Highly regio- and stereoselective hydrothiolation of acetylenes with thiols catalyzed by a well-defined supported Rh complex

Article abstract of DOI:10.1039/c1cc11605c

Highly regio- and stereoselective hydrothiolation of a wide range of alkynes with various thiols was demonstrated in the presence of a well-defined Rh complex supported on mesoporous SBA-15 silica. The catalyst was easily recovered and reused several times without significant loss of activity or selectivity.

Full text of DOI:10.1039/c1cc11605c

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Highly regio- and stereoselective hydrothiolation of acetylenes with thiols
catalyzed by a well-defined supported Rh complexw
Yong Yang and Robert M. Rioux*
Received 20th March 2011, Accepted 28th April 2011
DOI: 10.1039/c1cc11605c
Highly regio- and stereoselective hydrothiolation of a wide range
of alkynes with various thiols was demonstrated in the presence
of a well-defined Rh complex supported on mesoporous SBA-15
silica. The catalyst was easily recovered and reused several times
without significant loss of activity or selectivity.
and can even provide an enhancement in the reactivity, selectivity
and/or enantioselectivity in some cases.10,11 The chemical bonding
between metal complexes and functional groups of the support
maintains the isolated nature of metal complexes, which can
influence the catalytic performance in a manner that the analogous
homogeneous complex does not exhibit in solution.13 In spite of
tremendous effort dedicated to the immobilization of homo-
geneous complexes over the last two decades, very few examples
of alkyne hydrothiolation with thiols catalyzed by heterogeneous
catalysts with high activity and excellent regio- and stereo-
selectivity have appeared.6 Therefore, the development of a stable
heterogeneous rhodium catalyst that allows for highly regio- and
stereoselective hydrothiolation of a wide range of substrates (thiols
and alkynes) is worthwhile. Herein, we report the highly
regio- and stereoselective hydrothiolation of alkynes with thiols
catalyzed by a well-defined heterogeneous rhodium complex
catalyst supported on SBA-15 under mild reaction conditions.
Preparation of the supported rhodium complexes on SBA-15,
labeled as Rh–P–SBA-15, Rh–N–SBA-15, and Rh–2N–SBA-15,
respectively, was performed under a nitrogen atmosphere in a
step-by-step manner (Scheme S1, ESIw). Characterization results
from BET, XRD, and HR-TEM (Table S1, Fig. S1–S3, ESIw) for
a Rh–P–SBA-15 catalyst show that the ordered mesoporous
channel structure was preserved upon functionalization and
immobilization of RhCl(PPh3)3 occurred within the pores. The
appearance of new peaks at d = 18, 26, 33, 58, 68, and 128–132 ppm
in the 13C solid-state NMR spectrum further reveals that the
biphenylphosphine–propyl linker was grafted onto the SBA-15
surface (Fig. 1). The 31P solid-state NMR spectrum (Fig. S5,
ESIw) exhibited a broad resonance centered at d = 28.0 ppm
corresponding to the Rh–P complex along with a strong peak at
d = À15.8 ppm assignable to the free biphenylphosphine ligand
of the linker, indicating that both the biphenylphosphine ligand
and RhCl(PPh3)3 were successfully grafted and immobilized onto
SBA-15, respectively. There was no indication of an oxidized
phosphine peak at d = 38.0 ppm, or phosphonium species at
d = 24.0 ppm.14 The loading of the immobilized rhodium
complex was 0.92 wt% (Rh), which corresponds to a rhodium
density of 0.09 nmÀ2. This density ensured that the probability of
individual rhodium complexes that are site-isolated was high.
Our initial efforts concentrated on the optimization of the
reaction conditions for the regio-defined synthesis of vinyl sulfides.
The addition of phenylacetylene (2a) to thiophenol (1a) was
chosen as a model reaction, and the results are compiled in
Transition metal catalyzed addition of an S–H bond to alkynes is
a straightforward and atom-efficient method for the formation of
stereo- and regio-defined vinyl sulfides, which are versatile inter-
mediates for synthesis of biologically active compounds, organic
building blocks, and new materials.1 Several metal-based homo-
geneous catalysts such as Rh,2 Ir,3 Ni,4 Pd,5 Pt,6 Au,7 Zr,8a and
f-elements8b–d have been developed to produce regio- and stereo-
selective vinyl sulfides. Among these transition metal complexes
investigated, rhodium complexes have received considerable
attention, due to their high activity and regio- and stereoselectivity
for either Markovnikov or anti-Markovnikov products under
mild reaction conditions.2 However, industrial applications of
these homogeneous rhodium complexes remain a challenge
because they are expensive, cannot be recycled, and difficult to
separate from the product mixture, which is a particularly
significant drawback for their application in the pharmaceutical
industry. The immobilization of catalytically active species, i.e.
organometallic complexes, onto a solid support to produce a
molecular heterogeneous catalyst is one potential solution to the
latter two problems.9 The merits of surface organometallic
catalysts are derived not only from their ease of separation from
the reaction media but also their unique activity derived from
their site-isolation and the structure of their active sites.
The immobilization of rhodium complexes through covalent
bond formation with functional groups on silica is the most
commonly employed method to form surface organometallic
catalysts that are applicable for a variety of catalytic chemistries
including hydrogenation,10 hydroformylation,11 and hydro-
silylation.12 These structures reduce rhodium leaching from the
support and subsequent metal contamination of the products,
Department of Chemical Engineering, The Pennsylvania State
University, 165 Fenske Laboratory, University Park, PA 16802-4400,
USA. E-mail: rioux@engr.psu.edu; Fax: +1-814-865-7846;
Tel: +1-814-867-2503
w Electronic supplementary information (ESI) available: General
information, experimental details, catalyst characterization and recycl-
ability data and 1H/13C NMR, HR-MS data for (E)-vinyl sulfides. See
DOI: 10.1039/c1cc11605c
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6557–6559 6557

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reduced activity compared to DCE (Table 1, entries 5–8). The
Markovnikov addition product 4aa was produced simultaneously
when the reaction was performed with some solvents, such as
dichloromethane, acetone, and THF (Table 1, entries 9–11).
Among the solvents investigated, DCE was found to be the best
choice for the formation of the (E)-anti-Markovnikov vinyl
sulfide product. In addition, the transformation catalyzed by
Rh–P–SBA-15 proceeded to 480% conversion in the presence
of galvinoxy, a free radical inhibitor (galvinoxy/Rh = 3, molar
ratio), ruling out the possibility that a radical mechanism
contributes to the formation of the anti-Markovnikov addition
product (Table 1, entry 12).
Fig. 1 13C solid-state NMR spectra of (a) Cl–SBA-15; (b) P–SBA-15;
and (c) Rh–P–SBA-15.
Encouraged by this discovery, the scope of alkynes was next
studied using 1a as the thiol substrate in the presence of
Rh–P–SBA-15 in DCE; the results are summarized in Table 2.
Aromatic, aliphatic, and internal alkynes were hydrothiolated to
the (E)-anti-Markovnikov products with moderate to high
conversion with excellent regio- and stereoselectivity. Electron-
rich and electron-poor substituents at the 3 and 4 positions on the
phenyl ring of aromatic alkynes all gave satisfactory conversions
(Table 2, entries 2, 4, 5, 7, and 8). A methyl group at the 2-position
(2ac) did not hinder the reaction, but a methoxy group at the same
position (2af) significantly decreased the conversion (Table 2,
entries 3 and 6). Aliphatic alkynes reacted with 1a to afford
the corresponding (E)-anti-Markovnikov vinyl sulfides with
satisfactory conversion and exclusive regio- and stereoselectivity,
but required either a considerably longer reaction time, elevated
temperature or both (Table 2, entries 9–13). The internal alkyne
1-phenyl-1-propyne (2an) underwent stereoselective hydrothiol-
ation but also required a longer reaction time (Table 2, entry 14);
however no addition products were isolated when the trans-
formation of diphenylacetylene (2ao) with 1a was performed
under otherwise identical reaction conditions (Table 2, entry 15).
Table 1. Wilkinson’s catalyst, RhCl(PPh3)3, exhibited high activity
and excellent regio- and stereoselectivity, achieving up to 98%
conversion and 94% selectivity to E-3aa in DCE (1,2-dichloro-
ethane) solution within 45 min at room temperature (Table 1,
entry 1). Upon immobilization of RhCl(PPh3)3 onto the functio-
nalized SBA-15, the regio- and stereoselectivity depended on the
functional groups linked to the rhodium complex. Markovnikov
addition was totally suppressed. The stereoselectivity could be
switched by the type of functional group linked to SBA-15. The
addition of 2a to 1a catalyzed by Rh–N–SBA-15 gave a mixture of
anti-Markovnikov ((E + Z)-3aa) products with the (Z)-isomer
(3aa) as the main product (Table 1, entry 2). The catalyst
Rh–2N–SBA-15 produced excellent regio- and stereoselectivity
to Z-3aa with activity comparable to Rh–N–SBA-15 (Table 1,
entry 3). In sharp contrast, exclusive and reversed regio- and
stereoselectivity to E-3aa with a slightly higher conversion was
obtained for this transformation in the presence of Rh–P–SBA-15
under otherwise identical reaction conditions (Table 1, entry 4). In
order to synthesize (E)-anti-Markovnikov vinyl sulfides with
Rh–P–SBA-15, we next investigated the influence of solvents on
this transformation. With solvents such as ethanol, toluene, ethyl
acetate (EtOAc), and hexane, only E-3aa was obtained but with
Table 2 Catalytic hydrothiolation of thiophenol with a wide range of
alkynesa
Table 1 Hydrothiolation of thiophenol with phenylacetylene under
different conditionsa
Selectivityc/%
(E + Z) :
Temp/1C Convb/%
4aa-o
Selectivityc/%
E : Z
Entry R1
R2
1d
Ph
H 2aa 25
H 2ab 25
H 2ac 25
H 2ad 25
87.5
83.6
78.6
85.9
83.8
62.2
81.8
80.2
72.3
76.6
97.6
98.0
86.0
68.4
n.rf
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
98 : 2
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
n.r
Entry Catalyst
Solvent Convb/%
(Z + E) : 4aa E : Z
2d
4-Me–Ph
2-Me–Ph
3-Me–Ph
4-MeO–Ph H 2ae 25
2-MeO–Ph H 2af 25
1d
2
RhCl(PPh3)3
DCE
Rh–N–SBA-15 DCE
Rh–2N–SBA-15 DCE
98
94 : 6
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
65 : 35
94 : 6
100 : 0
29 : 71
1 : 99
3d
4d
84.3
74.9
87.5
34.4
5d
3
6d
4
5
6
7
8
9
10
11
12e
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
Rh–P–SBA-15
DCE
EtOH
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
100 : 0
7d
4-F–Ph
H 2ag 25
H 2ah 25
H 2ai 60
H 2aj 60
8d
4-Br–Ph
n-C5H11
n-C10H21
HO–(C2H4) H 2ak 60
Cl–(C2H4) H 2al 60
Cyclohexene H 2am 25
98 : 2
Toluene 74.2
EtOAc 7.4
Hexane 62.0
CH2Cl2 96.4
Acetone 96.9
9e
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
499 : 1
n.r
10e
11e
12e
13e
14e
15e
THF
DCE
14.6
81.8
96 : 4
93 : 7
Ph
Ph
Me 2an 60
Ph 2ao 60
a
Reaction conditions: 0.5 mmol phenylacetylene, 0.55 mmol thiophenol,
50 mg catalyst (4.5 mmol Rh), 2 mL solvent, room temperature and a
reaction time of 20 h. Conversion of phenylacetylene. Determined
a
Reaction conditions: 0.5 mmol alkynes, 0.55 mmol thiophenol,
b
b
c
50 mg catalyst (4.5 mmol Rh) and 2 mL DCE. Conversion of
alkynes. Determined by 1H NMR analysis of the crude mixture.
c
1
by H NMR analysis of the crude mixture. Reaction time of 45 min.
d
d,e
Reaction time of 20, 40 h. f No reaction.
e
In the presence of 3 mol% galvinoxyl free radical inhibitor.
c
6558 Chem. Commun., 2011, 47, 6557–6559
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Table 3 Catalytic hydrothiolation of phenylacetylene with a wide
range of thiolsa
to the oxidation of the phosphine ligands by traces of air entering
the system during the refilling steps.
In summary, a well-defined supported rhodium catalyst has
been developed for the hydrothiolation of alkynes with thiols. Due
to the high activity and excellent regio- and stereoselectivity
of the heterogeneous catalyst, the process represents a green
methodology for synthesizing regio-defined vinyl sulfides and
extends the synthetic utility of hydrothiolation reactions. Further
studies are underway on the scope of other substrates and in
understanding the role of the functional groups grafted to the
silica surface in the reaction regio- and stereoselectivity.
Selectivityc/%
(E + Z):
E : Z
Entry R
Temp/1C Time/h Convb/%
4bb-i
16
17
18
19
20
21
22
23
4-Me–Ph 2bb 25
4-MeO–Ph 2bc 25
4-Cl–Ph 2bd
4-Br–Ph 2be
PhCH2 2bf
Cyclohexane 2bj 60
CH3CH2 2bh
CF3CH2 2bi
20
20
20
20
40
40
40
24
87.5
83.6
78.6
85.9
83.8
62.2
81.8
80.2
499 : 1 100 : 0
499 : 1 100 : 0
499 : 1 100 : 0
499 : 1 100 : 0
91 : 9 100 : 0
80 : 20 100 : 0
71 : 29 100 : 0
92 : 8 100 : 0
25
25
60
This work was supported by the Pennsylvania State
University and the Penn State Institutes of Energy and the
Environment through start-up funds provided to R.M.R.
60
60
Notes and references
a
b
Reaction conditions are the same as Table 2. Conversion of
alkynes. Determined by 1H NMR analysis of the crude mixture.
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Functional groups such as fluoro, chloro, hydroxyl, methoxy,
and olefinic were compatible with this catalytic system
(Table 2, entries 7, 8, and 11–13). In all cases listed in
Table 2, the corresponding disulfide adduct was not formed
as a byproduct and no double bond dimerization occurred.
Likewise, various aromatic and aliphatic thiols reacted with 2a
in the presence of Rh–P–SBA-15 with high conversion with good
to excellent regio- and stereoselectivity in DCE, as shown in
Table 3. Phenylacetylene (2a) reacted efficiently with aromatic
thiols bearing electron-rich or electron-poor groups on the phenyl
ring with excellent regio- and stereoselectivity (Table 3, entries
16–19). The addition of aliphatic thiols to 2a proceeded smoothly
and required both longer reaction time and higher temperature to
achieve satisfactory conversion (Table 3, entries 20–23). Notably,
unlike aromatic thiols, the regioselectivity of aliphatic thiols
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instance, the regioselectivity to 3bf and 3bi was 91 and 92%
(Table 3, entries 20 and 23), but only 80 and 71% for 3bj and 3bh
and 20 and 29% for 4bj and 4bh were obtained, respectively
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heterogeneous catalyst Rh–P–SBA-15 or a leached rhodium
species in solution, we carried out the addition of phenylacetylene
(2a) to thiophenol (1a) and removed the catalyst from the reaction
mixture by filtration at approximately 50% conversion of 2a
(Fig. S6, ESIw). After removal of the Rh–P–SBA-15 catalyst,
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c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 6557–6559 6559