ORGANIC
LETTERS
2011
Vol. 13, No. 12
3242–3245
Potassium tert-Butoxide Promoted
Intramolecular Arylation via a Radical
Pathway
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Daniela Sustac Roman, Yoko Takahashi, and Andre B. Charette*
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Department of Chemistry, Universite de Montreal, Box 6128, Station Downtown,
Montreal, Quebec, Canada H3C 3J7
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ꢀ
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Received May 1, 2011
ABSTRACT
Potassium tert-butoxide mediated intramolecular cyclization of aryl ethers, amines, and amides was efficiently performed under microwave
irradiation to provide the corresponding products in high regioisomeric ratios. The reaction proceeds via single-electron transfer to initiate the
formation of an aryl radical, followed by a kinetically favored 5-exo-trig and subsequent ring expansion.
Direct CꢀH functionalization processes have recently
emerged as an alternative strategy to classic cross-coupling
chemistry in biaryl synthesis.1 The employment of the
highly versatile yet expensive noble metals such as Pd,2
Rh,3 and Ru4 in catalytic direct arylations has become well
established. Furthermore, the less privileged transition
metals (such as Cu, Fe, Ni) are capable of performing the
same task under appropriate conditions.5 More specifi-
cally, given its low toxicity and cost, Fe has rapidly made a
leading appearance and substantiated its promising status
in the realm of modern synthetic chemistry.6 Among other
seminal contributions to this field, our group also disclosed
an Fe-catalyzed direct arylation of unactivated arenes
through aryl radical transfer.6e In a short period of time,
however, the renowned dexterity of these transition metals
became rather overshadowed, once several pioneering
reports revealed that the presence of such metal catalysts
is not entirely necessary to promote biaryl coupling.7
Itami and co-workers first described an unprecedented
account on KO-t-Bu-mediated biaryl coupling of aryl
halides and electron-deficient heterocycles in the absence
of a transition metal catalyst.7a Subsequently, this discovery
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Aldrichim. Acta 2007, 40, 7.
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(b) Mousseau, J. J.; Vallee, F.; Lorion, M. M.; Charette, A. B. J. Am.
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Cao, H.; Lei, A. Angew. Chem., Int. Ed. 2010, 49, 2004. (e) Vallee, F.;
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2008, 10, 4673. (b) Yanagisawa, S.; Itami, K. ChemCatChem 2011, 3,
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(d) Sun, C.-L.; Li, H.; Yu, D.-G.; Yu, M.; Zhou, X.; Lu, X.-Y.;
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Angew. Chem., Int. Ed. 2011, DOI: 10.1002/anie.201008220. (g) Studer, A.;
Curran, D. P. Angew. Chem., Int. Ed. 2011, DOI: 10.1002/anie.201101597.
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(4) Ackermann, L.; Novak, P. Org. Lett. 2009, 11, 4966.
(5) (a) Do, H.-Q.; Khan, R. M. K.; Daugulis, O. J. Am. Chem. Soc.
2008, 130, 15185. (b) Hachiya, H.; Hirano, K.; Satoh, T.; Miura, M.
Angew. Chem., Int. Ed. 2010, 49, 2202. (c) Yoshikai, N.; Mieczkowski,
A.; Matsumoto, A.; Ilies, L.; Nakamura, E. J. Am. Chem. Soc. 2010, 132,
5568. (d) Li, H.; Sun, C.-L.; Yu, M.; Yu, D.-G.; Li, B.-J.; Shi, Z.-J.
Chem.;Eur. J. 2011, 17, 3593. (e) Liu, W.; Cao, H.; Xin, J.; Jin, L.; Lei,
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10.1021/ol201160s
Published on Web 05/13/2011
2011 American Chemical Society