Synthesis of a range of iodine(III) compounds directly from iodoarenes

Article abstract of DOI:10.1002/ejoc.201100360

The first direct synthesis of an alkynyl(phenyl)iodonium salt from iodobenzene and an unprotected alkyne is described. The synthesis of the corresponding alkenyl(phenyl)iodonium salt is achieved from the TMS-alkyne, simply by means of changing the solvent

Full text of DOI:10.1002/ejoc.201100360

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100360
Synthesis of a Range of Iodine(III) Compounds Directly from Iodoarenes
Eleanor A. Merritt*[a] and Berit Olofsson*[a]
Keywords: Hypervalent compounds / Alkynes / Iodine / Iodonium salts / Benziodoxolones
The first direct synthesis of an alkynyl(phenyl)iodonium salt
from iodobenzene and an unprotected alkyne is described.
The synthesis of the corresponding alkenyl(phenyl)iodonium
salt is achieved from the TMS-alkyne, simply by means of
changing the solvent. The one-pot synthesis of 1-arylbenz-
iodoxolones and other iodine(III) compounds from iodine(I)
precursors is also presented.
Introduction
In recent years hypervalent iodine reagents have received
considerable attention befitting their use as non-toxic and
mild reagents in many areas of organic synthesis.[1] Diaryl-
iodonium salts have found applications in many reactions
which traditionally employ transition metals, such as α-
arylation of carbonyl compounds[2] and cross-coupling re-
actions, as iodine(III) reagents bearing two carbon ligands
display similar properties to metals such as Pd, Hg and
Pb.[1d] Work within our research group has been directed
towards the development of efficient,[3] environmentally be-
nign,[4] and scalable methods for the preparation of these
versatile reagents.[5]
In continuation of our focus towards efficient one-pot
routes to hypervalent iodine reagents,[6] application of the
methodology to the preparation of other iodonium salts
was of interest. As depicted in Figure 1, alkynyl(aryl)iodon-
ium salts are versatile reagents in a wide range of transfor-
mations,[7] but despite their long history[8] the difficulty in
preparation of these compounds has limited their use in
organic synthesis.
Figure 1. Applications of alkynyl(aryl)iodonium salts.
Using the approach taken towards diaryliodonium salt
synthesis (Scheme 1, a),[3a] the envisioned one-pot route to
To date, the only synthetic routes to this class of com- alkynyl(aryl)iodonium salts was investigated using mCPBA
pounds employ iodine(III) compounds that must be pre- and various acids, in the hope to furnish products with a
pared in advance. Examples of such iodine(III) reagents are range of counterions (Scheme 1, b). Phenyl acetylene was
4-iodotoluene trifluoride,[9] (diacetoxyiodo)benzene,[10] chosen as model alkyne due to ease of handling, together
Zefirov’s reagent,[11] Koser’s reagent[12] and iodosobenzene with the commercial availability of both the terminal alkyne
activated either with boron trifluoride etherate,[13] tetra- and its TMS-protected analogue.
fluoroboric acid and mercury oxide,[14] or triflic acid.[15]
The alkyne source is usually a non-commercial alkynyl-
silane, alkynylstannane or alkynylboronate.[7]
[a] Department of Organic Chemistry, Arrhenius Laboratory,
Stockholm University,
10691 Stockholm, Sweden
Fax: +46-8-154908
E-mail: elliemerritt@gmail.com
berit@organ.su.se
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100360.
Scheme 1. a) Previous route to diaryliodonium salts. b) Envisioned
route to alkynyl(aryl)iodonium salts.
3690
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3690–3694

Iodine(III) Compounds Directly from Iodoarenes
Table 1. Synthesis of 1 from Koser’s reagent (3).[a]
Results and Discussion
Initial efforts employing triflic acid were unsuccessful
due to rapid degradation of the alkyne (whether phenyl-
acetylene or TMS-phenylacetylene) under the strongly
acidic and oxidizing reaction conditions. The use of 48%
aq. HBF4 was also troublesome; although the initial oxi-
dation was successful according to NMR, the desired prod-
uct was not formed cleanly and isolation of pure and identi-
fiable material proved impossible.
The combination of mCPBA and tosic acid had pre-
viously been used in our synthesis of diaryliodonium tosyl-
ates, where the milder reaction conditions enabled the use
of electron-rich arenes.[3b] When TsOH was used together
with TMS-phenylacetylene in dichloromethane at room
temperature, Koser’s reagent was obtained together with
minor amounts of the desired product 1 and vinyliodonium
salt 2 (Scheme 2).[16] While this indicated that the oxidation
step of the reaction was working as intended, subsequent
reaction of the iodine(III) intermediate with the alkyne was
sluggish. Heating the reaction mixture to 40 °C failed to
improve the outcome.
Entry
R
Solvent
Product(s)
1
2
3
4
H
TMS
H
CH2Cl2
1, isolated cleanly, 63% yield
mix of 1 and 2
mix of 1 and 2
predominantly 2
CH2Cl2
CH2Cl2/TFE[b]
CH2Cl2/TFE[b]
TMS
[a] Reactions carried out using equimolar quantities of 3 and
alkyne on a 0.10 mmol scale in 1 mL of solvent. [b] 1:1 mixture.
ficient, and uses no excess reagents. Indeed, excess mCPBA
proved detrimental to the reaction, and excess TsOH re-
sulted in purification difficulties. Increasing the quantity of
alkyne used had no discernible effect on the yield.
Scheme 3. One-pot synthesis of iodonium tosylate 1 from iodo-
benzene.
Intrigued by the ability of TFE to promote the formation
of vinyl salt 2 over alkynyl salt 1, an optimized route to
alkenyl(aryl)iodonium tosylates 2 was subsequently sought.
Scheme 2. Initial attempts towards a one-pot synthesis of 1.
Fluoroalcoholic solvents have been demonstrated to en- In keeping with the stoichiometry of the reaction, 2 equiva-
hance the reaction rates both in formation of iodine(III) lents of tosic acid were employed. TFE was used as the
species and in their subsequent reaction with other rea- solvent together with TMS-phenylacetylene, as this had
gents.[3b,4,6,17] This property is attributed to the ability of been shown to promote vinyl salt formation (Table 1). Dis-
the solvent to stabilise cationic and radical intermediates.[18] appointingly, compound 2 was isolated in only 23% yield
Indeed, the use of 2,2,2-trifluoroethanol (TFE) in the syn- (Table 2, entry 1). Employing 2 equivalents of mCPBA in-
thesis of 1 enhanced the reaction rates of both the oxidation creased the yield to 54% with no loss of selectivity (entry
and the coupling with the alkyne. Mixed solvent systems as 2), whereas excess alkyne resulted in increased alkynyl salt
well as neat TFE were investigated, but the desired alkynyl formation (entries 3, 4).
product 1 was always formed together with vinyliodonium
salt 2 both at room temperature and 40 °C (Scheme 2).
It was found that a 1:1 mixture of TFE and dichloro-
methane was as selective as neat TFE, and even led to in-
Thus, the formation of alkynyl salt 1 from Koser’s rea- creased yield (entry 5). Decreasing the proportion of TFE
gent (3) was further investigated (Table 1). Much to our de- further led to significant loss of selectivity (entry 6). Some-
light, the results obtained showed that not only could ter- what surprisingly, using phenylacetylene in place of TMS-
minal alkynes (R = H) be used in the synthesis of alk- phenylacetylene actually reversed the selectivity of the reac-
ynyl(aryl)iodonium salts 1, but also that their use promoted tion, favouring alkynyl salt 1 despite the fluorinated co-sol-
the formation of the desired product (entry 1). On the con- vent (entry 7). Reaction times of less than 1 hour gave non-
trary, TMS-protected alkynes favoured formation of vinyl reproducible results, both in terms of product ratios and
salt 2, as did the use of TFE (entries 2–4). This can be yields.
rationalized by the stabilizing effect of the silyl group on the
The optimized one-pot synthesis of 2 is depicted in
intermediate vinyl cation, allowing intermolecular attack by Scheme 4, and represents the first practical one-pot synthe-
tosylate to compete with elimination.
sis of an alkenyl(phenyl)iodonium salt from an iodoar-
With this information in hand, the first one-pot synthesis ene.[19] This reaction also proved to be reliable and scale-
of an alkynyl(phenyl)iodonium salt from an iodoarene was able, with no loss of yield up to a 2 mmol scale.
developed (Scheme 3). Gratifyingly, the reaction proved to
With novel and simple one-pot routes to three classes of
be both reproducible and scaleable, working reliably from iodonium salts from iodobenzene in hand, we turned our
0.10 mmol up to 20 mmol scale. The protocol is atom-ef- attention to the synthesis of 1-substituted benziodoxolones
Eur. J. Org. Chem. 2011, 3690–3694
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3691

E. A. Merritt, B. Olofsson
SHORT COMMUNICATION
Table 2. Optimization of the synthesis of 2.[a]
noted by the authors that the tosylate analogue of interme-
diate 6 was insufficiently reactive to participate in the subse-
quent reaction with the TMS alkyne.
Entry Alkyne mCPBA Solvent
Yield
(%)
Ratio
(equiv.)
(equiv.)
2/1[b]
1
2
3
4
5
6
7
1
1
2
2
1
1
2
1
2
2
2
2
TFE
TFE
TFE
TFE
23
54
38
52
64
n.d.
n.d.
25:1
25:1
14:1
2:1
CH2Cl2/TFE[c]
CH2Cl2/TFE[e]
CH2Cl2/TFE[c]
Ͼ 25:1[d]
7:1
1
Scheme 5. Zhdankin’s synthesis of 5 and related compounds.[24]
1[f]
1:2
[a] Reactions carried out on a 0.10 mmol scale with 2 equiv.
1
TsOH·H2O in 1 mL of solvent. [b] Ratio determined by H-NMR
Therefore, it was not surprising that our one-pot meth-
ods using tosic acid (see Schemes 3 and 4) were found un-
suitable for the preparation of compound 5, and that a
stronger acid was required. As the use of TfOH under oxi-
dative conditions had previously resulted in degradation of
the alkyne, our proposed one-pot synthesis of 5 seemed dif-
ficult to realize. Furthermore, the need for a base to cyclize
intermediate 7 renders this step incompatible with the
strongly acidic conditions needed for the oxidation.
spectroscopy. [c] 1:1 mixture. [d] Reaction repeated 4 times, yields
60–68% and ratios up to 36:1. [e] 2:1 mixture. [f] Phenylacetylene
used instead of TMS-phenylacetylene.
In order to overcome these setbacks, an investigation into
the stepwise synthesis of 1-substituted benziodoxolones was
undertaken. Our initial approach was to use the reaction
conditions depicted in Scheme 1 (a) in order to assess the
feasibility of the oxidation step. Gratifyingly, this reaction
worked reproducibly, albeit in moderate yield (Scheme 6).
Scheme 4. Synthesis of alkenyliodonium tosylate 2 from iodo-
benzene.
from 2-iodobenzoic acid. Many prominent hypervalent
iodine reagents are benziodoxolones or benziodoxoles, in-
cluding IBX, DMP and Togni’s reagent (Figure 2).[20]
Moreover, elegant new applications of 1-alkynylbenziod-
oxolones such as 4 have recently been demonstrated by
Waser and co-workers.[21]
Scheme 6. Synthesis of 6 from 2-iodobenzoic acid.
Due to the difficulties encountered when using alkynes
in the presence of triflic acid, the arylation of 6 to yield
diaryliodonium salt 8 was examined first. Unfortunately,
this reaction proved to be more problematic than the elec-
trophilic aromatic substitution step in the previous synthe-
sis of diaryliodonium triflates (cf. Scheme 1, a).[3a] When
the reaction shown in Scheme 5 was performed in the pres-
ence of benzene, only 6 was isolated even at elevated tem-
peratures or with a large excess of benzene (Table 3, entry
1). Further investigations demonstrated that rather forcing
conditions were necessary for this step to proceed to com-
pletion (entries 2–7).[25] Kitamura and co-workers have re-
ported the synthesis of 8 by treatment of IBA with 2 equiv.
Figure 2. Common cyclic hypervalent iodine reagents.
Given the synthetic utility of these compounds, together TfOH, which generates an unstable and active iodine(III)
with the lack of a direct route from readily available starting intermediate that reacts with arenes at room temperature.[26]
materials,[22,23] we envisioned to adapt our developed meth- It is therefore surprising that elevated temperature is needed
odology to the synthesis of 1-substituted benziodoxolones. also when 3 equiv. TfOH is used in our protocol (entry 2).
1-Alkynylbenziodoxolone 5 had previously been prepared
The final step in the synthesis of 1-phenylbenziodoxolone
by Zhdankin and co-workers via a one-pot 3-step route 9 is the cyclization of diaryliodonium triflate 8. Aqueous
from the iodine(III) compound IBA (Scheme 5).[24] It was ammonia proved to be ideal for this transformation,[22] as
3692
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3690–3694

Iodine(III) Compounds Directly from Iodoarenes
Table 3. Optimization of one-pot synthesis from 2-iodobenzoic
acid.[a]
[1]
a) T. Wirth, Angew. Chem. 2005, 117, 3722; Angew. Chem. Int.
Ed. 2005, 44, 3656–3665; b) P. J. Stang, J. Org. Chem. 2003, 68,
2997–3008; c) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008,
108, 5299–5358; d) E. A. Merritt, B. Olofsson, Angew. Chem.
2009, 121, 9214; Angew. Chem. Int. Ed. 2009, 48, 9052–9070;
e) R. J. Phipps, M. J. Gaunt, Science 2009, 323, 1593–1597.
[2] E. A. Merritt, B. Olofsson, Synthesis 2011, 517–538.
[3] a) M. Bielawski, B. Olofsson, Chem. Commun. 2007, 2521–
2523; b) M. Zhu, N. Jalalian, B. Olofsson, Synlett 2008, 592–
596; c) M. Bielawski, D. Aili, B. Olofsson, J. Org. Chem. 2008,
73, 4602–4607.
[4] E. A. Merritt, J. Malmgren, F. J. Klinke, B. Olofsson, Synlett
2009, 2277–2280.
[5] M. Bielawski, B. Olofsson, Org. Synth. 2009, 86, 308–314.
[6] E. A. Merritt, V. M. T. Carneiro, L. F. Silva, Jr., B. Olofsson,
J. Org. Chem. 2010, 75, 7416–7419.
[7] V. V. Zhdankin, P. J. Stang, Tetrahedron 1998, 54, 10927–10966.
[8] F. M. Beringer, S. A. Galton, J. Org. Chem. 1965, 30, 1930–
1934.
Entry TfOH
(equiv.)
Temp.
(°C)
Time
(h)
Yield
(%)
Ratio
8/6
1
2
3
4
5
6
7
2
3
2
2
2
2
2
room temp.
16
16
16
16
2
4
6
n.d.
77
72
12
61
62
74
trace of 6
only 8[b]
only 8
only 8
1:1.7
9.5:1
only 8
80
80
40
80
80
80
[a] Reactions carried out on a 0.20 mmol scale in 2 mL of CH2Cl2
with 1.1 equiv. mCPBA and benzene. [b] Contained traces of other
iodine(III) species.
[9] M. Yoshida, K. Osafune, S. Hara, Synthesis 2007, 1542–1546.
[10] T. Kitamura, M. Kotani, Y. Fujiwara, Synthesis 1998, 1416–
1418.
merely washing the crude reaction mixture with an equal [11]
volume of 25% aq. ammonia furnished the desired product
with no further need for purification. Based on the results
a) V. V. Zhdankin, P. J. Persichini III, R. Cui, Y. Jin, Synlett
2000, 719–721; b) M. D. Bachi, N. Bar-Ner, C. M. Crittell, P. J.
Stang, B. L. Williamson, J. Org. Chem. 1991, 56, 3912–3915.
[12] L. Rebrovic, G. F. Koser, J. Org. Chem. 1984, 49, 4700–4702.
[13] a) P. J. Stang, T. Kitamura, Org. Synth. 1992, 70, 215–225; b)
T. Kitamura, P. J. Stang, J. Org. Chem. 1988, 53, 4105–4106; c)
M. Ochiai, M. Kunishima, K. Sumi, Y. Nagao, E. Fujita, M.
Arimoto, H. Yamaguchi, Tetrahedron Lett. 1985, 26, 4501–
4504.
of the stepwise investigation, a one-pot synthesis of 9 from
2-iodobenzoic acid was devised and tested, ultimately yield-
ing 9 in 66% yield (Scheme 7). Disappointingly although
not surprisingly, these conditions proved to be incompatible
with alkynes, thus a direct route to 1-alkynylbenziod-
oxolones from iodoarenes remains elusive. A one-pot syn-
thesis of silylated benziodoxolones 4 is currently under in-
vestigation.
[14] M. Yoshida, N. Nishimura, S. Hara, Chem. Commun. 2002,
1014.
[15]
[16]
[17]
[18]
[19]
T. Kitamura, R. Furuki, H. Taniguchi, P. J. Stang, Tetrahedron
1992, 48, 7149–7156.
Formation of vinyliodonium salts from alkynes and PhI(OH)
OTs has been reported by Koser and co-workers, see ref.[12]
T. Dohi, M. Ito, K. Morimoto, Y. Minamitsuji, N. Takenaga,
Y. Kita, Chem. Commun. 2007, 4152–4154.
T. Dohi, M. Ito, N. Yamaoka, K. Morimoto, H. Fujioka, Y.
Kita, Tetrahedron 2009, 65, 10797–10815.
There is one previous report of a one-pot synthesis of vinyl-
iodonium salts from iodobenzene, employing the explosive rea-
gent xenon fluorotriflate. See T. M. Kasumov, N. S. Pirguliyev,
V. K. Brel, Y. K. Grishin, N. S. Zefirov, P. J. Stang, Tetrahedron
1997, 53, 13139–13148.
Reviews on IBX and DMP: a) V. V. Zhdankin, J. Org. Chem.
2011, 76, 1185–1197; b) A. Duschek, S. F. Kirsch, Angew.
Chem. Int. Ed. 2011, 50, 1524–1552; c) V. Satam, A. Harad, R.
Rajule, H. Pati, Tetrahedron 2010, 66, 7659–7706; Papers on
Togni’s reagent: ; d) I. Kieltsch, P. Eisenberger, A. Togni, An-
gew. Chem. 2007, 119, 768; Angew. Chem. Int. Ed. 2007, 46,
754–757; e) P. Eisenberger, S. Gischig, A. Togni, Chem. Eur. J.
2006, 12, 2579–2586; f) R. Koller, K. Stanek, D. Stolz, R. Aar-
doom, K. Niedermann, A. Togni, Angew. Chem. 2009, 121,
4396; Angew. Chem. Int. Ed. 2009, 48, 4332–4336.
a) J. P. Brand, D. F. Gonzalez, S. Nicolai, J. Waser, Chem. Com-
mun. 2011, 47, 102–115; b) J. P. Brand, J. Charpentier, J. Waser,
Angew. Chem. 2009, 121, 9510; Angew. Chem. Int. Ed. 2009,
48, 9346–9349; c) S. Nicolai, S. Erard, D. Fernández González,
J. Waser, Org. Lett. 2009, 11, 384–387; d) D. Fernández
González, J. Brand, J. Waser, Chem. Eur. J. 2010, 16, 9457–
9461; e) J. P. Brand, J. Waser, Angew. Chem. Int. Ed. 2010, 49,
7304–7307; f) Y. Ohta, Y. Tokimizu, S. Oishi, N. Fujii, H.
Ohno, Org. Lett. 2010, 12, 3963–3965.
Scheme 7. One-pot synthesis of 9 from 2-iodobenzoic acid.
Conclusions
[20]
The first direct synthesis of alkynyl(phenyl)iodonium
tosylates from iodobenzene and unprotected alkynes is de-
scribed. The synthesis of alkenyl(phenyl)iodonium tosylates
was achieved by employing the corresponding TMS-alkyne
in a mixture of TFE and CH2Cl2. An investigation into the
synthesis of 1-substituted benziodoxolones from iodine(I)
precursors was conducted, and delivered routes to the 1-
OTf and 1-phenyl species, whereas the 1-alkynyl compound
could not be made in a one-pot manner.
[21]
[22]
Supporting Information (see footnote on the first page of this arti-
cle): Experimental procedures, spectroscopic data and copies of
NMRs.
Acknowledgments
Early syntheses of benziodoxolones: a) G. F. Koser, G. Sun,
C. W. Porter, W. J. Youngs, J. Org. Chem. 1993, 58, 7310–7312;
b) M. Ochiai, Y. Masaki, M. Shiro, J. Org. Chem. 1991, 56,
5511–5513.
This work was financially supported by the Swedish Research
Council, Wenner-Gren Foundations and the K & A Wallenberg
Foundation.
Eur. J. Org. Chem. 2011, 3690–3694
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
3693

E. A. Merritt, B. Olofsson
SHORT COMMUNICATION
[23]
[25] The low isolated yield in entry 4 indicates that compound 6
forms (cf. Scheme 6), but is not stable to the reaction condi-
tions, and that the arylation of 6 needs higher temperature.
Indeed, when the reaction Scheme 6 was run at 80 °C, 6 was
isolated in only 35%.
For a one-pot route leading to 1-phenylbenziodoxolone from 2-
iodobenzoic acid, see: L. F. Fieser, M. J. Haddadin, Org. Synth.
1966, 46, 107–111. This method employs concentrated sulfuric
acid as the solvent and potassium persulfate as oxidant. In our
hands, this method furnished product 9 in 61% yield in a small
scale reaction.
[26] T. Kitamura, K. Nagata, H. Taniguchi, Tetrahedron Lett. 1995,
36, 1081–1084.
[24] V. V. Zhdankin, C. J. Kuehl, A. P. Krasutsky, J. T. Bolz, A. J.
Received: March 15, 2011
Simonsen, J. Org. Chem. 1996, 61, 6547–6551.
Published Online: April 21, 2011
3694
www.eurjoc.org
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2011, 3690–3694