Synthesis of Chiral Polyamides Containing an (R,R)-1,2-Diphenylethylenediamine Monosulfonamide Structure and Their Application to Asymmetric Transfer Hydrogenation Catalysis

Article abstract of DOI:10.1002/cctc.201601220

A chiral main-chain polyamide containing an (R,R)-1,2-diphenylethylenediamine monotoluenesulfonamide (TsDPEN) repeating unit was prepared. Polycondensation of dicarboxylic acid dichloride with the chiral bisaniline of N-tert-butoxycarbonyl-protected TsDPE

Full text of DOI:10.1002/cctc.201601220

Accepted Article
Title: Synthesis of chiral polyamides containing a (R,R)-1,2-
diphenylethylenediamine monosulfonamide structure and their
application to asymmetric transfer hydrogenation catalysis
Authors: Shinichi Itsuno and Shotaro Tkahashi
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10.1002/cctc.201601220
ChemCatChem
COMMUNICATION
Synthesis of chiral polyamides containing a (R,R)-1,2-
diphenylethylenediamine monosulfonamide structure and their application
to asymmetric transfer hydrogenation catalysis
Shinichi Itsuno,*[a] and Shotaro Takahashi[a]
Abstract: A chiral main-chain polyamide containing a (R,R)-1,2-
diphenylethylenediamine monotoluenesulfonamide (TsDPEN) repeat
unit was prepared. Polycondensation of dicarboxylic acid dichloride
Polymeric chiral ligands prepared from TsDPEN monomer and
amphiphilic achiral monomers, followed by complexation with
transition metals, showed high catalytic activity in asymmetric
with the chiral bisaniline of N-Boc-protected TsDPEN was successful, transfer hydrogenation.[12d,15] Interestingly, chiral main-chain
affording a chiral polyamide with TsDPEN repeat unit as the chiral
ligand structure. Treatment of the main-chain polymer chiral ligand
with transition metal complexes, such as [IrCl2Cp*]2, [RhCl2Cp*]2,
and [RuCl2(p-cymene)]2, afforded polymer chiral metal complexes.
Asymmetric transfer hydrogenation of a cyclic sulfonamide was
efficiently catalyzed by the chiral TsDPEN polymer–metal complex,
giving an optically active cyclic sulfonylamine in quantitative
conversion with high enantioselectivities. The polymer catalyst was
easily recovered from the reaction mixture and reused several times
without any loss in catalytic activity and enantioselectivity.
polymers containing TsDPEN ligands as repeat units have not
been synthesized. The introduction of a functional group onto
TsDPEN phenyl group is necessary for this purpose. We
previously synthesized (R,R)-N,N’-di(tert-butoxycarbonyl)-1,2-
bis(p-hydroxyphenyl)-1,2-diaminoethane (dihydroxy DPEN),
followed by the introduction of 4-vinylbenzyl ether, which was
then polymerized under radical polymerization conditions to
obtain polymeric chiral (R,R)-1,2-diphenylethylenediamine
(DPEN) ligands.[16] This chiral polymer was successfully used as
a chiral ligand in ketone-hydrogenation catalysts. However, the
synthesis of dihydroxy DPEN is tedious and low yielding,
requiring optical resolution of racemic dihydroxy DPEN after
separation of the meso compound. We also attempted the direct
introduction of functionality onto the phenyl ring of chiral DPEN,
which is commercially available, but all attempts at phenyl ring
halogenation failed.[17] We then decided to introduce amino
groups on both phenyl groups in TsDPEN. Nitration followed by
reduction successfully yielded a bisamino-DPEN derivative.
Using these aromatic amino functionalities, polycondensation
with diacid dichloride has been investigated. This is the first
example of the synthesis of main-chain TsDPEN polymers. The
chiral polyamides containing a TsDPEN repeat unit in their main
chain were subsequently investigated as polymer ligands for
catalysts of the asymmetric transfer hydrogenation of cyclic
sulfonimines.
Chiral synthetic polymers have attracted much attention due to
their unique properties, such as chiroptical properties, and their
applications, including asymmetric catalysis[1] and chiral
separation chemistry.[2,3] In asymmetric catalysis, the
immobilization of chiral catalysts onto solids, such as crosslinked
polystyrene[4,5] and silica,[6] has been frequently used to prepare
recoverable heterogeneous catalysts for asymmetric synthesis.
In addition to their easy recoverability and reusability, polymer
chains can provide specific chiral catalyst conformations in their
microenvironment, which sometimes increase the reactivity and
stereoselectivity in asymmetric reactions.[7] More precise control
of the microenvironment might be possible with chiral polymers
containing chiral catalyst sites in their main chain structure,
instead of side chain immobilization. Recently, some main-chain
chiral polymers have been synthesized and used as polymeric
chiral ligands or catalysts.[8,9]
The first step of chiral TsDPEN monomer synthesis was the
introduction of nitro groups onto the phenyl rings of DPEN.
Conventional nitration of the phenyl rings of DPEN proceeded
smoothly to afford bis(m-nitrophenyl)-1,2-diaminoethane 1, as
shown in Scheme 1.[18] Sulfonamide formation was then
conducted at one of the amino groups in 1, giving 2 (Scheme 2).
Another amino group in 2 was then Boc-protected to afford 3.
The nitro groups in 3 were then hydrogenated to amines, giving
chiral bisaniline 4, which was the monomer for polymerization.
Asymmetric transfer hydrogenation is a promising method
for the generation of chiral alcohols and amines. TsDPEN–
transition
metal
complexes
as
asymmetric
transfer
hydrogenation catalysts, first discovered by Ikariya and Noyori in
1995, are some of the most powerful catalysts for the
asymmetric reduction of C=O[10] and C=N.[11] Polymer-
supported[12] and silica-supported variants[13] of TsDPEN have
been developed, some of which showed high levels of catalytic
activity and enantioselectivity. We have also developed
crosslinked polymer-immobilized TsDPENs, which were
complexed with [IrCl2Cp*] to give polymeric chiral catalysts.[14]
[a]
Prof. Dr. S. Itsuno, S. Takahshi
Department of Environmental & Life Sciences
Toyohashi University of Technology
Tempaku-cho, Toyohashi 441-8580 Japan
E-mail: itsuno@ens.tut.ac.jp
Supporting information for this article is given via a link at the end of
the document.
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10.1002/cctc.201601220
ChemCatChem
COMMUNICATION
7a in DMSO-d6. At least 88% of the Boc groups were removed
by TFA treatment. However, 6a is soluble in high-polarity
solvents, such as DMSO and DMF. The molecular weights of 6
were determined by size-exclusion chromatography (SEC)
measurements of DMF solutions. In most cases, the
deprotection of
6 proceeded well in CH2Cl2, giving the
corresponding TsDPEN polymers in high yields (Table 1). The
molecular weights of the TsDPEN polymers synthesized using
this polymerization method were higher than 10,000.
Scheme 1. Synthesis of bis(m-nitrophenyl)-1,2-diaminoethane 1.
Scheme 3. Polymerization of 4 and dicarboxylic acid dichloride 5.
Scheme 2. Synthesis of chiral bisaniline monomer 4.
Polyamides are widely recognized for their excellent thermal,
mechanical, and chemical properties.[19] One typical polyamide
synthesis is the reaction of a diamine and dicarboxylic acid
dihalide.[20] For example, aramid (aromatic polyamide) fibers
have been prepared using this method.[21] Therefore, chiral
bisaniline monomer 4 was allowed to react with adipoyl chloride
(R = (CH2)4) to afford chiral polyamide 6a in high yield with a
molecular weight (Mn) of 12,200 (Scheme 3, Table 1, entry 1).
Several other dicarboxylic acid dichlorides (5) were also used as
comonomers in the chiral polymerization with TsDPEN monomer
4, as summarized in Table 1. Both aliphatic and aromatic
dicarboxylic acid dichlorides easily reacted with 4 to afford
corresponding chiral polymers 6 with high molecular weights.
After polymerization, Boc groups in the chiral polymers (6) were
removed using trifluoroacetic acid (TFA) in CH2Cl2 (Scheme 4).
In some cases, due to chemical modification of the high-
molecular-weight polymer, some Boc groups remained intact in
the polymer main chain after TFA treatment. For example, chiral
polymer 6a showed poor solubility in common organic solvents,
such as CH2Cl2, ethyl acetate, diethyl ether, and hexane;
therefore, the deprotection of 6a was achieved under
heterogeneous suspension conditions. The degree of
deprotection was confirmed by the 1H-NMR spectrum of polymer
Scheme 4. Preparation of chiral polymer Ir complex 8.
Table 1. Yield and gel permeation chromatography (GPC)
characterization of chiral polymers 6.
Polymeric
ligand [a]
Yield
%
[c]
-R-
Mn
Mw
Mw/Mn
[b]
6a
82
12,200
21,900
1.79
6b
6c
88
97
13,300
10,200
33,800
15,400
2.54
1.50
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COMMUNICATION
Table 2. Asymmetric transfer hydrogenation using Iridium
complex.[a]
6d
6e
94
76
6,800
13,600
25,200
1.99
1.99
entry
Ligand
TsDPEN
7a
Time h
Yield %[b]
Ee %[c]
89
12,700
1
2
3
4
5
6
7
10 min
91
92
76
96
80
92
81
1
1
1
1
1
1
90
6f
91
14,700
45,000
3.07
7b
87
7c
89
[a] Polymerized in DMF at 100 °C for 24 h. [b] Isolated yield. [c] Determined
by SEC (polystyrene standards) using DMF as an eluent at a flow rate of 1.0
mLmin-1 at 40 °C.
7d
89
7e
89
Based on the degree of deprotection in chiral polymers 7, a
transition metal complex was added to suspensions of 7 in
CH2Cl2 to form chiral polymeric transition metal complexes.
Preparation of the Ir complex of 7 is illustrated in Scheme 4.
During the reaction, the orange color of the Ir complex, dichloro-
(pentamethylcyclopentadienyl)iridium(III) dimer [IrCl2Cp*]2, in
CH2Cl2 solution completely disappeared and yellow polymer–Ir
complex 8 was obtained.
7f
87
[a] All reactions were carried out in HCOOH/Et3N (5:2, v/v, 5 equiv.
relative to 9) with a substrate/catalyst mole ratio (S/C) of 100 in 1 mL of
CH2Cl2 at rt. [b] Isolated yield. [c] Determined by HPLC analysis with
Daicel Chiralcel OD-H column. Major products had R configurations in all
cases.
In order to evaluate the catalytic activity of the chiral
polymer–Ir complexes, we chose the enantioselective hydrogen
Another polymer chiral catalyst was prepared from
transfer reaction of cyclic sulfonimine
9 to chiral cyclic
dichloro(pentamethylcyclopentadienyl)rhodium(III)
dimer
sulfonylamine 10 (Scheme 6). Cyclic sulfonimine 9 was easily
prepared from saccharine (Scheme 5).[22] In the presence of
polymeric chiral catalyst 8a, the reaction proceeded smoothly in
CH2Cl2. Cyclic sulfonimine 9 was completely converted to 10
with quantitative conversion within 1 h at room temperature. As
shown in Table 2, the enantioselectivity of 90% (entry 2)
obtained with 8a was almost equal to that obtained using the
original DPEN monosulfonamide–Ir complex (89% ee) (entry 1).
Other polymer–Ir catalysts prepared from polymer ligands (7a–
7f) showed similar performance in the asymmetric transfer
hydrogenation of 9 (entries 3–7).
[RhCl2Cp*]2. Polymeric Rh complexes prepared from 7 and
[RhCl2Cp*]2 were successfully applied to the asymmetric transfer
hydrogenation of 9. Compared with Ir complexes, polymeric Rh
complexes required longer reaction times to afford product 10
with lower enantioselectivities (Table 3). Ru complexes were
also prepared from chiral polymer ligands 7 and dichloro(p-
cymene)ruthenium(II) dimer [RuCl2(p-cymene)]2. As shown in
Table 4, the chiral polymer Ru complexes were efficient
catalysts in the same asymmetric reaction, giving chiral cyclic
sulfonylamine 10 with high enantioselectivities (>90% ee).
Compound 7a, prepared from adipoyl chloride, containing a C4
alkylene chain, always gave higher enantioselectivities than the
other polymer catalysts (Table 2, entry 2; Table 3, entry 1; Table
4, entry 1), indicating that appropriate flexible linker structures
might be suitable in chiral polymer catalysts. Notably, polymer
catalysts prepared from 7f, containing a rigid biphenyl linker,
gave relatively low enantioselectivities (Table 2, entry 7; Table 3,
entry 6; Table 4, entry 6).
Scheme 5. Preparation of cyclic sulfonamide.
Table 3. Asymmetric transfer hydrogenation using Rhodium complex.[a]
entry
Ligand
Time h
Yield %[b]
Ee %[c]
1
2
3
4
5
6
7a
7b
7c
7d
7e
7f
5
3
3
3
2
3
71
84
81
73
89
81
58
51
52
53
53
45
Scheme 6. Asymmetric transfer hydrogenation of cyclic sulfonamide.
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10.1002/cctc.201601220
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[a] All reactions were carried out in HCOOH/Et3N (5:2, v/v, 5 equiv.
relative to 9) with S/C=100 in 1 mL of CH2Cl2 at rt. [b] Isolated yield. [c]
Determined by HPLC analysis with Daicel Chiralcel OD-H column. Major
products had R configurations in all cases.
Table 4. Asymmetric transfer hydrogenation using Ruthenium
complex.[a]
entry
Ligand
7a
Time h
14
Yield %[b]
Ee %[c]
95
Scheme 7. Asymmetric transfer hydrogenation of acetophenone.
1
2
3
4
5
6
82
90
74
79
88
87
7b
12
93
In conclusion, a novel chiral polymer ligand was successfully
synthesized using a polycondensation method. This was the first
synthesis of a chiral main-chain polymer ligand with a TsDPEN
structure. The chiral polymer formed transition metal complexes
with Ir, Rh, and Ru. These chiral polymer–metal complexes
showed catalytic activity in the asymmetric transfer
hydrogenation of a cyclic sulfonimine and acetophenone, with
high enantioselectivities observed. These polymeric catalysts
were easily separated from the reaction mixture and reused
several times without any loss in catalytic activity or
enantioselectivity. As TsDPEN and its derivatives are known to
be excellent chiral ligands in catalysts of various asymmetric
reactions, the polymers developed in this study should find
further application as ligands in alternative asymmetric catalytic
transformations.
7c
12
90
7d
10
93
7e
10
93
7f
10
90
[a] All reactions were carried out in HCOOH/Et3N (5:2, v/v, 5 equiv. relative to
9) with S/C=100 in 1 mL of CH2Cl2 at rt. [b] Isolated yield. [c] Determined by
HPLC analysis with Daicel Chiralcel OD-H column. Major products were R
configurations in all cases.
Since the polymeric catalysts formed an insoluble
suspension in CH2Cl2, they were easily separated from the
reaction mixture by simple filtration. We confirmed that the
filtrate had no catalytic activity in the reaction.[23] The recovered
polymer powder was reused in subsequent reactions, without
any loss in catalytic activity or enantioselectivity. Polymeric
catalyst 8a could be reused at least four times (Table 5).
Acknowledgements
The authors would like to thank Dr. Naoki Haraguchi at the
Toyohashi University of Technology for useful discussions. This
work is financially supported by JSPS KAKENHI Grant Number
JP15H00732, JP15K05517.
Table 5. Reuse of 8a in the asymmetric transfer hydrogenation of 9.[a]
Cycle
Time h
Yield %[b]
Ee %[c]
90
1
2
3
4
5
1
1
1
2
2
92
89
88
94
92
Keywords: 1,2-diphenylethylenediamine • chiral polyamide •
asymmetric transfer hydrogenation • transition metal catalyst •
polymer catalyst
91
91
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[24]
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Shinichi Itsuno,* Shotaro Takahashi
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Synthesis of chiral polyamides
having (R,R)-1,2-
diphenylethylenediamine
monosulfonamide structure and
their application to Asymmetric
transfer hydrogenation catalysis
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