pubs.acs.org/joc
unstable molecules emerging as valuable reactive intermedi-
Selective Synthesis of o-Acylbenzylphosphonates by
Insertion Reactions of Arynes into
β-Ketophosphonates
ates in organic synthesis.1-10 However, the generation of
arynes in situ from the traditional aryne precursors is often
conducted under harsh conditions.1 Moreover, the tradi-
tional aryne precursors are prepared with difficulty. These
drawbacks limit their applications in organic synthesis.
Recently, many efficient methods have been developed on
the basis of o-silyl aryltriflates because o-silyl aryltriflates
could be readily prepared, and be converted into benzynes in
situ under mild conditions.1d-1f,2-10 These efficient transfor-
mations involve insertion of arynes into various nucleophi-
lic-electrophilic σ-bonds, such as hydrogen-heteroatom,
hydrogen-carbon, heteroatom-heteroatom, heteroatom-
carbon, and carbon-carbon σ-bonds, for the straightforward
synthesis of substituted arenes.1,3-9 In 2001, Shirakawa and
Hiyama first reported that palladium could promote the inser-
tion of arynes into C-Sn σ-bonds to afford ortho-substituted
arylstannanes using o-silyl aryltriflates as the aryne precursors.3
Shortly after, a variety of nucleophilic-electrophilic σ-bonds
were developed for these purposes.1f,4-9 However, only a few
papers on the insertion of an aryne into a carbon-carbon
σ-bond have been published.5-8 Stoltz and co-workers have
described an efficient and direct acyl-alkylation of arynes with
keto esters involving the net insertion of an arene unit into the
R,β-C-C σ-bond of β-ketoester in the presence of CsF and
MeCN.5 Subsequently, Yoshida and Kunai extended the
scopes to β-dicarbonyls,6 R-cyanocarbonyl,7 p-toluenesulfony-
lacetonitrile, and malononitrile8 using the KF/18-crown-6/
THF system. Very recently, Huang and co-workers also found
that β-keto sulfones were suitable substrates for the inser-
tion reaction with arynes under the same conditions.9 Thus,
the development of some new alternative carbon-carbon
σ-bonds for the insertion reaction with arynes is still interesting.
Yoshida and Kunai have reported the carbophosphinylations
Yi-Lin Liu, Yun Liang,* Shao-Feng Pi, and Jin-Heng Li*
Key Laboratory of Chemical Biology & Traditional Chinese
Medicine Research (Ministry of Education), Hunan Normal
University, Changsha 410081, China
liangyun1972@126.com; jhli@hunnu.edu.cn
Received April 24, 2009
A mild method for selective synthesis of o-acylbenzyl-
phosphonates has been developed by the reactions of
arynes with β-ketophosphonates. In the presence of CsF
and THF, the carbon-carbon σ-bonds of 2-oxopropyl-
phosphonates were selectively cleaved and added to
arynes providing the corresponding 2-acylbenzylphospho-
nates in moderate to good yields.
Aryne chemistry is an important topic in organic chem-
istry because arynes are highly strained and kinetically
(6) Yoshida, H.; Watanabe, M.; Ohshita, J.; Kunai, A. Chem. Commun.
2005, 3292.
(7) Yoshida, H.; Watanabe, M.; Ohshita, J.; Kunai, A. Tetrahedron Lett.
2005, 46, 6729.
(8) Yoshida, H.; Watanabe, M.; Morishita, T.; Ohshita, J.; Kunai, A.
Chem. Commun. 2007, 1505.
(1) For reviews, see: (a) Hoffmann, R. W. Dehydrobenzene and
Cycloalkynes; Academic Press: New York, 1967. (b) Hart, H. In The
Chemistry of Triple-Bonded Functional Groups, Supplement C2; Patai, S., Ed.;
Wiley: Chichester, UK, 1994; Chapter 18. (c) Wenk, H. H.; Winkler, M.;
Sander, W. Angew. Chem., Int. Ed. 2003, 42, 502. (d) Pellissier, H.; Santelli,
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~
M. Tetrahedron 2003, 59, 701. (e) Guitian, E.; Perez, D.; Pena, D. Top.
~
(9) (a) Xue, J.; Wu, L. L.; Huang, X. Chin. Chem. Lett. 2008, 19, 631. (b)
Huang, X.; Xue, J. J. Org. Chem. 2007, 72, 3965.
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Organomet. Chem. 2005, 14, 109. (f) Pena, D.; Perez, D.; Guitian, E. Angew.
Chem., Int. Ed. 2006, 45, 3579.
(2) (a) Himeshima, Y.; Sonoda, T.; Kobayashi, H. Chem. Lett. 1983,
1211. (b) Pena, D.; Cobas, A.; Perez, D.; Guitian, E. Synthesis 2002, 1454.
(3) Yoshida, H.; Honda, Y.; Shirakawa, E.; Hiyama, T. Chem. Commun.
2001, 1880.
(10) For selected recent papers on the use of o-silyl aryltriflates as the
benzyne precursors, see: (a) Huang, X.-C.; Liu, Y.-L.; Liang, Y.; Pi, S.-F.;
Wang, F.; Li, J.-H. Org. Lett. 2008, 10, 1525. (b) Shi, F.; Waldo, J. P.; Chen,
Y.; Larock, R. C. Org. Lett. 2008, 10, 2409. (c) Liu, Z.; Shi, F.; Martinez,
P. D. G.; Raminelli, C.; Larock, R. C. J. Org. Chem. 2008, 73, 219. (d) Waldo,
J. P.; Zhang, X.; Shi, F.; Larock, R. C. J. Org. Chem. 2008, 73, 6679. (e) Xie,
C.; Liu, L.; Zhang, Y.; Xu, P. Org. Lett. 2008, 10, 2393. (f) Yoshida, H.;
Morishita, T.; Ohshita, J. Org. Lett. 2008, 10, 3845. (g) Ganta, A.; Snowden,
T. S. Org. Lett. 2008, 10, 5103. (h) Bhuvaneswari, S.; Jeganmohan, M.; Yang,
M.-C.; Cheng, C.-H. Chem. Commun. 2008, 2158. (i) Bhuvaneswari, S.;
Jeganmohan, M.; Cheng, C.-H. Chem. Commun. 2008, 5013. (j) Morishita,
T.; Fukushima, H.; Yoshida, H.; Ohshita, J.; Kunai, A. J. Org. Chem. 2008,
73, 5452. (k) Allan, K. M.; Stoltz, B. M. J. Am. Chem. Soc. 2008, 130, 17270.
(l) Gilmore, C. D.; Allan, K. M.; Stoltz, B. M. J. Am. Chem. Soc. 2008, 130,
1558. (m) Gerfaud, T.; Neuville, L.; Zhu, J. Angew. Chem., Int. Ed. 2009, 48,
572. (n) Jeganmohan, M.; Bhuvaneswari, S.; Cheng, C.-H. Angew. Chem.,
Int. Ed. 2009, 48, 391. (o) Sha, F.; Huang, X. Angew. Chem., Int. Ed. 2009, 48,
3458. (p) Liu, Y.-L.; Liang, Y.; Pi, S.-F.; Huang, X.-C.; Li, J.-H. J. Org.
Chem. 2009, 74, 3199. (q) Pi, S.-F.; Tang, B.-X.; Li, J.-H.; Liu, Y.-L.; Liang,
Y. Org. Lett. 2009, 11, 2309. (r) Okuma, K.; Nojima, A.; Matsunaga, N.;
Shioji, K. Org. Lett. 2009, 11, 169. (s) Zhao, J.; Larock, R. C. Org. Lett. 2005,
7, 4273. (t) Zhao, J.; Larock, R. C. J. Org. Chem. 2007, 72, 583. (u) Yoshida,
H.; Kishida, T.; Watanabe, M.; Ohshita, J. Chem. Commun. 2008, 5963.
~
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(4) N-CO: (a) Yoshida, H.; Shirakawa, E.; Honda, Y.; Hiyama, T.
Angew. Chem., Int. Ed. 2002, 41, 3247. Si-Si: (b) Yoshida, H.; Ikadai, J.;
Shudo, M.; Ohshita, J.; Kunai, A. J. Am. Chem. Soc. 2003, 125, 6638. (c)
Yoshida, H.; Ikadai, J.; Shudo, M.; Ohshita, J.; Kunai, A. Organometallics
2005, 24, 156. Sn-Sn: (d) Yoshida, H.; Tanino, K.; Ohshita, J.; Kunai, A.
Angew. Chem., Int. Ed. 2004, 43, 5052. (e) Yoshida, H.; Tanino, K.; Ohshita,
J.; Kunai, A. Chem. Commun. 2005, 5678. S-Sn: (f) Yoshida, H.; Terayama,
T.; Ohshita, J.; Kunai, A. Chem. Commun. 2004, 1980. N-Si: (g) Yoshida,
H.; Minabe, T.; Ohshita, J.; Kunai, A. Chem. Commun. 2005, 3454. Cl-CO:
(h) Yoshida, H.; Mimura, Y.; Ohshita, J.; Kunai, A. Chem. Commun. 2007,
2405. N-C and N-S: (i) Liu, Z.; Larock, R. C. J. Am. Chem. Soc. 2005, 127,
13112. P-C: (j) Yoshida, H.; Watanabe, M.; Ohshita, J.; Kunai, A. Chem.
Lett. 2005, 34, 1538. Se-Se: (k) Toledo, F. T.; Marques, H.; Comasseto,
J. V.; Raminelli, C. Tetrahedron Lett. 2007, 48, 8125. N-O: (l) Raminelli, C.;
Liu, Z.; Larock, R. C. J. Org. Chem. 2006, 71, 4689.
(5) (a) Tambar, U. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 5340.
(b) Tambar, U. K.; Ebner, D. C.; Stoltz, B. M. J. Am. Chem. Soc. 2006, 128,
11752.
DOI: 10.1021/jo900847u
r
Published on Web 06/15/2009
J. Org. Chem. 2009, 74, 5691–5694 5691
2009 American Chemical Society