Reduction of aryl thiocyanates with SmI2 and Pd-catalyzed coupling with aryl halides as a route to mixed aryl sulfides

Article abstract of DOI:10.1021/jo961029h

A series of aryl iodides, with a range of substituents, has been successfully coupled using 10 mol percent Pd catalyst with samarium thiolates, derived from the corresponding aryl thiocyanates upon reductive cleavage with SmI₂. Reactions proceed in THF at 65°C in yields ranging from good to excellent and are compatible with both electron-donating and electron-withdrawing substituents, except NO₂. The reactions may also be conducted with aryl bromides although with somewhat lower yields.

Full text of DOI:10.1021/jo961029h

J . Org. Chem. 1996, 61, 7677-7680
7677
Red u ction of Ar yl Th iocya n a tes w ith Sm I2 a n d P d -Ca ta lyzed
Cou p lin g w ith Ar yl Ha lid es a s a Rou te to Mixed Ar yl Su lfid es
Ian W. J . Still* and F. Dean Toste
Department of Chemistry, Erindale College, University of Toronto, 3359 Mississauga Road North,
Mississauga, Ontario, Canada L5L 1C6
Received J une 3, 1996X
A series of aryl iodides, with a range of substituents, has been successfully coupled using 10 mol
% Pd catalyst with samarium thiolates, derived from the corresponding aryl thiocyanates upon
reductive cleavage with SmI2. Reactions proceed in THF at 65 °C in yields ranging from good to
excellent and are compatible with both electron-donating and electron-withdrawing substituents,
except NO2. The reactions may also be conducted with aryl bromides although with somewhat
lower yields.
Many applications of SmI2 are now known and there
have been several recent reviews of this topic.1 The use
of transition metals, notably palladium and nickel, in
catalyzing the coupling reaction between various aryl
derivatives and aryl halides to produce (mixed) aryl
compounds2-5 has been the subject of several recent
papers. Other methods for preparing mixed aryl sulfides
and sulfones have also appeared recently.6-9 There have
been two recent reports10,11 of the preparation of samari-
um(III) thiolates, although no attempts were made to
evaluate their synthetic utility.
We hoped to make use of aryl thiocyanates, readily
available by our recently described procedure,12 to extend
their synthetic utility13-15 to the preparation of mixed aryl
sulfides. Several methods already exist for preparing
mixed aryl sulfides7-9,16-21 and alkenyl aryl sulfides.22-24
While these procedures generally provide acceptable
yields, they suffer in several cases from drawbacks such
as the use of elevated temperatures or the need for rather
specialized and expensive solvents. In some cases also
the Pd(0) and Ni(0) catalytic species must be preformed,
and they are often difficult to handle. Since we have
already shown that samarium(II) iodide is a superior
reagent for the reductive cleavage of the S-CN bond, we
hoped that the (samarium) thiolates produced in this way
would react with aryl iodides in the presence of catalytic
Pd(0) species. These might, in turn, be generated during
the reaction from their more easily handled Pd (II)
progenitors, perhaps aided by the reducing power of the
SmI2 (Scheme 1). The results from this approach are
described below.
Resu lts a n d Discu ssion
We believe that the Sm(III) thiolates (Scheme 1)
generated from the corresponding aryl thiocyanates
during the course of this investigation are probably
covalent in nature. Marks and co-workers25 have re-
ported a value of 73.4 kcal/mol for the Sm-S bond
dissociation energy, remarkably similar to the value for
the Sm-I bond (72.7 kcal/mol).
X Abstract published in Advance ACS Abstracts, October 1, 1996.
(1) (a) Molander, G. A. Org. React. 1995, 44, 211. (b) Kamochi, Y.;
Tadahiro, K. Rev. Heteroatom Chem. 1994, 11, 165. (c) Soderquist, J .
A. Aldrichim. Acta 1991, 24, 15.
(2) Fujita, M.; Oka, H.; Ogura, K. Tetrahedron Lett. 1995, 36, 5247.
(3) Ciattini, P. G.; Morera, E.; Ortar, G. Synth. Commun. 1995, 25,
2883.
(4) Rai, R.; Aubrecht, K. B.; Collum, D. B. Tetrahedron Lett. 1995,
36, 3111.
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(6) Clayden, J .; Cooney, J . J . A.; J ulia, M. J . Chem. Soc., Perkin
Trans. 1 1995, 7.
(7) Wang, Z. Y.; Hay, A. S. Tetrahedron Lett. 1990, 31, 5685.
(8) Petrillo, G.; Novi, M.; Garbarino, G.; Dell’Erba, C. Tetrahedron
Lett. 1985, 26, 6365.
(9) Kita, Y.; Takada, T.; Mihara, S.; Tohma, H. Synlett 1995, 211.
(10) Cetinkaya, B.; Hitchcock, P. B.; Lappert, M. F.; Smith, R. G. J .
Chem. Soc., Chem. Commun. 1992, 932.
(11) Tatsumi, K.; Amemiya, T.; Kawaguchi, H.; Tani, K. J . Chem.
Soc., Chem. Commun. 1993, 773.
(12) Toste, F. D.; De Stefano, V.; Still, I. W. J . Synth. Commun. 1995,
25, 1277.
(13) Toste, F. D.; LaRonde, F.; Still, I. W. J . Tetrahedron Lett. 1995,
36, 2949.
(14) Toste, F. D.; Still, I. W. J . Tetrahedron Lett. 1995, 36, 4361.
(15) Toste, F. D.; Still, I. W. J . J . Am. Chem. Soc. 1995, 117, 7261.
(16) Dickens, M. J .; Gilday, J . P.; Mowlem, T. J .; Widdowson, D. A.
Tetrahedron 1991, 47, 8621.
(17) Cristau, H. J .; Chabaud, B.; Cheˆne, A.; Christol, H. Synthesis
1981, 892.
(18) Baran˜ano, D.; Hartwig, J . F. J . Am. Chem. Soc. 1995, 117, 2937.
(19) Kosugi, M.; Ogata, T.; Terada, M.; Sano, H.; Migita, T. Bull.
Chem. Soc. J pn. 1985, 58, 3657.
We initially investigated the reactivity of samarium-
(III) thiolate with iodobenzene in the presence of several
transition metal catalysts (Table 1). The use of a slight
excess of SmI2 during the reduction of aryl thiocyanates
to samarium(III) thiolates allows for the reduction of the
subsequently added transition metal catalyst to the M(0)
oxidation state. Addition of the aryl halide to this
reaction mixture, which now contains the samarium(III)
thiolate and the Pd(0) (or Ni(0)) complex generated in
situ, results in oxidative addition of ArX, as shown in
Scheme 1. Nucleophilic reaction of the samarium(III)
thiolate with the metal complex thus obtained provides
the thiolato-palladium(II) complex. Reductive elimina-
tion regenerates the Pd(0) catalyst, along with the mixed
aryl sulfide product. A similar mechanism presumably
operates for the nickel-catalyzed process, although this
may be complicated by the fact that nickel complexes
tend to equilibrate between tri- and tetracoordinate
species.26 A potential difficulty with the use of palladium-
catalyzed reactions involving thiol nucleophiles is the
poisoning of the catalyst, which is believed to occur
(20) Migita, T.; Shimizu, T.; Asami, Y.; Shiobara, J .; Kato, Y.; Kosugi,
M. Bull. Chem. Soc. J pn. 1980, 53, 1385.
(21) Takagi, K. Chem. Lett. 1987, 2221.
(22) Carpita, A.; Rossi, R.; Scamuzzi, B. Tetrahedron Lett. 1989, 30,
2699.
(23) Murahashi, S.; Yamamura, M.; Yanagisawa, K.; Mita, N.;
Kondo, K. J . Org. Chem. 1979, 44, 2408.
(24) Martinez, A. G; Barcina, J . O.; Cerezo, A. de F.; Subramanian,
L. R. Synlett 1994, 561.
(25) Nolan, S. P.; Stern, D.; Marks, T. J . J . Am. Chem. Soc. 1989,
111, 7844.
(26) Colon, I.; Kelsey, D. R. J . Org. Chem. 1986, 51, 2627.
S0022-3263(96)01029-8 CCC: $12.00 © 1996 American Chemical Society

7678 J . Org. Chem., Vol. 61, No. 22, 1996
Still and Toste
Sch em e 1
Ta ble 1. Com p a r ison of th e Efficien cy of Ca ta lysts in
th e Ta n d em Sm I2 Red u ction /Tr a n sition Meta l-Ca ta lyzed
Cou p lin g of Ar SCN w ith C6H5I
Ta ble 2. Cou p lin g of th e Sa m a r iu m (III) Th iola te fr om
1a w ith Va r iou s Ar yl Ha lid es, Ca ta lyzed by 10 Mol %
(P P h 3)2P d Cl2/d p p e a t 65 °C
during the reductive elimination. Baran˜ano and Hartwig18
have recently reported that the addition of (diphen-
ylphosphino)ethane (dppe) during the reaction slightly
alleviates this problem. In our work, the full role played
by the Sm species present is not clear.
The effectiveness of several catalysts in the tandem
samarium(II) iodide reduction/transition metal-catalyzed
coupling reaction of aryl thiocyanates is detailed in Table
1. In the absence of catalyst very little or no mixed aryl
sulfide could be isolated. The palladium(II) catalysts
generally appear to be more efficient than the nickel(II)
counterparts. These results suggest that palladium may
be the transition metal of choice for this reaction,
although other types of nickel(II) catalyst were not
examined. The yield of sulfide 2b obtained from the
reaction between compound 1b and iodobenzene, is very
similar in the presence of both a Pd(0) catalyst (entry 6)
and palladium(II) chloride (entry 7). Although not
conclusive proof, this does suggest that a similar mech-
anism may be operating in each case. This is in accord
with our proposal of in situ generation of a Pd(0) species
resembling (PPh3)4Pd (Scheme 1).
to use 1a , as perhaps a more representative prototype,
in our study of the synthetic scope of this reaction. A
brief study of the effect of varying the ligands employed
revealed little difference in effectiveness between tri-
phenylphosphine and triphenylarsine. The addition of
1,2-bis(diphenylphosphino)ethane (dppe), however, pro-
duced a significant enhancement in the yields obtained.
This is in accord with results obtained by Baran˜ano and
Hartwig,18 although Ortar and co-workers3 found dppe
to be quite ineffective in their catalytic system. The
results which we obtained in the study with 1a and a
number of different aryl halides appear in Table 2.
The yields obtained in Table 2 are generally good to
very good. While no clear-cut pattern of substituent
effects emerges from our results, it is perhaps significant
that the best two results were obtained with electron-
withdrawing groups (CF3, COCH3) in the para-position
Interestingly, 1b provided significantly higher yields
of the mixed aryl sulfide coupling products in Table 1.
This may be attributed to the increased electron-donating
power of the N,N-dimethylamino group, which presum-
ably results in increased nucleophilicity of the corre-
sponding samarium(III) thiolate. (Although tertiary
amines are known to enhance several coupling reactions
which involve the generation of HX as a byproduct,27
a
preliminary trial using a stoichiometric amount of N,N-
dimethylaniline in the coupling of 1a with iodobenzene
did not improve the yield of 2a observed.) In spite of this
enhanced reactivity observed for 1b, however, we decided
(27) Heck, R. F. Palladium Reagents in Organic Synthesis; Academic
Press: London, 1985.

Syntheses of Mixed Aryl Sulfides from Thiocyanates
J . Org. Chem., Vol. 61, No. 22, 1996 7679
heated in a water bath (temp ∼80 °C) until a yellow, nearly
insoluble solid formed. The reaction mixture was cooled to
ambient temperature and the yellow product (32.7 g, 93%)
collected by vacuum filtration, washed with methanol (25 mL),
and dried overnight in a desiccator prior to use.
P r ep a r a tion of (P P h 3)2NiCl2. Following the general
procedure of Venanzi,32 to a deep green solution of nickel(II)
chloride hexahydrate (2.38 g, 0.01 mol) in distilled water (3
mL) was added acetic acid (75 mL). The reaction mixture
turned from a dark green suspension to a clear light green
solution. To this light green solution was added triphen-
ylphosphine (5.25 g, 0.02 mol), resulting in the formation of a
dark blue solution, which was stirred for 25 h at 25 °C. After
24 h, the blue solid was collected by suction filtration and
washed with acetic acid to afford a greenish-blue solid (5.43
g, 83%).
Rep r esen ta tive P r oced u r e for Mixed Ar yl Su lfid es. 4′-
(N,N-Dim eth yla m in o)p h en yl P h en yl Su lfid e (2b). To a
deep blue solution of SmI2 (3.09 mmol) in dry THF (45 mL)
was added the aryl thiocyanate 1b (0.25 g, 1.24 mmol), and
the resulting reaction mixture was stirred at ambient tem-
perature for 1.5 h. After 1.5 h, the reaction mixture was
transferred via a double-ended needle to a refluxing solution
of bis(triphenylphosphine)palladium(II) chloride (0.09 g, 0.13
mmol, 10 mol %), diphenylphosphinoethane (0.05 g, 0.13
mmol), and iodobenzene (0.14 mL, 1.25 mmol) in dry THF (10
mL). The addition caused the reaction mixture to immediately
become orange and then deep red-brown. After refluxing an
additional 16 h, the reaction mixture was cooled to room
temperature and the solvent removed under reduced pressure.
The residual solid was treated in the usual way and finally
afforded a yellow oil. Flash chromatography (Rf ) 0.65)
afforded a yellow solid (0.19 g, 78%), which was recrystallized
from heptane, mp 63-64 °C [lit.33 mp 66.5-67 °C]. 1H NMR:
δ 7.39 (d, J ) 8.9 Hz, 2H), 7.16 (m, 5H), 6.71 (d, J ) 8.9 Hz,
2H), 3.02 (s, 6H); EIMS: m/z (%), 229(100), 152(21).
The following diaryl sulfides (see also Table 2) were pre-
pared by the (PPh3)2PdCl2/dppe-catalyzed coupling of samari-
um(III) thiolates and aryl halides, using the procedure detailed
above for the preparation of 2b.
4′-Meth ylp h en yl p h en yl su lfid e (2a ): colorless oil after
Kugelrohr distillation at 95-100 °C/12 mm [lit.34 bp 174 °C/
17 mm]. 1H NMR: δ 7.32 (d, J ) 8.0 Hz, 2H), 7.26 (m, 5H),
7.15 (d, J ) 8.0 Hz, 2H), 2.36 (s, 3H).
4-[(4′-Meth ylp h en yl)th io]a cetop h en on e (3a ): light yel-
low solid after recrystallization from CH2Cl2:hexanes, mp 86-
88 °C. 1H NMR: δ 7.80 (d, J ) 8.7 Hz, 2H), 7.41 (d, J ) 8.0
Hz, 2H), 7.22 (d, J ) 8.0 Hz, 2H), 7.15 (d, J ) 8.7 Hz, 2H),
2.55 (s, 3H), 2.40 (s, 3H); EIMS: m/z (%), 242(85), 227(100),
199(9); HR-EIMS calcd for C15H14OS 242.0765, found 242.0759.
Anal. Calcd for C15H14OS: C, 74.34; H, 5.82. Found: C, 73.88;
H, 5.99.
4-F lu or op h en yl 4′-m eth ylp h en yl su lfid e (3b): colorless
oil after Kugelrohr distillation at 135-140 °C/12 mm [lit.35 bp
100-104 °C/0.3 mm]. 1H NMR: δ 7.29 (m, 2H), 7.24 (d, J )
9.1 Hz, 2H), 7.12 (d, J ) 9.1 Hz, 2H), 6.99 (m, 2H), 2.33 (s,
3H); EIMS: m/z (%), 218(100), 203(29), 91(31); HR-EIMS calcd
for C13H11FS 218.0565, found 218.0562.
of the aryl iodide. As expected, no coupling product was
obtained when 4-iodonitrobenzene was used: we had
earlier observed that nitro groups are incompatible with
the use of SmI2, although they can be used with other
types of Pd(0) coupling reactions involving thiolates.3 No
coupling product was obtained from the reaction of
N-Boc-protected 4-iodoaniline, perhaps due to deblocking
of the protecting group during the reaction.
It appears that both aryl iodides and bromides can be
utilized in these reactions. In accord with earlier studies,
however, aryl iodides provide higher yields of the diaryl
sulfides than the corresponding bromides. Interestingly,
in an attempted competition reaction using 4-bromo-1-
iodobenzene, the only coupling product isolated was 2a .
This suggests that initial coupling (with the iodide
functionality) was accompanied by a dehalogenation step.
Aryl halides are known to be reduced by a wide variety
of reducing agents, including triphenylphosphine.28
This coupling reaction should be capable of extension
to a wide variety of aryl thiocyanates and aryl halides.
It offers several advantages over earlier literature meth-
ods in that it avoids the need to isolate the thiol, the
manipulation of air-sensitive transition metal complexes,
and the use of special solvents (THF was used through-
out), as well as being carried out under relatively mild
conditions.
Exp er im en ta l Section
All the starting aryl iodides and bromides used (with the
exceptions noted below) and other intermediates were obtained
from the Aldrich Chemical Co. and used without further
purification, unless indicated otherwise. 4-Fluoro-1-iodoben-
zene was obtained from 4-fluoroaniline by diazotization and
subsequent reaction with potassium iodide.29 4-Methyl-1-
thiocyanatobenzene (1a ) was prepared from 4-methylben-
zenethiol by the procedure of Harpp et al.30 and N,N-dimethyl-
4-thiocyanatoaniline (1b) by our previously reported procedure.12
Samarium(II) iodide was generated in situ from samarium
metal (40 mesh; Alfa Aesar) and either 1,2-diiodoethane or
diiodomethane (Lancaster Synthesis Inc.) by literature pro-
cedures.31 Tetrahydrofuran was dried by refluxing over
sodium and benzophenone until a permanent purple coloration
was present. All reactions were run in oven- or flame-dried
glassware under an atmosphere of argon. The products were
isolated by evaporation to dryness on the rotary evaporator,
redissolving the organic residue in CH2Cl2:hexanes (1:1),
washing with water, and drying (Na2SO4). Purification was
conducted by flash chromatography on silica gel, eluting with
CH2Cl2, unless otherwise stated.
Melting points and boiling points are uncorrected: the latter
represent oven temperatures recorded during Kugelrohr (bulb-
to-bulb) vacuum distillation. Mass spectra were recorded at
an ionizing voltage of 70 eV. FTIR spectra were recorded
under the conditions indicated. 1H NMR spectra were ob-
tained in CDCl3 at 200 MHz and 13C NMR spectra were
recorded at 100.6 or 125.7 MHz. Elemental analyses were
performed by the Scandinavian Microanalytical Laboratory,
Box 25, DK-2730, Herlev, Denmark.
4-Meth oxyp h en yl 4′-m eth ylp h en yl su lfid e (3c): light
yellow solid after recrystallization from hexanes, mp 43-45
°C [lit.36 mp 43-45 °C, from 95% EtOH]. 1H NMR: δ 7.37 (d,
J ) 8.9 Hz, 2H), 7.14 (d, J ) 8.3 Hz, 2H), 7.07 (d, J ) 8.9 Hz,
2H), 6.87 (d, J ) 8.3 Hz, 2H), 3.81 (s, 3H), 2.30 (s, 3H); EIMS:
P r ep a r a tion of (P P h 3)2P d Cl2. Following the general
procedure of Heck,27 to a solution of palladium(II) chloride
(8.85 g, 0.05 mol) and lithium chloride (4.25 g, 0.10 mol) in
dry methanol (80 mL) was added triphenylphosphine (27.5 g,
0.11 mol). The resulting reddish brown reaction mixture was
m/z (%), 230(100), 215(49), 91(10). Anal. Calcd for C14H14
-
OS: C, 73.00; H, 6.13; S, 13.92. Found: C, 72.68; H, 6.15; S,
13.58.
4′-Meth ylph en yl 4-(tr iflu or om eth yl)ph en yl su lfide (3d):
light yellow solid after recrystallization from hexanes, mp 93-
95 °C. 1H NMR: δ 7.45 (d, J ) 8.5 Hz, 2H), 7.40 (d, J ) 8.4
(28) March, J . Advanced Organic Chemistry, 4th ed.; J ohn Wiley &
Sons, Inc.: New York, 1992; p 566.
(29) Vogel, A. I. Practical Organic Chemistry, 3rd ed.; Longmans,
Green & Co. Ltd.: London, 1956; p 598.
(30) Harpp, D. N.; Friedlander, B. T.; Smith, R. A. Synthesis 1979,
181.
(31) Girard, P.; Namy, J . L.; Kagan, H. B. J . Am. Chem. Soc. 1980,
102, 2693.
(32) Venanzi, L. M. J . Chem. Soc. 1958, 719.
(33) Bunnett, J . F.; Scamehorn, R. G.; Traber, R. P. J . Org. Chem.
1976, 41, 3677.
(34) Modena, G.; Maioli, L. Gazz. Chim. Ital. 1957, 87, 1306.
(35) Dayal, S. K.; Taft, R. W. J . Am. Chem. Soc. 1973, 95, 5595.
(36) Hyne, J . B.; Greidanus, J . W. Can. J . Chem. 1969, 47, 803.

7680 J . Org. Chem., Vol. 61, No. 22, 1996
Still and Toste
Hz, 2H), 7.22 (d, J ) 8.4 Hz, 2H), 7.20 (d, J ) 8.5 Hz, 2H),
2.39 (s, 3H); EIMS: m/z (%), 268(100), 249(9), 199(14), 184-
(18), 91(40); HR-EIMS calcd for C14H11F3S 268.0534, found
268.0531. Anal. Calcd for C14H11F3S: C, 62.67; H, 4.13; S,
11.95. Found: C, 62.94; H, 4.30; S, 11.80.
Eth yl 4-[(4′-Meth ylp h en yl)th io]ben zoa te (3e): low melt-
ing solid from cold hexanes, mp 22-24 °C. 1H NMR: δ 7.88
(d, J ) 8.5 Hz, 2H), 7.40 (d, J ) 7.9 Hz, 2H), 7.22 (d, J ) 7.9
Hz, 2H), 7.15 (d, J ) 8.5 Hz, 2H), 4.34 (q, J ) 7.2 Hz, 2H),
2.40 (s, 3H), 1.37 (t, J ) 7.2 Hz, 3H); EIMS: m/z (%), 272-
(100), 244(26), 227(68), 199(20), 184(54), 91(33); HR-EIMS
calcd for C16H16O2S 272.0871, found 272.0872.
4′-Meth ylp h en yl 2-(tr iflu or om eth yl)p h en yl su lfid e (4):
pale yellow oil after Kugelrohr distillation at 230 °C/15 mm.
1H NMR: δ 7.66 (dd, J ) 7.2, 1.2 Hz, 1H), 7.37 (d, J ) 8.2 Hz,
2H), 7.30 (m, 2H), 7.19 (d, J ) 8.2 Hz, 2H), 7.08 (dd, J ) 7.9,
1.2 Hz, 1H), 2.38 (s, 3H); EIMS: m/z (%) 268(100), 199(10),
184(14), 91(39); HR-EIMS calcd for C14H11F3S 268.0534, found
268.0521.
Ack n ow led gm en t. This work was supported in part
by the Natural Sciences and Engineering Research
Council of Canada (NSERC). The authors are grateful
for financial assistance from Glaxo Group Research Ltd
and from Du Pont Agricultural Products. F.D.T. ac-
knowledges the award of an Ontario Graduate Scholar-
ship for 1994-95.
Su p p or tin g In for m a tion Ava ila ble: FT-IR spectral de-
tails for the mixed aryl sulfides obtained are listed, along with
a table of 13C-NMR chemical shift data for these compounds
and reproductions of the individual 13C-NMR (and APT)
spectra for each (16 pages). This material is contained in
libraries on microfiche, immediately follows this article in the
microfilm version of the journal, and can be ordered from the
ACS; see any current masthead page for ordering information.
J O961029H