Vicinal Difunctionalization of Alkenes under Iodine(III) Catalysis involving Lewis Base Adducts

Article abstract of DOI:10.1002/adsc.201601178

The influence of a 2-pyridinyl substituent on the catalytic performance of aryl iodides as catalyst in iodine(III) chemistry was explored. An efficient Lewis 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. (Figure presented.).

Full text of DOI:10.1002/adsc.201601178

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DOI: 10.1002/adsc.201601178
Vicinal Difunctionalization of Alkenes under Iodine(III) Catalysis
involving Lewis Base Adducts
Kristina Aertker,a Raquel J. Rama,a Julita Opalach,a and Kilian MuÇiza,b,*
a
Institute of Chemical Research of Catalonia (ICIQ), The Barcelona Institute of Science and Technology, 16 Avgda. Paisos
Catalans, 43007 Tarragona, Spain
E-mail: kmuniz@iciq.es
ICREA, Pg. Lluꢀs Companys 23, 08010 Barcelona, Spain
b
Received: October 25, 2016; Revised: February 7, 2017; Published online: && &&, 0000
Supporting information for this article can be found under http://dx.doi.org/10.1002/adsc.201601178.
Abstract: The influence of a 2-pyridinyl substituent
on the catalytic performance of aryl iodides as cata-
lyst in iodine(III) chemistry was explored. An effi-
cient Lewis base adduct between the pyridine nitro-
gen and the electrophilic iodine(III) center was
identified and confirmed by X-ray analysis. This ar-
rangement was shown to generate a kinetically
competent superior catalyst structure for the cata-
lytic dioxygenation of alkenes. It introduces the
concept of Lewis base adduct formation as a kinetic
factor in iodine(I/III) catalysis.
nation site at iodine. The same observation was re-
cently made in the development of an enantioselec-
tive catalytic diacetoxylation of styrenes, in which co-
catalysis by TfOH was a crucial factor.[8] Alternative-
ly, the activation of iodine(III) derivatives with the
aid of fluorinated alcohols was discussed.[9]
It appears reasonable to investigate further struc-
tural diversification for the discrete formation of elec-
trophilic iodine(III) catalyst states with free coordina-
tion sites. One approach in this direction should con-
sist of the use of weakly coordinating Lewis bases.
The pyridine unit displays a long history of success-
ful stabilization of electrophilic iodine centers. Bar-
luengaꢁs reagent [I(py)2]BF4 is certainly the most
prominent example to this end,[10,11] while pyridine co-
ordination to electrophilic iodine(III) centers has
been less investigated.
Keywords: alkenes; catalysis; iodine; Lewis bases;
oxidation
Examples in this area include the compound
Hypervalent iodine(III) reagents[1] have been identi- [PhI(py)2](OTf)2 (2),[12] the corresponding benziodox-
fied as versatile reagents for the difunctionalization of olone adduct 3[13] and the chiral derivatives 4 and 5,
alkenes.[2] The general versatility of these oxidizing re- which were introduced by Wirth (Figure 1).[14,15] Inter-
agents in organic chemistry is further expressed by estingly, the solid state structure of 4 does not display
recent developments, which involve their application any interaction between the iodine(III) center and
in metal-free, environmentally benign oxidation catal- the nitrogen atom of the pyridinyl group. In agree-
ysis.[3] In these cases, the iodine(III) state represents ment with this, the reported catalysis relied on co-ac-
the active catalyst, which is continuously regenerated tivation by a Brønsted acid.[15]
from a conventional iodine(I) precatalyst.
In the prominent field of dioxygenation reactions
of alkenes,[4,5] the application of the standard hyperva-
lent iodine reagent PhI(OAc)2 1 for diacetoxylation is
hampered by its notoriously low reactivity towards al-
kenes.
The desired reaction can be accelerated through ad-
dition of catalytic amounts of a strong Brønsted acid,
for example TfOH. In seminal work, Gade and Kang
demonstrated that such an acid catalysis significantly
accelerates the alkene oxidation, presumably through
protonolysis of PhI(OAc)2 forming a cationic iodine
center (Scheme 1).[6,7] The latter displays enhanced
Scheme 1. Brønsted acid acceleration in the diacetoxylation
electrophilicity and reactivity due to the free coordi- of alkenes.
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Figure 1. Pyridine coordination to iodine(III) in compounds
2 and 3, and chiral pyridinyl derivatives 4 and 5.
To probe the supportive context of pyridine coordi-
nation in an iodine(III) catalyst, the aryliodine 6 was
synthesized from 2-phenylpyridine[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) de-
rivative 7 was observed.
Figure 2. Solid-state structures of compounds 7 and 8 (ellip-
soids at 50% probability).[18] Selected bond lengths [ꢃ] and
angles [8]: 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).
on oxygen coordination.[19] In general, intramolecular
Suitable crystals of the new chelate 7 were grown coordination of oxygen donor atoms to hypervalent
from a solution in cyclohexane-dichloromethane. X- iodine centers has been a common strategy, while re-
ray analysis confirmed the expected structure includ- lated nitrogen donor coordination appears significant-
ing the coordination of the pyridine group to the cen- ly less encountered.
tral iodine atom indicating the Lewis base-assisted ac-
The crystal structure determination also provides
tivation of the former iodine-acetoxy bond the corresponding iodoso benzene 8 (Figure 2), which
(Figure 2).[18] The corresponding I–N bond length was undergoes intermolecular hydrogen bonding with 7.[18]
determined to be 2.443 ꢃ, which is in good agreement Iodoso derivative 8 originates from compound 7 upon
with bond distances of 2.44 to 2.46 ꢃ in related nitro- loss of acetic acid (Scheme 3), presumably throughout
gen coordination[17] and of 2.24 to 3.13 ꢃ in similar the crystallization process. In an analogous manner, 7
derivatives of chelated iodine(III) complexes based can be restored from 8 by addition of acetic acid char-
acterizing it as the acetic acid adduct of 7.
Scheme 3. Relation between iodine(III) compounds 7 and 8.
Subsequent work addressed the diacetoxylation of
alkenes with compound 6 as catalyst. Given the effec-
tive oxidation of 6 to 7, we decided to employ perace-
tic acid as the terminal oxidant and to follow condi-
tions 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
Scheme 2. Oxidation of iodine(I) compound 6 to iodine(III)
compound 7.
commonly observed,[5,6,8,20] styrenes represent the pre-
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n.[6,20] Finally, linear aliphatic alkenes give direct rise
to the diacetoxylated products 10o–q without require-
ment for peracetoxylation, which indicates a Prevost
pathway[22] to be operative.
The beneficial effect of the 2-pyridinyl group was
demonstrated within a kinetic competition experi-
ment between catalyst 6 and iodobenzene 1. Monitor-
ing by 19F NMR the progress of the oxidation of 4-flu-
orostyrene 9d in acetic acid-d4 as solvent, a clear ac-
celeration 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 kinet-
ic finding clearly demonstrates that the concept of
Lewis base coordination can accelerate hypervalent
iodine catalysis to a significant extent.
Scheme 4. Catalytic diacetoxylation of alkenes. Given yields
refer to isolated material after purification.
Figure 3. Initial kinetic profiles for the dioxygenation of 4-
fluorostyrene 9d with catalyst 6 and iodobenzene 1.
ferred 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 result-
ed from clean diacetoxylation without any potentially
The proposed catalytic cycle (Figure 4) comprises
competing rearrangement or allylic oxidation. From the documented oxidation of catalyst 6 to 7 with the
observations of the crude reaction mixture of 10d, it iodine(III) catalyst state. Coordination of alkene 9 to
was concluded that these reactions proceed through the electrophilic iodine center in 7 may involve an as-
initial formation of the 1-hydroxy-2-acetoxy deriva- sociative process through A or directly arrive at A’
tive, which derives from the Woodward pathway.[21] with a three-coordinate iodine center. Subsequent io-
They are converted into uniform vicinal diacetoxy doacetoxylation initiates the difunctionalization via B,
products upon treatment with acetic anhydride. In from which catalyst 6 is regenerated via reductive
contrast, (E)- and (Z)-b-methylstyrene and (E)-O- oxygenation (as discussed, for styrenes 9a–h, this step
acetoxycinnamic ester yield the corresponding prod- should consist of a Woodward pathway).
ucts 10j–10l as diastereomeric mixtures due to com-
In summary, we have reported a new catalyst for
the iodine(III)-catalyzed dioxygenation of alkenes.
peting Woodward and Prevost[22] pathways.
Cyclic aliphatic alkenes can also be employed as The kinetic competence of this catalyst relies on an
demonstrated for formation of the products 10m and efficient Lewis base coordination of a pyridine group
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rectly 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 mL, 0.5 mmol, 2.5 equiv.), pyridine
(40 mL, 0.5 mmol, 2.5 equiv.) and DMAP (6.1 mg,
0.05 mmol, 0.25 equiv.) were added. After stirring at room
temperature for 5 h, the reaction was quenched with aque-
ous HCl (6M, 3 mL) and EtOAc (3 mL). The aqueous
phase was extracted twice with EtOAc and the combined or-
ganic layers were dried over Na2SO4, and concentrated
under reduced pressure. The crude product was purified by
flash column chromatography on silica gel to provide analyt-
ically 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, SEV-2013-0319) and the CERCA Programme/Govern-
ment of Catalonia for financial support and Dr. E. Escudero-
Adꢀn for the X-ray analysis. KA is an undergraduate student
from LMU Munich.
Figure 4. Catalytic cycle for the diacetoxylation of styrenes
9.
to the electrophilic iodine(III) catalyst. This concept References
should provide space for new catalyst design in the
field of hypervalent iodine catalysis.
[1] a) V. V. Zhdankin, Hypervalent Iodine Chemistry Prep-
aration, Structure and Synthetic Applications of Poly-
valent Iodine Compounds, Wiley, Chichester, 2013;
b) Iodine Chemistry and Applications, (Ed.: T. Kaiho),
Wiley, Hoboken, New Jersey, 2015; c) Topics in Current
Chemistry, Vol. 224, (Ed.: T. Wirth), Springer, Berli,
2003; d) Topics in Current Chemistry, Vol. 373, (Ed.: T.
Wirth), Springer, Berlin, 2016; e) A. Yoshimura, V. V.
Zhdankin, Chem. Rev. 2016, 116, 3328.
Experimental Section
Synthesis of Catalyst 6[17]
2-(2-Bromophenyl)pyridine (162 mg, 0.7 mmol) was dis-
solved in absolute THF (5.5 mL), cooled to À788C and n-
BuLi (0.38 mL, 2M in hexane, 0.76 mmol, 1.1 equiv.) was
added. The reaction mixture was stirred at À788C for 2 h.
An iodine solution (3 mL, 1M in THF, 3.01 mmol,
4.3 equiv.) was then added at À788C. The mixture was
warmed to room temperature, stirred for 20 h and evaporat-
ed to dryness. Column chromatography (SiO2, 10% ethyl
acetate/hexane/EtOAc, 90/10, v/v) provided the title com-
pound 6 as a white solid; yield: 106.8 mg (54%).
[2] a) R. M. Romero, T. H. Wçste, K. MuÇiz, Chem. Asian
J. 2014, 9, 972; b) M. Uyanik, K. Ishihara, J. Synth.
Org. Chem. Jpn. 2012, 70, 1116; c) F. V. Singh, T. Wirth,
Chem. Asian J. 2014, 9, 950; d) F. Berthiol, Synthesis
2015, 47, 587.
[3] a) R. D. Richardson, T. Wirth, Angew. Chem. 2006, 118,
4510; 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 dioxygenation reactions, see: 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, see: 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.
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 mL, 0.44 mmol,
2.2 equiv.) was added and the reaction mixture was stirred
at room temperature for 1 h. Then the respective alkene
(0.2 mmol, 1.0 equiv.) 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 com-
bined organic phases were dried over Na2SO4 and concen-
trated under reduce pressure. Compounds 10n–q were di-
Adv. Synth. Catal. 0000, 000, 0 – 0
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COMMUNICATIONS
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[6] Y.-B. Kang, L. H. Gade, J. Am. Chem. Soc. 2011, 133,
3658.
[7] For Lewis acid activation, see: 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. Wçste, C. Martꢀnez, K. Ishi-
hara, K. MuÇiz, Angew. Chem. 2016, 128, 422; Angew.
Chem. Int. Ed. 2016, 55, 413; b) T. H. Wçste, K. MuÇiz,
Synthesis 2016, 48, 816.
[9] I. Colomer, C. Batchelor-McAuley, B. Odell, T. J. Do-
nohoe, R. G. Compton, J. Am. Chem. Soc. 2016, 138,
8855.
Nekoueishahraki, J. Grafensetin, K. Rissanen, M. Erde-
lyi, 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. ErdØlyi, 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. 1994, 106, 900;
Angew. Chem. Int. Ed. Engl. 1994, 33, 891.
[13] V. V. Zhdankin, A. Y. Koposov, N. V. Yashin, Tetrahe-
dron Lett. 2002, 43, 5735.
[10] a) J. Barluenga, J. M. Gonzꢄlez, P. J. Campos, G. Asen-
sio, Angew. Chem. 1985, 97, 341; Angew. Chem. Int.
Ed. Engl. 1985, 24, 319; b) J. Barluenga, Pure Appl.
Chem. 1999, 71, 431; c) M. Justin, L. Amber, G. Benja-
min, Org. Synth. 2010, 87, 28; for recent examples, see:
d) J. Barluenga, E. Campos-Gꢅmez, A. Minatti, D. Ro-
drꢀguez, J. M. Gonzꢄlez, Chem. Eur. J. 2009, 15, 8946;
e) J. Barluenga, H. Vꢄzquez-Villa, I. Merino, A. Balles-
teros, J. M. Gonzꢄlez, Chem. Eur. J. 2006, 12, 5790; f) J.
Barluenga, H. Vꢄzquez-Villa, A. Ballesteros, J. M.
Gonzꢄlez, Adv. Synth. Catal. 2005, 347, 526; g) J. Bar-
luenga, M. Trincado, M. Marco-Arias, A. Ballesteros,
E. Rubio, J. M. Gonzꢄlez, Chem. Commun. 2005, 2008;
h) J. Barluenga, M. Trincado, E. Rubio, J. M. Gonzꢄlez,
Angew. Chem. 2006, 118, 3212; Angew. Chem. Int. Ed.
2006, 45, 3140.
[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 the 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] CCDC 1507745 (compound 7/8) contains the supple-
mentary crystallographic data for this paper. These
data can be obtained free of charge from The
Cambridge
Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
[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.
[11] For structural studies: a) C. ꢆlvarez-Rffla, S. Garcꢀa-
Granda, A. Ballesteros, F. Gonzꢄlez-Bobes, J. M. Gon-
zꢄlez, Acta Crystallogr. 2002, E58, o1381; b) A. C. C.
Carlsson, K. Mehmeti, M. Uhrbom, A. Karim, M.
Bedin, R. Puttreddy, R. Kleinmeier, A. A. Neverov, B.
[22] C. PrØvost, Compt. Rend. 1933, 196, 1129.
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6 Vicinal Difunctionalization of Alkenes under Iodine(III)
Catalysis involving Lewis Base Adducts
Adv. Synth. Catal. 2017, 359, 1 – 6
Kristina Aertker, Raquel J. Rama, Julita Opalach,
Kilian MuÇiz*
Adv. Synth. Catal. 0000, 000, 0 – 0
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