revealed that a metal-enamide species was involved as a
key reactive intermediate to react with imines forming the
amine product 3, where the sp3 CÀH bond was activated
by the transition metal and the proton was abstracted by
an endogenous basic counteranion of the metal complexes.
On the basis of these results a working hypothesis was
conceived that the product 3 could further interact with the
appropriate catalyst MXn that could activate the CÀH
bond again, thus leading to the formation of the inter-
mediate A or B, in which the endogenous basic counter-
anion will act as a base or some outer base was involved to
cleave the CÀH bond and the CdC double bond will form
through an E2-elimination process in high regioselectivity
(Scheme 1).
CÀN bond,7 which is a very efficient route to synthesize
2-alkenyl azaarenes.
Our initial investigation focused on the reaction of
8-methoxy-2-methylquinoline 1a and tosylimine 4a with
iron salt as catalyst. After some initial experiments, we
found in the presence of Fe(OAc)2, the coupling of 1a and
4a could afford the desired product 2aa in 68% yield at
120 °C. Significantly, the 1H NMR analysis of the reaction
mixture and X-ray crystallographic analysis of the product
2aa indicated that only the (E)-isomer was formed (Figure 1).
The interesting initial results encouraged us to optimize
the reaction conditions based on the iron catalyst. A screen
of solvents revealed that the experiments performed in
DMF, DMA, dioxane, CH2ClCH2Cl, 2-PrOH, toluene,
and mesitylene proceeded with more than 90% isolated
yield (Table 1, entries 7À16). The effect of reaction tem-
perature was examined, and it was confirmed that reac-
tions conducted at 120 °C gave the best results (Table 1,
entries 15, 17, and 18). Although the reactions ran at 80
and 100 °C can give high conversion, greater amounts of
amine product 3aa were obtained in high yields. These
results suggested that the alkenylation product 2 was most
likely to be produced from the intermediate 3. The effect of
catalyst loading was also examined, and we were delighted
to find that when the catalyst loading of Fe(OAc)2 was
decreased to 1 mol %, 2aa was still obtained in 99% yield,
the same as that obtained with 10 mol % catalyst, although
a longer reaction time was required in the latter case
(Table 1, entries 19 and 20). Control experiments revealed
that no reaction was observed in the absence of Fe(OAc)2.
Scheme 1. New Strategy for Alkenylation of 2-Substituted
Azaarenes
Iron complexes are inexpensive, nontoxic, and environ-
mentally benign, which have been extensively used as
catalysts to promote a broad range of reactions such as
cross-couplings, allylations, hydrogenations, and direct
CÀH bond functionalizations.6 Iron salts are also well-
known as good Lewis acid catalysts for many classic
reactions. These interesting features of iron catalysts have
prompted us to envision that it may be suitable for
promotion of the above-proposed reaction. Herein, we
present a novel iron-catalyzed direct alkenylation of 2-sub-
stituted azaarenes with readily accessible N-sulfonyl aldi-
mines through cleavage of two sp3 CÀH bonds and one
(5) (a) Qian, B.; Guo, S.; Shao, J.; Zhu, Q.; Yang, L.; Xia, C.; Huang,
H. J. Am. Chem. Soc. 2010, 132, 3650. (b) Qian, B.; Guo, S.; Xia, C.;
Huang, H. Adv. Synth. Catal. 2010, 352, 3195. Other groups reported
similar reactions using the same strategy: (c) Rueping, M.;Tolstoluzhsky,
N. Org. Lett. 2011, 13, 1095. (d) Komai, H.; Yoshino, T.; Matsunaga, S.;
Kanai, M. Org. Lett. 2011, 13, 1706.
(6) For reviews: (a) Bolm, C.; Legros, J.; Le Paih, J.; Zani, L. Chem.
€
Rev. 2004, 104, 6217. (b) Furstner, A.; Martin, R. Chem. Lett. 2005, 34,
624. (c) Correa, A.; Garcıa Mancheno, O.; Bolm, C. Chem. Soc. Rev.
2008, 37, 1108. (d) Enthaler, S.; Junge, K.; Beller, M. Angew. Chem., Int.
Figure 1. X-ray crystal structure of 2aa.
´
€
Ed. 2008, 47, 3317. (e) Sherry, B. D.; Furstner, A. Acc. Chem. Res. 2008,
41, 1500. (f) Furstner, A. Angew. Chem., Int. Ed. 2009, 48, 1364. (g)
Czaplik, W. M.; Mayer, M.; Cvengros, J.; Jacobi von Wangelin, A.
To eliminate the contaminants which may affect the
catalysis, a high purity Fe(OAc)2 (>99.995%, from
Aldrich) was used under the standard conditions, and the
yield remained unchanged. Furthermore, when Cu(OAc)2,
CuCl, CuCl2, CuBr, and Cu(OTf)2 were tested as catalysts
under the standard conditions, both conversion and yield
became relatively low (less than 60% yield), thus suggest-
ing that Cu salts were much less effective catalysts for this
transformation (see the Supporting Information). These
results further indicate that the Fe catalyst plays a crucial
role in this alkenylation reaction.
€
ꢁ
ChemSusChem 2009, 2, 296. (h) Nakamura, E.; Yoshikai, N. J. Org.
Chem. 2010, 75, 6061. (i) Buchwald, S. L.; Bolm, C. Angew. Chem., Int.
Ed. 2009, 48, 5586. (j) Sun, C.-L.; Li, B.-J.; Shi, Z.-J. Chem. Rev. 2011,
111, 1293.
(7) For CdC bond formation through cleavage of CÀN bond: (a)
Bestmann, H. J.; Seng, F. Angew. Chem., Int. Ed. 1963, 2, 393. (b) Dong,
D.-J.; Li, H.-H.; Tian, S.-K. J. Am. Chem. Soc. 2010, 132, 5018. (c)
Dong, D.-J.; Li, Y.; Wang, J.-Q.; Tian, S.-K. Chem. Commun. 2011, 47,
2158. The CÀN cleavage was also involved in Hofmann elimination,
Cope elimination, and BamfordÀStevensÀShapiro olefination; see re-
views: (d) Cope, A. C.; Trumbull, E. R. Org. React. 1960, 11, 317. (e)
Shapiro, R. H. Org. React. 1976, 23, 405. (f) Adlington, R. M.; Barrett,
A. G. M. Acc. Chem. Res. 1983, 16, 55.
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