Arylation of n-hexylthiol and n-hexyl phenyl sulfide using diphenyliodonium triflate: Synthetic and mechanistic aspects - Application to the transformation of n-hexylthiol to n-hexylselenide

Article abstract of DOI:10.1055/s-2006-926235

n-Hexyl diphenylsulfonium triflate has been efficiently prepared from n-hexylthiol and diphenyliodonium triflate and has been efficiently transformed to n-hexyl selenide. Georg Thieme Verlag Stuttgart.

Full text of DOI:10.1055/s-2006-926235

4
84
LETTER
Arylation of n-Hexylthiol and n-Hexyl Phenyl Sulfide Using Diphenyl-
iodonium Triflate: Synthetic and Mechanistic Aspects – Application to the
Transformation of n-Hexylthiol to n-Hexylselenide
a
a
a,b
Arylation of
n
-Hex
l
ylthiol
a
and
n
-Hex
i
yl Phen
n
yl
S
ulfide Krief,* Willy Dumont, Michael Robert
a
Laboratoire de Chimie Organique de Synthèse, Facultés Universitaires N.-D. de la Paix, 61 rue de Bruxelles, Namur 5000, Belgium
Fax +32(81)724536; E-mail: alain.krief@fundp.ac.be
b
Fonds pour la Formation à la Recherche dans l’Industrie et l’Agriculture, 5 rue d’Egmont, Bruxelles 1000, Belgium
Received 9 December 2005
2
We now found that diphenyliodonium triflate (4b), readi-
ly available from bis(acetoxy)iodobenzene on sequential
treatment with triflic acid and benzene (–30 °C to 20 °C,
Abstract: n-Hexyl diphenylsulfonium triflate has been efficiently
prepared from n-hexylthiol and diphenyliodonium triflate and has
been efficiently transformed to n-hexyl selenide.
5
h, 93% yield), not only advantageously replaces diphen-
Key words: arylations, thiols, desulfurization, selenium, substitu-
tions
yliodonium tetrafluoroborate to arylate n-hexyl phenyl
sulfide (3a) but is also an extremely valuable arylating
agent of n-hexylthiol 2a.
The later reaction requires neither the use of palladium
catalyst nor heating to 110 °C. It has been achieved, in
almost quantitative yield at room temperature, in polar
solvents such as DMSO, DMF, or pyridine, on the pre-
formed n-hexylthiolate (Scheme 2, entries a–c, compare
to Scheme 1).3
We recently described that n-hexyl selenides 1 can be pre-
pared from n-hexylthiol (2a) in a three-step sequence.
This involves its diarylation to produce sequentially n-
hexyl phenyl sulfide (3a) then n-hexyl diphenyl sulfo-
nium tetrafluoroborate (5a) and subsequent substitution
of the diphenylsulfide moiety of 5a by selenolates 6
1
(
Scheme 1).
Results are poorer in ethereal solvents (Scheme 2, entries
d, e) although the yield is slightly better when the reaction
is carried out in DME (Scheme 2, entry e).
0
1
equiv PhI, Pd , toluene
CsOH, 110 °C, 4 h
1.5 equiv Ph2I BF4 4a
n-Hex-SH
n-Hex-S-Ph
3a 85 %
5
% Cu(OAc)2,
2a
Diphenyliodonium triflate (4b) proved to be much better
than the corresponding tetrafluoroborate for the arylation
of n-hexyl phenyl sulfide (3a, Scheme 3, entry a, compare
toluene, 110 °C, 1 h
1
equiv RSeNa 6, DMF
n-Hex-Se-R
1
~80%
n-Hex-SPh2 BF4
a 62 %
or EtHO, 20 °C, 1 h
1,3d
5
R = Me, CH2Ph, Ph, o-NO2Ph
to Scheme 1). This reaction is best achieved at 110 °C
with an excess of 4b (1.5 equiv, Scheme 3, compare en-
Scheme 1 Arylation of n-hexylthiol and n-hexyl phenyl sulfide
using iodobenzene and diphenyliodonium tetrafluoroborate
tries a, b) in toluene (1 M) in the presence of cupric acetate
4
(
5%). It is, however, heterogeneous and requires an in-
duction period of about 0.8 hours before proceeding at
This synthetic scheme although quite efficient possesses
few drawbacks due to the high temperature required in the
first two steps (110 °C, 2a to 3a and 3a to 5a), the modest
yield of the second step (3a to 5a) and the lengthy syn-
thesis of diphenyliodonium tetrafluoroborate (4a) from
once, in a very short time (0.2 h).5
a
The reaction between 3a and 4b (1.5 equiv) is highly de-
pendent on the amount of cupric acetate. It does not occur
in its absence (110 °C, 1 h, 100% recovery of 3a), is best
achieved in the presence of a 5% molar amount of cupric
1
benzene (54%).
solvent
Ph I Ph CF SO 4b
3 3
n-Hex SH + NaH
n-Hex SNa
n-Hex S Ph + PhI
2
0 °C, 1 h
2a
20 °C, 1 h
3a
a
b
c
d
e
f
DMSO
DMF
pyridine
Et2O or THF
DME
93%
75%
82%
45%
60%
70%
toluene
Scheme 2 Solvent effects in the synthesis of n-hexyl phenyl sulfide from n-hexylthiol
SYNLETT 2006, No. 3, pp 0484–0486
1
5.
0
2.
2
0
0
6
Advanced online publication: 06.02.2006
DOI: 10.1055/s-2006-926235; Art ID: G37405ST
©
Georg Thieme Verlag Stuttgart · New York

LETTER
Arylation of n-Hexylthiol and n-Hexyl Phenyl Sulfide
485
5% equiv copper catalyst
n-Hex
S
Ph + Ph
I
Ph CF SO3
3
8
toluene
3a
4b
N
N
Ph
n-Hex
n-Hex
S
CF3SO3
+
n-Hex S
CF3SO3
Figure 1 Structure of cuproine
Ph
Ph
5b
7b
In conclusion, we disclose new efficient arylation reac-
tions of n-hexylthiol as well as n-hexyl phenyl sulfide
which both use diphenyliodonium triflate as the arylating
agent.
Scheme 3 Arylation of n-hexyl phenyl sulfide using diphenyl-
iodonium triflate
acetate (Table 1, entry a), but delivers poor yield of 5b
when the catalyst is used either in lower or in higher quan-
tities (1% or 20% molar equiv, 5b:3a ratio: 63:32, 78:00,
respectively).
We finally observed that substitution of n-hexyl diphenyl
sulfonium triflate by selenium nucleophiles is as good as
that of the corresponding fluoroborate (Scheme 4, com-
pare to Scheme 1).
At the difference of the corresponding tetrafluoroborate
4
a, diphenyliodonium triflate (4b), is able to arylate n-
Se2Na2, DMF, 20 °C, 1 h
(
Hex-Se)2
hexyl phenyl sulfide at temperature lower than 110 °C (80
8
3%
1a
5
a
°
C or even 60 °C in toluene). In such cases, the induction
Ph
Ph
KSeCN, DMF, 20 °C, 6 h
2%
Hex
S
CF3SO3
period is longer and unpredictable (2–8 h and 24 h, re-
spectively) and therefore the reaction time is not repro-
ducible. Similar observations have been made using other
solvents and other copper(II) salts.6
Hex-SeCN
8
5
b
1b
PhSeNa, EtOH or DMF,
20 °C, 1 h
Hex-SePh
7
6%
1c
Reproducible results (80 °C, 3.5 h, up to 85% yield over 8
attempts) have been, however, observed when the solu- Scheme 4 Synthesis of n-hexyl phenyl selenide, di (n-hexyl)di-
tion is carefully degassed and the reaction carried out selenide and n-hexylselenocyanate from n-hexyl diphenyl sulfonium
5
b
triflate
under argon.
These results led us to suspect that Cu(I) is the real cata-
7
,8
lyst and that Cu(II) acts as a precatalyst. This is support-
ed by the observation that, under the conditions described
above, n-hexyl diphenyl sulfonium triflate 5b is:
Typical Experimental Procedure
A suspension of copper (I) salt (5 mol%), n-hexyl phenyl sulfide
(
3a, 1 mmol) and diphenyliodonium salt 4b (1 mmol) in toluene (1
(
i) produced in only 28% yield when the reaction is car-
ried out under an oxygen atmosphere (80 °C, 18 h);
ii) not formed when it is carried out in the presence of
mL) is sonicated. Argon is then bubbled for few minutes. The re-
sulting mixture is then stirred and heated (110 °C, 80 °C or 60 °C)
under argon for the required time (Scheme 3, Table 1). The aspect
of the mixture changes leading to a triphasic system, which deposits
on standing at 20 °C, a small amount of crystalline material (copper
(
2
,2¢-biquinoline (cuproine (8), Figure 1; 10% M in tolu-
7,9
ene, 80 °C or 110 °C, 1 h) which is known to bind Cu(I)
–
in such case an intense purple color characteristic of a salt) and a heavy liquid (sulfonium salt). The latter is dissolved on
7
,9
addition of CH Cl (5 mL) to the mixture. The copper salt is filtered
2 2
Cu(I) complex develops; and
iii) efficiently generated using copper (I) chloride or
triflate in toluene at 110, 80 °C or even 60 °C (Table 1,
on a pad of celite, which is then washed with CH Cl . Evaporation
of the liquid under vacuum delivers a semi-solid material (mixture
of 3a, 5b and 7b and iodobenzene) which leads to the crystalline
sulfonium salts after trituration with anhydrous Et O.
2
2
(
5
b,10
entries d–h).
2
Table 1 Arylation of n-Hexyl Phenyl Sulfide
Entry
Compd 4b (equiv)
Catalyst
Cu(OAc)2
Cu(OAc)2
Cu(OAc)2
CuCl
Conditions
Yield of 5b (3a, %)
93 (1)
Yield of 7b (%)
a
b
c
d
e
f
1.5
1
110 °C, 1 h5a
110 °C, 1 h5a
80 °C, 2–8 h5a
110 °C, 0.2 h5b
110 °C, 0.2 h5b
80 °C, 1.8 h5b
80 °C, 0.3 h5b
60 °C, 6 h5b
0
56 (38)
0
1.5
1
65–81 (7–15)
90 (1)
0–8
5
1
CuOTf
CuCl
87
11
5
1
90 (1)
g
h
1
CuOTf
CuCl
96 (1)
1
1
34 (65)
0
Synlett 2006, No. 3, 484–486 © Thieme Stuttgart · New York

4
86
A. Krief et al.
LETTER
(4) We have proved in many instances that iodobenzene is
References and Notes
formed as a by-product in these reactions (70–84% isolated
yield).
(
(
1) Krief, A.; Dumont, W.; Robert, M. Chem. Commun. 2005,
167.
2) (a) Shah, A.; Pike, V. W.; Widdowson, D. A. J. Chem. Soc.,
Perkin Trans. 1 1997, 2463. (b) Kitamura, T.; Matsuyuki,
J.; Taniguchi, J. Synthesis 1994, 147.
2
(
5) (a) Reaction performed under argon. (b) Reaction initiated
after sonication and bubbling argon into the solution.
6) Those reactions are being investigated in detail and will be
reported in the full paper.
(
(
3) (a) Arylation of n-hexylthiol has been also achieved in
toluene by in situ formation of the corresponding thiolate
using either potassium (18% yield of 3a) or better cesium
(
(
7) Lockhart, T. P. J. Am. Chem. Soc. 1983, 105, 1940.
8) Crivello, J. V.; Lam, J. H. W. J. Am. Chem. Soc. 1978, 43,
3055.
(
65% yield of 3a) hydroxide. (b) We found that
(9) (a) Breckenridge, J. G.; Lewis, R. W.; Quick, L. A. Can. J.
diphenyliodonium tetrafluoroborate and diphenyliodonium
chloride also allow, under identical experimental conditions,
the arylation of hexylthiolate (79% and 64% yield,
respectively). (c) Thiophenol has been previously arylated
with diaryl iodonium salts in the presence of tributylamine to
Res. Sect. B 1939, 17, 258. (b) Hoste, J. Anal. Chim. Acta
1950, 4, 23.
(
10) We found that Cu(I) triflate is a poorer catalyst for the
arylation of n-hexyl phenyl sulfide (3a) using
diphenyliodonium tetrafluoroborate (4a) instead of the
corresponding triflate 4b (4a:3a:CuOTf ratio: 1:1:5):
3
d
produce directly triaryl sulfonium salts. (d) Crivello, J. V.;
Lam, J. H. W. Synth. Commun. 1979, 151.
(
1
i) 110 °C, 0.2 h, 5a: 72%, 3a: 24% or (ii) 80 °C, 1.5 h, 5a:
3%, 3a: 73%; compare to Scheme 3, Table 1, entries e
and g.
Synlett 2006, No. 3, 484–486 © Thieme Stuttgart · New York