Practical and efficient ipso-iodination of arylboronic acids via KF/I2 system

Article abstract of DOI:10.1016/j.tetlet.2015.01.040

A facile and effective iododeboronation of variously substituted aryl and heteroarylboronic acids through activation and subsequent ipso-introduction of iodine is presented. The use of KF and I₂ at 80 °C in 1,4-dioxane furnishes iodinated compounds in high yields.

Full text of DOI:10.1016/j.tetlet.2015.01.040

Tetrahedron Letters xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Practical and efficient ipso-iodination of arylboronic acids via KF/I2
system
⇑
Francesco Tramutola, Lucia Chiummiento , Maria Funicello, Paolo Lupattelli
Dipartimento di Scienze, Università degli Studi della Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, Italy
a r t i c l e i n f o
a b s t r a c t
Article history:
A facile and effective iododeboronation of variously substituted aryl and heteroarylboronic acids through
activation and subsequent ipso-introduction of iodine is presented. The use of KF and I2 at 80 °C in 1,4-
dioxane furnishes iodinated compounds in high yields.
Received 25 November 2014
Revised 21 December 2014
Accepted 6 January 2015
Available online xxxx
Ó 2015 Elsevier Ltd. All rights reserved.
Keywords:
Boronic acids
Iodination
Deboronation
Iodoarenes
A major role in modern chemistry is played by organoboron
compounds, among which boronic acids have emerged in a leading
position.1 With the discovery of a wealth of new chemistry, in par-
ticular the Suzuki–Miyaura cross-coupling reaction, together with
their accessibility and ease of handling, boronic acids and boronates
are now established as intermediates of great value and versatility.
Applications abound in synthesis, catalysis, analytical chemistry
and biological systems. Functional group interconversion of the
boronic acid moiety is possible and expands the realm of application
accessed through these reagents. For example, the ready availability
of organoboronic acids makes their use as precursors for aryl iodides
especially appealing. To date, KI,2 NaI,3 or NH4I4 in the presence of
mild oxidizing agents, N-iodosuccinimide5, NH4I3 or CsI36, 1,3-
dihalo-5,5-dimethylhydantoin7 or I2 and Cu salts8 are generally
used to make boron-halide exchange. However, these methods pref-
erentially involve: (1) boronic esters and trifluoroborates, because
boronic acids containing electron-withdrawing groups on the aro-
matic ring are not iodinated effectively;3 (2) several halide sources
but not the elemental one because this can react through electro-
philic aromatic substitution on arenes by using the boron moiety
as a blocking group.9
On the basis of our previous experience with arylboronic acids
involving reactions, we decided to use KF and 1,4-dioxane in this
protocol as the base and the solvent, respectively.10 We found
more convenience in using 1.1 equiv of arylboronic acid and
1.0 equiv of iodine to inhibit the formation of potential doubly
iodinated products.
As shown in Table 1, the presence of KF, which serves to activate
the boronic acid, is crucial to the success of the reaction (entry 1). A
lower amount of KF can be tolerated (entry 2) but gives worse
Table 1
Optimization of the reaction conditions
OMe
(HO)2B
I
OMe
KF
I2
+
1,4-dioxane (0.1 M)
(1.0 equiv)
temp
OMe
1a (1.1 equiv)
OMe
time
2a
Entry
KF (equiv)
Temp (°C)
Time (h)
Yielda (%)
1
2
3
4
—
80
80
80
20
80
80
80
1
1
1
1
24
1
10
72
84b
75
84
<5
<5
1.1
3.3
3.3
3.3
3.3
3.3
Thus, herein we want to report the practical and efficient iod-
odeboronation of a large array of variously substituted aryl and
heteroarylboronic acids mediated by KF and I2. Our initial studies
focused on the ipso-iodination of 3,5-dimethoxybenzeneboronic
acid as a model reaction to find optimized conditions (Table 1).
5
6c
7d
1
a
b
c
Determined by GC–MS analysis versus a calibrated internal standard.
Isolated yield (average of two experiments).
2.5 mol % of Pd(OAc)2 and 5 mol % of (t-Bu)2PMeHBF4 were added.
2.5 mol % of Pd(OAc)2 was added.
⇑
Corresponding author. Tel.: +39 0971 205492; fax: +39 0971 205678.
E-mail address: lucia.chiummiento@unibas.it (L. Chiummiento).
d
http://dx.doi.org/10.1016/j.tetlet.2015.01.040
0040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Tramutola, F.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.01.040

2
F. Tramutola et al. / Tetrahedron Letters xxx (2015) xxx–xxx
Table 2
Scope of the ipso-iodination of arylboronic acidsa
KF (3.3 equiv)
I2
+
ArB(OH)2
ArI
2
1,4-dioxane (0.1 M)
1 (1.1 equiv) (1.0 equiv)
80 °C
1h
I
I
I
I
I
SMe
OH
NMe2
t-Bu
2f
2c
2b
2e
(84%)
2d
(88%)
(82%)
(90%)
(78%)
I
I
NO2
I
I
I
Cl
Ph
CN
Br
2g
(93%)
2k
(82%)
2h
(86%)
2i
(85%)
2j
(80%)
I
I
I
I
CF3
I
I
S
S
N
SO2Me
CHO
SO2Ph
2q
2o
2p
(81%)
2l
(81%)
2m
(80%)
2n
(83%)
(93%)
(87%)
a
Isolated yields of the products are reported (average of two experiments).
Acknowledgments
I2
(1.0 equiv)
1a
+
2a
(84%)
+
Financial support has been provided by MIUR (Italian Ministry
of University)—PRIN 20109Z2XRJ_009: ‘Progettazione e sintesi ste-
reoselettiva di composti attivi verso bersagli proteici coinvolti in
(1.1 equiv)
see Table
2
MeO
MeO
3 (1.1 equiv)
3
patologie virali
Basilicata.
e tumorali’ and Università degli Studi della
Scheme 1. Competition experiment.
References and notes
results than the use of 3.3 equiv of the base (entry 3). Moreover
this reaction proceeds better at higher temperature then room
temperature (entry 4). Reaction time does not affect the yield of
desired product, which demonstrated high stability under selected
conditions (entry 5). Finally, the addition of a Pd source in the reac-
tion, both with (entry 6) and without (entry 7) a phosphinic ligand,
totally impedes this process. This effect precludes the potential to
achieve biaryls through a one pot iododeboronation/cross-coupling
reaction.
With optimized conditions in hand, we set out to explore the
substrate scope for the conversion of arylboronic acids to
iodoarenes (Table 2).11 We found that either electron-rich or elec-
tron-deficient arylboronic acids, as well as heteroarylboronic acids
such as thiophenes, benzothiophenes and indoles could be effi-
ciently converted into the corresponding aryliodides in good to
excellent yields.12 Notably a broad range of functional groups is
well tolerated.
In addition we performed a competition experiment between
the ipso-iododeboronation and the iodination of an activated
terminal alkyne. The outcomes displayed the iodine substantial
propensity to react with arylboronic acids rather than give electro-
philic addition on the alkyne (Scheme 1).
In conclusion, we have developed a practical and easy method
to convert aryl and heteroarylboronic acids to corresponding iodo-
arenes by ipso-iodination. This protocol can be efficiently applied
to a number of readily available boronic acids bearing a wide range
of functional groups.
1. (a) Lennox, A. J. J.; Lloyd-Jones, G. C. Chem. Soc. Rev. 2014, 43, 412–443; (b) Hall,
D. J. In Boronic Acid: Preparation and Applications in Organic Synthesis, Medicine
and Materials, 2nd ed. Completely Revised Edition; Wiley-Interscience: New
York, 2011.
2. (a) Akula, M. R.; Yao, M.-L.; Kabalka, G. W. Tetrahedron Lett. 2010, 51, 1170–
1171; (b) Zhang, G.; Lv, G.; Li, L.; Chen, F.; Cheng, J. Tetrahedron Lett. 2011, 52,
1993–1995.
3. (a) Kabalka, G. W.; Mereddy, A. R. Tetrahedron Lett. 2004, 45, 343–345; (b) Yong,
L.; Yao, M.-L.; Green, J. F.; Kelly, H.; Kabalka, G. W. Chem. Commun. 2010, 46,
2623–2625.
4. Kim, J.; Choi, J.; Shin, K.; Chang, S. J. Am. Chem. Soc. 2012, 134, 2528–2531.
5. (a) Thiebes, C.; Prakash, G. K. S.; Petasis, N. A.; Olah, G. A. Synlett 1998, 141–
142; (b) Wu, H.; Hynes, J. Org. Lett. 2010, 12, 1192–1195.
6. Yao, M.-L.; Kabalka, G. W.; Blevins, D. W.; Reddy, M. S.; Yong, L. Tetrahedron
2012, 68, 3738–3743.
7. Szumigala, R. H.; Devine, P. N.; Gauthier, D. R.; Volante, R. P. J. Org. Chem. 2004,
69, 566–569.
8. (a) Ren, Y.-L.; Tian, X.-Z.; Dong, C.; Zhao, S.; Wang, J.; Yan, M.; Qi, X.; Liu, G.
Catal. Commun. 2013, 32, 15–17; (b) Luo, Y.; Wen, Q.; Wu, Z.; Jin, J.; Lu, P.;
Wang, Y. Tetrahedron 2013, 69, 8400–8404; (c) Thompson, A. L. S.; Abalka, G.
W.; Akula, M. R.; Huffman, J. W. Synthesis 2005, 547–550; (d) Murphy, J. M.;
Liao, X.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 15434–15435; (e) Partridge,
B. M.; Hartwig, J. F. Org. Lett. 2013, 15, 140–143.
9. Ahn, S.-J.; Lee, C.-Y.; Kim, N.-K.; Cheon, C.-H. J. Org. Chem. 2014, 79, 7277–7287.
10. Chiummiento, L.; Funicello, M.; Lupattelli, P.; Tramutola, F. Org. Lett. 2012, 14,
3928–3931.
11. General procedure: A mixture of the arylboronic acid (0.55 mmol), KF (96 mg,
1.65 mmol) and I2 (127 mg, 0.50 mmol) in 1,4-dioxane (5 mL) was stirred at
80 °C for 1 h. Then it was filtered through silica gel, eluting with Et2O (10 mL)
and the solvent was removed by rotary evaporation. When necessary, the
product was purified by chromatography on silica gel (petroleum ether/Et2O
98:2).
12. The products were characterized by 1H NMR, 13C NMR and MS (ESI). All these
compounds are known in the literature and their characterizations are
consistent with the reported ones.
Please cite this article in press as: Tramutola, F.; et al. Tetrahedron Lett. (2015), http://dx.doi.org/10.1016/j.tetlet.2015.01.040