ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
One-Pot Synthesis of 1‑Iodoalkynes and
Trisubstituted Alkenes from Benzylic and
Allylic Bromides
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Guillaume Pelletier, Sharon Lie, James J. Mousseau, and Andre B. Charette*
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Centre in Green Chemistry and Catalysis, Department of Chemistry, Universite de
Montreal, P.O. Box 6128, Station Downtown, Montreal, Quebec, Canada H3C 3J7
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Received September 14, 2012
ABSTRACT
1-Iodoalkynes are formed in moderate to high yields from readily accessible benzylic and allylic alkyl bromides by a one-pot homologation/double
elimination procedure with iodoform (CHI3). The developed conditions include facile purification and avoid the use of an excess of
triphenylphosphine (PPh3), as described in classical CoreyÀFuchs iodoalkynylation conditions. Replacing CHI3 with CHI2Cl allows the
isolation of the corresponding gem-(Z)-chloro-(E)-iodoalkene in good yield and stereoselectivity. Moreover, the use of benzhydryl bromides
as nucleophiles enables the synthesis of trisubstituted alkenes under similar reaction conditions.
The importance of 1-iodoalkynes as versatile build-
ing blocks has been demonstrated in several synthetic
methodologies,1 total syntheses,2 pharmaceutical applica-
tions,3 and material/polymer sciences.4 Such compounds are
operative in copper-catalyzed azideÀalkyne cycloadditions,
exhibiting exceptional regioselectivities and reactivities.1eÀ4a
Moreover, these haloalkynes are increasingly involved
in cross-coupling processes, particularly in the synthesis
of 1,3-diynes (CadiotÀChodkiewicz reaction),1h,2bÀ2d,5
and in NozakiÀHiyamaÀKishiÀTakai couplings.1a,2a,6
However, there are few commercially available 1-iodoalkynes,
and new methods enabling their synthesis remain
desired.
(1) For selected examples, see: (a) Usanov, D. L.; Yamamoto, H.
J. Am. Chem. Soc. 2011, 133, 1286. (b) Liu, H.; Chen, C.; Wang, L.; Tong,
X. Org. Lett. 2011, 13, 5072. (c) Panteleev, J.; Geyer, K.; Aguilar-
Aguilar, A.; Wang, L.; Lautens, M. Org. Lett. 2010, 12, 5092. (d)
Crossley, J. A.; Browne, D. L. J. Org. Chem. 2010, 75, 5414. (e) Hein,
J. E.; Tripp, J. C.; Krasnova, L. B.; Sharpless, K. B.; Fokin, V. V. Angew.
Chem., Int. Ed. 2009, 48, 8018. (f) Tsuji, H.; Fujimoto, T.; Endo, K.;
Nakamura, M.; Nakamura, E. Org. Lett. 2008, 10, 1219. (g) Damle,
S. V.; Seomoon, D.; Lee, P. H. J. Org. Chem. 2003, 68, 7085. (h) Alami,
M.; Ferri, F. Tetrahedron Lett. 1996, 37, 2763.
(2) For selected examples, see: (a) Inuki, S.; Iwata, A.; Oishi, S.; Fujii,
N.; Ohno, H. J. Org. Chem. 2011, 76, 2072. (b) Yang, W.-Q.; Kitahara,
T. Tetrahedron 2000, 56, 1451. (c) Shair, M. D.; Yoon, T. Y.; Mosny,
K. K.; Chou, T. C.; Danishefsky, S. J. J. Am. Chem. Soc. 1996, 118, 9509.
(d) Hoye, T. R.; Hanson, P. R. Tetrahedron Lett. 1993, 32, 5043. (e) Doi,
T.; Shimizu, K.; Takahashi, T.; Tsuji, J.; Yamamoto, K. Tetrahedron
Lett. 1990, 31, 3313. (f) Boutin, R. H.; Rapoport, H. J. Org. Chem. 1986,
51, 5320. (g) Roush, W. R.; Peseckis, S. M.; Walts, A. E. J. Org. Chem.
1984, 49, 3429.
(3) For selected examples, see: (a) Lu, Y.-F.; Harwig, C. W.; Fallis,
A. G. Can. J. Chem. 1995, 73, 2253. (b) Hofmeister, H.; Annen, K.;
Laurent, H.; Wiechert, R. Angew. Chem., Int. Ed. 1984, 23, 727. (c)
Jeffrey, T. J. Chem. Soc., Chem. Commun. 1988, 909 and references cited
therein.
(5) For insights of the CadioÀChodkiewicz reaction, see: Tsuji, J. In
Palladium Rreagents and Catalysis: New Perspectives for the 21st
Century, 2nd ed.; Wiley: Chichester, 2004; Chapter 3, pp 226À228 and
references cited therein.
(6) (a) Wang, C.; Forsyth, C. J. Org. Lett. 2006, 8, 2997. (b) Nerenberg,
J. B.; Hung, D. T.; Somers, P. K.; Schreiber, S. L. J. Am. Chem. Soc. 1993,
113, 12621. (c) Aicher, T. D.; Kishi, Y. Tetrahedron Lett. 1987, 28, 3463.
(d) Takai, K.; Kuroda, T.; Nakatsukasa, S.; Oshima, K.; Nozaki, H.
Tetrahedron Lett. 1985, 26, 5585.
(7) (a) Kabalka, G. W.; Mereddy, A. R. Tetrahedron Lett. 2004, 45,
1417. (b) Luithle, J. E.; Pietruszka, J. Eur. J. Org. Chem. 2000, 2557. (c)
Blackmore, I. J.; Boa, A. N.; Murray, E. J.; Dennis, M.; Woodward, S.
Tetrahedron Lett. 1999, 40, 6671. (d) Mandai, T.; Matsumoto, T.;
Kawada, M.; Tsuji, J. J. Org. Chem. 1992, 57, 6090. (e) Ricci, A.;
Taddei, M.; Dembech, P.; Guerrini, A.; Seconi, G. Synthesis 1989, 461.
(4) For selected examples, see: (a) Schwartz, E.; Breitenkamp, K.;
Folkin, V. V. Macromolecules 2011, 44, 4735. (b) Luo, L.; Wilhelm, C.;
Sun, A.; Grey, C. P.; Lauher, J. W.; Goroff, N. S. J. Am. Chem. Soc.
2008, 130, 7702. (c) Sun, A.; Lauher, J. W.; Goroff, N. S. Science 2006,
312, 1030.
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(f) Barluenga, J.; Gonzalez, J. M.; Rodrıguez, M. A.; Campos, P. J.;
Asensio, G. Synthesis 1987, 661.
r
10.1021/ol302544s
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