Communications
DOI: 10.1002/anie.201100631
Copper Catalysis
Allyl-, Allenyl-, and Propargyl-Transfer Reactions through Cleavage of
À
C C Bonds Catalyzed by an N-Heterocyclic Carbene/Copper
Complex: Synthesis of Multisubstituted Pyrroles**
Masahiro Sai, Hideki Yorimitsu,* and Koichiro Oshima*
Development of efficient methods for transition-metal-cata-
À
lyzed selective cleavage of C C bonds and their application
has been a challenging subject of modern organic synthesis.[1]
Recently, our research group[1g,2] and others[3] have developed
transition-metal-catalyzed retro-allylation of homoallyl alco-
À
hols as a C C bond-cleavage strategy and thus have
succeeded in the generation and use of allylmetals under
mild conditions. However, expensive transition metals such as
palladium, rhodium, and ruthenium were required in these
Scheme 1. Methallylation of aldehyde 2a catalyzed by [Cu(IPr)Cl].
reactions.[4] Thus, it is more cost-efficient to replace such
expensive transition-metal catalysts with cheaper ones. With
this in mind, we have focused on the possibility of copper-
the allylation (Table 1, entries 1 and 2). The reaction of
electron-poor 4-fluorobenzaldehyde gave a moderate yield of
3d (Table 1, entry 3). Steric hindrance around the carbonyl
functionality did not significantly retard the allylation
(Table 1, entries 4 and 5). Heteroaromatic aldehydes were
also suitable substrates (Table 1, entries 6 and 7). Selective
1,2-addition occurred in the reaction of cinnamaldehyde with
alcohol 1a (Table 1, entry 8).
This allyl transfer is applicable to the allylation of an
imine (Table 1, entry 9). Remarkably, the present catalytic
system has proved to be effective for allyl transfer from
secondary homoallyl alcohols (Table 1, entries 10–12). Metal-
mediated retro-allylation of secondary homoallyl alcohols is
difficult because the process always suffers from overwhelm-
ingly smooth oxidation through b-hydrogen elimination from
the corresponding metal alkoxides. To the best of our
knowledge, this represents the first example of catalytic
allyl transfer reaction by retro-allylation using secondary
homoallyl alcohols as allyl donors.[10]
À
catalyzed selective cleavage of C C bonds by retro-allylation
of homoallyl alcohols. While copper can often replace
palladium and rhodium in many catalytic bond-forming
processes,[5] use of this cheaper and ubiquitous alternative in
À
catalytic C C bond cleavage reactions has remained unex-
plored.[6,7]
Initially, we examined the reaction of homoallyl alcohol
1a with aldehyde 2a using phosphine-ligated copper com-
plexes, however, these reactions failed to proceed. To our
delight, the use of the NHC (N-heterocyclic carbene)-ligated
copper complex[8,9] [Cu(IPr)Cl] led to the desired methally-
lated product 3a in 71% yield (Scheme 1). Naturally, copper-
catalyzed retro-allylation should generate allylcopper species,
3
3
À
which represents the first copper-catalyzed C(sp ) C(sp )
bond cleavage.
The scope of the allyl transfer was then examined
(Table 1). Electron-rich aldehydes successfully underwent
Encouraged by the success of the allylation reaction
catalyzed by [Cu(IPr)Cl], we next applied this catalytic
system to allenylation and propargylation of imines. Pleas-
ingly, the reaction of allenic alcohol 6a with imine 4a
proceeded to afford allenylated product 7aa in excellent
yield (Scheme 2). Intriguingly, the reaction exhibited high
selectivity in favor of the formation of 7aa (7aa/8aa = 96:4).
Allenylmetal species are generally in equilibrium with the
corresponding propargylmetal.[11] Therefore, controlling the
regioselectivity in the reactions using allenyl- and propargyl-
metals remains an important challenge in organic synthesis.[12]
When the crude product containing 7aa was heated in
aqueous ethanol before chromatographic purification, 7aa
was converted into 3-pyrroline 9aa (Table 2, entry 1).[13]
Notably, purified 7aa did not isomerize into 9aa under the
same reaction conditions. We eventually found that [Cu-
(IPr)Cl] was also highly effective for the cyclization to 9aa
(Scheme 3) as well as the allenyl transfer reaction. Although
[*] M. Sai, Prof. Dr. K. Oshima
Department of Material Chemistry
Graduate School of Engineering, Kyoto University
Kyoto-daigaku Katsura, Nishikyo-ku, Kyoto 615-8510 (Japan)
Fax: (+81)75-383-2438
E-mail: oshima@orgrxn.mbox.media.kyoto-u.ac.jp
Prof. Dr. H. Yorimitsu
Department of Chemistry
Graduate School of Science, Kyoto University
Kitashirakawa, Sakyo-ku, Kyoto 606-8502 (Japan)
Fax: (+81)75-753-3970
E-mail: yori@kuchem.kyoto-u.ac.jp
[**] This work was supported by Grants-in-Aid for Scientific Research
and GCOE Research from the JSPS. M.S. thanks the JSPS for
financial support. H.Y. acknowledges financial support from The
Uehara Memorial Foundation, the Novartis Foundation (Japan) for
the Promotion of Science, and the Takeda Science Foundation.
Supporting information for this article is available on the WWW
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ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Angew. Chem. Int. Ed. 2011, 50, 3294 –3298