Efficient generation and trapping of acylbenzynes from hypervalent iodine compounds

Article abstract of DOI:10.1016/j.tetlet.2006.01.042

[5-Acyl-2-(trimethylsilyl)phenyl]iodonium triflates were prepared for the generation of benzynes bearing ketone function. Treatment of the iodonium triflates with Bu₄NF in CH₂Cl₂ in the presence of furan at room temperatur

Full text of DOI:10.1016/j.tetlet.2006.01.042

Tetrahedron Letters 47 (2006) 1709–1712
Efficient generation and trapping of acylbenzynes from
hypervalent iodine compounds
Tsugio Kitamura,a,* Yoshiki Aoki,a Shingo Isshiki,b Kanako Wasaib and Yuzo Fujiwarab
aDepartment of Chemistry and Applied Chemistry, Faculty of Science and Engineering, Saga University,
Honjo-machi, Saga 840-8502, Japan
bDepartment of Applied Chemistry, Faculty of Engineering, Kyushu University, Hakozaki, Fukuoka 812-8512, Japan
Received 10 December 2005; revised 5 January 2006; accepted 12 January 2006
Available online 26 January 2006
Abstract—[5-Acyl-2-(trimethylsilyl)phenyl]iodonium triflates were prepared for the generation of benzynes bearing ketone function.
Treatment of the iodonium triflates with Bu4NF in CH2Cl2 in the presence of furan at room temperature gave 6-acyl-1,4-epoxy-1,4-
dihydronaphthalenes in high yields. The mild conditions and the tolerance of the ketone function on benzyne generation are attri-
butable to the advantage of hypervalent iodine compounds.
Ó 2006 Elsevier Ltd. All rights reserved.
Benzyne is an important reactive intermediate and has
been used in organic synthesis, mechanistic studies,
and synthesis of functional materials.1 Recently, there
has been considerable progress in the application of benz-
yne chemistry to natural product synthesis.2 If benzynes
having various functional groups can be generated read-
ily, the synthetic applications using benzynes become
more important.
However, the generation of a benzyne bearing a more
reactive functional group such as an acyl group is still
limited. For the generation of 4-acetylbenzyne, for
example, it is necessary that the carbonyl group is pro-
tected as an acetal because the acetyl group cannot be
tolerable under the reaction conditions.6 To the best of
our knowledge, there are no examples of benzynes bear-
ing an acyl group. Here, we wish to report a more effi-
cient and milder method for generation of benzynes
bearing acyl groups.
The carbonyl group is one of the most important func-
tional groups. Introduction of a carbonyl group into a
benzyne skeleton greatly increases the potential for syn-
thetic utility. Although generation of various types of
benzynes has been studied to date, surprisingly, there
are only a few examples concerning benzynes bearing
carbonyl groups. Benzynes with ester and amide groups
were generated from different precursors, aryliodonium
salts,3 and triflates,4 respectively. Very recently, it has
been reported that benzynes bearing electrophilic sub-
stituents such as ester, amide, and cyano groups can
be generated by the reaction of functionalized bromo-
benzenes with lithium dialkyltetramethylpiperidino-
zincates.5
Taking efficient generation and mild reaction conditions
into consideration, the combination of a hypervalent
iodine and a silyl group is the best way to generate a
functionalized benzyne under mild conditions.7 In order
to avoid the basic conditions which ketones cannot
tolerate, we adopted the Diels–Alder reaction of 5-acyl-
pyran-2-ones
with
1,2-bis(trimethylsilyl)acetylene,
directly giving 1,2-bis(trimethylsilyl)benzenes bearing
acyl groups at the 5 position. Cycloaddition of 5-acyl-
pyran-2-ones 18,9 with 1,2-bis(trimethylsilyl)acetylene
was conducted in a sealed tube in the absence or
presence of xylene as a solvent. For example, heating a
mixture of 5-benzoylpyran-2-one (1a), bis(trimethyl-
silyl)acetylene, and xylene at 200 °C for 24 h gave
4-benzoyl-1,2-bis(trimethylsilyl)benzene (2a) in 72%
yield. The results are given in Table 1.
Keywords: Benzyne; Cycloaddition; Hypervalent iodine compounds;
Ketones.
*
The benzyne precursors, [2-(trimethylsilyl)phenyl]iodo-
Corresponding author. Tel.: +81 952 28 8550; fax: +81 952 28
8548; e-mail: kitamura@cc.saga-u.ac.jp
nium triflates 3 bearing an acyl group, were prepared
0040-4039/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2006.01.042

1710
T. Kitamura et al. / Tetrahedron Letters 47 (2006) 1709–1712
Table 1. Synthesis of 4-acyl-1,2-bis(trimethylsilyl)benzenes 2
SiMe3
ketones are reactive toward hypervalent iodine reagents.
It is well-known that ketones react with hypervalent
iodine reagents to give a-functionalized ketones.10 How-
ever, even in this case, we considered that the keto
groups were still tolerable under the reaction conditions
because more reactive silyl groups existed on the benz-
ene ring. Thus, we used iodosylbenzene (PhIO) instead
of PhI(OAc)2, where a Lewis acid, BF3ÆEt2O, was used
for activating PhIO. When 4-acetyl-1,2-bis(trimethyl-
silyl)benzene (2d) was reacted with iodosylbenzene acti-
vated with BF3ÆEt2O and then treated with aqueous
NaOTf solution, the yield of 3d was much improved
to be 43% (Table 2, entry 5).11
O
Me3Si
SiMe3
R
O
R
xylene, 200 oC
SiMe3
O
O
1
2
Entry
Product
Yielda (%)
1
2
3
4
2a R = Ph
2b R = 4-MeC6H4
2a R = tBu
72
59
91
60
2a R = Me
a Isolated yields.
The generation of benzynes 4 bearing keto groups was
induced by desilylation of [2-(trimethylsilyl)phenyl]iodo-
nium triflates 3 with a fluoride anion and confirmed by
the trapping reaction of 4 with furan to give 1,4-
epoxy-1,4-dihydronaphthalene derivatives 5, which
method is conventionally used for the confirmation of
benzyne formation because of their reactive and short-
lived nature.1 In the present case, a solution of acyl
by the reaction of 1,2-bis(trimethylsilyl)benzenes 2 with
(diacetoxyiodo)benzene [PhI(OAc)2] activated with tri-
fluoromethanesulfonic acid (TfOH) in CH2Cl2 at room
temperature. The results are shown in Table 2. The
phenyliodination of the silyl groups occurred only at
the meta position to the acyl group to give the meta-acyl
substituted benzyne precursors 3. No benzyne precur-
sors bearing the acyl group at the para-position were
obtained at all. The high regioselectivity of the
phenyliodination is attributable to the para-deactivating
effect of the carbonyl group. In the cases of aroyl
and pivaloyl-substituted 1,2-bis(trimethylsilyl)benzenes
2a–c, [2-(trimethylsilyl)phenyl]iodonium triflates 3a–c
were obtained in good yields, while the yield of [5-acet-
yl-2-(trimethylsilyl)phenyl]iodonium triflate (3d) was
low (Table 2, entries 1–4). This result means that
group-substituted
[2-(trimethylsilyl)phenyl]iodonium
triflate 3 in CH2Cl2 was treated with a THF solution
of Bu4NF in the presence of furan at 0 °C and the reac-
tion mixture was stirred at room temperature for
30 min. Usual workup of the reaction mixture (extrac-
tion with CH2Cl2 and separation by column chromato-
graphy on silica gel) gave benzyne adduct 5 in a high
yield.12 This simple procedure was enough to generate
acylbenzynes 4 and to trap them with an appropriate
agent. As shown in Scheme 1, the cycloadducts 5 were
isolated in high yields in all cases employed in the pres-
ent study.
Table 2. Synthesis of benzyne precursors 3
SiMe
SiMe3
3 PhI(OAc)2, TfOH
Apparently, it is synthetically useful that benzynes 4
bearing an acyl group were generated and trapped with
furan without any damage to the acyl group to give the
corresponding 1,4-epoxy-1,4-dihydronaphthalenes 5 in
high yields. The benzyne 4c with a sterically hindered
pivaloyl group was generated quantitatively to give the
cycloadduct 5c in 98% yield. Similarly, it was found that
the acetyl group on the benzyne 4d did not suffer serious
damage under the reaction conditions and acetyl-substi-
tuted benzyne 4d was efficiently trapped with furan to
give the cycloadduct 5d in 74% yield. These results
indicate that [2-(trimethylsilyl)phenyl]iodonium triflates
3 bearing acyl groups generate the corresponding
R
R
CH2Cl2
SiMe3
I(Ph)OTf
0 oC to r.t.
O
O
3
2
Entry
Reagent
Product
3a R = Ph
3b R = 4-MeC6H4
3c R = tBu
3d R = Me
3d R = Me
Yielda (%)
1
2
3
4
5
PhI(OAc)2/TfOH
PhI(OAc)2/TfOH
PhI(OAc)2/TfOH
PhI(OAc)2/TfOH
PhIO/BF3ÆEt2Ob
63
54
49
10
43
a Isolated yields.
b Reaction with PhIO/BF3ÆEt2O followed by treatment with aqueous
NaOTf.
SiMe3
Bu4NF, furan
CH2Cl2, 0 oC to r.t., 30 min
O
R
R
I(Ph)OTf
O
O
5
3
5a: R = Ph
5b: R = 4-MeC6H4
5c: R = tBu
94%
86%
98%
74%
O
R
5d: R = Me
O
4
Scheme 1. Generation of acylbenzynes 4 and the trapping reaction with furan.

T. Kitamura et al. / Tetrahedron Letters 47 (2006) 1709–1712
1711
Chemistry of Polycoordinated Iodine; VCH: New York,
1992; (d) Varvoglis, A. Hypervalent Iodine in Organic
Synthesis; Academic Press: Sandiego, 1997.
benzynes 4 almost quantitatively and provide the cyclo-
adducts 5 with furan in high yields. The successful gen-
eration of benzynes 4 bearing a reactive ketone function
is attributable to the selective desilylation by the fluoride
anion due to the high affinity and to the extremely high
leaving ability of the hypervalent iodine. Therefore, it is
considered that the hypervalent iodine benzyne precur-
sors have excellent advantages over the previously
reported benzyne precursors.
11. General procedure for synthesis of [2-(trimethylsilyl)-
phenyl]iodonium triflates 3: A glass tube was charged with
1 (4 mmol), 1,2-bis(trimethylsilyl)acetylene (6 mmol), and
mesitylene (2 mL). The tube was placed in a 20-mL
stainless steel autoclave. The autoclave was closed and
heated at 200 °C for 24 h. The product 2 was purified by
column chromatography on silica gel (eluent: EtOAc/
hexane). To a suspension of PhI(OAc)2 (1 mmol) in
CH2Cl2 (5 mL) was added TfOH (1.6 mmol) at 0 °C and
the mixture was stirred at that temperature for 30 min. A
solution of 2 (1 mmol) in CH2Cl2 (2 mL) was added at
0 °C and then the reaction mixture was stirred at room
temperature for 30 min. After evaporation of the solvent,
the residue was treated with ether and crystallized. The
crystals were collected, washed with ether, and dried to
give 3. The spectral data are as follows. Compound 3a: 1H
NMR (300 MHz, CDCl3): d 0.50 (s, 9H), 7.45–7.53 (m,
4H), 7.58–7.68 (m, 2H), 7.75–7.80 (m, 4H), 7.84 (d,
J = 7.8 Hz, 1H), 8.04 (dd, J = 7.8, 1.5 Hz, 1H), 8.36 (d,
J = 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): d 0.02,
114.00, 121.94, 128.77, 130.23, 132.05, 132.30, 132.48,
133.30, 133.57, 135.70, 138.23, 139.37, 141.68, 151.64,
193.61. Anal. Calcd for C23H22F3IO4SSi: C, 45.55; H,
In conclusion, we have found a mild and general method
for generation of functionalized benzynes, especially
benzynes with a ketone function. The high efficiency
for generation of benzynes and the high yields of the
cycloadducts are important factors in mechanistic stud-
ies as well as synthetic applications. In addition to the
ketone function, the resultant 1,4-epoxy-1,4-dihydro-
naphthalene moiety also has high synthetic utility for
transformation into new functionalized naphthalene
derivatives.13
References and notes
1
3.66. Found: C, 45.55; H, 3.70. Compound 3b: H NMR
1. (a) Hoffmann, R. W. Dehydrobenzene and Cycloalkynes;
New York: Academic Press, 1967; (b) Gilchrist, T. L. In
The Chemistry of Functional Groups, Supplement C; Patai,
S., Rappoport, Z., Eds.; Wiley: Chichester, 1983, Chapter
11; (c) Hart, H. In The Chemistry of Triple-Bonded
Functional Groups, Supplement C2; Patai, S., Ed.; Wiley:
Chichester, 1994, Chapter 18; (d) Wenk, H. H.; Winkler,
M.; Sander, W. Angew. Chem., Int. Ed. 2003, 42, 502–528.
2. (a) Rudas, M.; Nyerges, M.; Toke, L.; Groundwater, R.
W. Heterocycles 2003, 60, 817–824; (b) del Mar Real, M.;
Sestelo, J. P.; Sarandeses, L. A. Tetrahedron Lett. 2002,
43, 9111–9114; (c) Birkett, M. A.; Knight, D. W.; Little, P.
B.; Mitchell, M. B. Tetrahedron 2000, 56, 1013–1023; (d)
Kaelin, D. E., Jr.; Sparks, S. M.; Plake, H. R.; Martin, S.
F. J. Am. Chem. Soc. 2003, 125, 12994–12995; (e)
Hamura, T.; Hosoya, T.; Yamaguchi, H.; Kuriyama, Y.;
Tanabe, M.; Miyamoto, M.; Yasui, Y.; Matsumoto, T.;
Suzuki, K. Helv. Chim. Acta 2002, 85, 3589–3602.
3. Kitamura, T.; Wasai, K.; Todaka, M.; Fujiwara, Y.
Synlett 1999, 731–732.
4. Shankaran, K.; Snieckus, V. Tetrahedron Lett. 1984, 25,
2827–2830.
5. Uchiyama, M.; Miyoshi, T.; Kajihara, Y.; Sakamoto, T.;
Otani, Y.; Ohwada, T.; Kondo, Y. J. Am. Chem. Soc.
2002, 124, 8514–8515.
6. Lautens, M.; Schmid, G. A.; Chau, A. J. Org. Chem. 2002,
67, 8043–8053.
7. (a) Kitamura, T.; Yamane, M. J. Chem. Soc., Chem.
Commun. 1995, 983–984; (b) Kitamura, T.; Yamane, M.;
Inoue, K.; Todaka, M.; Fukatsu, N.; Meng, Z.; Fujiwara,
Y. J. Am. Chem. Soc. 1999, 121, 11674–11679.
(300 MHz, CDCl3): d 0.49 (s, 9H), 2.45 (s, 3H), 7.30 (d,
J = 7.8 Hz, 2H), 7.47 (t, J = 7.8 Hz, 2H), 7.60 (t,
J = 7.8 Hz, 1H), 7.68 (d, J = 7.8 Hz, 2H), 7.78 (d, J =
7.8 Hz, 2H), 7.83 (d, J = 7.5 Hz, 1H), 8.02 (dd, J = 7.5,
1.2 Hz, 1H), 8.35 (d, J = 1.2 Hz, 1H); 13C NMR (75 MHz,
CDCl3): d 0.06, 21.77, 114.01, 129.55, 130.42, 132.36,
132.59, 132.63, 133.03, 133.38, 138.36, 139.02, 142.36,
144.89, 148.45, 151.36, 193.05. Anal. Calcd for
C24H24F3IO4SSi: C, 46.46; H, 3.90. Found: C, 46.68; H,
1
4.00. Compound 3c: H NMR (300 MHz, CDCl3): d 0.45
(s, 9H), 1.30 (s, 9H), 7.46 (t, J = 7.8 Hz, 2H), 7.59 (t,
J = 7.8 Hz, 1H), 7.74 (d, J = 7.7 Hz, 1H), 7.83 (d, J =
7.8 Hz, 2H), 7.90 (dd, J = 7.7, 1.5 Hz, 1H), 8.29 (d,
J = 1.5 Hz, 1H); 13C NMR (75 MHz, CDCl3): d À0.02,
27.48, 44.50, 114.05, 121.93, 130.60, 132.24, 132.46,
133.49, 137.43, 137.91, 142.55, 149.97, 206.30. Anal. Calcd
for C21H26F3IO4SSi: C, 43.01; H, 4.47. Found: C, 42.83;
1
H, 4.38. Compound 3d: H NMR (300 MHz, CDCl3): d
0.45 (s, 9H), 2.62 (s, 3H), 7.46 (t, J = 7.8 Hz, 2H), 7.59 (t,
J = 7.8 Hz, 1H), 7.80–7.84 (m, 3H), 8.15 (d, J = 7.2 Hz,
1H), 8.65 (s, 1H). Anal. Calcd for C18H20F3IO4SSi: C,
39.71; H, 3.70. Found: C, 39.48; H, 3.67.
12. General procedure for trapping reaction of benzynes 4: To a
solution of 3 (0.2 mmol) and furan (1.0 mmol) in CH2Cl2
(3 mL) was added a THF solution of Bu4NF (1.0 M in
THF, 0.24 mL) at 0 °C, and the mixture was stirred at
room temperature for 30 min. Then, water was added and
the product was extracted with CH2Cl2. The organic
extracts were dried over anhydrous Na2SO4 and concen-
trated. The residue was purified by column chromatogra-
phy on silica gel (eluent: hexane/CH2Cl2) to give benzyne
adducts 5. The spectral data are as follows. Compound 5a:
1H NMR (300 MHz, CDCl3): d 5.78–5.79 (m, 2H), 7.04
(dd, J = 1.8, 5.4 Hz, 1H), 7.08 (dd, J = 1.8, 5.4 Hz, 1H),
7.33 (d, J = 7.5 Hz, 1H), 7.45–7.50 (m, 3H), 7.58 (t,
J = 7.8 Hz, 1H), 7.72 (d, J = 1.8 Hz, 1H), 7.77 (d,
J = 7.8 Hz, 2H); 13C NMR (75 Hz, CDCl3): d 82.16,
119.67, 121.07, 128.25, 129.10, 129.89, 132.28, 134.87,
137.86, 142.32, 143.35, 149.51, 153.89, 196.41. Anal. Calcd
for C17H12O2: C, 82.24; H, 4.87. Found: C, 82.02; H, 4.94.
Compound 5b: 1H NMR (300 MHz, CDCl3): d 2.36 (s,
3H), 5.69 (s, 2H), 6.95 (dd, J = 1.8, 5.6 Hz, 1H), 6.99
8. 5-Aroylpyran-2-ones 1 were prepared according to the
literatures (a) Fried, J.; Elderfield, R. C. J. Org. Chem.
1941, 6, 566–576; (b) Wiley, R. H.; Slaymarker, S. C. J.
Am. Chem. Soc. 1956, 78, 2393–2398.
9. 5-Alkanoylpyran-2-ones 1 were prepared by the reaction
of coumaloyl chloride with alkylcopper reagents Rahman,
M. T.; Hogue, A. K. M.; Siddique, I.; Chowdhury, D. A.
N.; Nahar, S. K.; Saha, S. L. J. Organomet. Chem. 1980,
188, 293–300.
10. (a) Moriarty, R. M.; Prakash, O. Acc. Chem. Res. 1984,
19, 244–250; (b) Stang, P. J.; Zhdankin, V. V. Chem. Rev.
1996, 96, 1123–1179; (c) Varvoglis, A. The Organic

1712
T. Kitamura et al. / Tetrahedron Letters 47 (2006) 1709–1712
(dd, J = 1.8, 5.6 Hz, 1H), 7.18–7.25 (m, 3H), 7.36 (dd, J =
C15H16O2: C, 78.92; H, 7.06. Found: C, 78.55; H, 7.04.
Compound 5d: 1H NMR (300 MHz, CDCl3): d 2.48 (s,
3H), 5.67 (s, 2H), 6.91 (dd, J = 1.5, 5.4 Hz, 1H), 6.97 (dd,
J = 1.5, 5.4 Hz, 1H), 7.23 (d, J = 7.5 Hz, 1H), 7.56 (dd,
J = 1.2, 7.5 Hz, 1H), 7.74 (d, J = 1.2 Hz, 1H); 13C NMR
(75 Hz, CDCl3): d 26.63, 81.99, 82.03, 119.02, 119.82,
127.20, 134.52, 142.19, 143.27, 149.71, 154.39, 197.47.
Anal. Calcd for C12H10O2: C, 77.40; H, 5.41. Found: C,
77.12; H, 5.43.
1.2, 7.2 Hz, 1H), 7.59–7.62 (m, 3H); 13C NMR (75 Hz,
CDCl3): d 21.59, 82.14, 119.58, 121.02, 128.78, 128.91,
130.10, 135.11, 135.19, 142.32, 143.04, 143.30, 149.41,
153.58, 196.13. Anal. Calcd for C18H14O2: C, 82.42;
H, 5.38. Found: C, 82.21; H, 5.40. Compound 5c: 1H
NMR (300 MHz, CDCl3): d 1.34 (d, 9H), 5.75 (s, 2H), 7.01
(dd, J = 1.5, 5.4 Hz, 1H), 7.05 (dd, J = 1.5, 5.4 Hz, 1H),
7.26 (d, J = 7.4 Hz, 1H), 7.42 (dd, J = 1.2, 7.4 Hz, 1H),
7.59 (d, J = 1.2 Hz, 1H); 13C NMR (75 Hz, CDCl3): d
28.15, 44.12, 82.11, 82.23, 119.49, 119.81, 125.88, 135.44,
142.37, 143.20, 149.09, 151.99, 208.57. Anal. Calcd for
13. (a) Woo, S.; Keay, B. A. Synthesis 1996, 669–686; (b)
Lautens, M.; Fagnou, K.; Hiebert, S. Acc. Chem. Res.
2003, 36, 48–58.