[2 + 2] cycloaddition adducts, generated by the insertion of
arynes into the CdO bond, with organometallic reagents.
In this paper, we describe the sequential reaction involving
the insertion into the carbonyl group of amides and the
subsequent trapping process of the intermediates with di-
alkylzincs. In general, the [2 + 2] adducts containing
heteroatoms are considerably unstable due to strain energy.
Thus, the success of this sequential transformation reflects
the overall difference in the strain energy of arynes and the
four-membered intermediates.11e,f
Table 1. Reaction of Aryne Precursor 1 with DMFa
Figure 1. Insertion of arynes into the CdO bond of amides.
When nucleophile and electrophile belong to the same
molecule, however, most useful reactions are restricted to
insertion into the σ-bond (X-Y)7 and [2 + 3] cycloaddition8
(Figure 1). Little success was achieved in the insertion into
the π-bond (XdY) classified as [2 + 2] cycloaddition,9,10
except for Suzuki’s study on the insertion into the CdC bond
giving stable benzocyclobutenes.11 Thus, the insertion of
arynes into the carbon-heteroatom double bond is a chal-
lenging task. As the only example of the synthetically useful
insertion into the π-bond of carbonyl compounds, the 2:1
coupling reaction of arynes and aldehydes was recently
developed by Yoshida, Kunai, and others.12 Therefore, there
have been no reports on the trapping reaction of the formal
entry reagent (3.0 equiv) DMF (equiv) solvent yieldb (%)
1
2
3
4
5
TBAF·3H2O
TBAF
TBAF
TBAF
TBAF
3.0
3.0
3.0
3.0
3.0
CH3CN 31c
CH3CN 56
THF
46
CH2Cl2 43
CH3OH no reaction
CH3CN 70
6
TBAF
10
7
8
9
10
TBAF
CsF
TBAHF2
TBAT
DMF
DMF
DMF
DMF
84
72
67
31
a Reactions were carried out at rt for 3 h. b Isolated yield. c The starting
material 1 was recovered in 31% yield.
(7) For selected examples of insertion into the σ-bond, see: (a) Yoshida,
H.; Terayama, T.; Ohshita, J.; Kunai, A. Chem. Commun. 2004, 1980. (b)
Tambar, U. K.; Stoltz, B. M. J. Am. Chem. Soc. 2005, 127, 5340. (c)
Yoshida, H.; Watanabe, M.; Ohshita, J.; Kunai, A. Tetrahedron Lett. 2005,
46, 6729. (d) Tambar, U. K.; Ebner, D. C.; Stoltz, B. M. J. Am. Chem. Soc.
2006, 128, 11752. (e) Huang, X.; Xue, J. J. Org. Chem. 2007, 72, 3965. (f)
Yoshida, H.; Mimura, Y.; Ohshita, J.; Kunai, A. Chem. Commun. 2007,
2405. (g) Zhang, T.; Huang, X.; Xue, J.; Sun, S. Tetrahedron Lett. 2009,
50, 1290. (h) Stoltz, B. M.; Ebner, D.; Tambar, U. K.; Storgaard, M.; Ide,
N. D. J. A. Org. Synth. 2009, 86, 161.
As a preliminary experiment, we selected amides as a
carbonyl compound10 and first probed the utility of N,N-
dimethylformamide (DMF) without organometallic reagents
(Table 1). 3-Methoxy-2-(trimethylsilyl)phenyl triflate 1 was
employed as an aryne precursor, since the electronic effect of
polarized aryne having an electron-donating group was expected
to show excellent reactivity and regioselectivity toward the
CdO bond. All reactions of triflate 1 with DMF were evaluated
at room temperature for 3 h in the presence of several fluoride
ion sources. Initially, we allowed triflate 1 to react with 3 equiv
of DMF and 3 equiv of TBAF·3H2O in CH3CN. The desired
salicylaldehyde derivative 2 was obtained in 31% yield,
accompanied by 31% yield of the recovered starting material 1
(entry 1). The presence of water influenced the chemical
efficiency; thus, improvement in the chemical yield was
observed by changing TBAF·3H2O into anhydrous TBAF (entry
2). In regard to the solvent effect, the replacement of CH3CN
with THF or CH2Cl2 led to a decrease in the chemical yields
and the reaction in MeOH did not proceed effectively (entries
3-5). Increasing the amount of DMF improved the chemical
yields (entry 6). The chemical yield was increased into 84%
when DMF was used as a solvent (entry 7). Next, the effect of
fluoride ion sources was studied (entries 8-10). The good
chemical yields were also observed when CsF or tetrabutylam-
monium bifluoride (TBAHF2) was employed, although the use
of tetrabutylammonium difluorotriphenylsilicate (TBAT) was
(8) For selected examples of [3 + 2] cycloaddition reactions of arynes,
see: (a) Jin, T.; Yamamoto, Y. Angew. Chem., Int. Ed. 2007, 46, 3323. (b)
Liu, Z.; Shi, F.; Martinez, P. D. G.; Raminelli, C.; Larock, R. C. J. Org.
Chem. 2008, 73, 219. (c) Huang, X.-C.; Liu, Y.-L.; Liang, Y.; Pi, S.-F.;
Wang, F.; Li, J.-H. Org. Lett. 2008, 10, 1525. (d) Dai, M.; Wang, Z.;
Danishefsky, S. J. Tetrahedron Lett. 2008, 49, 6613. (e) Huang, X.; Zhang,
T. Tetrahedron Lett. 2009, 50, 208.
(9) For reports on insertion into the π-bond, see: (a) Gompper, R.; Kutter,
E.; Seybold, G. Chem. Ber. 1968, 101, 2340. (b) Heaney, H.; Jablonski,
J. M.; McCarty, C. T. J. Chem. Soc., Perkin Trans. 1 1972, 2903. (c)
Nakayama, J.; Yoshida, M.; Simamura, O. Chem. Lett. 1973, 451. (d)
Nakayama, J.; Midorikawa, H.; Yoshida, M. Bull. Chem. Soc. Jpn. 1975,
48, 1063. (e) Aly, A. A.; Mohamed, N. K. A. A.; Hassan, A. A.; Mourad,
A.-F. E. Tetrahedron 1999, 55, 1111. (f) Okuma, K.; Shiki, K.; Sonoda,
S.; Koga, Y.; Shioji, K.; Kitamura, T.; Fujiwara, Y.; Yokomori, Y. Bull.
Chem. Soc. Jpn. 2000, 73, 155. (g) Okuma, K.; Okada, A.; Koga, Y.;
Yokomori, Y. J. Am. Chem. Soc. 2001, 123, 7166.
(10) Yaroslavsky, S. Tetrahedron Lett. 1965, 6, 1503.
(11) (a) Hamura, T.; Ibusuki, Y.; Uekusa, H.; Matsumoto, T.; Suzuki,
K. J. Am. Chem. Soc. 2006, 128, 3534. (b) Hamura, T.; Ibusuki, Y.; Uekusa,
H.; Matsumoto, T.; Siegel, J. S.; Baldridge, K. K.; Suzuki, K. J. Am. Chem.
Soc. 2006, 128, 10032. (c) Hamura, T.; Arisawa, T.; Matsumoto, T.; Suzuki,
K. Angew. Chem., Int. Ed. 2006, 45, 6842. (d) Kraus, G. A.; Wu, T.
Tetrahedron 2010, 66, 569. For some examples of the reaction of
benzocyclobutenes, see: (e) Suzuki, T.; Hamura, T.; Suzuki, K. Angew.
Chem., Int. Ed. 2008, 47, 2248. (f) Feltenberger, J. B.; Hayashi, R.; Tang,
Y.; Babiash, E. S. C.; Hsung, R. P. Org. Lett. 2009, 11, 3666.
(12) Yoshida, H.; Watanabe, M.; Fukushima, H.; Ohshita, J.; Kunai, A.
Org. Lett. 2004, 6, 4049.
Org. Lett., Vol. 12, No. 9, 2010
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