Discovery of stabilized bisiodonium salts as intermediates in the carbon-carbon bond formation of alkynes

Article abstract of DOI:10.1002/anie.201007640

(Chemical Equation Presented) Ways and means to spirocycles: Pseudocyclic bisiodonium salts 1 stabilized by a secondary bonding interaction - an I ^III...O...I^III pseudobridge linkage (circle) -were prepared by C-C bond formation betw

Full text of DOI:10.1002/anie.201007640

Communications
DOI: 10.1002/anie.201007640
Hypervalent Compounds
Discovery of Stabilized Bisiodonium Salts as Intermediates in the
Carbon–Carbon Bond Formation of Alkynes**
Toshifumi Dohi, Daishi Kato, Ryo Hyodo, Daisuke Yamashita, Motoo Shiro, and Yasuyuki Kita*
The oxidation of carbon–carbon triple bonds with hyper-
valent iodine reagents is an expedient strategy for the
synthesis of 1,2-difunctionalized alkenes or their tautomers
from alkynes through successive carbon–heteroatom bond-
forming events [Eq. (1), Nu = heteroatom].[1,2] The postulated
iodonium species, which have two carbon groups bound to an
iodine atom, are putative reaction intermediates, but would
sometimes be isolable as the salt forms, depending on the
reaction conditions.[3] However, the possibility that similar
iodonium-intermediate formation could accompany the
installation of a new carbon–carbon bond has never been
thoroughly confirmed. Such a transformation, to the best of
our knowledge, has not appeared as a general method for
alkyne functionalization in the long history of the chemistry
of hypervalent iodine compounds.
Herein, we describe the discovery of a carbon–carbon
bond-forming spirocyclization of alkynes with a hypervalent
iodine reagent. We focus on the stabilization of unique and
synthetically useful bisiodonium salts 1 through a hypervalent
secondary bonding interaction: the IIII···O···IIII pseudobridge
linkage (Scheme 1). The results indicate a new concept and
Scheme 1. Generation of stabilized bisiodonium salts 1a–d. Tf=tri-
fluoromethanesulfonyl, Ts=toluenesulfonyl.
strategy for stabilizing iodonium intermediates during the
course of alkyne transformations.
Iodonium salts 1 were isolated as precipitates following
the carbon–carbon bond-forming reaction of methoxy-sub-
stituted aryl alkynes 3 (3a: R = Br, 3b: R = Me, 3c: R = Ph,
[*] Dr. T. Dohi, D. Kato, R. Hyodo, D. Yamashita, Prof. Dr. Y. Kita
3d: aryl moiety: naphthalene, R = Br) with the hypervalent
College of Pharmaceutical Sciences, Ritsumeikan University
iodine compound 2[4] in the presence of sulfonic acids in good
1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)
yields (1a/OTs: 85%, 1b/OTs: 87%, 1c/OTs: quant., 1c/OTf:
Fax: (+81)77-561-5829
85%, 1d/OTs: 85%). The reactions were carried out in wet
polar solvents, acetonitrile, or 2,2,2-trifluoroethanol. The
quantitative formation of the salts 1 was very surprising,
since we had difficulty in detecting the iodonium salt when we
treated ordinary hypervalent iodine compounds with alkynes
3. Indeed, PhI(OAc)2 did not react at all with the alkyne 3,
and neither PhI(OCOCF3)2 nor PhI(OH)OTs afforded the
corresponding iodonium compound upon treatment with 3, as
expected.[2] Even the dimeric reagents PhI(OAc)O(AcO)IPh
and PhI(OCOCF3)O(CF3COO)IPh, parent m-oxo com-
pounds of 2 without the biaryl linkage, gave a complex
mixture. Apparently, only the use of compound 2 could
enable the formation and isolation of iodonium salts such as 1;
E-mail: kita@ph.ritsumei.ac.jp
Dr. M. Shiro
Rigaku Corporation
3-9-12, Matsubara, Akishima, Tokyo 196-8666 (Japan)
[**] 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 Young Scientists (B) from the Ministry of
Education, Culture, Sports, Science and Technology (MEXT), and
the Ritsumeikan Global Innovation Research Organization (R-
GIRO). T.D. also acknowledges support from the Industrial
Technology Research Grant Program of the New Energy and
Industrial Technology Development Organization (NEDO) of Japan.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201007640.
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Angew. Chem. Int. Ed. 2011, 50, 3784 –3787

other hypervalent iodine reagents would lead to undesirable
oxidation reactions.
are equal at around 2.8 ꢀ and rather shorter than the sum of
the van der Waals radii of iodine and oxygen atoms (ca.
3.5 ꢀ). Accordingly, the O8* atom is located trans to the
alkenyl moiety, and the I1···O8*···I2 bond angle is reasonably
large at 107.698. The dicoordinated oxygen atom was first
found in the sulfonate ligand of an iodonium salt of this
study.[6] Each iodine atom is cationic and surrounded by four
atoms in an almost square-planar arrangement. The bisiodo-
nium salt 1c/OTf has slightly distorted bond angles, probably
as a result of the unique configuration derived from the
pseudocyclic structure. This new concept for stabilization
observed in 1c/OTf could provide a blueprint for the use of
the postulated iodonium species in many alkyne transforma-
tions with hypervalent iodine reagents.[7]
The unit structure of the salts 1 should consist of cationic
bisiodonium parts and two anionic sulfonate ligands. All salts
1 obtained were solids stable enough to be stored under
ambient conditions. Crystals suitable for X-ray crystallo-
graphic analysis were grown from solutions in acetonitrile/
ether. Thus, 1c/OTf, with triflate as a ligand, was subjected to
structural refinement by X-ray crystallographic analysis
(Figure 1).[5] The unique feature of 1c/OTf is its unexpected
It should be possible to exploit the chemical behavior of
the series of isolable bisiodonium salts 1 and use them as a
new synthetic module for the synthesis of spirocyclic com-
pounds.[8] A preliminary investigation of the reactivity of salts
1 toward weak anionic nucleophiles could determine their
usefulness for the synthesis of a wide array of functionalized
spirocycles. Upon the treatment of 1c/OTs with inorganic and
organic salts, that is, CsF,[9a] KX (X = OAc, SCN),[9b,c] NaX
(X = N3, NO2),[9c,d] and Bu4NBr,[9d] the smooth replacement of
the aryliodonio group in 1c/OTs led to the generation of
various functionalized spirocycles 4c-X (X = F, Br, OAc,
SCN, N3, NO2, etc.) under mild conditions (Table 1).[10] The
Figure 1. Snapshot of the stabilized bisiodonium salt oligomer 1c/OTf.
(The O8 atom with an asterisk belongs to another molecule of 1c/
OTf.) Selected bond lengths [ꢀ] and angles [8]: I1–C2 2.127(6), I1–C17
2.091(6), I2–C32 2.072(7), I1···O8* 2.810(2), I2···O8* 2.782(3), I1···O9
2.844(2); C2-I1-C17 94.9(2), I1-C2-C1 120.3(4), I1-C2-C3 115.8(5), I1-
C17-C18 117.8(4), I1-C17-C20 130.1(4), I1···O8*···I2 107.69(9),
O8*···I1-C2 86.5(2), O8*···I1···O9 97.75(8), O8*···I1-C17 170.8(2),
O9···I1-C2 175.2(2), O9···I1-C17 80.5(2).
Table 1: Derivation of the bisiodonium salt 1c/OTs to form functional-
ized spirocycles 4c-X by the introduction of nucleophiles, XÀ.[a]
pseudocyclic structure with I1···O8*···I2 secondary bonding
interactions; the pseudobridging O8* atom is from a OTf
group of another molecule in the salt (Figure 2). Thus, the
pseudobridging O*Tf group is crystallographically identical
to the other two OTf groups in Figure 1. Essentially, the m-oxo
bridging interaction seems to render the direct preparation of
salts 1 and their isolation possible.
Entry
Conditions
X
Yield [%][b]
1
2
3
4
5
6
A
A
A
B
B
B
F
Br
OAc
SCN
N3
64
99
85
94
76
70
In the salt 1c/OTf, both the I1 and I2 atoms contact the
O8* oxygen atom of the triflate ion. The interatomic distances
NO2
[a] Conditions A: CsF, Bu4NBr, or KOAc, CH3CN, 608C. Conditions B:
KSCN or NaX (for X=N3, NO2), CHCl3/H2O (3:1), room temperature.
[b] Yield of the isolated pure product 4c-X as calculated on the basis of
the amount of 1c/OTs used.
introduction of nucleophiles in known spirocyclization pro-
cedures has rarely been reported.[11] Thus, the range of
products 4 obtained by our method was quite different from
that described by others,[12] and various spirocycles that are
difficult to obtain, such as spiro products containing fluoro,
oxygen, and nitrogen functionalities, could be prepared. This
flexibility is the distinct advantage of the method with the
stabilized salts 1.
Figure 2. Solid-state packing of 1c/OTf (dimeric structure).
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3785

Communications
On the basis of these results, we developed a one-pot
synthesis of spirocycles 4 by the spirocyclization of aryl
alkynes 3, followed by facile substitution at the iodonio
position of intermediates
1
by added nucleophiles
(Scheme 2). An extensive series of stabilized bisiodonium
salts 1 were prepared as intermediates from aryl alkynes 3 in
this one-pot procedure and converted into a variety of
functionalized spirocycles 4-I (Table 2).[13] Detailed investi-
gations should enable the establishment of bisiodonium salts
1 as more useful synthetic tools owing to their potentially rich
chemistry.[14,15]
In summary, we have reported the first carbon–carbon
bond-forming reaction of alkynes with hypervalent iodine
reagents, and the preparation and unique structure of these
newly discovered stabilized iodonium salts 1. The series of
salts 1 obtained was found to serve as an excellent synthetic
module for the preparation of various functionalized spiro-
cyclic compounds 4. The chiral structure of the m-oxo-bridged
hypervalent iodine compounds promises further extension of
the utility of salts 1 to asymmetric synthesis.[16]
Scheme 2. One-pot approach to functionalized spirocycles from aryl
alkynes 3 with bisiodonium salts 1 as intermediates.
Table 2: Scope of the one-pot spirocyclization–functionalization strategy
with respect to the substrate 3.[a]
Entry
Aryl alkyne 3
Product 4-I
(Yield [%][b])
1
3d
4d-I (85)
Received: December 6, 2010
Published online: March 21, 2011
Keywords: alkynes · bridging ligands · cyclization · iodine ·
.
spiro compounds
2
3
4
5
3 f: R1 =Cl, R2 =H
3g: R1 =Ac, R2 =H
3h: R1 =tBu, R2 =H
3i: R1 =H, R2 =OMe
4 f-I (83)
4g-I (86)
4h-I (78)
4i-I (94)
[1] a) V. V. Zhdankin, P. J. Stang, Chem. Rev. 2008, 108, 5299;
b) R. M. Moriarty, O. Prakash, Hypervalent Iodine in Organic
Chemistry: Chemical Transformations, Wiley, New York, NY,
2007; c) T. Wirth, Angew. Chem. 2005, 117, 3722; Angew. Chem.
Int. Ed. 2005, 44, 3656; d) “Hypervalent Iodine Chemistry:
Modern Developments in Organic Synthesis”: T. Wirth, M.
Ochiai, V. V. Zhdankin, G. F. Koser, H. Tohma, Y. Kita, Topics in
Current Chemistry, Vol. 224, Springer, Berlin, 2003.
[2] a) N. S. Zefirov, S. I. Kozhushkov, V. V. Zhdankin, Zh. Org.
Khim. 1988, 24, 1560; b) R. M. Moriarty, R. Penmasta, A. K.
Awasthi, I. Prakash, J. Org. Chem. 1988, 53, 6124; c) R. M.
Moriarty, C. Condeiu, A. Tao, O. Prakash, Tetrahedron Lett.
1997, 38, 2401; d) M. S. Yusubov, G. A. Zholobova, I. L.
Filimonova, K.-W. Chi, Russ. Chem. Bull. 2004, 53, 1735; e) I.
Tellitu, S. Serna, M. T. Herrero, I. Moreno, E. Domꢁnguez, R.
SanMartin, J. Org. Chem. 2007, 72, 1526; f) X. Du, H. Chen, Y.
Liu, Chem. Eur. J. 2008, 14, 9495.
6
7
8
3j
4j-I (87)
4k-I (99)
3k
[3] a) G. F. Koser, L. Rebrovic, R. H. Wettach, J. Org. Chem. 1981,
46, 4324; b) L. Rebrovic, G. F. Koser, J. Org. Chem. 1984, 49,
4700; c) T. Kitamura, R. Furuki, H. Taniguchi, P. J. Stang,
Tetrahedron Lett. 1990, 31, 703.
[4] T. Dohi, N. Takenaga, K.-I. Fukushima, T. Uchiyama, D. Kato,
M. Shiro, H. Fujioka, Y. Kita, Chem. Commun. 2010, 46, 7697.
[5] CCDC 779156 contains the supplementary 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. For more detailed crystallographic
data, see the CIF.
3l
4l-I (55)
9
[6] For X-ray crystal structures of representative iodonium triflates,
see: a) D. A. Gately, T. A. Luther, J. R. Norton, M. M. Miller,
O. P. Anderson, J. Org. Chem. 1992, 57, 6496; b) P. Murch, A. M.
Arif, P. J. Stang, J. Org. Chem. 1997, 62, 5959; c) D. Bykowski, R.
McDonald, R. J. Hinkle, R. R. Tykwinski, J. Org. Chem. 2002,
67, 2798.
3m
4m-I (99)
[a] Reactions were performed by a similar procedure to that outlined in
Scheme 2 with Bu4NI instead of NaN3. [b] Yield of the isolated product
after purification.
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[7] We have confirmed that the concept is also applicable to other
types of carbon–carbon and carbon–heteroatom bond-forming
events. Details will be summarized in due course.
Liu, Z. Wang, F. Zhao, Z. Xi, J. Org. Chem. 2007, 72, 3484;
c) B. X. Tang, Q. Yin, R. Y. Tang, J. H. Li, J. Org. Chem. 2008, 73,
9008.
[8] For the utility of spirocyclic compounds, see the following
reviews: a) S. Kotha, A. C. Deb, K. Lahiri, E. Manivannan,
Synthesis 2009, 165, and references therein; b) T. P. I. Saragi, T.
Spehr, A. Siebert, T. Fuhrmann-Lieker, J. Salbeck, Chem. Rev.
2007, 107, 1011; c) V. I. Minkin, Chem. Rev. 2004, 104, 2751.
[9] a) S. Martꢁn-Santamarꢁa, M. A. Carroll, C. M. Carroll, C. D.
Carter, H. S. Rzepa, D. A. Widdowson, V. W. Pike, Chem.
Commun. 2000, 649; b) R. R. Tykwinski, P. J. Stang, Tetrahedron
1993, 49, 3043; c) J.-M. Chen, X. Huang, Synlett 2004, 552; d) M.
Ochiai, K. Sumi, Y. Takaoka, M. Kunishima, Y. Nagao, M. Shiro,
E. Fujita, Tetrahedron 1988, 44, 4095.
[10] Exceptionally, a small amount of an iodinated spirocycle was
obtained from 1c/OTs in the case of fluorination as a result of
cleavage of the Caryl–I bond.
[11] For the synthesis of spirocyclic compounds with the introduction
of a nucleophile, see: a) F. C. Pigge, J. J. Coniglio, N. P. Rath,
Organometallics 2005, 24, 5424; b) F. C. Pigge, J. J. Coniglio, R.
Dalvi, J. Am. Chem. Soc. 2006, 128, 3498.
[13] In similar transformations, the corresponding functionalized
spirocycles 4-X (X = F, Br, OAc, SCN, N3, NO2) could also be
obtained from a series of aryl alkynes 3 in good yields.
[14] For the general utility of alkenyl iodonium salts, see: a) N. S.
Pirkuliev, V. K. Brel, N. S. Zefirov, Russ. Chem. Rev. 2000, 69,
105; b) “Hypervalent Iodine Chemistry”: M. Ochiai in Topics in
Current Chemistry, Vol. 224 (Ed.: T. Wirth), Springer, Berlin,
2003, p. 5; c) P. J. Stang, J. Org. Chem. 2003, 68, 2997; d) E. A.
Merritt, B. Olofsson, Angew. Chem. 2009, 121, 9214; Angew.
Chem. Int. Ed. 2009, 48, 9052; see also Ref. [1].
[15] For new reactivities of iodonium salts uncovered by us, see: 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) Y. Kita, K. Morimoto, M. Ito, C. Ogawa, A. Goto, T.
Dohi, J. Am. Chem. Soc. 2009, 131, 1668.
[16] For chiral hypervalent iodine compounds developed by us with
m-oxo-bridged structures, see: a) T. Dohi, A. Maruyama, N.
Takenaga, K. Senami, Y. Minamitsuji, H. Fujioka, S. Caem-
merer, Y. Kita, Angew. Chem. 2008, 120, 3847; Angew. Chem. Int.
Ed. 2008, 47, 3787; b) T. Dohi, Y. Kita, Chem. Commun. 2009,
2073.
[12] Most established methods for the synthesis of functionalized
spirocyclic compounds could accommodate the introduction of
electrophiles into the structures; for recent studies, see: a) X.
Zhang, R. C. Larock, J. Am. Chem. Soc. 2005, 127, 12230; b) L.
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