"This is the peer reviewed version of the following article: Vicinal Difunctionalization of Alkenes under Iodine(III) Catalysis involving Lewis-Base
Adducts, which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/adsc.201601178/abstract . This article may be used for
non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id820227.html)".

Vicinal Difunctionalization of Alkenes under Iodine(III)
Catalysis involving Lewis-Base Adducts
Kristina Aertker,a Raquel J. Rama,a Julita Opalacha and Kilian Muñiza,b*
a

b

Institute for Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, 16 Avgda.
Països Catalans, E-43007 Tarragona, Spain
Phone: +34 977 920 813; email: kmuniz@iciq.es
ICREA, Pg. Lluís Companys 23, 08010 Barcelona, Spain

Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.
Abstract. The influence of a 2-pyridinyl substituent on the
catalytic performance of aryliodide as a catalyst in
iodine(III) chemistry was explored. An efficient Lews-base
adduct between the pyridine nitrogen and the electrophilic
iodine(III) center was identified and confirmed by X-ray
analysis. This arrangement was shown to generate a
kinetically competent superior catalyst structure for the
catalytic dioxygenation of alkenes. It introduces the
concept of Lewis-base adduct formation as a kinetic factor
in iodine(I/III) catalysis.
Keywords: Alkenes; Catalysis; Iodine; Lewis Base;
Oxidation

Hypervalent iodine(III) reagent[1] have been
identified
as
versatile
reagents
for
the
difunctionalisation of alkenes.[2] The general
versatility of these oxidizing reagents in organic
chemistry is further expressed by recent
developments, which make use of their application in
metal-free, environmentally benign oxidation
catalysis.[3] In these cases, the iodine(III) state
represents the active catalyst, which is continuously
re-generated from a conventional iodine(I) precatalyst.
In the prominent field of dioxygenation reactions of
alkenes,[4,5] the application of the standard
hypervalent iodine reagent PhI(OAc)2 1 for
diacetoxylation is hampered by its notoriously low
reactivity towards alkenes.

Scheme 1. BrØnsted acid
diacteoxylation of alkenes.

acceleration

in

The desired reaction can be accelerated through
addition of catalytic amounts of a strong BrØnstedt
acid, for example TfOH. In seminal work, Gade and
Kang demonstrated that such acid catalysis
significantly accelerates the alkene oxidation,
presumably through protonolysis toward a cationic
iodine center (Scheme 1).[6,7] The latter displays
enhanced electrophilicity and reactivity due to the
free coordination site at iodine. The same observation
was recently made in the development of an
enantioselective catalytic diacetoxylation of styrenes,
in which co-catalysis by TfOH was a crucial factor.[8]
Alternatively, activation of iodine(III) derivatives
with the aid of fluorinated alcohols was discussed.[9]
It appears reasonable to investigate further structural
diversification for the discrete formation of
electrophilic iodine(III) catalyst states with free
coordination sites. One approach in this direction
should consist in the use of weakly coordinating
Lewis bases.
The pyridine unit displays a long history of
successful stabilization of electrophilic iodine centers.
Barluenga´s reagent [I(py)2]BF4 is certainly the most
prominent example to this end,[10,11] while pyridine
coordination to electrophilic iodine(III) centers has
been less investigated.

the

1

Figure 1. Pyridine coordination to iodine(III) in
compounds 2 and 3, and chiral pyridinyl derivatives 4 and
5.

Examples in this area include the compound
[PhI(py)2](OTf)2
(2),[12]
the
corresponding
benziodoxolone adduct 3[13] and the chiral derivatives
4 and 5, which were introduced by Wirth (Figure
1).[14,15] Interestingly, the solid state structure of 4
does not display any interaction between the
iodine(III) center and the nitrogen atom of the
pyridinyl group. In agreement with this, the reported
catalysis relied on co-activation by BrØnsted acid.[15]
To probe the supportive context of pyridine
coordination in an iodine(III) catalyst, the aryliodine
6 was synthesized from 2-phenyl pyridine[16,17] and
submitted to oxidation. Exploring several established
oxidation agents, we observed that only peracetic
acid provided an oxidation product (Scheme 2). With
this particular oxidant, clean formation of the desired
iodine(III) derivative 7 was observed.

The crystal structure determination also provides the
corresponding iodoso benzene 8 (Figure 2), which
undergoes intermolecular hydrogen bonding with
7.[18] Iodoso derivative 8 originates from compound 7
upon loss of acetic acid (Scheme 3), presumably
throughout the crystallization process. In an
analogous manner, 7 can be restored from 8 by
addition of acetic acid characterizing it as the acetic
acid adduct of 7.

Figure 2. Solid-state structures of compounds 7 and 8
(ellipsoids at 50% probability).[18] Selected bond lengths
[Å] and angles [°]: 7: I1A-O1A 1.921(5), I1A-N1A
2.443(6), I1A-O1 2.850(4), O1A-I1A-N1A167.2(2); 8:
I1B-O1B 1.946(5), I1B-N1B 2.406(6), O1B-I1B-N1B
167.2(2).

Scheme 2. Oxidation of iodine(I) compound 6 to
iodine(III) compound 7. [a] n.r. = no reaction. [b] isolated
yield.

Suitable crystals of the new chelate 7 were grown
from a solution in cyclohexane-dichloromethane
solution. X-ray analysis confirmed the expected
structure including the coordination of the pyridine
group to the central iodine atom indicating the Lewis
base assisted activation of the former iodine-acetoxy
bond (Figure 2).[18] The corresponding I-N bond
length was determined to 2.443 Å, which is in good
agreement to related bond distances of 2.44 to 2.46 Å
in related nitrogen coordination[17] and of 2.24 to 3.13
Å in related derivatives of chelated iodine(III)
complexes based on oxygen coordination.[19] In
general, intramolecular coordination of oxygen donor
atoms to hypervalent iodine centers has been a
common strategy, while related nitrogen donor
coordination appears significantly less encountered.

Scheme 3. Relation between iodine(III) compounds 7 and
8.

Subsequent work addressed the diacetoxylation of
alkenes with compound 6 as catalyst. Given the
effective oxidation of 6 to 7, we decided to employ
peracetic acid as the terminal oxidant and to follow
conditions
established
previously
for
the
diacetoxylation of alkenes. [20]
A number of different alkenes were submitted to
diacetoxylation
(Scheme
4),
leading
to
chemoselective oxidation of the C-C double bonds in
all cases. As commonly observed, [5,6,8,20] styrenes
represent the preferred substrate class in this reaction,
and products 10a-10h could be obtained in 66-92%
isolated yields. The same was observed for product
10i, which gave clean diacetoxylation without any
potentially competing rearrangement or allylic

2

oxidation. From observation of the crude reaction
mixture of 10d, it was concluded that these reactions
proceed through initial formation of the 1-hydroxy-2acetoxy derivative, which derives from the
Woodward pathway.[21] They are converted into
uniform vicinal diacetoxy products upon treatment
with acetic anhydride. In contrast, (E)- and (Z)-bmethyl styrene and (E)-O-acetoxy cinnamic ester
yield the corresponding products 10j-10l as
diastereomeric mixtures due to competing Woodward
and Prevost[22] pathways.

9d in acetic acid-d4 as solvent, a clear acceleration of
the reaction was found to result from the presence of
the coordinating pyridine group (Figure 3).
Comparison of the initial rates indicate that 6
outperforms 1 by a factor of over 2. This kinetic data
clearly demonstrates that the concept of Lewis-base
coordination can accelerate hypervalent iodine
catalysis to a significant extent.

Figure 3. Initial kinetic profiles for the dioxygenation of 4fluorostyrene 9d with catalyst 6 and iodobenzene 1,
respectively.

Scheme 4. Catalytic diacetoxylation of alkenes. Given
yields refer to isolated material after purification. [a] From
reaction with (E)-b-methyl styrene 9j. [b] From reaction
with (E)-O-acetoxy cinnamic alcohol 9l. [c] Without
treatment with acetic anhydride.

Cyclic aliphatic alkenes can also be employed as
demonstrated for formation of products 10m,n.[6,20]
Finally, linear aliphatic alkenes give direct rise to the
diacetoxylated products 10o-q without required
treatment with acetic anhydride, which indicates a
Prevost pathway[22] to be operative.
The beneficial effect of the 2-pyridinyl group was
demonstrated within a kinetic competition experiment
between catalyst 6 and iodobenzene 1. Monitoring by
19
F NMR the progress of oxidation of 4-fluorostyrene

Figure 4. Catalytic cycle for the catalytic diacetoxylation
of styrenes 9.

The proposed catalytic cycle (Figure 4) comprises
the documented oxidation of catalyst 6 to 7 with the
iodine(III) catalyst state. Coordination of alkene 9 to

3

the electrophilic iodine center in 7 may involve an
associative process through A or directly arrive at A’
with three-coordinate iodine center. Subsequent
nucleoacetoxylation initiates the difunctionalization
via B, from which catalyst 6 is regenerated via
reductive oxygenation (As discussed, for styrenes 9ah, this step should consist of a Woodward pathway).
In summary, we have reported a new catalyst for
the iodine(III) catalyzed dioxygenation of alkenes.
The kinetic competence of this catalyst relies on an
efficient Lewis-base coordination of a pyridine group
to the electrophilic iodine(III) catalyst. This concept
should provide space for new catalyst design in the
field of hypervalent iodine catalysis.

Experimental Section
Synthesis of catalyst 6.[17] 2-(2-bromophenyl) pyridine
(162 mg, 0.7 mmol) was dissolved in absolute THF (5.5
mL), cooled to -78 ºC and nBuLi (0.38 mL, 2M in hexane,
0.76 mmol, 1.1 equiv.) was added. The reaction was stirred
at -78 ºC for 2 h. An iodine solution (3 mL, 1 M in THF,
3.01 mmol, 4.3 equiv.) was then added at -78 ºC. The
reaction was warmed to r.t., stirred for 20 hours and
evaporated to dryness. Column chromatography (SiO2,10%
ethyl acetate/hexane/EtOAc, 90/10, v/v) provided the title
compound 6 as a white solid (106.8 mg, 54%).
General Procedure for Diacetoxylation. A Pyrex tube
equipped with a stirrer bar was charged with iodine(I)
catalyst 6 (5.62 mg, 0.02 mmol, 10 mol%) and AcOH (1
mL). AcOOH (36% in AcOH, 90 µL, 0.44 mmol, 2.2 eq.)
was added and the reaction mixture was stirred at room
temperature for 1 h. Then the respective alkene (0.2 mmol,
1.0 eq.) was added and the reaction mixture was stirred at
room temperature for further 18 h. H2O (2 mL), brine (1.5
mL) and CH2Cl2 were added and the aqueous layer was
extracted twice with CH2Cl2. The combined organic phases
were dried over Na2SO4 and concentrated under reduce
pressure. Compounds 10n-q were directly purified by flash
column chromatography on silica gel to provide
analytically pure products. For compounds 10a-m, the
crude product was dissolved in CH2Cl2 (0.5 mL) and acetic
anhydride (55 µL, 0.5 mmol, 2.5 eq.), pyridine (40 µL, 0.5
mmol, 2.5 eq.) and DMAP (6.1 mg, 0.05 mmol, 0.25 eq.)
were added. After stirring at room temperature for 5 h, the
reaction was quenched with aqueous HCl (6M, 3 mL) and
EtOAc (3 mL). The aqueous phase was extracted twice
with EtOAc and the combined organic layers were dried
over Na2SO4, and concentrated under reduced pressure.
The crude product was purified by flash column
chromatography on silica gel to provide analytically pure
products.

Acknowledgements
The authors thank the Spanish Ministry for Economy and
Competitiveness and FEDER (CTQ2014-56474R grant to K. M.,
Severo Ochoa Excellence Accreditation 2014-2018 to ICIQ, SEV2013-0319) and the CERCA Programme/Government of
Catalonia for financial support and Dr. E. Escudero-Adán for the
X-ray analysis. KA is an undergraduate student from LMU
Munich.

References
[1] a) V. V. Zhdankin, V. V. Hypervalent Iodine Chemistry
Preparation, Structure and Synthetic Applications of

Polyvalent Iodine Compounds, Wiley, Chichester 2013;
b) Iodine Chemistry and Applications (Ed.: T. Kaiho),
Wiley, New Jersey 2015; c) Top. Curr. Chem. 2003,
Vol. 224 (Ed.: T. Wirth), Springer, Berlin; d) Top. Curr.
Chem. 2016, Vol. 373 (Ed.: T. Wirth), Springer, Berlin;
e) A. Yoshimura, V. V. Zhdankin, Chem. Rev. 2016,
116, 3328.
[2] a) R. M. Romero, T. H. Wöste, K. Muñiz, Chem. Asian
J. 2014, 9, 972; b) M. Uyanik, K. Ishihara, J. Synth.
Org. Chem. Jpn. 2012, 70, 1116; c) Singh, F. V.; Wirth,
T. Chem. Asian J. 2014, 9, 950; d) F. Berthiol,
Synthesis 2015, 47, 587.
[3] a) R. D. Richardson, T. Wirth, Angew. Chem. Int. Ed.
2006, 45, 4402; b) M. Ochiai, K. Miyamoto, Eur. J.
Org. Chem. 2008, 4229; c) M. Ochiai, Chem. Rec. 2007,
7, 12; d) T. Dohi, Y. Kita, Chem. Commun. 2009, 2073;
e) M. Uyanik, K. Ishihara, Chem. Commun. 2009, 2086.
[4] For initial dioxygeation reactions: a) U. H. Hirt, B.
Spingler, T. Wirth, J. Org. Chem. 1998, 63, 7674; b) T.
Wirth, U. H. Hirt, Tetrahedron: Asymmetry 1997, 8,
23; c) U. H. Hirt, M. F. H. Schuster, A. N. French, O. G.
Wiest, T. Wirth, Eur. J. Org. Chem. 2001, 1569; d) A.
C. Boye, D. Meyer, C. K. Ingison, A. N. French, T.
Wirth, Org. Lett. 2003, 5, 2157.
[5] For recent catalytic dioxygenation reactions: a) M.
Fujita, K. Mori, M. Shimogaki, T. Sugimura, Org. Lett.
2012, 14, 1294; b) M. Fujita, K. Mori, M. Shimogaki, T.
Sugimura, RSC Adv. 2013, 3, 17717; c) M. Shimogaki,
M. Fujita, T. Sugimura, Eur. J. Org. Chem. 2013, 7128.
[6] Y.-B. Kang, L. H. Gade, J. Am. Chem. Soc. 2011, 133,
3658.
[7] For Lewis acid activation: a) M. Fujita, M. Wakita, T.
Sugimura, Chem. Commun. 2011, 47, 3983; b) W.
Zhong, J. Yang, X. Meng, Z. Li, J. Org. Chem. 2011,
76, 9997.
[8] a) S. Haubenreisser, T. H. Wöste, C. Martínez, K.
Ishihara, K. Muñiz, Angew. Chem. Int. Ed. 2016, 55,
413; b) T. H. Wöste, K. Muñiz, Synthesis 2016, 48, 816.
[9] I. Colomer, C. Batchelor-McAuley, B. Odell, T. J.
Donohoe, R. G. Compton, J. Am. Chem. Soc. 2016,
138, 8855.
[10] a) J. Barluenga, J. M. González, P. J. Campos, G.
Asensio, Angew. Chem. Int. Ed. 1985, 24, 319; b) J.
Barluenga, Pure Appl. Chem. 1999, 71, 431; c) M.
Justin, L. Amber, G. Benjamin, Org. Synth. 2010, 87,
28; recent examples: d) J. Barluenga, E. CamposGómez, A. Minatti, D. Rodríguez, J. M. González,
Chem. Eur. J. 2009, 15, 8946; e) J. Barluenga, H.
Vázquez-Villa, I. Merino, A. Ballesteros, J. M.
González, Chem. Eur. J. 2006, 12, 5790; f) J.
Barluenga, H. Vázquez-Villa, A. Ballesteros, J. M.
González, Adv. Synth. Catal. 2005, 347, 526; g) J.
Barluenga, M. Trincado, M. Marco-Arias, A.
Ballesteros, E. Rubio, J. M. González, Chem. Commun.
2005, 2008; h) J. Barluenga, M. Trincado, E. Rubio, J.
M. González, Angew. Chem. Int. Ed. 2006, 45, 3140.

4

[11] For structural studies: a) C. Álvarez-Rúa, S. GarcíaGranda, A. Ballesteros, F. González-Bobes, J. M.
González, Acta Cryst. 2002, E58, o1381; b) A. C. C.
Carlsson, K. Mehmeti, M. Uhrbom, A. Karim, M.
Bedin, R. Puttreddy, R. Kleinmeier, A. A. Neverov, B.
Nekoueishahraki, J. Grafensetin, K. Rissanen, M.
Erdelyi, J. Am. Chem. Soc. 2016, 138, 9853; c) M.
Bedin, A. Karim, M. Reitti, A.-C. C. Carlsson, F. Tepic,
M. Cetina, F. Pan, V. Havel, F. Al-Ameri, V. Sindelar,
K. Rissanen, J. Gräfenstein, M. Erdélyi, Chem. Sci.
2015, 6, 3746; d) Y. Kim, E. J. Mckinley, K. E.
Christensen, N. H. Rees, A. L. Thompson, Cryst.
Growth Des. 2014, 14, 6294; e) T. Okitsu, S. Yumitate,
K. Sato, Y. In, A. Wada, Chem. Eur. J. 2013, 19, 4992.
[12] R. Weiß, J. Seubert, Angew. Chem. int. Ed. 1994, 33,
891.
[13] V. V. Zhdankin, A. Y. Koposov, N. V. Yashin,
Tetrahedron Lett. 2002, 43, 5735.
[14] P. Mizar, A. Laverny, M. El-Sherbini, U. Farid, M.
Brown, F. Malmedy, T. Wirth, Chem. Eur. J. 2014, 20,
9910.
[15] F. Malmedy, T. Wirth, Chem. Eur. J. 2016, 22,
16072-16077.
[16] See Supporting Information for details.
[17] K. Niedermann, J. M. Welch, R. Koller, J. Cvengros,
N. Santchi, P. Battaglia, A. Togni, Tetrahedron 2010,
66, 5753.
[18] X-ray crystallographic data for compound 5/6 have
been deposited with the Cambridge Crystallographic
Data Centre database (http://www.ccdc.cam.ac.uk/)
under code CCDC 1507745.
[19] A. Yoshimura, M. S. Yusubov, V. V. Zhdankin, Org.
Biomol. Chem. 2016, 14, 4771.
[20] Y.-B. Kang, L. H. Gade, J. Org. Chem. 2012, 77,
1610.
[21] R. B. Woodward, F. V. Brutcher, Jr., J. Am. Chem.
Soc. 1958, 80, 209.
[22] C. Prévost, Compt. Rend. 1933, 196, 1129.

5

COMMUNICATION
Vicinal Difunctionalization of Alkenes under
Iodine(III) Catalysis involving Lewis-Base
Adducts
Adv. Synth. Catal. Year, Volume, Page – Page
Kristina Aertker, Raquel J. Rama, Julita Opalach
and Kilian Muñiz*

6