Synthesis of boron-substituted diaryliodonium salts and selective transformation into functionalized aryl boronates

Article abstract of DOI:10.1002/anie.201206917

Dormant boron awaits its true destiny in diaryliodonium salts synthesized from aryl boronate derivatives according to two alternative general methods with hypervalent iodine(III) reagents and fluoroalcohol solvents: transformation of an aryl C-H bond and

Full text of DOI:10.1002/anie.201206917

Angewandte
Chemie
DOI: 10.1002/anie.201206917
Boron Compounds
Synthesis of Boron-Substituted Diaryliodonium Salts and Selective
Transformation into Functionalized Aryl Boronates**
Motoki Ito, Itsuki Itani, Yosuke Toyoda, Koji Morimoto, Toshifumi Dohi, and Yasuyuki Kita*
Functionalized aryl boronates are highly important building
blocks for the construction of complex and valuable mole-
cules, such as natural products, pharmaceuticals, and opto-
electric materials.[1] For the synthesis of these compounds, the
boronate group has usually been introduced into a prefunc-
tionalized arene during the last step of the synthesis, tradi-
tionally by a two-step transformation involving metalation or
recently by catalytic borylation [Eq. (1), left].[2] In contrast,
another possible approach, the postfunctionalization of aryl
boronates, has been rarely investigated [Eq. (1), right] owing
to the sensitivity of boronate groups to common organic
reagents. However, this strategy would enable rapid access to
complex aryl boronates because their molecular diversity and
complexity could be readily increased by coupling with
a range of partners. For example, a recent advancement in
the boron-protection strategy with remarkable advantages
was the concise synthesis of oligoarenes by iterative Suzuki–
Miyaura coupling and deprotection processes.[3] However, the
protective functionalization of a conventional aryl boronate
for later straightforward deprotection and further transfor-
mations is still limited.[4]
ized aryl boronates owing to their accessibility from various
arenes, their stability, and the ability to convert the iodonium
moiety into a wide range of functional groups by catalyst-free
aromatic nucleophilic substitution (SNAr) or metal-catalyzed
coupling.[6]
We previously reported the direct and efficient synthesis
of diaryliodonium salts from electron-rich aromatic substrates
with iodine(III) reagents, such as PhI(OCOCF3)2 (PIFA) or
PhI(OH)OTs, in high-polarity and low-nucleophilicity fluo-
roalcohol solvents, CF3CH2OH (TFE) or (CF3)2CHOH
(HFIP).[7] We attempted to apply this method to boron-
À
substituted aromatic substrates containing reactive C H
bonds, such as aryl boronates 1a–f (Table 1). The selective
À
C H transformation of the aryl boronate pinacol esters 1a,b
and neopentylglycol ester 1c successfully proceeded at the
para position to the oxygen atom, and the boron-substituted
salts 2a–c were obtained in excellent yields without the loss of
the boronate group.[8] Substrate 1d was converted into the salt
2d with an additional chlorine functionality. Salt 2e was
obtained as the sole product from substrate 1e, in which the
To develop a new precursor that would permit the
postfunctionalization of aryl boronates, we focused on novel
boron-substituted[5] diaryliodonium salts [Eq. (2)]. These
unique hypervalent iodine(III) species were expected to be
efficient synthetic modules for the preparation of functional-
Table 1: Direct synthesis of boron-substituted iodonium salts.[a]
[*] Dr. M. Ito, I. Itani, Y. Toyoda, Dr. K. Morimoto, Dr. T. Dohi,
Prof. Dr. Y. Kita
College of Pharmaceutical Sciences, Ritsumeikan University
1-1-1 Nojihigashi, Kusatsu, Shiga, 525-0058 (Japan)
E-mail: kita@ph.ritsumei.ac.jp
Homepage: http://www.ritsumei.ac.jp/pharmacy/kita/index.html
[**] This research was partially supported by a Grant-in-Aid for Scientific
Research (A) from the Japan Society for the Promotion of Science
(JSPS), a Grant-in-Aid for Scientific Research on Innovative Areas
(“Advanced Molecular Transformation by Organocatalysts”) from
The Ministry of Education, Culture, Sports, Science, and Technology
(MEXT), and the Ritsumeikan Global Innovation Research Organ-
ization (R-GIRO). M.I. also acknowledges a Research Activity Start-
up grant from the JSPS.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201206917.
[a] The yield based on substrate 1 is reported in each case for the pure
product. Bn=benzyl, Ts=p-tosyl.
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À
Table 3: Generality of iodonium salt formation from (hetero)aryl dibor-
boronate group, like the C H bond cleaved in the reaction,
was located in a para position to the activating oxygen atom.
Thiophene 1 f was also transformed into the desired salt 2 f;
the reaction proceeded at the a position of the thiophene
onates.[a]
ring.[9] This C H transformation was quite straightforward,
À
and the boron-substituted salts obtained were highly stable.
We considered a partial boron–iodine(III) exchange[10] of
aryl diboronates with iodine(III) reagents as an efficient
alternative route to boron-substituted iodonium salts. Such an
approach would expand the range of possible substrates and
enable the control of regioselectivity. However, the aryl
diboronate 1g was unexpectedly inert to PhI(OH)OTs. The
reaction did not proceed in various ordinary solvents (CH2Cl2,
CH3CN, and MeOH)[11] or even in HFIP (Table 2, entry 1).
Upon further investigation, we found that the addition of
acetic acid to HFIP led to the production of 2g (YÀ = TsOÀ)
as the sole product (Table 2, entry 2). Overreaction leading to
Table 2: Synthesis of boron-substituted salts 2g and 2h from aryl
diboronates 1g and 1h.
[a] The yield based on substrate 1 is reported in each case for the pure
product. [b] TFE was used instead of HFIP. [c] A larger amount of
substrate 1n was used (1.2 equiv with respect to PIFA). [d] Pinacol esters
were used instead of neopentylglycol esters, because the neopentylglycol
esters were difficult to synthesize.
Entry
1
IIII reagent
Additive
Product
Yield [%][a]
obtained from the diboronate 1j with complete regioselec-
tivity.[12] The ortho-boronated salt 2k was obtained from
1
2
3
4
1g PhI(OH)OTs none
1g PhI(OH)OTs AcOH
1g PhI(OH)OTs CF3CO2H 2g (Y=OTs)
1g PhI(OH)OTs TsOH
1g PhI(OH)OTs AcOH
1g PhI(OH)OTs none
1g PIFA
1h PhI(OH)OTs AcOH
1h PIFA AcOH
ND
2g (Y=OTs)
52
44
11
13
a
dimethoxy-substituted diboronate 1k. A symmetrical
biphenyl substrate 1l was transformed into the monoiodo-
nium salt 2l without any overreaction. Salts with other
aromatic backbones, such as naphthalene (compound 2m) or
heteroaromatic structures (compounds 2n and 2o), were also
obtained in good yields.
2g (Y=OTs)
2g (Y=OTs)
NR[d]
2g (Y=OCOCF3) 62
2h (Y=OTs) 77
2h (Y=OCOCF3) 89
5[b]
6[c]
7
AcOH
8
9
Although the effect of acetic acid is still unclear, we
propose that the acid activates diboronates 1 by coordination
to the boron atom. This coordination counteracts the
electron-withdrawing resonance effect of the boronate
groups.[4b,c] A competition experiment with a 1:1 mixture of
1h and m-xylene provided support for this hypothesis
(Scheme 1). Under the optimized conditions with acetic
acid, the reaction gave the salt 2h as the major product,
along with a small amount of the m-xylyliodonium salt 3. In
contrast, the reaction in the absence of acetic acid gave 3 as
the sole product. Therefore, the boronate 1h must be
specifically activated by the acid.
[a] Yield of the pure product with respect to substrate 1. [b] TFE was used
instead of HFIP. [c] AcOH was used as the solvent. [d] A large amount of
PhI(OH)OTs (80%) was recovered. ND=not determined, NR=no
reaction.
the bisiodonium salt should be suppressed by the strong
deactivation effect of the introduced electron-withdrawing
iodonium moiety. The much stronger acids CF3CO2H and
TsOH were less effective than acetic acid (Table 2, entries 3
and 4). When TFE was used instead of HFIP, the yield
decreased (Table 2, entry 5). The reaction did not proceed in
acetic acid as the solvent, although acetic acid was not only an
efficient activator in HFIP, but is also the classically used
solvent to promote the formation of iodonium salts (Table 2,
entry 6). This result indicated that both acetic acid and HFIP
play a crucial role in the reaction. The use of PIFA gave
a superior result to that observed with PhI(OH)OTs (Table 2,
entry 7). The selection of the boronate was also important:
the use of the less bulky neopentylglycol ester 1h significantly
improved the yield (Table 2, entries 8 and 9).
To demonstrate the utility of the boron-substituted salts as
precursors to functionalized boronates, we examined their
reactivity with various reaction partners (Scheme 2). We
À
tested synthetically valuable C C bond formation in an SNAr
The optimized conditions were subsequently applied to
other substrates (Table 3). Methyl-substituted 1i was con-
verted into the sterically hindered salt 2i in excellent yield.
The salt 2j with methoxy and chlorine substituents was
Scheme 1. Competitive iodonium-salt formation with substrates 1h
and m-xylene.
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[1] a) D. G. Hall, Boronic Acids, Wiley-VCH, Weinheim, 2005;
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[2] a) N. Miyaura, Top. Curr. Chem. 2002, 219, 11; b) C. Kleeberg, L.
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[3] For reviews, see: a) C. Wang, F. Glorius, Angew. Chem. 2009,
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Burke, Angew. Chem. 2012, 124, 2721; Angew. Chem. Int. Ed.
2012, 51, 2667.
Scheme 2. Transformation of boron-substituted iodonium salts. [a] The
product included a small amount of the compound resulting from
arylation at the 2-position of the indole. Tf=trifluoromethanesulfonyl.
[4] a) O. Baron, P. Knochel, Angew. Chem. 2005, 117, 3193; Angew.
Chem. Int. Ed. 2005, 44, 3133; b) F. Shi, M. R. Smith III, R. E.
Maleczka, Org. Lett. 2006, 8, 1411; c) C. C. Caires, S. Guccione,
Organometallics 2008, 27, 747; d) D. Qiu, F. Mo, Z. Zheng, Y.
Zhang, J. Wang, Org. Lett. 2010, 12, 5474; e) K. Durka, J. Gꢀrka,
´
P. Kurach, S. Lulinski, J. Serwatowski, J. Organomet. Chem. 2010,
reaction of the salt 2g with a 1,3-dicarbonyl compound and
obtained the desired boron-functionalized product 4 as the
major product (32%). Thus, the reaction was confirmed to
proceed without any loss of the boronate moiety, but the yield
was low owing to the formation of an undesired phenylated
product. In unsymmetrical iodonium salts, SNAr reactions are
known to occur preferentially at the more electron deficient
ring of the two aromatic rings bound to an iodine atom.[13]
Therefore, we synthesized the salt 2p with an electron-rich 4-
methoxyphenyl dummy aromatic ring from 1g[14] and used it
in the a arylation. With 2p, the selectivity was completely
controlled, and the yield of 4 was improved to a satisfactory
level. Similarly, the coupling of 2p with 2-naphthol as an
oxygen nucleophile proceeded to give the diaryl ether 5 in
695, 2635; f) T. Ikawa, A. Takagi, Y. Kurita, K. Saito, K. Azechi,
M. Egi, K. Kakiguchi, Y. Kita, S. Akai, Angew. Chem. 2010, 122,
5695; Angew. Chem. Int. Ed. 2010, 49, 5563.
[5] For the preparation of a boronic acid containing an iodine(III)
moiety, see: V. N. Nemykin, A. V. Maskaev, M. R. Geraskina,
M. S. Yusubov, V. V. Zhdankin, Inorg. Chem. 2011, 50, 11263.
[6] a) A. Varvoglis, Hypervalent Iodine in Organic Synthesis,
Academic Press, San Diego, 1997; b) M. Ochiai in Chemistry
of Hypervalent Compounds (Ed.: K. Akiba), Wiley-VCH, New
York, 1999, chap. 12; c) T. Wirth, M. Ochiai, A. Varvoglis, V. V.
Zhdankin, G. F. Koser, H. Tohma, Y. Kita, Hypervalent Iodine
Chemistry—Modern Developments in Organic Synthesis, Top.
Curr. Chem, Springer, Berlin, 2003; d) V. V. Zhdankin, P. J.
Stang, Chem. Rev. 2008, 108, 5299; e) E. A. Merritt, B. Olofsson,
Angew. Chem. 2009, 121, 9214; Angew. Chem. Int. Ed. 2009, 48,
9052; f) M. S. Yusubov, A. V. Maskaev, V. V. Zhdankin, ARKI-
VOK 2011, i, 370.
good yield.[15] Furthermore, a copper-catalyzed C H coupling
À
with N-methylindole led to the biaryl compound 6 without the
loss of the boronate group even in the presence of a metal
catalyst.[16] As metal catalysts are reported to transfer the less
sterically hindered ring of unsymmetrical iodonium salts, we
facilitated the selective transfer of the boron-substituted ring
by employing the highly congested mesityl-substituted sub-
[7] a) T. Dohi, M. Ito, K. Morimoto, Y. Minamitsuji, N. Takenaga, Y.
Kita, Chem. Commun. 2007, 4152; b) T. Dohi, M. Ito, N.
Yamaoka, K. Morimoto, H. Fujioka, Y. Kita, Tetrahedron
2009, 65, 10797; c) T. Dohi, N. Yamaoka, Y. Kita, Tetrahedron
2010, 66, 5775.
À
[8] Only a few examples of C H transformations of aryl boronates
with iodine(III) compounds have been described previously:
a) T. Dohi, M. Ito, N. Yamaoka, K. Morimoto, H. Fujioka, Y.
Kita, Angew. Chem. 2010, 122, 3406; Angew. Chem. Int. Ed.
2010, 49, 3334; b) D. Qiu, Z. Zheng, F. Mo, Q. Xiao, Y. Tian, Y.
Zhang, J. Wang, Org. Lett. 2011, 13, 4988.
À
strate 2q, which was prepared by the C H transformation of
1a with the corresponding iodine reagent in 80% yield.[14]
In conclusion, we have developed the first efficient
synthesis of boron-substituted diaryliodonium salts. The
iodonium moiety of the synthesized salts underwent various
catalyst-free and metal-catalyzed organic reactions, and the
retained boronate group is suitable for further transforma-
tion. Therefore, this series of iodonium salts is expected to be
remarkably useful for the construction of complex function-
alized compounds.
[9] These results were partially described in a previous report.[7c]
[10] For syntheses of diaryliodonium salts by the boron–iodine(III)
exchange of aryl boronates, see: a) M. A. Carroll, V. W. Pike,
D. A. Widdowson, Tetrahedron Lett. 2000, 41, 5393; b) M.
Bielawski, D. Aili, B. Olofsson, J. Org. Chem. 2008, 73, 4602.
[11] Nonprotected 1,4-benzenediboronic acid was also inert to the
iodine(III) reagents in CH2Cl2. The addition of a Lewis acid
(trimethylsilyl triflate or BF3·Et2O) was examined for the
reaction of 1g in CH2Cl2; however, the product was obtained
in less than 30% yield.
Received: August 27, 2012
Published online: November 8, 2012
[12] For the regioselective transformation of unsymmetrical aryl
diboronates, a strong donating group, such as a methoxy group,
was necessary to direct the reaction at the ortho or para position.
Keywords: aromatic nucleophilic substitution · boron ·
cross-coupling · hypervalent iodine · iodonium salts
.
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Other examples concerning the regioselectivity of the reaction
will be reported at a later date.
[14] For the synthesis of the salts 2p and 2q, see the Supporting
Information.
[15] N. Jalalian, E. E. Ishikawa, L. F. Silva, Jr., B. Olofsson, Org. Lett.
[13] a) C. H. Oh, J. S. Kim, H. H. Jung, J. Org. Chem. 1999, 64, 1338;
b) J.-H. Chun, S. Lu, Y.-S. Lee, V. W. Pike, J. Org. Chem. 2010,
75, 3332.
2011, 13, 1552.
[16] R. J. Phipps, N. P. Grimster, M. J. Gaunt, J. Am. Chem. Soc. 2008,
130, 8172.
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