C O M M U N I C A T I O N S
hypervalent iodine(III) reagents8 and reaction conditions, the method
showed a broad scope of functional group compatibility. As the
coupling partners 2, the nucleophilic characteristics of the aromatic
rings were found to be the most important factor, and thus various
aromatic nucleophiles, i.e., phenyl ethers, pyrroles, and thiophene,
could be used for the transformations. In the thiophene-pyrrole
cross-couplings, the pyrrole nucleophiles 2e-g were introduced
with a high degree of product selectivities (entries 7-9). These
unknown types of mixed biaryls would become the potential core
structures for a variety of new thiophene-pyrrole hybrid materials
by extending the π-conjugated systems.
The new iodine(III)-mediated cross-coupling method apparently
has several synthetic advantages over other reported methods. The
most intriguing feature is that the intermediacy of the stable
iodine(III) intermediates like 4-OTs (see, below) in the mechanism
enables selective cross-couplings between two arene molecules
having closely related structures. Even in the coupling reactions
between thiophenes (entry 10) or pyrroles (entry 11), the desired
mixed biaryls were successfully obtained. Furthermore, the aryl-aryl
bond was exclusively formed at the 2-position of the thiophene
ring of 2h (entry 10).9
Regarding the mechanism, the transformations mainly consist
of two sequential steps (Scheme 2). First, the electron-rich
heteroaromatic compounds 1 could selectively react at the 2-posi-
tions with the iodine oxidant, PhI(OH)OTs, to form the stable
iodonium(III) salts, 4-OTs. The process rapidly occurred with the
aid of the fluoroalcohol solvent.6 The formed 4-OTs salts are
usually inert toward the neutral aromatic nucleophiles 2 but are
activated by the added TMSBr in hexafluoroisopropanol (HFIP) to
induce further reactions and provide the mixed biaryl products 3,
probably through the formal hydroarylation with nucleophiles 2
and successive elimination of iodobenzene. The intermediacy and
In conclusion, we now suggest a novel metal-free selective cross-
coupling method for thiophenes and pyrroles based on the unusual
reactivities of the σ-aryl trivalent iodine intermediates 4-Br developed
in fluoroalcohol media in the presence of TMSBr. Our biaryl synthetic
procedure has the following characteristic features and various synthetic
merits such as (i) a metal catalyst-free method, (ii) mild reaction
conditions (the use of trivalent organoiodine oxidants, room temper-
ature), (iii) high yields and regioselectivities of the obtained mixed
biaryls, (iv) no oligomer formations, (v) a broad scope of substrate
availability that allows the use of a wide range of heteroaromatic
compounds 1 and aromatic nucleophiles 2, and (vi) no required excess
amount of arenes. This is the first successful example of a cross-
coupling between two molecules of unfunctionalized heteroaromatic
compounds with high product selectivities. The new R-free electron-
rich mixed heteroaromatic biaryls effectively obtained by the method
should be promising synthetic precursors in many scientific fields, and
hence utilization of the new mixed biaryls will be expected to appear
in the near future.
Acknowledgment. This work was supported by a Grant-in-Aid
for Scientific Research (A) and Young Scientists (B) and for
Scientific Research on Priority Areas “Advanced Molecular Trans-
formations of Carbon Resources” from the Ministry of Education
Culture, Sports, Science, and Technology, Japan. T.D. acknowl-
edges support from the Industrial Technology Research Grant
Program from the New Energy and Industrial Technology Develop-
ment Organization (NEDO) of Japan. K.M. thanks research
fellowship of JSPS for Young Scientists.
Supporting Information Available: The experimental procedures
and detailed spectroscopic data of the products 3. This material is
References
Scheme 2. Possible Reaction Mechanism
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unique reactivities of 4-OTs and 4-Br leading to the products 3
were confirmed by the following control experiments using the
isolated iodine(III) 4c-X (Scheme 3). Thus, both 4c-OTs and 4c-
Br reacted with 2b in the presence of TMSBr to produce 3cb in
comparable yields under the same reaction conditions,10 though
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these observations, the iodine(III) bromides 4-Br could be involved
in the reactions.11
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Scheme 3. Metal-Free R-Arylation of 4c-X with Arene 2b
(10) We have confirmed that the addition of several Lewis acids such as TMSOTf
or TMSBr could accelerate the reaction of 4c-Br with the arene nucleophile
2b. On the other hand, treatment of the corresponding 4c-OTs with 2b did
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4c-OTs by treatment with 1 equiv of TMSBr in HFIP (4c-Br: 79% isolated
yield).
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