the traces of the anti- of the reaction (Table 3, entries 1–4). The highest value
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Valentine P. Ananikov et al.
Table 3. The influence of the g-terpinene on the selectivity of the catalytic PhSH addition to 1-heptyne.[a]
FULL PAPERS
Entry
g-Terpinene[b]
Yield [%][c]
Selectivity[d]
1
2
3
4
0.00
0.05
0.20
1.00
95
95
95
95
7.9: 1.0
10.9: 1.0
13.0: 1.0
19.0: 1.0
[a]
1 mmol of PhSH, 0.5 mmol of alkyne, 3 mol % NiCl2, 6 mol % Et3N in 1 mL of toluene at 1208C for 3 h in a sealed tube with
stirring.
Equivalents to alkyne.
Determined by NMR and calculated based on initial amount of alkyne.
The ratio of Markovnikov/anti-Markovnikov products (1þ1aþ1b):(2aþ2b).
[b]
[c]
[d]
Table 4. Effect of solvent on the catalytic addition of PhSH to 1-heptyne.[a]
Entry
Solvent
Yield [%][b]
Selectivity[d]
1
2
3
4
5
6
CHCl3
99
95
92
19: 1
18: 1
17: 1
17: 1
18: 1
15: 1
Dioxane
Hexane
Toluene
Acetonitrile
THF
90
81[c]
79
[a]
1 mmol of PhSH, 0.5 mmol of alkyne, 0.5 mmol of g-terpinene, 3 mol % of NiCl2, 6 mol % of Et3N and 1 mL of solvent at
958C for 10 h in a sealed tube with stirring.
Determined by NMR and calculated based on initial amount of alkyne.
Unknown products were formed with a yield of about 10–15%.
[b]
[c]
[d]
The ratio of Markovnikov/anti-Markovnikov products (1þ1aþ1b):(2aþ2b).
of 19/1 was achieved using 1 equivalent of the radical trap
The Ni-catalyzed reaction was successfully performed
to alkyne (Table 3, entry 4). The further increase of the g- in different solvents (Table 4). Excellent yields (90–
terpinene decreased the yield of the Markovnikov prod- 95%) and selectivity (19/1–17/1) were achieved in
uct, since in that case it dilutes the toluene solution and chloroform, dioxane, hexane and toluene (Table 4, en-
acts like a co-solvent with unfavourable properties.
tries 1–4). Among the studied solvents toluene is a sol-
A significant drawback of most modern catalytic reac- vent of choice for reactions at high temperature, in other
tions is their high sensitivity to the purity of the solvent. cases chloroform may be also used. Dioxane is less con-
Quite often even traces of water in organic solvents di- venient due to more complicated product separation
minish the yield and selectivity of the reactions. In our procedure. It is interesting to note that even solvents
case the catalytic reaction was not sensitive to water. Us- that are rarely used in catalytic reactions, such ashexane,
ing NiCl2, its hexahydrate NiCl2 ·6 H2O or a mixture of gave good results in the studied reaction (Table 4, en-
NiCl2 þ6 H2O as a catalyst did not cause noticeable try 3).
changes in the selectivity and yield of the PhSH addition
For developing an efficient synthetic procedure the
to 1-heptyne. Moreover, utilizing a 90%:10% mixture of optimal reagents ratio should be determined. With an
toluene and water as a solvent led to 90% yield and 7.7/ equimolar ratio of the reagents incomplete conversion
1.0 selectivity. The same reaction in pure toluene gave was observed, while increasing the amount of alkyne
95% yield with 7.9/1.0 selectivity (Table 3, entry 1).
led to the formation of oligomerization products (Ni
1996
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Nickel(II) Chloride-Catalyzed Regioselective Hydrothiolation of Alkynes
FULL PAPERS
Table 5. NiCl2-catalyzed PhSH addition to alkynes.[a]
Entry
Alkyne
Conditions[b]
Yield [%][c]
Selectivity[d]
1
2
3
4
5
6
7
8
HCꢀC-n-C5H11 (A)
HCꢀC-CH2NMe2 (B)
HCꢀC-CH2OMe (C)
HCꢀC-CH2SPh (D)
HCꢀC-C6H10(OH) (E)
HCꢀC-(CH2)3 CN (F)
HCꢀC-Ph (G)
2.5 h., 808C, CHCl3
6 h, 958C, CHCl3
4 h, 1008C, toluene
4 h, 1008C, toluene
4 h, 1008C, toluene
2.5 h, 808C, CHCl3
5 h, 808C, CHCl3
5 h, 808C, CHCl3
95(80)
93(85)
85(75)
93(60)
75(63)
95(84)
27(5)
18.0: 1.0
7.7: 1.0
8.6: 1.0
7.7: 1.0
7.0: 1.0
13.3: 1.0
0.3: 1.0
0: 1.0
HCꢀC-COOMe (H)
100(0)
[a]
1.0 mmol of PhSH, 0.5 mmol of alkyne, 0.5 mmol of g-terpinene, 3 mol % of NiCl2, 10 mol % of Et3N and 1.0 mL of solvent
in a sealed tube with stirring.
The reactions were monitored with NMR to determine the optimal time.
The yields determined by NMR and the isolated yields (in parenthesis) of 1.
The ratio of Markovnikov/anti-Markovnikov products 1:(2aþ2b).
[b]
[c]
[d]
complexes are known to catalyze alkyne polymeriza- t1/2 ¼110 min at 808C. The optimal reaction conditions
tion, see ref.[14]). The best yields and selectivity were ob- for this alkyne were ~4 h at 1008C.
served with the ratio of PhSH:alkyne¼2:1. The further
Under optimized conditions, the Ni-catalyzed reac-
increase of benzenethiol amount does not improve the tion was performed with high selectivity and yields for
yield of the reaction. Therefore, the PhSH:alkyne¼ different alkynes (Table 5, entries 1–6). For the alkynes
2:1 ratio was used throughout this study.
A–F the isolated yields of the products (1A–1F) were
Another very interesting question concerns the iso- 60–85% with the selectivity 18/1–7/1 (Table 5, en-
merization of the Markovnikov product 1 to internal al- tries 1–6). Obtaining good yields for the alkynes bear-
kenes 1a and 1b (Scheme 1). It was shown that the iso- ing heteroatoms (which could coordinate to the metal)
merization of vinyl sulphides can be catalyzed by palla- required longer reaction time and higher temperature
dium complexes.[6] The isomerization may also proceed (Table 5, entries 2–5). Most likely competitive binding
without transition metal complexes.[12] NMR monitor- of heteroatom lone pair to the metal retards alkyne co-
ing of the catalytic reaction has shown that only com- ordination and breaks the catalytic cycle. Due to the
pound 1 is formed at the beginning of the reaction rather fast non-catalytic side-reaction for the activated
(2–3 h at 808C). Heating at higher temperature alkynes (G–H) we were unable to achieve good yields
(>1008C) facilitated formation of the isomers 1a and of the Markovnikov products 1G and 1H.
1b. Decreases in the intensity of the NMR signals corre-
The structures of the products were determined by 1H
sponding to 1 were accompanied with simultaneous in- and 13C NMR spectroscopy and the stereochemistry was
creases in the intensities of the signals corresponding established by 2D NOESYand COSY-LR experiments.
to 1a and 1b. This observation suggests that 1 is a kinetic The molecular structure of one of the Markovnikov
product of the catalytic reaction, while 1a and 1b are the product was determined by an X-ray study (see below).
thermodynamic products. Therefore, to minimize the
As we have already mentioned, the formation of bis-
contribution of the double bond isomerization, the cat- (phenylthio)alkene 3 was observed in the case of palla-
alytic reaction should be carried out during a short peri- dium complexes containing phosphine or phosphite li-
od of time and avoiding overheating.
gands.[6,12,15,16] A similar behaviour was found for the
To estimate the optimal reaction time we have per- nickel complexes as well (Table 6). Addition of
formed NMR monitoring of the catalytic reactions of P(OPh)3, P(OBu)3, P(O-i-Pr)3 or DPPE to the catalytic
PhSH with 1-heptyne and methyl propargyl ether. The system facilitated the formation of compound 3 (Ta-
time needed for 50% conversion of 1-heptyne at 808C ble 6, entries 2–5). Moreover, the yield of 3 was in-
was t1/2 ¼24 min and 90% conversion of the alkyne was creased upon increasing the amount of the added ligand
achieved after ~3.5 h. Increasing the temperature to (Table 6, entries 5, 6). Triphenylphosphine suppressed
958C decreased the t1/2 value to 9 min and 90% conver- both catalytic reactions leading to the Markovnikov
sion of the alkyne was achieved after ~1 h of reaction. product 1 and compound 3 (Table 6, entry 1). Therefore,
Methyl propargyl ether was significantly less reactive, the best results in the Ni-catalyzed Markovnikov-type
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Valentine P. Ananikov et al.
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Table 6. Effect of phosphine ligands on the NiCl2-catalyzed
Recently we haveþ reported the X-ray sꢁtructure of
PhSH addition to 1-heptyne.[a]
¼
ꢁ
H2C C(SePh)CH2N HMe2 ·HOOC COO ,
which
was prepared by PhSeH addition to HCꢀCCH2NMe2
and crystallized as the 1:1 oxalic acid salt.[12] In the
present study we have successfully applied this method-
ology for preparing X-ray quality single cryꢁstals of
þ
¼
ꢁ
the H2C C(SPh)CH2N HMe2 ·HOOC COO (1-B·
ꢁ
HOOC COOH). The molecular structure of the com-
pound is shown in Figure 1 (main geometric parameters
are listed in the Supporting Information). Similar to the
selenium analogue, two slightly different conformations
were found in the crystal.[12] The alkene unit possesses
the typical geometry expected for the Markovnikov
product, with C C distances of 1.261(13) and
1.330(8) Š; C C S bond angles of 127.6(10)8 and
125.7(3)8 close to expected value of 1208. Two sulphur
atoms are located at the 1.782(11) and 1.755(8) Š distan-
ces from the C2 and C13 vinyl atoms, respectively. The
hydrogen bonds involving the carboxylic oxygen atoms
Entry
Ligand
Yield [%][b]
1þ1aþ1b
0
72
0
62
65
16
2aþ2b
3
¼
[c]
1
2
3
4
5
6
PPh3
15
11
52
16
15
18
0
¼ ꢁ
DPPE
12
8
[c]
P(OPh)3 [c]
P(OBu)3
7
5
[c]
P(O-i-Pr)3[c, d]
P(O-i-Pr)3
16
ꢁ
and N H hydrogen were found in the studied molecules.
[a]
1.0 mmol of PhSH, 0.5 mmol of alkyne, 3 mol % of NiCl2,
12 mol % of ligand and 1.0 mL of toluene at 1208C for 3 h
in a sealed tube with stirring.
The yields were determined by NMR.
Unidentified products were formed with approximate
yields of 10–30%.
In addition, the non-covalent S...O interactions were
found in the crystal: S1–O2¼3.323, S1–O4¼3.636,
S2–O6¼3.346, S2–O8¼3.667 Š. A similar conforma-
tion has been found for the selenium analogue suggest-
ing that this could be a general property of the Markov-
nikov-type products.
[b]
[c]
[d]
50 mol % of P(O-i-Pr)3.
Conclusions
The present study describes the first example of regiose-
ꢁ
addition of PhSH to alkynes were obtained in the ab- lective S H bond addition to alkynes catalyzed by nickel
sence of phosphine or phosphite ligands.
complexes. The usage of easily available and cheap
Excluding PR3 ligands also made the catalytic system NiCl2 is an important advantage compared to traditional
insensitive to the Ph2S2 impurity in PhSH, which is methods based on expensive palladium, platinum or
formed due to easy oxidation of the latter by air. Indeed, rhodium catalysts.
in the nickel-catalyzed reaction, product 3 was not
We have found that a catalytic amount of Et3N facili-
formed and Ph2S2 remained unreacted. In contrast to tated Markovnikov-type addition and significantly in-
NiCl2, phosphine complexes of palladium are efficient creased the yield of the product. Triethylamine may be
catalysts of the PhS-SPh addition to alkynes.[15,16]
used as an activating agent for a broad range of transi-
It is interesting to understand the role of the amine in tion metal chlorides MCln.
the studied reaction. The mechanism of the reaction
The non-catalytic pathway leading to the anti-Mar-
may include generation of the nucleophilic anion PhSꢁ kovnikov products was suppressed for non-activated al-
from PhSH, followed by substitution of chloride ligands kynes using a radical trap. The formation of bis(phe-
in NiCl2 by PhSꢁ. A similar reaction was observed in the nylthio)alkenes was avoided by excluding phosphine
case of chloride complexes of palladium.[17] It was shown and phosphite ligands from the catalytic system. Sup-
that chloride ligand substitution in PdCl2(PPh3)2 gave pressing these side-reactions greatly improved the yield
the same product as PhS-SPh oxidative addition to and selectivity. An important practical advantage of the
Pd(PPh3)4.[17] This suggests that Ni(SPh)2 [or the oligom- developed catalytic system is the tolerance to common
er (Ni(SPh)2)n] could be the active form of the catalyst in impurities like Ph2S2 in PhSH and water in solvents
the studied reaction. Another possibility concerns coor- and reagents.
dination of the amine as a ligand. This explanation has
Further studies on the scope of Ni-catalyzed reactions
been proposed for the amine effect in palladium-cata- in carbon-element bond formation are in progress in our
lyzed hydroselenation reactions.[18] At the moment it is group.
difficult to say which of the mechanisms (or both) takes
place in the studied catalytic system. This question will
be addressed in our future studies.
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Nickel(II) Chloride-Catalyzed Regioselective Hydrothiolation of Alkynes
FULL PAPERS
þ
ꢁ
¼
ꢁ
Figure 1. Molecular structure (top) and crystal packing (bottom) for the H2C C(SPh)CH2N HMe2 ·HOOC COO (1-B·
HOOC COOH).
ꢁ
The structure and stereochemistry of the products were proven
Experimental Section
with 2D COSY-LR and NOESY spectra as described earlier.[20]
All 2D spectra were recorded using inverse triple resonance
General
probehead with active shielded Z-gradient coil.
Unless otherwise stated, the synthetic work was carried out un-
der an argon atmosphere. The reagents were obtained from
commercial sources (Aldrich, Acros) and checkedby NMR be-
fore usage. The alkyne HCꢀC-CH2-SPh was prepared accord-
ing the literature method.[19] All NMR measurements were
performed using a three-channel Bruker DRX500 spectrome-
ter operating at 500.1, and 125.8 MHz for 1H and 13C nuclei, re-
spectively. 1H and 13C chemical shifts are reported relative to
the corresponding solvent signals used as internal reference.
General Synthetic Procedure for 1-A–1-E
NiCl2 ·6 H2O (3 mol %, 3.6 mg, 1.5ꢂ10ꢁ5 mol), PhSH
(110.2 mg, 1.0ꢂ10ꢁ3 mol), g-terpinene (68.1 mg, 5.0ꢂ10ꢁ4
mol), triethylamine (6 mol %, 3.0 mg, 3.0ꢂ10ꢁ5 mol), alkyne
(5.0ꢂ10ꢁ4 mol) and solvent (1 mL) were added into the reac-
tion tube and purged with argon. The tube was sealed in an ar-
Adv. Synth. Catal. 2005, 347, 1993 – 2001
ꢁ 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
1999

Valentine P. Ananikov et al.
FULL PAPERS
gon atmosphere and reaction mixture was heated (other reac-
tion conditions are given in Table 5). The colour of the solution
changed to dark brown upon addition of Et3N. After comple-
tion of the reaction the precipitate was filtered off, the solvent
was removed on a rotary evaporator and the crude product ex-
tracted with 2.0 mL of CHCl3. The products (except 1-B) were
purified by rapid flash chromatography[21] on silica L5/40 with
hexane/ethyl acetate gradient elution. Compared to a regular
column chromatography this gives a slightly smaller isolated
yield, however it is very economical in respect of solvents
and silica. After drying under vacuum the pure products
were obtained as light oils. The isolated yields are given in Ta-
NMRMonitoring of the PhSH Reaction with
Pd(PPh3)4 and Hydrogen Evolution
At room temperature PhSH (22.0 mg, 2.0ꢂ10ꢁ4 mol) was dis-
solved in 0.5 mL of C6D6 and placed in an NMR tube under an
argon atmosphere. Pd(PPh3)4 (46.2 mg, 4.0ꢂ10ꢁ5 mol) was
added to the solution, immediately changing from a colourless
solution to dark. Gas evolution occurred for the time period
1
over 10–15 min. H NMR spectra indicated the appearance
of the H2 peak at 4.5 ppm, which vanishes after purging the sol-
ution with argon. An authentic H2 sample was prepared by
purging hydrogen from a balloon through the C6D6 and d¼
4.5 ppm was the only new peak seen.[12] Literature data: d ꢃ
4.5 ppm for H2 dissolved in toluene-d8.[25]
ble 5. The products H2C C(SPh)-C6H10(OH) (1-E),[22]
¼
[23]
¼
¼
H2C C(SPh)-(CH2)4-CH3 (1-A), H2C C(SPh)-(CH2)3-CN
(1-F),[24] were identified according to the published data. The
data for the other compounds is given below.
Supporting Information
¼
ꢁ
ꢁ
H2C C(SPh)-CH2-NMe2 ·HOOC COOH (1-B·HOOC
COOH): White solid. After completing the reaction and re-
moving the solvent on a rotary evaporator a THF solution of
HOOC-COOH (0.065 g in 1 mL of THF) was added to the res-
idue resulting in immediate white precipitate formation. The
solid was washed with THF (3ꢂ3 mL) extracted with 5 mL
of methanol and dried in vacuum. 1H NMR (500 MHz;
CD3OD); d¼7.50 (d, J¼7.5, 2H, o-Ph), 7.43 (m, 3H, m- and
Crystal structure determination, selected bond lengths and
bond angles and data collection and processing parameters.
ꢁ
Crystallographic data for the structure 1-B·HOOC COOH
have been deposited with the Cambridge Crystallographic
Data Centre as supplementary publication no. CCDC-
269630. Copies of thedata can be obtained free of chargeon ap-
plication to CCDC, 12 Union Road, Cambridge CB21EZ, UK
[fax.: (internat.) þ441223/336-033; e-mail: deposit@ccdc.ca-
m.ac.uk].
¼
¼
p-Ph), 5.71 (s, 1H, HC ), 5.28 (s, 1H, HC ), 3.90 (s, 2H,
-CH2-), 2.90 (s, 6H, -CH3); 13C{1H} NMR (126 MHz; CD3
¼
¼
OD); d¼166.5 (C O), 137.4 [ C(SPh)-], 131.6 (i-Ph), 134.8,
¼
131.0 (o- and m-Ph), 130.4 (p-Ph), 123.2 (CH2 ), 61.8 (-CH2-
Acknowledgements
), 43.4 (-CH3); anal. calcd for C13H17NO4S: %: C 55.11, H
6.05, N 4.94; founþd: 54.79; H 6.12; N 4.65; mass spectrum
þ
ꢁ
The work was supported by the President of the Russian Feder-
ation (Grant for YoungScientists MD-2384.2004.3), the Russian
Foundation for Basic Research (Project No. 04-03-32501), and
the Division of Chemistry and Material Sciences of the Russian
Academy of Sciences (under program “Theoretical and Exper-
imental Investigation of the Nature of Chemical Bond and
Mechanisms of the Most Important Chemical Reactions and
Processes”).
(EI): m/e¼193 (M ꢁHOOC COOH, 3), 109 (SPh , 50), 84
(CH2 C-CH2-NMe2þ, 65); 58 (CH2-NMe2þ, 100).
¼
1
¼
H2C C(SPh)-CH2-OCH3 (1-C): Colourless oil. H NMR
(500 MHz; CDCl3) d¼7.44 (d, J¼7.5 Hz, 2H, o-Ph), 7.31 (t,
J¼7.5 Hz, 2H, m-Ph), 7.28 (d, J¼7.5 Hz, 1H, p-Ph), 5.48
¼
¼
ꢁ
(s, 1H, HC ), 5.12 (s, 1H, HC ), 3.97 (s, 2H, CH2-), 3.33
(s, 3H, -CH3); 13C{1H} NMR (126 MHz; CDCl3): d¼141.8
¼
[CH2 C(SPh)-], 132.5 (i-Ph), 132.8, 129.1 (o- and m-Ph),
¼
ꢁ
ꢁ
127.8 (p-Ph), 115.1 (CH2 ), 74.3 ( CH2-), 58.0 ( CH3); anal.
calcd. for C10H12OS, %: C 66.63, H 6.71; found: C 66.30, H
6.91; mass spectrum (EI): m/e¼180 (Mþ, 50).
References
H2C C(SPh)-CH2-SPh (1-D): Colourless oil. 1H NMR
¼
(500 MHz; CDCl3): d¼7.20–7.40 (m, 10H, Ph), 5.38 (s, 1H,
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