trans-Cyclooctenes as Chiral Ligands in Rhodium-Catalyzed Asymmetric 1,4-Additions

Article abstract of DOI:10.1002/ejoc.202000956

trans-Cyclooctenes serve as asymmetric ligands for the rhodium-catalyzed 1,4-additions of organotin reagents to enones. We demonstrate, for the first time, that these chiral olefins can provide efficient coordination spheres for asymmetric metal catalysis. As the asymmetric environment around the reaction site is constructed by the trans-cyclooctene framework, the introduction of a substituent at the allylic position further improves enantioselectivity to 93 % ee. These findings provide new chiral framework designs for the asymmetric ligands of metal catalysts.

Full text of DOI:10.1002/ejoc.202000956

Communication
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Asymmetric Catalysis | Very Important Paper |
trans-Cyclooctenes as Chiral Ligands in Rhodium-Catalyzed
Asymmetric 1,4-Additions
[
a]
[a]
[a]
[a]
Tagui Nagano, Shunsuke Einaru, Kenta Shitamichi, Keisuke Asano,* and
Seijiro Matsubara*[
a]
Abstract: trans-Cyclooctenes serve as asymmetric ligands for reaction site is constructed by the trans-cyclooctene framework,
the rhodium-catalyzed 1,4-additions of organotin reagents to the introduction of a substituent at the allylic position further
enones. We demonstrate, for the first time, that these chiral improves enantioselectivity to 93 % ee. These findings provide
olefins can provide efficient coordination spheres for asymmet- new chiral framework designs for the asymmetric ligands of
ric metal catalysis. As the asymmetric environment around the metal catalysts.
[
1]
Since the discovery of Zeise's salt, metal-olefin complexes with sodium hydride afforded racemic trans-cyclooctene 7a.
[
2]
have been extensively studied and used in synthetic organic The enantiomers were subsequently separated by liquid col-
chemistry. In particular, olefins with planar chirality, such as op- umn chromatography with a chiral stationary phase to give op-
tically active dienes, have contributed significantly to advance- tically active 7a with > 99 % ee. Platinum complex 8 was pre-
[
3]
ments in asymmetric transition-metal catalysis. Among olefins pared in order to confirm the olefin geometry and absolute
[
8]
bearing molecular asymmetry, trans-cyclooctene, which was the configuration of 7a, and a single crystal was grown for X-ray
[
4]
first chiral olefin synthesized, is also known to coordinate to analysis (Figure 1). The ORTEP drawing unambiguously shows
[
9]
transition metals more strongly than normal olefins due to its that the alkene is trans-configured and is the R
-enantiomer.
p
strained structure that favors π back donation from a metal In addition, trans-cyclooctene 7a bearing the pyridyl group was
[
5]
atom; its coordination as a substrate to a metal complex bear- shown to be a bidentate ligand.
ing a chiral amine ligand was used to synthesize optically active
[
4b,4c]
trans-cyclooctene.
However, to the best of our knowledge,
the behavior of trans-cyclooctene derivatives as chiral ligands
for asymmetric catalysis is unknown despite their potential as
novel molecular-catalyst platforms.[ Here, we introduce trans-
cyclooctenes as asymmetric ligands for the rhodium-catalyzed
6]
1,4-additions of organotin reagents and describe their perform-
ance, thereby providing new chiral platforms for asymmetric
catalysis.
Initially, we designed trans-cyclooctene 7a bearing a pyridyl
group as a bidentate ligand, the synthesis of which is shown in
[
7]
Scheme 1. Starting from cyclooctanone (1), epoxidation with
a sulfur ylide followed by ring opening with (pyridin-2-yl-
methyl)lithium yielded 3a, which was then transformed into cis-
cyclooctene 4a by treatment with methanesulfonyl chloride in
the presence of triethylamine. Subsequent epoxidation and ring
opening with lithium diphenylphosphide followed by oxidation
gave the corresponding phosphine oxide 6a. Finally, treatment
[
a] T. Nagano, S. Einaru, K. Shitamichi, Prof. Dr. K. Asano,
Prof. Dr. S. Matsubara
Department of Material Chemistry, Graduate School of Engineering,
Kyoto University
Kyotodaigaku-katsura, Nishikyo, Kyoto 615-8510, Japan
E-mail: asano.keisuke.5w@kyoto-u.ac.jp
Scheme 1. Synthesis of trans-cyclooctene 7a.
matsubara.seijiro.2e@kyoto-u.ac.jp
https://smatsubara.wixsite.com/matsubara-kyoto-u/home
Supporting information and ORCID(s) from the author(s) for this article are
available on the WWW under https://doi.org/10.1002/ejoc.202000956.
We next investigated the rhodium-catalyzed 1,4-addition of
organotin reagent 10a to cyclohexenone (9a) using 5.0 mol-%
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Figure 2. Cyclooctene ligands.
ones and other organotin reagents investigated did not provide
the corresponding products under these conditions (see
Scheme S2 in the Supporting Information for details). The abso-
lute configurations of 11 were determined by comparing their
[
11]
optical rotation with literature values
Information for details).
(see the Supporting
Figure 1. Synthesis and ORTEP drawing of platinum complex 8.
of 7a.[10] The reaction proceeded in toluene and ethanol with
promising enantioselectivities, while product 11aa was not ob-
tained in 1,4-dioxane (Table 1, entries 1–3). The enantioselec-
tivities were further improved using 10 mol-% of 7a (Table 1,
entries 4 and 5). In addition, reactions with cyclooctene ligands
1
2 and 13 did not provide any products (Table 1, entries 6
and 7); the trans-cyclooctene framework bearing an additional
coordinating group (i.e., pyridyl) was found to be essential for
generating an active catalytic species. Furthermore, even higher
loadings of 7a also led to higher enantioselectivities (Table 1,
entries 8–10). Cyclooctene ligands see Figure 2.
Table 1. Performance of cyclooctene ligands in rhodium-catalyzed asymmet-
[
a]
ric 1,4-additions.
Scheme 2. Reactions with various organotin reagents and substrates.
On the basis of the absolute configurations of the obtained
[
3,12]
products and previous studies,
these reactions are pro-
posed to proceed through the formation of the rhodium com-
plexes shown in Scheme 3. The pyridyl group and the alkene
constitute a bidentate ligand; the enone approaches syn to the
trans-cyclooctene moiety, and the asymmetric environment
around the reaction site is constructed by the trans-cyclooctene
framework (highlighted in red and blue in Scheme 3), noting
that the methylene group (R = H) is sterically bulkier than a
hydrogen atom. Therefore, the enone preferentially approaches
in a manner that avoids the bulkier group, which results in high
enantioselectivity.
Entry Ligand
Loading of 7 [mol-%] Solvent
Yield [%][b] ee [%]
1
2
3
4
5
6
7
8
9
7a
7a
7a
7a
7a
12
13
7a
7a
7a
5
1,4-dioxane
< 5
9
8
–
5
5
toluene
EtOH
71
77
78
80
–
10
10
10
10
15
20
25
toluene
EtOH
EtOH
EtOH
EtOH
8
10
< 5
< 5
7
[c]
–
84
86
84
EtOH
EtOH
6
13
10
[
(
[
2 4 2 2
a] Reactions were run using 9a (0.25 mmol), 10a (0.28 mmol), [RhCl(C H ) ]
0.0063 mmol), NaOMe (0.013 mmol), and the ligand in the solvents (1.0 mL).
b] NMR yields. [c] A racemate of 13 was used.
Other enones and organotin reagents were also reacted us-
ing 10 mol-% of 7a in ethanol (Scheme 2). While 11ba and
Scheme 3. Proposed reaction pathway.
1
1
1ca were formed with moderate ee, cycloheptenone (9c) gave
1ca with higher enantioselectivity (84 % ee). In addition, the
This mechanistic insight inspired us to introduce substituents
electron-poor reagent 10b provided the corresponding product at the allylic position (R ≠ H) in order to further improve enan-
1ab in slightly higher enantioselectivity, but the electron-rich tioselectivity; hence, ligands 7b and 7c were synthesized, and
reagent 10c did not give useful amounts of 11ac. Acyclic en- the reactions of 9a and 9c with these ligands were investigated
1
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Scheme 4).[13] As expected, enantioselectivities were improved
[1] W. C. Zeise, Poggendorffs Ann. Phys. 1827, 9, 632.
(
[
2] a) A. D. Walsh, Nature 1947, 159, 712; b) M. J. S. Dewar, Bull. Soc. Chim.
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L. A. Duncanson, J. Chem. Soc. 1953, 2939; f) J. Chatt, L. A. Duncanson,
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Angew. Chem. 2020, 132, 8408.
in all cases, and especially for the reaction of 9c with 7b, which
afforded 9c with 93 % ee, suggesting that these trans-cyclooct-
[
14]
enes are appropriately designed asymmetric ligands.
[
3] For selected reviews, see: a) C. Defieber, H. Grützmacher, E. M. Carreira,
Angew. Chem. Int. Ed. 2008, 47, 4482; Angew. Chem. 2008, 120, 4558; b)
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1
26, 1628; g) W.-L. Duan, H. Iwamura, R. Shintani, T. Hayashi, J. Am. Chem.
Soc. 2007, 129, 2130; h) C. Defieber, M. A. Ariger, P. Moriel, E. M. Carreira,
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Winkler, J. Am. Chem. Soc. 1963, 85, 3276.
[
Scheme 4. Reactions using 7a and 8-substituted trans-cyclooctene ligands
7b and 7c.
[
5] F.-W. Grevels, V. Skibbe, J. Chem. Soc., Chem. Commun. 1984, 681.
In summary, we demonstrated that trans-cyclooctenes serve
[6] S. Einaru, K. Shitamichi, T. Nagano, A. Matsumoto, K. Asano, S. Matsubara,
Angew. Chem. Int. Ed. 2018, 57, 13863; Angew. Chem. 2018, 130, 14059.
as asymmetric ligands in the rhodium-catalyzed 1,4-additions
of organotin reagents to enones. These chiral olefins provide
high enantioselectivities and can create efficient coordination
spheres for asymmetric metal catalysis. Although further studies
are required to improve catalytic activity, these findings offer
new avenues for the design of novel asymmetric metal cata-
lysts. Studies into more sophisticated ligands and applications
to a variety of metal catalysts are currently underway in our
laboratory.
[
7] a) E. Vedejs, K. A. J. Snoble, P. L. Fuchs, J. Org. Chem. 1973, 38, 1178;
b) K. J. Shea, J.-S. Kim, J. Am. Chem. Soc. 1992, 114, 3044.
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6632.
[
[9] Deposition Numbers 2024941–2024942 contain the supplementary crys-
tallographic data for this paper. These data are provided free of charge
by the joint Cambridge Crystallographic Data Centre and Fachinforma-
tionszentrum Karlsruhe Access Structures service www.ccdc.cam.ac.uk/
structures.
[10] Although 1,4-addition using phenylboronic acid was also investigated,
the enantioselectivity was much lower than that obtained using the
organotin reagents. See Scheme S1 in the Supporting Information for
details.
Acknowledgments
[
[
[
11] a) Y. Suzuma, S. Hayashi, T. Yamamoto, Y. Oe, T. Ohta, Y. Ito, Tetrahedron:
Asymmetry 2009, 20, 2751; b) G. Chen, J. Gui, L. Li, J. Liao, Angew. Chem.
Int. Ed. 2011, 50, 7681; Angew. Chem. 2011, 123, 7823.
We thank Dr. Hiroyasu Sato (RIGAKU) and Professor Takuya Kura-
hashi (Kyoto University) for X-ray crystallographic assistance. This
work was supported financially by the Japanese Ministry of Edu-
cation, Culture, Sports, Science and Technology (JP15H05845,
JP16K13994, JP17K19120, JP18K14214, JP18H04258, and
JP20K05491). K.A. also acknowledges Tokyo Institute of Technol-
ogy Foundation, the Naito Foundation, Research Institute for
Production Development, the Tokyo Biochemical Research Foun-
dation, the Uehara Memorial Foundation, the Kyoto University
Foundation, the Institute for Synthetic Organic Chemistry, Toyo
Gosei Memorial Foundation, the Sumitomo Foundation, Fuku-
oka Naohiko Memorial Foundation, Inoue Foundation for
Science, and Mizuho Foundation for the Promotion of Sciences.
12] Small nonlinear effects were observed (see Scheme S3 in the Supporting
Information for details), consistent with a previous report that used chiral
phosphine-olefin ligands. See ref.[
3g]
.
13] trans-Cyclooctene ligand 7d bearing a 2-methylbenzyl group was also
synthesized and investigated. See Scheme S4 in the Supporting Informa-
tion for details.
[14] trans-Cyclooctene to cis-cyclooctene isomerization was also detected at
the end of these catalytic reactions, and may be one of the reasons for
the observed low chemical yields. As 7a isomerizes faster at higher load-
ings, isomerization may be caused by the coordination of two molecules
of 7a to a rhodium center. Actually, the isomerizations of 7b and 7c
were suppressed to some extent, and the yields from the reactions cata-
lyzed by 7b and 7c were slightly higher than those catalyzed by 7a
(
Scheme 4), which suggests that the bulkiness of the ligand also inhibits
the extra coordination of 7 in addition to constructing a better asymmet-
ric environment. See Scheme S5 in the Supporting Information for de-
tails.
Keywords: trans-Cyclooctene · Planar chirality · Chiral
ligands · Rhodium · 1,4-Addition
Received: July 8, 2020
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Communication
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Asymmetric Catalysis
T. Nagano, S. Einaru, K. Shitamichi,
K. Asano,* S. Matsubara* ................ 1–4
trans-Cyclooctenes as Chiral Ligands
in Rhodium-Catalyzed Asymmetric
trans-Cyclooctenes serve as asymmet- coordination spheres for asymmetric
ric ligands during the rhodium-cata- metal catalysis are demonstrated for
lyzed 1,4-additions of organotin rea- the first time. These findings provide
gents to enones. The potentials of chiral frameworks for the design of
these chiral olefins to provide efficient asymmetric ligands for metal catalysts.
1,4-Additions
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