Planar Chiral Cyclic (Amino)(ferrocenyl)carbene as Ligand for Transition Metals

Article abstract of DOI:10.1002/adsc.201600999

Planar chiral ferrocene-fused iminium salts were synthesized in enantiomerically pure form. The novel planar chiral cyclic (amino)(ferrocenyl)carbene successfully generated from such salt was subjected to carbene trapping experiments with sulfur and copper chloride. The utility of the carbene as a chiral ligand for transition metals was preliminarily demonstrated in the copper-catalyzed enantioselective β-boration of an α,β-unsaturated ester. (Figure presented.).

Full text of DOI:10.1002/adsc.201600999

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DOI: 10.1002/adsc.201600999
Planar Chiral Cyclic (Amino)(ferrocenyl)carbene as Ligand for
Transition Metals
a
a
a,b,
Risa Yasue, Masaru Miyauchi, and Kazuhiro Yoshida *
a
Department of Chemistry, Graduate School of Science, Chiba University, Yayoi-cho, Inage-ku, Chiba 263-8522, Japan
Fax : (+81)-43-290-2790; phone: (+81)-43-290-2790; e-mail: kyoshida@faculty.chiba-u.jp
Molecular Chirality Research Center, Chiba University, Yayoi-cho, Inage-ku, Chiba 263–8522, Japan
b
Received: September 8, 2016; Revised: November 2, 2016; Published online: && &&, 0000
Supporting information for this article can be found under: http://dx.doi.org/10.1002/adsc.201600999.
Abstract: Planar chiral ferrocene-fused iminium
salts were synthesized in enantiomerically pure
form. The novel planar chiral cyclic (amino)(ferro-
cenyl)carbene successfully generated from such salt
was subjected to carbene trapping experiments with
sulfur and copper chloride. The utility of the car-
bene as a chiral ligand for transition metals was
preliminarily demonstrated in the copper-catalyzed
enantioselective b-boration of an a,b-unsaturated
ester.
delight, just as we had expected, the new Ir complex
prepared from 2 was an excellent catalyst precursor
for the Ir-catalyzed asymmetric transfer hydrogena-
[
6]
tion of ketones.
In the course of development of new types of chiral
NHCs with different rigid chiral environments, we
have studied the synthesis of iminium salts 5 having
[7,8]
a planar chiral ferrocene structure (Scheme 1b).
Although cyclic (amino)(ferrocenyl)carbenes 6 gener-
ated from 5 seemed to belong to the cyclic (amino)-
AHCTUNGTNERN(GU aryl)carbenes that have only one nitrogen atom to
[9]
Keywords: asymmetric synthesis; chiral N-heterocy-
clic carbenes (NHCs); copper; planar chirality
stabilize the carbene atom, we had expected an ad-
[
10]
ditional stabilization of the carbene atom by the ad-
jacent ferrocenyl group at the beginning of this
[
11,12]
study.
In addition, we envisioned that 6 would
have an attractive chiral environment due to its struc-
tural similarity to ferrocene-fused 4-dialkylaminopyri-
N-heterocyclic carbenes (NHCs) are multipotent mol- dines (Fc*-DAAPs), which are well-known nucleo-
[13]
ecules that can be used in organocatalysis and transi- philic asymmetric organocatalysts developed by Fu.
[
1]
tion metal catalysis. As ligands for transition metal Herein we report our results: the stereoselective syn-
catalysis, NHCs are often compared with phosphines,
and it is no longer unusual that the former shows
higher performance than the latter. However, as re-
gards enantioselective reactions using optically active
chiral ligands, the number of successful examples
using NHCs compares rather unfavorably with that
using phosphines. It seems that the design concept of
chiral phosphine ligands, which has been accumulated
over the years, cannot be simply applied to chiral
NHCs. Fundamental structural differences exist be-
tween cone-shaped phosphines and wedge-shaped
[2]
NHCs.
In 2010, we reported a modular synthesis of chiral
bicyclic imidazolium salts 2, which are precursors of
optically active cyclic diaminocarbenes 3, from newly
[
3,4]
prepared imidazoles 1 (Scheme 1a).
We had ex-
pected that the fused bicyclic molecular structure with
a rigid chiral environment would reflect superior
Scheme 1. Modular synthesis of carbene precursors (2 and
asymmetric induction ability when NHCs generated 5) and their conversion into the corresponding carbenes (3
[
5]
from these salts were used as chiral ligands. To our and 6).
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thesis of new chiral module 4, its conversion into car- pare free carbene (R)-6a from (R)-5a by simple de-
bene precursors 5, trapping experiments of generated protonation with NaHMDS. Contrary to our expecta-
1
carbene 6 with sulfur and copper chloride, and the tion, H NMR experiments in THF-d indicated that
8
preliminary result of an enantioselective reaction cat- 6a was not isolable and decomposed to a complex
alyzed by a copper complex bearing 6 as the new mixture even at low temperature, suggesting the ab-
chiral NHC ligand.
sence of additional stabilization of the carbene atom
Recently, in a joint research project, we have re- by the adjacent ferrocenyl group
(6 in
[
11,12]
ported a stereoselective synthesis of Fc*-DAAPs Scheme 1b).
where Kaganꢁs chiral acetal (À)-7 was employed as indirectly confirmed by carbene trapping experiments
However, the generation of 6a was
[
14]
[
15]
the starting material.
That study motivated us to (Scheme 3). The addition of sulfur or copper chloride
use (À)-7 also in the present study as the starting ma-
terial for synthesizing the new chiral module 4
(
Scheme 2). After the conversion of (À)-7 into iodo-
[14b]
ferrocene 8 via diastereoselective ortho-lithiation,
the Mizoroki–Heck reaction of 8 with acrylamide was
performed to give coupling product 9. Then, the
carbon-carbon double bond and the amide group of
the side chain of 9 were reduced at once with LiAlH4
to afford primary amine 10. Subsequent acetal hydrol-
ysis of 10 followed by a spontaneous intramolecular
cyclization reaction successfully provided the ferro-
cene-fused cyclic aldimine (R)-(À)-4.
Scheme 3. Carbene trapping experiments.
to a mixture of 5a and NaHMDS at À788C resulted
in the formation of sulfur adduct 12a or copper com-
[
16,17]
plex 13a, respectively.
Sulfur adduct (R)-(+)-12a
was obtained as a quite stable crystalline solid and its
structure was unambiguously determined by single-
[
18]
crystal X-ray diffraction analysis (Figure 1). On the
other hand, 13a was found to be an air-sensitive cat-
ionic bis-carbene copper complex, and its structure
[
19,20]
was determined by HR-MS experiments.
Scheme 2. Stereoselective synthesis of (R)-(À)-4.
The catalytic activity of the copper complex was ex-
amined in the enantioselective b-boration of an a,b-
[
21]
With the desired compound in hand, the conversion unsaturated ester (Scheme 4). To our delight, (R)-
of 4 into various carbene precursors 5 and 11 was per- 13a showed good catalytic activity for the reaction,
formed (Table 1). Whereas the introduction of an iso- giving the chiral product in 80% ee. The preliminary
propyl group or a mesityl group on the nitrogen atom result clearly indicates the potential utility of the new
required high temperatures (entries 1 and 5), the in- carbene as a chiral ligand for transition metals.
troduction of benzyl-type groups proceeded even at
In conclusion, we have developed a modular syn-
ambient temperature (entries 2–4 and 7). In compari- thesis of iminium salts 5 having a planar chiral ferro-
son with imidazole 1, the nucleophilicity of 4 is con- cene structure. The chiral cyclic (amino)(ferrocenyl)-
siderably high to enable the introduction of many carbene was prepared for the first time from a salt
[
3]
substituents on the nitrogen atom.
and its existence was confirmed by carbene trapping
As we were interested in the generation of car- experiments. The utility of the carbene as a chiral
benes from the iminium salts, we attempted to pre- ligand was successfully demonstrated in a Cu-cata-
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[a]
Table 1. Modular synthesis of iminium salts (R)-(À)-5 and (R,R)-(À)-11 from (R)-(À)-4.
[
[
a]
b]
All reactions were carried out in CH CN, DMF, or toluene at room temperature to 1008C.
Isolated yield after reprecipitation.
3
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characterized by comparison of the spectroscopic data with
[22] 1
those reported previously;
H NMR: d=1.45 (s, 9H), 2.63
(
dd, J=16.4, 4.4 Hz, 1H), 2.70 (dd, J=16.8, 8.8 Hz, 1H),
3
7
.47 (d, J=3.6 Hz, 1H), 5.08 (dt, J=8.0, 3.6 Hz, 1H), 7.25–
19
.29 (m, 1H), 7.32–7.39 (m, 4H); [a] : À28.4 (c 0.1, CHCl ).
D
3
The enantiomeric excess of 15 was determined by HPLC
analysis with a chiral stationary phase column [Daicel Chir-
À1
alcel As-H, hexane/i-PrOH=100/1, 0.3 mLmin ]: t =
R
4
3.6 min (R), t =47.9 min (S).
S
Acknowledgements
We appreciate the financial support in the form of a Grant-
in-Aid for Scientific Research from the Ministry of Educa-
tion, Culture, Sports, Science and Technology, Japan (Grant
Figure 1. Crystal structure of (R)-(+)-12a.
#
15K05494).
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Planar Chiral Cyclic (Amino)(ferrocenyl)carbene as Ligand
for Transition Metals
Adv. Synth. Catal. 2017, 359, 1 – 6
Risa Yasue, Masaru Miyauchi, Kazuhiro Yoshida*
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