has received much less attention,9 despite their potential utility
to produce useful organosulfur compounds. The first anionic
thia-Fries rearrangement of aryl triflate was reported by
Lloyd-Jones in 2003.10a After that, more studies have been
devoted to the synthetic potential of this reaction,10bÀh
probably because its product aryl triflones are frequently
used as structural units in bioactive compounds,11 chiral
catalysts,10c,d and functional materials.12 However, no at-
tention has been paid to use this method for preparing
heteroaryl triflones, which are potentially important hetero-
aromatic compounds because of the unique properties of
the SO2CF3 group.13 The synthesis of heteroaryl triflones
still remains challenging, with synthesis often suffering from
poor regioselectivity and low yields due to oxidative
degradation. Our group has recently developed two meth-
ods for preparation of heteroaryl triflones, including mod-
ified FriedelÀCrafts sulfonylation for indole triflones14a
and cyclization of SO2CF3-containing building blocks for
isoxazole triflones.14b In continuation of our research on
fluorinated heterocycles,15 we herein report the efficient
synthesis of previously unknown heteroaryl triflones includ-
ing oxindole, pyrazolone, pyridine, and quinoline deriva-
tives by lithium diisopropylamide (LDA)-mediated thia-
Fries rearrangement (Scheme 1). All of these heteroaryl
triflones are synthesized for the first time, and their char-
acterization reveals that they exist as enol tautomers rather
than as amido forms.
(8) (a) Reed, M. A.; Chang, M. T.; Snieckus, V. Org. Lett. 2004, 6,
2297–2300. (b) Macklin, T. K.; Reed, M. A.; Snieckus, V. Eur. J. Org.
Chem. 2008, 1507–1509. (c) James, C. A.; Snieckus, V. J. Org. Chem.
2009, 74, 4080–4093.
Scheme 1. Synthesis of Heteroaryl Triflones by LDA-Mediated
Regioselective Thia-Fries Rearrangement
(9) For acid-catalyzed thia-Fries rearrangement, see: (a) Pitchumani,
K.; Pandian, A. J. Chem. Soc., Chem. Commun. 1990, 1613–1614. (b)
Das, B.; Madhusudhan, P.; Venkataiah, B. J. Chem. Res., Synop. 2000,
200–201. (c) Moghaddam, F. M.; Dakamin, M. G. Tetrahedron Lett.
2000, 41, 3479–3481. (d) Benson, G.; Maughan, P. J.; Shelly, D. P.;
Spillane, W. J. Tetrahedron Lett. 2001, 42, 8729–8731. (e) Sharghi, H.;
Shahsavari-Fard, Z. Helv. Chim. Acta 2005, 88, 42–52. For photoche-
mical thia-Fries rearrangement, see: (f) Kato, J.; Maekawa, Y.; Yoshida,
M. Chem. Lett. 2005, 34, 266–267. (g) Kato, J.; Kakehata, H.; Maekawa,
Y.; Yamashita, T. Chem. Commun. 2006, 4498–4500. (h) Crevatın, L. K.;
Bonesi, S. M.; Erra-Balsells, R. Helv. Chim. Acta 2006, 89, 1147–1157.
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€
Commun. 2003, 380–381. (b) Zhao, Z.; Messinger, J.; Schon, U.;
€
Wartchow, R.; Butenschon, H. Chem. Commun. 2006, 3007–3009. (c)
Kargbo, R.; Takahashi, Y.; Bhor, S.; Cook, G. R.; Lloyd-Jones, G. C.;
Indolyl triflate 1a was initially chosen as the test
substrate. Several types of bases (1.50 equiv) were
screened (Table 1). No reaction happened when 1a was
treated with DMAP (Table 1, entry 1). When n-BuLi or
LDA was used as the base, the reaction was complete
after 2 h (Table 1, entries 2 and 3). Some starting material
was not converted under the condition of phosphazene
P4-t-Bu after 24 h (Table 1, entry 4). Among these three
bases, LDA was proven to be the best, giving the product
2a in good yield with much less byproduct. To our
delight, when the amount of LDA was decreased from
1.50 to 1.10 equiv, almost single product was obtained
(Table 1, entry 5). Thus it was concluded that not only
LDA but also its amount were important to this
rearrangement.16 Interestingly, characterization of 2a
conducted by 13C NMR and DEPT-45 analysis reveals
all quaternary 13C signals, which is in accord with the
structure of enol tautomer 2a but is not consistent with
another structural tautomer, the amido form, which is
theoretically possible.
Shepperson, I. R. J. Am. Chem. Soc. 2007, 129, 3846–3847. (d) Barta, K.;
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Harvey, J. N.; Hester, A. J.; Lloyd-Jones, G. C.; Munoz, M. P.;
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G.; Butts, C. P.; Lloyd-Jones, G. C. Chem.;Eur. J. 2008, 14, 7808–7812.
(g) Werner, G.; Lehmann, C. W.; Butenschon, H. Adv. Synth. Catal. 2010, 352,
ꢀ
~
€
€
1345–1355. (h) Yoshioka, E.; Kohtani, S.; Miyabe, H. Org. Lett. 2010, 12,
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ꢀ
ꢀ
Under the optimized reaction condition, the scope of
this rearrangement was first investigated with a variety of
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