Efficient photolytic C-H bond functionalization of alkylbenzene with hypervalent iodine(iii) reagent

Article abstract of DOI:10.1039/c5cc07647a

A practical approach to radical C-H bond functionalization by the photolysis of a hypervalent iodine(iii) reagent is presented. The photolysis of [bis(trifluoroacetoxy)iodo]benzene (PIFA) leads to the generation of trifluoroacetoxy radicals, which allows the smooth transformation of various alkylbenzenes to the corresponding benzyl ester compounds under mild reaction conditions.

Full text of DOI:10.1039/c5cc07647a

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DOI: 10.1039/C5CC07647A
Journal Name
COMMUNICATION
Efficient Photolytic C–H Bond Functionalization of Alkylbenzene
with Hypervalent Iodine(III) Reagent
Ryu Sakamoto, Tsubasa Inada, Sermadurai Selvakumar, Shin A. Moteki and Keiji Maruoka*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
A practical approach in the radical C–H bond functionalization by
the photolysis of hypervalent iodine(III) reagent is presented. The
photolysis of [bis(trifluoroacetoxy)iodo]benzene (PIFA) leads to the
generation of trifluoroacetoxy radicals that allows the smooth
transformation of various alkylbenzenes to the corresponding
benzyl ester compounds under mild reaction conditions.
With growing demands for developing environment-conscious
synthetic approaches, hypervalent iodine(III) compounds have
attracted great interest in synthetic community due to their low
toxicity, environment-friendly, unique reactivity and ready
availability. In the last past decades, a wide variety of polar
reactions such as oxidations, cyclizations, α-functionalizations
of carbonyl compounds and C–H aminations have been
successfully achieved by using various hypervalent iodine(III)
reagents.1 In contrast, radical reactions with hypervalent
iodine(III) reagents have been less investigated to date, and
most of them were achieved by combining use of transition-
metal reagents, and/or with relatively high temperature.2 Thus,
the development of milder and metal-free radical reactions
using hypervalent iodine(III) reagents is particularly valuable in
organic chemistry.3
Metal-free generation methods of radical species from
hypervalent iodine(III) reagents can be mainly categorized into
four groups (Scheme 1); 1) ligand exchange, 2) single-electron
transfer (SET) approach, 3) thermal decomposition and 4)
photolysis. Among them, the ligand exchange approach is most
frequently utilized.4 This approach can provide radical species
under mild conditions by the homolysis of a weak I−Nu bond,
which is formed through the ligand exchange on the iodine
center (Scheme 1a). However, the ligand exchange has the
limitation due to the narrow range of nucleophiles, which can
construct weak I−Nu bonds. In SET approach, hypervalent
Scheme 1 Generation of Radical Species from Hypervalent Iodine(III) Reagents.
iodine(III) reagents act as efficient SET oxidizing agents for
electron-rich aromatic compounds to generate cation radical
species (Scheme 1b).5 In contrast to these two approaches, the
thermal decomposition and the photolysis approach can
directly provide radical species from hypervalent iodine(III)
reagents. The thermal decomposition, however, often requires
high temperature, leading to a limited choice of solvent as well
as substrate scope (Scheme 1c).6 On the other hand, the
photolysis of hypervalent iodine(III) reagents can readily occur
to generate radical species by the irradiation of UV or visible
light under mild reaction condition (Scheme 1d). In spite of that
kind of advantage, only a few examples of radical reactions by
the photolysis of hypervalent iodine(III) reagents have been
reported to date with limited success.7 In this context, we have
been interested in the development of photoinduced radical
reactions using hypervalent iodine(III) reagents under metal-
free conditions.8 Herein, we describe our recent results on this
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo,
Kyoto 606-8502, Japan. E-mail: maruoka@kuchem.kyoto-u.ac.jp;
Fax: +81-75-753-4041; Tel: +81-75-753-4041;
†Electronic Supplementary Information (ESI) available: Experimental Details. See
DOI: 10.1039/x0xx00000x
study, which establishes the direct benzylic
C–H bond
esterification of alkylbenzenes by the combination of
electrophilic hypervalent iodine(III) reagents and visible light
irradiation.
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J. Name., 2013, 00, 1-3 | 1
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The direct benzylic C−H bond esterification of alkylbenzenes 1a or (dibenzoyloxyiodo)benzene 1b under the visible light (400
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provides an attractive approach toward the construction of nm), the desired products were not observed, and
benzyl esters, which are valuable building blocks in organic were almost remained (entries 1 and 2). More electrophilic
DOI: 10.1039/C51CaC0o7r6417bA
synthesis. Recently, several metal-free direct esterification of hypervalent
benzylic C−H bond have been reported; however, most of them [bis(trifluoroacetoxy)iodo]benzene
iodine(III)
reagent
1c or
(PIFA)
required relatively high temperature (>60 °C) or an excess [bis(pentafluorobenzoyloxy)iodo]benzene 1d provided low
amount of acid.9 Therefore, the development of milder and yields of
, along with the substantial amount of unreacted
7
practical methods is still an attractive and a challenging goal. iodine reagents (entries 3 and 4). The significant increase of the
Our strategy for the direct esterification of alkylbenzenes with product yield was observed by using benzene as a solvent (entry
the photolysis of hypervalent iodine(III) reagent is depicted in 5).10 Use of 1a in benzene under 400 nm gave the trace amount
Scheme 2. First, the photolysis of hypervalent iodine(III) of the product, and 1a was recovered quantitatively (entry 6).
reagents
radical
would afford a benzylic radical
between and would furnish a desired benzyl ester
pathway). Alternatively, ionic reaction between a carboxylate decarboxylation to give the trifluoromethyl radical.3 In the
anion and a benzyl cation , which would be formed by single- absence of light, both 4a and 1c were recovered (entry 8).
electron transfer (SET) of
We initially tested hypervalent iodine(III) reagents 1a
1
would generate a carboxyl radical
. Then, hydrogen abstraction of alkylbenzene
. Finally, the radical coupling product in large quantity, which indicated that the strong UV
(radical light further decomposed trifluoroacetoxy radical via
2
and an iodanyl The use of strong UV light (365 nm) sligthly reduced the yield of
3
4
by 7a (entry 7), and trifluoromethylbenzene was obtained as a by-
2
5
5
2
7
a
6
5
, would afford
7
(ionic pathway).
With the optimized conditions in hand, the substrate scope
–d
with of this reaction was explored, and the results are summarized
ethylbenzene 4a as a model substrate (Table 1). When the in Table 2. First, we found that alkyl or aryl substituents at
reactions were conducted with (diacetoxyiodo)benzene (DIB)
benzylic positions of
products 7a
in good yields. The use of 4e (R1, R2 = H) as a
substrate afforded 7e in low yield. The electronic nature of the
4 did not affect the reaction, giving
–d
aryl group has some effect on the reaction. In the case of 4f–i
with electron-withdrawing groups on the aryl rings, desired
Table 2 Trifluoroacetoxylation of Various Alkylbenzenes 4. [a]
Scheme 2 Proposed Mechanism of the Direct Esterification of Alkylbenzenes.
Table 1 Optimization of Reaction Conditions using Ethylbenzene 4a. [a]
entry
reagent, 1
solvent
MeCN
% yield[b]
no reaction
no reaction
16
1
2
1a
1b
1c
1d
1c
1a
1c
1c
MeCN
3
MeCN
4
MeCN
7
5
benzene
benzene
benzene
benzene
98
6
no reaction
62
7[c]
8[d]
no reaction
[a]Unless otherwise specified, reactions were conducted in the presence of 4a (0.5
mmol), 1 (1.4 equiv.) in solvent (0.5 M) with irradiation by visible light (400 nm).
[b] Yield was determined by 1H NMR spectroscopy using 1,1,2,2-tetrachloroethane
as an internal standard. [c] Use of 365 nm black light. [d] The reaction was
performed under dark atmosphere.
[a] Yield was determined by 1H NMR spectroscopy using 1,1,2,2-tetrachloroethane
as an internal standard. [b] Isolated yield in parentheses. [c] Chloroform was used
as a solvent. [d] 2 equiv. of 1c was used. Bz = benzoyl, Phth = phthaloyl.
2 | J. Name., 2012, 00, 1-3
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products 7f 7i were obtained in moderate to high yields. In
COMMUNICATION
To expand the substrate scope of the reaction, iVsioewchArrtoicmle Oannlin8e
–
contrast, introduction of an electron-donating group, such as was used as substrate under the standaDrdOI:re10a.c10ti3o9n/Cc5oCnCd07it6i4o7nA,
methoxy group, provided complex mixtures (not shown). Use of giving a hydroxylated product 9a in 62% yield, instead of 9b
indan gave bis(trifluoroacetoxyl) product 7j in 77% yield, insted (Scheme 3). We hypothesized that due to the relatively high
of mono-oxidized product 7k. We assume that the elimination leaving ability of the trifluoroacetoxy group, 9b existed in
of TFA from 7k gave inden, and the subsequent olefin bis- equilibrium with an oxocarbocation 9c under the reaction
trifluoroacetoxylation of inden by PIFA occured to give 7j 11
of isopropylbenzene also resulted in the formation of up to give 9a. This hypothesis was confirmed by the addition of
bis(trifluoroacetoxy) product 7l in 21% yield and in the recovery nucleophiles after the photoreaction with
and 1c (Table 3).14
of strating material in 42% yield. Next, we examined Thus, the addition of several Grignard reagents worked well to
disubstituted arenes in this reaction. When 1,4-diethylbenzene afford the corresponding alkylation products 10a in moderate
was used, mono-oxidized product 7n was obtained as a major yields.10 Use of isocyanides as nucleophiles gave amide 10d and
product in 73% yield, along with bis(trifluoroacetoxy) product 10e 15
Nitrogen nucleophiles and an oxygen nucleophile also
7o in 15% yield. It shoud be noted that the present photolysis gave the corresponding products 10f in moderate to good
. Use condition, and the hydrolysis of 9c took place during the work-
8
–c
.
–h
reaction using disubstituted arene showed better results in yields. Additionally, the reaction of acyclic benzyl ether
terms of yield and chemoselectivity, in comparison with the derivative 11 proceeded smoothly to afford α-hydroxy carbonyl
similar direct C–H esterification using hypervalent iodine 1a 9c
.
compound 12 in 54% yield (Scheme 4).
Oxidation reactions with other disubstituted arenes also
proceeded smoothly at less hindered secondary benzylic Csp3–
H bond to give 7p
use of 4-ethylpyridine resulted in decrease in yield of 7r 13
–s
in good yields.12 Unfortunately, attempted
.
Scheme 4 Direct C–H Functionalization of Benzyl Ether.
Finally, we conducted several control experiments for the
understanding of the reaction mechanism (Scheme 5). When
the reaction using 4a under oxygen atmosphere was performed,
acetophenone 13 was obtained in 50% yield (Scheme 5a). This
implies that a benzyl radical was generated during the reaction.
On the other hand, the addition of AcOH in the reaction gave
acetoxylated product 14 in 15% yield along with 7a (Scheme 5b).
And also, when the reaction was performed in the presence of
5 equivalent of acetonitrile, the formation of N-(1-phenylethyl)-
acetamide 15 was observed (Scheme 5c). On the basis of these
results, we tentatively considered that the benzyl cation
Scheme 3 Photolytic C–H Bond Oxidation of Isochroman.
Table 3 Direct C–H Functionalization of Isochroman.
intermediate
C–O bond forming step of
pathway to furnish benzyl ester
6
was formed during the reaction, indicating that
proceeded through an ionic
(Scheme 2).
5
7
Scheme 5 Control Experiment Reactions.
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Journal Name
Sumida, I. Itani, H. Kubo, Y. Ohnishi, S. Sekiguchi, T. Dohi, Y.
In summary, we have succeeded in the development of the
direct benzylic C–H bond esterification of alkylbenzenes by the
combination of electrophilic hypervalent iodine(III) reagents
and visible light irradiation. With this approach, various
alkylbenzenes were converted to the corresponding benzyl
ester derivatives in good yield. This process represents a rare
example of radical reaction from hypervalent iodine(III)
reagents induced by photolysis. Further investigations on more
detailed mechanism and applications of the present
photoreaction for the development of new oxidation reactions
is under investigation.
View Article Online
Kita, Chem. Eur. J. 2013, 19, 15004.
6
Selected reports: see (a) J. E. Leffler, LD. OJ.I:S1t0o.1r0y,39J/.CA5mCC. 0C7h6e4m7A.
Soc. 1967, 89, 2333; (b) J. E. Leffler, D. C. Ward, A. Burduroglu,
J. Am. Chem. Soc. 1972, 94, 5339; (c) H. Togo, R. Takiguchi, K.
Yamaguchi, M. Yokoyama, J. Chem. Soc. Perkin Trans 1 1995,
2135; (d) A. P. Krasutsky, C. J. Kuehl, V. V. Zhdankin, Synlett
1995, 1081; (e) V. V. Zhdankin, A. P. Krasutsky, C. J. Kuehl, A.
J. Simonsen, J. K. Woodward, B. Mismash, J. T. Bolz, J. Am.
Chem. Soc. 1996, 118, 5192; (f) V. V. Zhdankin, C. J. Kuehl, A.
P. Krasutsky, J. T. Bolz, B. Mismash, J. K. Woodward, A. J.
Simonsen, Tetrahedron Lett. 1995, 36, 7975; (g) V. V.
Zhdankin, M. McSherry, B. Mismash, J.T. Bolz, J. K. Woodward,
R. M. Arbit, S. Erickson, Tetrahedron Lett. 1997, 38, 21.
(a) F. Minisci, E. Vismara, F. Fontana, M. C. N. Barbosa,
Tetrahedron Lett. 1989, 30, 4569; (b) H. Togo, M. Aoki, M.
Yokoyama, Tetrahedron Lett. 1991, 32, 6559; (c) H. Togo, M.
Aoki, M. Yokoyama, Chem. Lett. 1992, 21, 2169; (d) H. Togo,
M. Aoki, M. Yokoyama, Tetrahedron 1993, 49, 8241; (e) H.
Togo, T. Muraki, M. Yokoyama, Synthesis 1995, 155; See also
ref. 4b and 6c.
7
Notes and references
1
For recent reviews, see: (a) V. V. Zhdankin, P. J. Stang, Chem.
Rev, 2002, 102, 2523; (b) T. Wirth, M. Ochiai, V. V. Zhdankin,
G. F. Koser, H. Tohma, Y. Kita, Top. Curr. Chem.: Hypervalent
Iodine Chemistry-Modern Developments in Organic Synthesis,
Springer, Berlin, 2003; (c) H. Tohma, Y. Kita, Adv. Synth. Catal.
8
9
S. A. Moteki, A. Usui, S. Selvakumar, T. Zhang, K. Maruoka,
Angew. Chem. Int. Ed. 2014, 53, 11060.
2004, 346, 111; (d) T. Wirth, Angew. Chem. Int. Ed. 2005, 44
,
,
(a) T. M. Shaikh, A. Sudalai, Tetrahedron Lett. 2005, 46, 5587;
(b) V. Kumar, A. Sharma, M. Sharma, U. K. Sharma, A. K. Sinha,
Tetrahedron 2007, 63, 9718; (c) H. Baba, K. Moriyama, H. Togo,
Tetrahedron Lett. 2011, 52, 4303; (d) H. Yi, Q. Liu, Z. Zeng, Y.
3656; (e) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008, 108
5299; (f) M. Ochiai, Synlett 2009, 159; (g) T. Dohi, Y. Kita, Chem.
Commun. 2009, 2073; (h) F. V. Singh, T. Wirth, Chem. Asian. J,
2014, 9, 950.
Yang, A. Lei, ChemSusChem. 2012, 5, 2143; (e) Feng, S. Liang,
2
Selected reports: see (a) K. Smith, C. D. Hupp, K. L. Allen, G. A.
Slough, Organometallics 2005, 24, 1747; (b) S. H. Cho, J. Yoon,
S. Chang, J. Am. Chem. Soc. 2011, 133, 5996; (c) S. Mizuta, O.
Galicia-López, K. M. Engle, S. Verhoog, K. Wheelhouse, G.
Rassias, V. Gouverneur, Chem. Eur. J. 2012, 18, 8583; (d) E.
S.-Y. Chen, J. Zhang, S.-S. Fu, X.-Q. Yu, Adv. Synth. Catal. 2012,
354, 1287; (f) J. Huang, L.-T. Li, H.-Y. Li, E. Husan, P. Wang, B.
Wang, Chem. Commun. 2012, 48, 10204; (g) G. Majji, S. Guin,
A. Gogoi, S. K. Rout, B. K. Patel, Chem. Commum. 2013, 49
,
3031; (h) L. Liu, L. Yun, Z. Wang, X. Fu, C.-h. Yan, Tetrahedron
Lett. 2013, 54, 5383, See also ref. 4f.
Mejía, A. Togni, ACS Catal. 2012,
2, 521; (e) Y. Wang, L. Zhang,
Y. Yang, P. Zhang, Z. Du, C. Wang, J. Am. Chem. Soc. 2013, 135
,
10 See ESI for details of optimization.
18048; (f) Z. He, M. Bae, J. Wu, T. F. Jamison, Angew. Chem.
Int. Ed. 2014, 53, 14451; (g) H. Huang, K. Jia, Y. Chen, Angew.
Chem. Int. Ed. 2015, 54, 1881.
11 (a) M. Çelik, C. Alp, B. Coşkun, M. S. Gültekin, M. Balci,
Tetrahedron Lett. 2006, 47, 3659; (b) I. Tellitu, E. Domínguez,
Tetrahedron 2008, 64, 2465.
3
4
H. Togo, M. Katohgi, Synlett 2001, 565.
12 Use of 1-ethyl-4-isobutylbenzene underwent undesired
trifluoroacetoxylation on the isobutyl group to afford 4-
(CH3CH2)C6H4-CH(OTFA)- (CH3)2 as a regiosiomer of 7o in 25%
yield. For details, see ESI.
13 Use of other heteroaromatic compounds, such as furan or
indole derivatives, afforded the trace amounts of the desired
products.
Selected reports: see (a) F. Fontana, F. Minisci, Y. M. Yan, L.
Zhao, Tetrahedron Lett. 1993, 34, 2517; (b) H. Togo, M. Aoki,
T. Kuramochi, M. Yokoyama, J. Chem. Soc. Perkin Trans 1 1993,
2417; (c) M. Ochiai, T. Ito, H. Takahashi, A. Nakanishi, M.
Toyonari, T. Sueda, S. Goto, M. Shiro, J. Am. Chem. Soc. 1996,
118, 7716; (d) D.-J. Chen, Z.-C. Chen, Tetrahedron Lett. 2000,
41, 7361; (e) M. Catir, H. Kilic, Synlett 2004, 2151; (f) T. Dohi,
14 (a) M. Ghobrial, K. Harhammer, M. D. Mihovilovic, M.
Schnürch, Chem. Commun. 2010, 46, 8836; (b) M. Ghobrial, M.
Schnürch, M. D. Mihovilovic, J. Org. Chem. 2011, 76, 8781; (c)
S. J. Park, J. R. Price, M. H. Todd, J. Org. Chem. 2012, 77, 949;
N. Takenaga, A. Goto, A. Maruyama, Y. Kita, Org. Lett. 2007, 9,
3129; (g) W. Zhou, L. Zhang, N. Jiao, Angew. Chem. Int. Ed.
2009, 48, 7094; (h) X.-Q. Li, W.-K. Wang, Y.-X. Han, C. Zhang,
Adv. Synth. Catal. 2010, 352, 2588; (i) Y. Zhao, Y.-Y. Yeung, Org.
Lett. 2010, 12, 2128; (j) M. Catir, H. Kilic, Synlett 2010, 1319;
(k) Y. Zhao, W.-L. Yim, C. K. Tan, Y.-Y. Yeung, Org. Lett. 2011,
13, 4308; (l) A. P. Antonchick, L. Burgmann, Angew. Chem. Int.
Ed. 2013, 52, 3267; (m) S. A. Moteki, A. Usui, T. Zhang, C. R. S.
Alvarado, K. Maruoka, Angew. Chem. Int. Ed. 2013, 52, 8657;
(n) S. A. Moteki, S. Selvakumar, T. Zhang, A. Usui, K. Maruoka,
(d) W. Muramatsu, K. Nakano, C.-J. Li, Org. Lett. 2013, 15
,
3650; (e) K. Qvortrup, D. A. Rankic, D. W. C. MacMillan, J. Am.
Chem. Soc. 2014, 136, 626; (f) W. Muramatsu, K. Nakano, Org.
Lett. 2015, 17, 1549.
15 (a) T. Mukaiyama, K. Watanabe, M. Shiono, Chem. Lett. 1974,
3
, 1457; (b) H. Pellissier, A. Meou, G. Gil, Tetrahedron Lett.
1986, 27, 2979; (c) B. Schweitzer-Chaput, M. Klussmann, Eur.
J. Org. Chem. 2013, 666; (d) M. Tobisu, A. Kitajima, S. Yoshioka,
Asian. J. Org. Chem. 2014,
3, 932; (o) R. Narayan. A. P.
Antonchick, Chem. Eur. J. 2014, 20, 4568.
I. Hyodo, M. Oshita, N. Chatani, J. Am. Chem. Soc. 2007, 129
11431.
,
5
(a) For recent reviews, see T. Dohi, M. Ito, N. Yamaoka, K.
Morimoto, H. Fujioka, Y. Kita, Tetrahedron 2009, 65, 10797;
(b) T. Dohi, M. Ito, N. Yamaoka, K. Morimoto, H. Fujioka, Y.
Kita, Angew. Chem. Int. Ed. 2010, 49, 3334; (c) T. Dohi, M. Ito,
I. Itani, N. Yamaoka, K. Morimoto, H. Fujioka, Y. Kita, Org. Lett.
2011, 13, 6208; (d) K. Morimoto, T. Nakae, N. Yamaoka, T.
Dohi, Y. Kita, Eur. J. Org. Chem, 2011, 6326; (e) T. Dohi, M. Ito,
S. Sekiguchi, Y. Ishikado, Y. Kita, Heterocycles 2012, 86, 767;(f)
K. Morimoto, K, Sakamoto, Y. Ohnishi, T. Miyamoto, M. Ito, T.
Dohi, Y. Kita, Chem. Eur. J. 2013, 19, 8726; (g) N. Yamaoka, K.
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