ORGANIC
LETTERS
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Vol. XX, No. XX
000–000
Cobalt(III) Porphyrin Catalyzed
Aza-DielsꢀAlder Reaction
Ryota Wakabayashi, Takuya Kurahashi,* and Seijiro Matsubara*
Department of Material Chemistry, Graduate School of Engineering, Kyoto University,
Kyoto 615-8510, Japan
kurahashi.takuya.2c@kyoto-u.ac.jp; matsubara.seijiro.2e@kyoto-u.ac.jp
Received July 28, 2012
ABSTRACT
An efficient protocol for the aza-DielsꢀAlder reaction of electron-deficient 1,3-dienes with unactivated imines in the presence of a cationic
cobalt(III) porphyrin complex was developed. The transformation proceeded smoothly to afford the desired piperidine scaffold within 2 h at
ambient temperature. Highly chemoselective cycloaddition of imines with dienes in the presence of a variety of carbonyl compounds was also
demonstrated.
The [4 þ 2] cycloaddition of dienes with imines, namely,
the aza-DielsꢀAlder reaction, is a versatile method for
constructing privileged scaffolds such as the piperidine
scaffold and is hence considered to have potential applica-
tions in the synthesis of natural products and pharmaceu-
ticals. Therefore, the development of [4 þ 2] cycloaddition
strategies involving the use of a catalyst and a mediator
has been a research topic of great interest.1 Many of the
precedent aza-DielsꢀAlder reactions demonstrate high
regioselectivity and enantioselectivity but require the use
of electron-rich and extremely reactive Danishefsky-type
dienes, which severely restricts their widespread applica-
tion in organic synthesis.2 Herein, we report that the aza-
DielsꢀAlder reaction of simple 1,3-dienes, which are less
reactive than Danishefsky dienes, with imines is efficiently
catalyzed by a cationic cobalt-porphyrin complex toafford
piperidines.
of metalloporphyrins can be attributed to their character-
istic structure, in which the tetradentate porphyrin ligand
shows rigid in-plane coordination to the metal. Hence,
we presumed that a hard Co3þ Lewis acid catalyst could
be prepared using a porphyrin ligand and a weakly co-
ordinating axial ligand, so that the cationic nature of Co3þ
is revealed.3 Such a complex would preferentially coordi-
nate with a hard Lewis base such as an imine and chemo-
selectively activate simple dienes, thus compensating for
their low reactivity; consequently, [4 þ 2] cycloaddition
would proceed efficiently to afford the corresponding
piperidines.4 To test our hypothesis, we carried out the
reaction of imine 1a with diene 2a in the presence of
[Co(TPP)]BF4 (1 mol %) in toluene. The reaction pro-
ceeded to completion within 2 h at ambient temperature to
afford piperidine 3aa in 79% yield (Table 1, entry 1). We
also examined the effect of various counteranions such
as ClO4ꢀ, SbF6ꢀ, OTfꢀ, and Clꢀ, which would act as axial
ligands, on the cationic nature of Co3þ (entries 2ꢀ5).
When [Co(TPP)]SbF6 was used as the catalyst, 3aa was
obtained in 92% isolated yield (entry 3). The desired
Metalloporphyrins have been used as catalysts in var-
ious organic transformations that are difficult to perform
using other metal complexes. The distinct catalytic ability
(1) (a) Jørgensen, K. A. Angew. Chem., Int. Ed. 2000, 39, 3558. (b)
Buonora, P.; Olsen, J.-C.; Oh, T. Tetrahedron 2001, 57, 6099. (c)
Weinreb, S. M. Hetero Dienophile Additions to Dienes. In Comprehe-
sive Organic Synthesis; Trost, B. M., Fleming, I., Eds.; Pergamon: Oxford,
1991; Vol. 5, p 401.
(2) Leighton and coworkers reported novel silicon Lewis acid
mediated aza-DielsꢀAlder reactions of an unactivated imine with three
different dienes, see: Tambar, U. K.; Lee, S. K.; Leighton, J. L. J. Am.
Chem. Soc. 2010, 132, 10248.
(3) For some selected examples on the synthesis and properties of
cationic cobalt-porphyrin complexes, see: (a) Satoh, M.; Ohba, Y.;
Yamauchi, S.; Iwaizumi, M. Inorg. Chem. 1992, 31, 298. (b) Sakurai, T.;
Yamamoto, K.; Naito, H.; Nakamoto, N. Bull. Chem. Soc. Jpn. 1976, 49,
3042. (c) Fukuzumi, S.; Okamoto, K.; Tokuda, Y.; Gros, C. P.; Guilard, R.
J. Am. Chem. Soc. 2004, 126, 17059.
(4) (a) Person, R. G. J. Am. Chem. Soc. 1963, 85, 3533. (b) Ho, T.-L.
Chem. Rev. 1975, 75, 1. (c) Woodward, S. Tetrahedron 2002, 58, 1017.
r
10.1021/ol3020946
XXXX American Chemical Society