Angewandte
Chemie
DOI: 10.1002/anie.201300485
Asymmetric Auto-Tandem Catalysis
Asymmetric Auto-Tandem Catalysis with a Planar-Chiral Ruthenium
Complex: Sequential Allylic Amidation and Atom-Transfer Radical
Cyclization**
Naoya Kanbayashi, Kazuhiro Takenaka, Taka-aki Okamura,* and Kiyotaka Onitsuka*
[
10]
The efficient synthesis of complex molecules with multiple
stereogenic centers is a challenging task in synthetic organic
chemistry. One-pot reactions have received considerable
attention for the improvement of reaction efficiency, because
they can avoid time-consuming workups and the often
reaction.
ATRC is an atom-economical method for the
formation of cyclic compounds, which proceeds under mild
conditions and exhibits broad functional group tolerance.
Hence, it was hypothesized that complex 1 could realize an
asymmetric auto-tandem catalysis consisting of allylic sub-
stitution and ATRC.
To test this theory, we envisioned the facile synthesis of
optically active g-lactams, an important structural motif found
in a variety of biologically active molecules. Nagashima and
[
1]
formidable isolation of intermediary products. A represen-
tative example is domino catalysis, in which two or more
mechanistically similar reactions proceed in only one oper-
[1,2]
[11]
ation.
Another method, auto-tandem catalysis is also an
ideal and eco-friendly synthetic process, which involves two or
more mechanistically distinct reactions promoted by only
co-workers reported that ATRC reaction of branched allylic
amides using
a
Ru catalyst proceeded diastereoselec-
[
3]
[12,13]
a single catalyst. Despite numerous examples of domino
catalysis, there are limited numbers of reports on auto-
tively,
with the configuration at the new stereogenic
carbon controlled by the stereochemistry of the substrate. The
preparation of optically active allylic amides by 1-catalyzed
enantioselective allylic amidation would therefore provide
g-lactams with multiple stereogenic centers in a pure form
through 1-catalyzed ATRC (Scheme 1). Herein, we report
[4]
tandem catalysis, this is probably due to the difficulty of
optimizing the reaction conditions.
We have shown that planar-chiral cyclopentadienyl-
ruthenium (Cp’Ru) complex 1 is a proficient catalyst for
[
5,6]
asymmetric allylic substitutions. Recently, we succeeded in
the development of regio- and enantioselective reactions of
monosubstituted allylic halides with oxygen nucleophiles,
which produced enantiomerically enriched branched allylic
[7]
ethers, esters, and alcohols in good yields. These products
possess a reactive terminal olefin, which can be potentially
[7d,8]
applied in a further transformation.
As the catalytic
activity of 1 is preserved, even at the end of the allylic
[7b]
substitution, and ruthenium complexes show various desir-
[
9]
able oxidation states for catalytic behavior, we conceived an
extension of our system to auto-tandem asymmetric catalysis.
As a candidate for the transformation of a terminal olefin on
a branched allylic compound, we focused on the atom-
transfer radical cyclization (ATRC) because half-sandwiched
Ru complexes similar to 1 are known to promote this
Scheme 1. Synthesis of enantiomerically enriched g-lactams through
auto-tandem asymmetric catalysis using 1.
[
*] N. Kanbayashi, Dr. T. Okamura, Prof. K. Onitsuka
Department of Macromolecular Science
Graduate School of Science, Osaka University
Machikaneyama 1-1, Toyonaka
Osaka 560-0043 (Japan)
E-mail: tokamura@chem.sci.osaka-u.ac.jp
a sequential regio-, enantio-, and diastereoselective reaction
of allylic chlorides with amide derivatives promoted by
a single catalyst, 1, and involving completely different
reaction mechanisms. To the best of our knowledge, this is
a novel example of asymmetric auto-tandem catalysis.
To accomplish the asymmetric auto-tandem catalysis, we
Dr. K. Takenaka
The Institute of Scientific and Industrial Research (ISIR)
Osaka University, Mihogaoka, Ibaraki, Osaka 567-0047 (Japan)
[13–15]
initially examined the enantioselective allylic amidation
of cinnamyl chloride (2a) using (S)-1 (Ar= 3,5-Me C H ) as
2
6
3
[
**] This work was supported by a Grant-in-Aid for Scientific Research
from the Ministry of Education, Culture, Sports, Science and
Technology (Japan), and partly by the Sumitomo Foundation and
a JSPS Research Fellowship.
the catalyst. After optimization of the conditions in the
reaction of trifluoroacetoamide (3a), we observed the for-
mation of desired branched allylic amide 4a with high regio-
and enantioselectivity. Thus, treatment of 2a and 3a with (S)-
1 (1 mol%) in the presence of K CO and 3ꢀ molecular
2
3
Angew. Chem. Int. Ed. 2013, 52, 4897 –4901
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
4897