reported the allylation11a and propargylation11b of aro-
matic systems.
agent in MeCN (entry 1), the allylation product 2a was
observed as a minor component. Changing the solvent to
CH2Cl2 improved the reaction slightly (entries 2À3), while
heating was not helpful. The use of Tf2O (trifluoro-
methanesulfonic anhydride) significantly enhanced the re-
action to give 2a in 53% yield (entry 7).13 In contrast, when
investigating the reaction of pyrrole sulfoxide 1b, TFAA
appears to be the better activating agent (entry 9) and
employing MeCN as solvent (entry 10) gave 2b in an
excellent yield of 98%.13
Table 1. Optimization of the ortho-Allylation
Figure 1. Selected biologically active pyrroles and pyrazoles.
Herein we report a nucleophilic ortho-allylation of pyr-
role and pyrazole sulfoxides, such as 1, that proceeds by a
heterocycle accelerated, interrupted Pummerer/thio-Claisen12
rearrangement sequence involving allylsulfonium salts 4
(Scheme 1). The procedure is general, metal-free, and regio-
specific with regard to both coupling partners.
entry HetAr solvent anhyd.
conditions
yield (%)
1
1a
1a
1a
1a
1a
1a
1a
1b
1b
1b
1b
1b
MeCN
CH2Cl2
CH2Cl2
DCE
TFAA À40 °C to rt; 2 h
TFAA À78 °C to rt; 2 h
TFAA À78 °C to rt; 18 h
TFAA À78 to 60 °C 2 h
<5
2
14
3
24
4
13
5
DCE
Tf2O
Tf2O
À78 to 60 °C; 2 h
À78 °C to rt; 2 h
-78 °C to rt; 18 h
À78 °C to rt; 18 h
18
Scheme 1. Nucleophilic ortho-Allylation (X = N, CH)
6
CH2Cl2
47
7
CH2Cl2 Tf2O
53
8
CH2Cl2
CH2Cl2
MeCN
MeCN
MeCN
Tf2O
14a
41a
98a
95a
92a
9
TFAA À78 °C to rt; 18 h
TFAA -40 °C to rt; 18 h
TFAA À40 °C to rt; 2 h
TFAA À40 °C; 2 h
10
11
12
a Yields determined by 1H NMR.13
We began investigating the ortho-allylation reaction of
pyrazole sulfoxide 1a with allyltrimethylsilane 3a (Table 1).
Using our previously established conditions11a with TFAA
(trifluoroacetic anhydride) as the electrophilic activating
Having identified optimized conditions for the allylation
of both pyrazoles and pyrroles, we next investigated the
substrate scope. Pleasingly, the ortho-allylation of pyrrole
was not restricted with regard to the position of the sulf-
oxide moiety; both 1b and its regioisomer 1c (entries 1 and
6; Table 2) underwent allylation in high yields. The reac-
tion is also tolerant to various allylsilanes, allowing high
yielding allylation when using functionalized silanes 3bÀc
(entries 2À3) and the extended allylsilanes 3dÀe (entries
4À5). Interestingly, the reaction is stereoconvergent with
regard toalkene geometry, since both silanes3d and 3egive
products of allylation favoring the E-isomer (entries 4À5).
Although we mainly explored the reactivity with tosyl-
protected pyrrole, the unprotected NÀH pyrrole 1d also
successfully underwent allylation (entry 7). Analogously,
phenylsulfinyl-pyrazoles 1a, 1e, 1f, and 1g were success-
fully allylated under theseconditions ingood yields(entries
8À10 and 13), showing more efficient reactivity when
ortho-allylation at the 4-position of pyrazole is possible.14
A variety of commonly used protecting groups are toler-
ated in the allylation of pyrazoles (entries 9, 10, and 13).
Functionalized silanes 3b and 3c can also be used with
(9) (a) Akai, S.; Kawashita, N.; Wada, Y.; Satoh, H.; Alinejad, A. H.;
Kakiguchi, K.; Kuriwaki, I.; Kita, Y. Tetrahedron Lett. 2006, 47, 1881.
(b) Akai, S.; Kawashita, N.; Satoh, H.; Wada, Y.; Kakiguchi, K.;
Kuriwaki, I.; Kita, Y. Org. Lett. 2004, 6, 3793. (c) Akai, S.; Morita,
N.; Iio, K.; Nakamura, Y.; Kita, Y. Org. Lett. 2000, 2, 2279. (d)
Feldman, K. S.; Vidulova, D. B. Org. Lett. 2004, 6, 1869. (e) Feldman,
K. S.; Skoumbourdis, A. P. Org. Lett. 2005, 7, 929. (f) Feldman, K. S.;
Vidulova, D. B.; Karatjas, A. G. J. Org. Chem. 2005, 70, 6429. (g)
Feldman, K. S.; Karatjas, A. G. Org. Lett. 2006, 8, 4137. (h) Feldman,
K. S.; Fodor, M. D. J. Org. Chem. 2009, 74, 3449. (i) Padwa, A.; Nara, S.;
Wang, Q. Tetrahedron Lett. 2006, 47, 595.
(10) (a) Yoshida, S.; Yorimitsu, H.; Oshima, K. Org. Lett. 2009, 11,
2185. (b) Kobatake, T.; Fujino, D.; Yoshida, S.; Yorimitsu, H.; Oshima,
K. J. Am. Chem. Soc. 2010, 132, 11838. (c) Kobatake, T.; Yoshida, S.;
Yorimitsu, H.; Oshima, K. Angew. Chem., Int. Ed. 2010, 49, 2340.
(d) Ookubo, Y.; Wakamiya, A.; Yorimitsu, H.; Osuka, A. Chem.;
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ꢁ
2011, 133, 8510. (f) Huang, X.; Patil, M.; Fares, C.; Thiel, W.; Maulide,
N. J. Am. Chem. Soc. 2013, 135, 7312.
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52, 4008.
(12) For thio-Claisen rearrangements of sulfonium ylides and sulfo-
nium salts formed by alternative approaches, see: (a) Huang, X.;
Klimczyk, S.; Maulide, N. Synthesis 2012, 44, 175. (b) Harvey, N. J.;
Viehe, H. G. J. Chem. Soc., Chem. Commun. 1995, 22, 2345. (c)
Boyarskikh, V.; Nyong, A.; Rainier, J. D. Angew. Chem., Int. Ed.
2008, 47, 5374. (d) Furukawa, N.; Shima, H.; Ogawa, S. Heteroat.
Chem. 1995, 6, 559. (e) Shima, H.; Furukawa, N. Tetrahedron 1995, 51,
12239.
(13) See Supporting Information for complete optimization table.
(14) This is in agreement with the typical relative reactivities of the
positions on pyrazoles; see ref 3.
Org. Lett., Vol. 15, No. 15, 2013
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