Metallacrown ether catalysts containing phosphine-phosphite polyether ligands for Rh-catalyzed asymmetric hydrogenation - Enhancements in activity and enantioselectivity

Article abstract of DOI:10.1002/ejoc.201402735

A new class of tunable metallacrown ether rhodium catalysts based on α,ω-(phosphine-phosphite) polyether ligands were prepared either by a template-induced method or by a nontemplate procedure. For the asymmetric hydrogenation of α-arylenamides with the a

Full text of DOI:10.1002/ejoc.201402735

FULL PAPER
DOI: 10.1002/ejoc.201402735
Metallacrown Ether Catalysts Containing Phosphine–Phosphite Polyether
Ligands for Rh-Catalyzed Asymmetric Hydrogenation – Enhancements in
Activity and Enantioselectivity
Feng-Tao Song,[a] Guang-Hui Ouyang,[a] Yong Li,[a,b] Yan-Mei He,*[a] and
Qing-Hua Fan*[a]
Keywords: Asymmetric catalysis / Hydrogenation / Supramolecular chemistry / Crown compounds / Rhodium
A new class of tunable metallacrown ether rhodium catalysts
based on α,ω-(phosphine–phosphite) polyether ligands were
prepared either by a template-induced method or by a non-
template procedure. For the asymmetric hydrogenation of α-
arylenamides with the addition of K+ cations, the ortho-di-
comparable to or better than the results obtained for phos-
phine–phosphite ligands with two or more chiral elements.
Remarkable enhancements in enantioselectivity and notice-
ably increased catalytic activity were achieved through the
supramolecular recognition between K+ cations and the
phenylphosphine-substituted metallacrown ether catalyst metallacrown ether catalyst.
showed high enantioselectivities (up to 99%ee), which are
Later, Vidal-Ferran and co-workers reported a similar chi-
Introduction
ral bis(phosphite)-containing metallacrown ether catalyst
bearing a 1,1Ј-biphenyl unit in the oligo(ethylene glycol)
backbone. This catalyst was successfully applied in the
Rh-catalyzed asymmetric hydroformylation of terminal ole-
fins with an increase of up to 62%ee caused by the addition
of CsBArF.[2l] On the basis of these successes, we anticipate
that such a strategy could be extended to other bidentate
ligands, including heterobidentate ligands containing a
poly(ether) linkage. However, the preparation of metalla-
crown ethers bearing different coordinating groups is still
challenging. To the best of our knowledge, no successful
example has been reported.
The enantiopure phosphine–phosphite ligands represent
a class of tunable and nonsymmetric chiral phosphorus li-
gands with binding groups that differ in their electronics
and sterics, diverse carbon backbones with varied linkages
of different distances, and a variety of stereogenic ele-
ments.[4] These ligands are accessible by standard covalent
chemistry[5] or supramolecular interactions[6] and have been
extensively studied in asymmetric catalysis such as hydro-
formylation, copper-mediated conjugate additions, palla-
dium-mediated allylic substitutions and, particularly, the
asymmetric hydrogenation of functionalized alkenes and
prochiral imines. High efficiency and enantioselectivity have
usually been achieved by utilizing such phosphine–phos-
phite ligands with more than one chiral element.[4a] How-
ever, for enamide substrates, rather few phosphine–phos-
phite/metal catalysts have been found to be highly enantio-
selective in the asymmetric hydrogenation.[5a,5b,5g,6c] Con-
sidering the widespread application of phosphine–phos-
phite ligands[4a] and as a continuation of our ongoing en-
Owing to their unique features of selective recognition
and structural tunability upon supramolecular regulation,
metallacrown ethers have received extensive attention in re-
cent years.[1,2] Among them, monocyclic metallacrown
ethers, which are often formed by the chelation of α,ω-
(multidentate donor) polyether ligands to transition metal
ions, are of great interest as catalysts owing to the potential
bifunctionality of such hard–soft dimetallic complexes. The
introduction of a macrocyclic crown ether skeleton with se-
lective binding properties into the catalyst structure is ex-
pected to result in distinctive catalytic performance involv-
ing a host–guest recognition process.[3] However, to the best
of our knowledge, the application of metallacrown ethers
as catalysts has not been widely studied,[2d,2f–2l] especially
the use of chiral metallacrown ethers in asymmetric cataly-
sis.[2g,2l] Recently, we have developed a new class of readily
available and tunable bis(phosphite) ligands with an oligo-
(ethylene glycol) backbone, and a pronounced enhancement
of enantioselectivity was achieved in the rhodium-catalyzed
asymmetric hydrogenation of α-dehydroamino acid esters by
the addition of NaBArF {BArF = [3,5-(CF3)2C6H3]4B}.[2g]
[a] Beijing National Laboratory for Molecular Sciences, CAS Key
Laboratory of Molecular Recognition and Function, Institute
of Chemistry, University of Chinese Academy of Sciences,
Beijing 100190, P. R. China
E-mail: heym@iccas.ac.cn
fanqh@iccas.ac.cn
http://www.iccas.ac.cn/
[b] Department of Chemistry, Henan Institute of Education,
Zhengzhou 450046, P. R. China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402735.
Eur. J. Org. Chem. 2014, 6713–6719
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
6713

F.-T. Song, G.-H. Ouyang, Y. Li, Y.-M. He, Q.-H. Fan
FULL PAPER
deavor to develop effective chiral supramolecular catalysts the reactions of monohydroxy-substituted triphenylphos-
based on crown ethers,[2g,6h,6i] herein, we report the prepa- phines 1a–1c with monotosylated hexa(ethylene glycol) in
ration of a new class of metallacrown ether catalysts. The the presence of Cs2CO3 afforded 2a–2c in excellent yields.
catalysts were prepared by the intramolecular coordination The α,ω-(phosphine–phosphite) polyether ligands 3a–3c
of achiral phosphine–chiral phosphite ligands with a Rh were readily prepared from the corresponding 2a–2c by the
center in both the presence[7] and absence of a template treatment with the binol-derived phosphorochloridite 4 and
(Scheme 1), and their application in the asymmetric hydro- Et3N as a base in moderate yields. All of these phosphine–
genation of enamides was studied with an emphasis on the phosphite ligands were unambiguously characterized by
elucidation of the effects of host–guest recognition between 1H, 13C, and 31P NMR spectroscopy as well as HRMS
alkali metal cations and metallacrown ether catalysts on the spectrometry. The obtained results are in full agreement
catalytic performance.
with the compounds synthesized. As a control experiment,
the known monophosphite ligand 5 with a septa(ethylene
glycol) monomethyl ether chain was prepared in high yield
by the same method as that for ligands 3.[2g]
With these polyether-linked phosphine–phosphite li-
gands in hand, we first investigated the association of K+
1
cations with the ligands through H and 31P NMR spec-
troscopy studies by mixing the corresponding ligands 3a–
3c with KBArF in dry CD2Cl2 in a 1:1 molar ratio (concen-
1
tration: 11.8 mm). In general, the H NMR signals of the
oxyethylene protons remarkably shifted upfield and wid-
ened owing to the strong shielding effect of the BArF–
1
anion (see Supporting Information).[8] Specifically, the H
NMR spectrum of [K(3a)]BArF showed a dispersed array
of relatively well-defined resonances that differenced greatly
from those of 3a; three sets of multiple peaks with the same
integration were observed in the more upfield region of δ =
Scheme 1. Schematic representation of two synthetic routes to the
chiral metallacrown ether catalysts.
1
2.0–2.6 ppm compared to the H NMR spectra of [K(3b)]
BArF and [K(3c)]BArF. There were also distinct changes in
the aromatic region upon the addition of KBArF. In the
31P{1H} NMR spectra, the addition of KBArF caused pro-
nounced downfield shifts to the signals of the phosphite
Results and Discussion
1. Ligand Synthesis and Association Study with K+ Cations
The designed α,ω-(phosphine–phosphite) polyether li- moiety for all ligands 3a–3c (see Supporting Information).
gands were synthesized by the stepwise coupling of the re- For instance, the phosphite signal for 3a shifted from δ =
spective phosphine or phosphite ligand with a hexa(ethyl- 142.9 to 146.4 ppm upon the addition of KBArF. For the
ene glycol) building block, which was selected according to phosphine moiety, the signal changes for 3a–3c were signifi-
the results of our previous study.[2g] As shown in Scheme 2, cantly different. For 3a, the phosphine signal shifted upfield
Scheme 2. Synthesis of phosphine–phosphite ligands 3a–3c and monophosphite ligand 5.
6714
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6713–6719

Metallacrown Ether Catalysts for Asymmetric Hydrogenation
from δ = –15.8 to –17.4 ppm upon the addition of KBArF; solutions (11.8 mm) before the coordination of the ligand
for 3b and 3c, however, negligible signal changes were ob- to the transition metal ion, the rhodium complexes were
served upon the addition of KBArF. All of these results generated in situ with an equal amount of the metal precur-
suggested that the distinct effect of alkali cation association sor Rh(cod)2BF4 (cod = cyclooctadiene). As expected, two
with 3a was possibly due to the different electronic and sets of double doublet peaks were observed in the 31P NMR
steric properties of the ortho-substituted phosphine ligand. spectra (Figure 1) of Rh/(3b+K) and Rh/(3c+K). Notably,
Furthermore, with 3a as an example, the association con- for Rh/(3a+K), a set of broad double peaks in the down-
stant calculated from the 31P NMR spectroscopy titration field region was observed, probably because of the steric
data by nonlinear data fitting[9] was 68 Ϯ7 m–1 at 25 °C in effect of the ortho substitution. Although the most intense
anhydrous acetone. Furthermore, a 1:1 guest–host ratio was signals in the ESI-HRMS spectrum were assigned to a Rh/
supported by the Job plot analysis (see Figures S1–S3). The 3a species, the peaks for Rh/(3a+K) were also observed
above results qualitatively and quantitatively demonstrated (Figure S4).
the supramolecular binding of K+ cations to the hexa(ethyl-
ene glycol) moiety in the bidentate phosphine–phosphite li-
gands.
2. Preparation and Characterization of Metallacrown
Ethers
Having demonstrated the supramolecular interactions
between K+ cations and the phosphine–phosphite polyether
ligands, which have two terminal ligating groups close to-
gether, we started to investigate the preparation of rhodium
metallacrown ether catalysts by selecting the template meth-
Figure 1. Stacked plot of the 31P NMR spectra (121.5 MHz, 295 K,
11.8 mm in CD2Cl2) of (a) [3a + KBArF] + Rh(cod)2BF4, (b) [3b
od[2g] as the initial procedure. As illustrated in Scheme 1, by
the addition of an equal amount of KBArF into the ligand + KBArF] + Rh(cod)2BF4, and (c) [3c + KBArF] + Rh(cod)2BF4.
Table 1. Summary of the Rh coordination 31P NMR spectroscopic data with and without KBArF.
Ligand + Rh(cod)2BF4
3a + Rh(cod)2BF4
3b + Rh(cod)2BF4
3c + Rh(cod)2BF4
31P NMR [ppm] without KBArF
31P NMR [ppm] with KBArF
126.8 (d, JOP,Rh = 269.1 Hz), 25.7 (dd, JP, Rh
144.8 Hz, JP,OP = 37.2 Hz)
125.9 (dd, JOP,Rh = 265.7 Hz, JOP,P = 37.4 Hz),
33.8 (dd, JP,Rh = 145.2 Hz, JP,OP = 37.4 Hz)
123.2 (dd, JOP,Rh = 266.8 Hz, JOP,P = 38.0 Hz),
29.6 (dd, JP,Rh = 142.3 Hz, JP,OP = 38.0 Hz)
=
127.6 (d, JOP,Rh = 279.6 Hz), 26.6 (dd, JP, Rh
143.5 Hz, JP,OP = 36.5 Hz)
125.8 (dd, JOP,Rh = 265.2 Hz, JOP,P = 37.6 Hz),
33.8 (dd, JP,Rh = 145.4 Hz, JP,OP = 37.6 Hz)
123.1 (dd, JOP,Rh = 267.0 Hz, JOP,P = 37.7 Hz),
29.7 (dd, JP,Rh = 143.2 Hz, JP,OP = 37.7 Hz)
=
Figure 2. ESI-HRMS spectrum for Rh/3a complex.
Eur. J. Org. Chem. 2014, 6713–6719
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6715

F.-T. Song, G.-H. Ouyang, Y. Li, Y.-M. He, Q.-H. Fan
FULL PAPER
Alternatively, metallacrown ethers are often prepared un- (Table 2, Entries 7–8). The above results indicate that the
der dilute conditions without the addition of a tem- performance of the Rh/3a metallacrown ether catalyst was
plate.[2a–2e] Thus, we attempted to prepare the rhodium positively improved by the addition of K+ cations, as evi-
metallacrown ether catalysts through the direct coordina- denced by the clear enhancement of catalytic enantio-
tion of the cationic Rh(cod)2BF4 and ligands 3a–3c in an selectivity. Therefore, 3a was selected as the optimal ligand.
equimolar ratio (concentration: 11.8 mm) without the par- The addition of K+ cations after the coordination between
ticipation of an alkali metal cation as a template. Gratify- Rh and ligand 3a gave the same enantioselectivity in the
ingly, the obtained 31P NMR spectra were very similar to hydrogenation (Table 2, Entry 9); this suggests that the
those acquired by the template-induced method, albeit with preparation method of the supramolecular Rh/ligand/K+
slight differences in both the chemical shifts and the cou- metallacrown ether catalysts does not affect the enantiose-
pling constants (Table 1). The formation of metallacrown lective outcome of the hydrogenation.
ethers for Rh/3a–3c was also verified by ESI-HRMS
(Figures 2 and S4). In contrast to the low efficiency and
Table 2. Asymmetric hydrogenation of enamide 6a with Rh/3a–
3c.[a]
selectivity of previously reported nontemplate syntheses of
metallacrown ethers,[2f] the success might be ascribed to the
cationic nature of the metal precursor. When [Rh(cod)Cl]2
was used, multiple Rh complex species were observed (Fig-
ure S5).
By comparing the chemical shifts in the 31P NMR spec-
tra of the in situ prepared metallacrown ethers with and
Entry
Ligand
Additive (M+/ligand)
ee [%][b]
without the binding of K+ cations, differences shown by
Rh/3a were noticed. Downfield shifts of 0.8 and 0.9 ppm
for the phosphite and phosphine moieties were recorded,
respectively, whereas the signal changes for Rh/3b and Rh/
3c were negligible. These results implied that the catalytic
performance for these metallacrown ether catalysts might
be different.
1
2
3
4
5
6
7
8
3a
–
–
–
–
84
5
11
87
0
93
9
13
93
89
91
92
90
87
81
84
84
3b
3c
5
5/PPh3 (1:1)
–
3a
3b
3c
3a
3a
3a
3a
3a
3a
3a
3a
3a
KBArF (1:1)
KBArF (1:1)
KBArF (1:1)
KBArF (1:1)
LiBArF (1:1)
NaBArF (1:1)
CsBArF (1:1)
KBArF (0.5:1)
KBArF (2:1)
KBArF (5:1)
KBArF (1:1)
KBArF (1:1)
9[c]
10
11
12
13
14
15
16[d]
17[e]
3. Asymmetric Hydrogenation of Enamides
Having realized the effective formation of chiral rhodium
metallacrown ether catalysts, we then evaluated their cata-
lytic properties in the asymmetric hydrogenation of α-
arylenamide derivatives. In general, rather few phosphine–
phosphite/metal catalysts have been found to be highly
enantioselective in the asymmetric hydrogenation of en-
amide substrates,[5a,5b] although such phosphorus ligands
offer the advantages of easy preparation and derivatization
as well as high air-stability. Gratifyingly, 100% conversions
were achieved within 12 h for all of the reactions screened.
By selecting nonpolar organic solvents that favor host–
guest assembly between alkali cations and metallacrown
ethers, ligand 3a with the diphenylphosphine group at the
ortho position provided a good enantioselectivity (84%ee)
in the Rh-catalyzed hydrogenation of enamide 6a in toluene
[a] Unless otherwise stated, the hydrogenations were performed
with 0.1 mmol of 6a in 1 mL of toluene under the following
conditions: 6a/3a–3c/Rh(cod)2BF4 (100:1.1:1), 6a/5/Rh(cod)2BF4
(100:2.2:1), 20 atm of H2, room temp. for 12 h. The Rh/ligand/K+
catalysts were prepared by a template-induced method. [b] 100%
conversions were observed in all cases, and the enantioselectivities
were determined by chiral GC analysis. [c] KBArF was added after
the formation of the metallacrown ether Rh/3a. [d] 18-Crown-6 was
added during the preparation of the catalyst. [e] 18-Crown-6 was
added directly into the mixed solution of the in situ prepared cata-
lyst and the substrate.
To identify the effects of alkali cations on the catalytic
(Table 2, Entry 1; also see Table S2 for solvent optimiza- performance, different alkali metal salts with the same
tion); the ee with 3a is much better than those obtained counteranion were screened (Table 2, Entries 6, 10–12). The
with 3b and 3c (Table 2, Entries 2–3). Although 5 itself af- K+ cation gave the best result, and lower enantioselectivities
forded the reduced product with high enantioselectivity were observed for Na+, Li+, and Cs+, possibly owing to the
(Table 2, Entry 4), a racemic product was obtained by using difference in the match with the metallacrown ether cata-
a mixed ligand system with the monophosphite 5 and PPh3 lyst. When the amount of KBArF was increased or de-
in a 1:1 molar ratio (Table 2, Entry 5). To our delight, in creased, the enantioselectivity dropped (Table 2, Entries 13–
the presence of 1.0 mol-% KBArF and under otherwise the 15). In the above optimization experiments, the best result
same reaction conditions, a higher enantioselectivity of was obtained with the combination of 3a and K+ (1 equiv.
93%ee was obtained with ligand 3a (Table 2, Entry 6). Li- to 3a) to give the hydrogenation product in 93%ee (Table 2,
gands 3b and 3c also gave the product with a slight en- Entry 6; 9% enhancement of ee value). Control experiments
hancement of enantioselectivity in the presence of KBArF were also performed to ascertain the key role played by the
6716
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6713–6719

Metallacrown Ether Catalysts for Asymmetric Hydrogenation
Scheme 3. Removal of K+ cation from the metallacrown ether catalyst with 18-crown-6.
K+ cations (Scheme 3). Owing to the stronger binding of
To establish the positive effects of the supramolecular re-
18-crown-6 to K+ cations than Rh/3a, the addition of 18- cognition between alkali cations and the metallacrown ether
crown-6 before or after the formation of the Rh/3a/K+ catalysts on both hydrogenation activity and enantio-
metallacrown ether catalyst provided decreased enantio- selectivity, a series of α-arylenamides were hydrogenated by
selectivities similar to that obtained without K+ cations employing the Rh/(3a+K) complex as the catalyst under the
(Table 2, Entries 16–17 vs. Entry 1). These results clearly optimized conditions. As shown in Table 3, the hydrogen-
demonstrated that the addition of alkali metal cations could ation of α-para-substituted phenylenamides 6a–6f pro-
effectively improve the catalytic enantioselectivity of the ceeded smoothly with full conversions and excellent
rhodium metallacrown ether catalysts through a supra- enantioselectivities (93–99%ee), which are comparable to
molecular recognition adjustment.
or even better than the best results obtained for phosphine–
Subsequently, we investigated the influence of the ad- phosphite ligands with a chiral backbone.[5a,5b] For meta-
dition of KBArF on the reaction rate for the asymmetric chlorophenylenamide 6g, fairly good enantioselectivity was
hydrogenation of 6a. The reaction conditions were identical observed (Table 3, Entry 7). For the more challenging
to the optimized conditions (Table 2, Entry 6) except that ortho-chlorophenylenamide 6h, only 39% conversion was
the hydrogen pressure was set to 5 atm. As explicitly shown achieved; this was still higher than the 12% conversion ob-
in the time-conversion curves in Figure 3, the hydrogen-
ation rate was accelerated with the addition of KBArF; this
clearly indicates that the addition of alkali metal cations
can effectively improve the catalytic activity of the rhodium
metallacrown ether catalyst.
Table 3. Asymmetric hydrogenation of α-arylenamides catalyzed by
Rh/(3a+K).[a]
Entry
Substrate (R1, R2)
ee [%][b]
1
2
3
4
5
6
7
8
9
6a (Ph, H)
93 (84)
96 (84)
94 (85)
99 (92)
99 (94)
98 (93)
87 (81)
70 (66)
58 (50)
6b (4-Me-Ph, H)
6c (4-F-Ph, H)
6d (4-CF3-Ph, H)
6e (4-Cl-Ph, H)
6f (4-Br-Ph, H)
6g (3-Cl-Ph, H)
6h (2-Cl-Ph, H)
6i (Ph, Me)
[a] The hydrogenations were performed with 0.1 mmol of 6 in 1 mL
of toluene under the following conditions: 6/3a/KBArF/Rh-
(cod)2BF4 = 100:1.1:1.1:1, 20 atm of H2, room temp. for 12 h. [b]
100% conversions were observed in all cases except Entry 8 (39%
conversion vs. 12% conversion without KBArF). The enantio-
selectivities were determined by chiral GC analysis except for that
of 7h (determined by chiral HPLC). The configuration of the prod-
uct is (S). The data in parentheses were obtained without an alkali
metal.
Figure 3. Conversion plotted against time for the asymmetric
hydrogenation of 6a.
Eur. J. Org. Chem. 2014, 6713–6719
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6717

F.-T. Song, G.-H. Ouyang, Y. Li, Y.-M. He, Q.-H. Fan
FULL PAPER
72.7, 111.4, 115.6, 121.3, 126.1, 126.3, 128.4, 128.5, 128.7, 130.3,
133.6, 133.9, 134.2, 136.8, 136.9, 160.2, 160.4 ppm. 31P NMR
(121 MHz, CDCl3): δ = –15.3 ppm. HRMS (ESI): calcd. for
C30H40O7P [M + H]+ 543.2506; found 543.2504.
tained in the absence of KBArF (Table 3, Entry 8). For tri-
substituted α-phenylenamide 6i, only moderate enantio-
selectivity was obtained (Table 3, Entry 9). Most import-
antly, a remarkable enhancement in enantioselectivity was
observed in all cases in the presence of K+ cations. For ex-
ample, the (S)/(R) enantiomeric ratio of 7d reached 199 in
the presence of K+ cations, which is greatly improved from
that obtained [(S)/(R) = 24] without the cation regulation.
Compound 2b: Prepared by the same procedure as that for 2a; 80%
1
yield. H NMR (300 MHz, CDCl3): δ = 2.69 (br, 1 H), 3.49–3.64
(m, 20 H), 3.70–3.73 (m, 2 H), 3.95 (t, J = 4.8 Hz, 2 H), 6.79 (t, J
= 7.3 Hz, 3 H), 7.13–7.26 (m, 11 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 61.8, 67.4, 69.8, 70.4, 70.6, 70.7, 70.9, 72.7, 115.2,
119.5, 119.8, 126.2, 126.4, 128.5, 128.6, 128.8, 129.5, 129.6, 133.7,
134.0, 137.1, 137.2, 138.7, 138.9, 158.8, 158.9 ppm. 31P NMR
(121 MHz, CDCl3): δ = –4.8 ppm. HRMS (ESI): calcd. for
C30H40O7P [M + H]+ 543.2506; found 543.2505.
Conclusions
A new class of readily available and tunable metalla-
crown ether catalysts based on α,ω-(phosphine–phosphite)
polyether ligands was successfully prepared and applied
in the rhodium-catalyzed asymmetric hydrogenation of α-
arylenamides. It has been demonstrated that the addition
of alkali metal cations leads to positive enhancements of
enantioselectivity and activity through the coordination of
Compound 2c: Prepared by the same procedure as that for 2a; 96%
1
yield. H NMR (300 MHz, CDCl3): δ = 2.61 (br, 1 H), 3.58–3.74
(m, 20 H), 3.85 (t, J = 4.9 Hz, 2 H), 4.13 (t, J = 4.8 Hz, 2 H), 6.90
(d, J = 8.1 Hz, 2 H), 7.23–7.34 (m, 12 H) ppm. 13C NMR (75 MHz,
CDCl3): δ = 61.9, 67.5, 69.8, 70.5, 70.7, 70.8, 72.7, 115.0, 115.1,
128.5, 128.6, 128.7, 133.5, 133.7, 135.6, 135.8, 137.7, 159.8 ppm.
K+ cations to the metallacrown ether. Studies of this supra- 31P NMR (121 MHz, CDCl3): δ = –7.1 ppm. HRMS (ESI): calcd.
for C30H40O7P [M + H]+ 543.2506; found 543.2506.
molecular approach in the preparation of other chiral tun-
able catalysts are in progress.
General Synthetic Procedure for 3a–3c: Under nitrogen atmosphere,
a
solution of (R)-[1,1Ј-binaphthyl-2,2Ј-diyl]chlorophosphite (4,
0.70 g, 2.44 mmol) in tetrahydrofuran (THF, 10 mL) was added to
a solution of 2a (1.10 g, 2.03 mmol) and Et3N (1.7 mL, 6.0 mmol)
in deoxygenated THF (30 mL) at 0 °C. The resulting mixture was
warmed to room temperature and stirred for 16 h. The precipitated
Et3NHCl was removed by filtration through a pad of Celite. After
the solvent was removed under reduced pressure, the residue was
purified by flash column chromatography to give 3a (1.1 g,
Experimental Section
General: Unless otherwise noted, all experiments were performed
under an inert atmosphere of dry nitrogen by using standard
Schlenk-type techniques or in a nitrogen-filled glovebox. All of the
solvents were treated before use according to the standard methods.
Commercially available reagents were used without further purifi-
cation. 1H, 13C, and 31P NMR spectra were recorded at ambient
temperature with a Bruker Advance DMX 300 Spectrometer (1H
300 MHz, 13C 75 MHz, and 31P 121 MHz) with samples in CDCl3
1
1.26 mmol) as a colorless and viscous oil in 62% yield. H NMR
(300 MHz, CD2Cl2): δ = 3.43–3.62 (m, 20 H), 3.92–4.08 (m, 4 H),
6.64–6.69 (m, 1 H), 6.83–6.92 (m, 2 H), 7.24–7.54 (m, 19 H), 7.93–
or CD2Cl2. Chemical shifts (δ) are given in ppm and are referenced 8.02 (m, 4 H) ppm. 13C NMR (75 MHz, CD2Cl2): δ = 64.8, 64.9,
to the residual solvent peaks (1H and 13C NMR) or to an external
standard (85% H3PO4 for 31P NMR). Coupling constants (J) are 122.2, 123.0, 124.4, 124.5, 125.3, 125.5, 126.6, 126.6, 126.7, 126.7,
68.1, 68.8, 69.7, 70.9, 70.9, 71.0, 71.0, 71.1, 71.1, 111.9, 121.5,
reported in Hertz. The ESI-HRMS spectra were recorded with a
Thermo Scientific® apparatus. The conversions and enantiomeric
excesses of the reduced products were determined either by chiral
GC with a Chrompack Chiralsil-DEX CB column and Chrompack
Chirasil-l-Val column or by chiral HPLC with a Chiralcel OD col-
umn. Flash column chromatography was performed with silica gel
of 200–300 mesh.
127.1, 128.7, 128.8, 128.8, 129.0, 130.5, 130.6, 130.8, 131.5, 132.0,
132.9, 133.2, 133.7, 133.8, 134.2, 134.5, 137.3, 137.5, 148.0, 148.0,
149.0, 160.6, 160.8 ppm. 31P NMR (121 MHz, CD2Cl2): δ = 142.9,
–15.8 ppm. HRMS (ESI): calcd. for C50H51O9P2 [M + H]+
857.3003; found 857.3005.
Compound 3b: Prepared by the same procedure as that for 3a; 60%
yield. 1H NMR (300 MHz, CD2Cl2): δ = 3.58–3.76 (m, 20 H), 3.93–
4.12 (m, 4 H), 6.84–6.93 (m, 3 H), 7.25–7.56 (m, 19 H), 7.95–8.03
(m, 4 H) ppm. 13C NMR (75 MHz, CD2Cl2): δ = 64.8, 64.9, 67.7,
69.9, 70.9, 71.0, 71.0, 71.1, 115.2, 119.8, 120.0, 122.2, 123.1, 124.1,
124.4, 124.5, 125.3, 125.5, 126.3, 126.6, 126.7, 127.1, 127.5, 128.8,
128.8, 128.8, 128.9, 129.2, 129.9, 130.0, 130.5, 130.8, 131.3, 131.5,
132.0, 132.9, 133.2, 134.0, 134.2, 137.5, 137.7, 139.3, 139.4, 148.0,
148.9, 149.0, 159.2, 159.3 ppm. 31P NMR (121 MHz, CD2Cl2): δ =
144.0, –4.0 ppm. HRMS (ESI): calcd. for C50H51O9P2 [M + H]+
857.3003; found 857.3004.
Compounds 1a–1c and monotosylated hexa(ethylene glycol) were
synthesized by modified literature procedures.[10,11] Compound 4
and all of the α-arylenamide substrates were prepared according to
the published method.[12,13]
General Synthetic Procedure for 2a–2c: Under nitrogen atmosphere,
cesium carbonate (0.75 g, 2.3 mmol) was added in one portion to a
solution of 2-(diphenylphosphanyl)phenol (1a, 0.47 g, 1.7 mmmol)
and monotosylated hexa(ethylene glycol) (0.66 g, 1.5 mmol) in
deoxygenated CH3CN (20 mL). The resulting mixture was heated
to reflux overnight. After removal of the solvent, the residue was
extracted with ethyl acetate (EA, 50 mL ϫ2). The combined or-
ganic layers were washed with brine, subsequently dried with anhy-
drous Na2SO4, and finally purified by flash chromatography to give
2a (0.81 g, 1.5 mmol) as a white to pale yellow viscous oil in almost
Compound 3c: Prepared by the same procedure as that for 3a; 52%
yield. 1H NMR (300 MHz, CD2Cl2): δ = 3.59–3.71 (m, 18 H), 3.80
(t, J = 6.9 Hz, 2 H), 3.91–3.96 (m, 1 H), 4.07–4.14 (m, 3 H), 6.92
(d, J = 6.3 Hz, 2 H), 7.26–7.55 (m, 20 H), 7.94–8.03 (m, 4 H) ppm.
13C NMR (75 MHz, CD2Cl2): δ = 64.8, 64.9, 67.9, 68.2, 69.9, 70.9,
quantitative yield (98%). 1H NMR (300 MHz, CDCl3): δ = 2.67 71.0, 71.0, 71.0, 71.1, 71.2, 115.2, 115.3, 122.2, 123.1, 124.4, 124.7,
(br, 1 H), 3.45–3.73 (m, 22 H), 4.04 (t, J = 5.0 Hz, 2 H), 6.64–6.68 125.4, 125.5, 126.7, 126.7, 127.1, 127.5, 128.2, 128.3, 128.8, 128.9,
(m, 1 H), 6.83–6.90 (m, 2 H), 7.27–7.35 (m, 11 H) ppm. 13C NMR 130.5, 130.8, 131.5, 132.0, 132.9, 133.2, 133.7, 133.9, 135.8, 136.1,
(75 MHz, CDCl3): δ = 61.8, 68.5, 69.4, 70.5, 70.6, 70.7, 70.7, 70.9,
138.4, 138.5, 148.0, 149.0, 149.0, 160.2 ppm. 31P NMR (121 MHz,
6718
www.eurjoc.org
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2014, 6713–6719

Metallacrown Ether Catalysts for Asymmetric Hydrogenation
5, 2454–2458; h) A. A. Kaisare, S. B. Owens Jr., E. J. Valente,
G. M. Gray, J. Organomet. Chem. 2010, 695, 2658–2666; i) W.
Zhang, X. Zhang, M. Luo, Chin. J. Chem. 2012, 30, 1423–
1428; j) J.-W. Wang, L.-Y. Gao, F.-H. Meng, J. Jiao, L.-Y. Ding,
L.-F. Zhang, J. Inclusion Phenom. Macrocyclic Chem. 2012, 73,
119–128; k) W. Tang, W.-G. Yuan, B. Zhao, H.-L. Zhang, F.
Xiong, L.-H. Jing, D.-B. Qin, J. Organomet. Chem. 2013, 743,
147–155; l) I. Mon, D. A. Jose, A. Vidal-Ferran, Chem. Eur. J.
2013, 19, 2720–2725.
CD2Cl2): δ = 142.9, –7.4 ppm. HRMS (ESI): calcd. for C50H51O9P2
[M + H]+ 857.3003; found 857.3005.
The monophosphite 5, as a known compound, was synthesized in
86% yield by the same method as that for ligand 3.[2g]
Typical Procedure for the in-situ-Preparation of the Metallacrown
Catalysts for Identification: A mixture of the corresponding phos-
phine–phosphite ligand 3a–3c (5.9ϫ10–3 mmol) and Rh(cod)2BF4
(5.9ϫ10–3 mmol) was dissolved in CD2Cl2 (0.5 mL), and the solu-
tion was stirred for 30 min in a glovebox. The in situ formed com-
plexes were characterized by 31P NMR spectroscopy and ESI-
HRMS. For the template-induced strategy, the preparation was
identical except that an equimolar amount of KBArF was added
to the ligand 3a–3c solution before the coordination with Rh(cod)2-
BF4.
[3] M. Sawamura, H. Nagata, H. Sakamoto, Y. Ito, J. Am. Chem.
Soc. 1992, 114, 2586–2592.
[4] For representative reviews, see: a) H. Fernández-Pérez, P.
Etayo, A. Panossian, A. Vidal-Ferran, Chem. Rev. 2011, 111,
2119–2176; b) P. W. N. M. van Leeuwen, P. C. J. Kamer, C. Cla-
ver, O. Pàmies, M. Diéguez, Chem. Rev. 2011, 111, 2077–2118;
c) J.-H. Xie, S.-F. Zhu, Q.-L. Zhou, Chem. Rev. 2011, 111,
1713–1760; d) J. Xie, Q. Zhou, Acta Chim. Sinica 2012, 70,
1427–1438.
[5] a) H. Fernández-Pérez, M. A. Pericàs, A. Vidal-Ferran, Adv.
Synth. Catal. 2008, 350, 1984–1990; b) H. Fernández-Pérez,
S. M. A. Donald, I. J. Munslow, J. Benet-Buchholz, F. Maseras,
A. Vidal-Ferran, Chem. Eur. J. 2010, 16, 6495–6508; c) A. Suá-
rez, A. Pizzano, Tetrahedron: Asymmetry 2001, 12, 2501–2504;
d) M. Rubio, A. Suárez, E. Álvarez, A. Pizzano, Chem. Com-
mun. 2005, 628–630; e) M. Rubio, S. Vargas, A. Suárez, E.
Álvarez, A. Pizzano, Chem. Eur. J. 2007, 13, 1821–1833; f) S.
Vargas, A. Suárez, E. Álvarez, A. Pizzano, Chem. Eur. J. 2008,
14, 9856–9859; g) I. Arribas, M. Rubio, P. Kleman, A. Pizzano,
J. Org. Chem. 2013, 78, 3997–4005.
[6] a) V. F. Slagt, M. Röder, P. C. J. Kamer, P. W. N. M.
van Leeuwen, J. N. H. Reek, J. Am. Chem. Soc. 2004, 126,
4056–4057; b) J. N. H. Reek, M. Röder, P. E. Goudriaan,
P. C. J. Kamer, P. W. N. M. van Leeuwen, V. F. Slagt, J. Or-
ganomet. Chem. 2005, 690, 4505–4516; c) X.-B. Jiang, L. Le-
fort, P. E. Goudriaan, A. H. M. de Vries, P. W. N. M.
van Leeuwen, J. G. de Vries, J. N. H. Reek, Angew. Chem. Int.
Ed. 2006, 45, 1223–1227; Angew. Chem. 2006, 118, 1245–1249;
d) X.-B. Jiang, P. W. N. M. van Leeuwen, J. N. H. Reek, Chem.
Commun. 2007, 2287–2289; e) G. Hattori, T. Hori, Y. Miyake,
Y. Nishibayashi, J. Am. Chem. Soc. 2007, 129, 12930–12931; f)
B. Breit, Angew. Chem. Int. Ed. 2005, 44, 6816–6825; Angew.
Chem. 2005, 117, 6976–6986; g) J. M. Takacs, K. Chaiseeda,
S. A. Moteki, D. S. Reddy, D. Wu, K. Chandra, Pure Appl.
Chem. 2006, 78, 501–509; h) Y. Li, Y. Feng, Y.-M. He, F. Chen,
J. Pan, Q.-H. Fan, Tetrahedron Lett. 2008, 49, 2878–2881; i) L.
Wu, Y.-M. He, Q.-H. Fan, Adv. Synth. Catal. 2011, 353, 2915–
2919; j) N. C. Thacker, S. A. Moteki, J. M. Takacs, ACS Catal.
2012, 2, 2743–2752; k) Z. Kokan, S. I. Kirin, Eur. J. Org. Chem.
2013, 8154–8161; l) M. Raynal, P. Ballester, A. Vidal-Ferran,
P. W. N. M. van Leeuwen, Chem. Soc. Rev. 2014, 43, 1660–
1733.
Typical Procedure for the Asymmetric Hydrogenation of α-Arylen-
amides (Template-Induced Method): A mixture of the corresponding
phosphine–phosphite ligand 3a–3c (3.3ϫ10–3 mmol) and KBArF
(3.3ϫ10–3 mmol) in dichloromethane (1.5 mL) was stirred at room
temperature for 20 min under nitrogen atmosphere. To the resulting
solution, Rh(cod)2BF4 (3.0ϫ10–3 mmol) was added, and the solu-
tion was stirred for another 30 min. Then, the above in situ prepared
catalyst (0.5 mL, 1.0 ϫ10–3 mmol) was added to a 50 mL glass-lined
stainless steel reactor with a magnetic stirring bar, which was charged
with enamide 6a (16.1 mg, 0.1 mmol) in dichloromethane (0.5 mL).
The reactor was closed and transferred outside the glovebox, and
the solvent was evaporated under reduced pressure. The reactor was
transferred into the glovebox again; toluene (1.0 mL) was added,
and then the autoclave was closed and pressurized with hydrogen to
20 atm. The mixture was stirred at ambient temperature for 12 h.
After careful venting of the hydrogen, the conversions and enantio-
selectivities of the reduced products were determined by chiral GC
with a Chrompack Chiralsil-DEX CB column and Chrompack Chir-
asil-l-Val column or chiral HPLC with a Chiralcel OD column.
Supporting Information (see footnote on the first page of this article):
Details of experimental procedures and characterization data, includ-
ing spectra for binding studies, optimization of asymmetric hydro-
1
genation reactions, and copies of H, 13C and 31P NMR spectra.
Acknowledgments
Financial support from the National Natural Science Foundation
of China (NSFC) (grant numbers 21232008 and 21373231), the
National Basic Research Program of China (973 Programs, grant
numbers 2010CB833300 and 2011CB808600), and the Chinese
Academy of Sciences is gratefully acknowledged.
[7] a) J. Meeuwissen, J. N. H. Reek, Nat. Chem. 2010, 2, 615–621;
b) P. E. Goudriaan, P. W. N. M. van Leeuwen, M.-N. Birkholz,
J. N. H. Reek, Eur. J. Inorg. Chem. 2008, 2939–2958.
[1] For reviews on metallamacrocycles, see: a) F. C. J. M. van Veg-
gel, W. Verboom, D. N. Reinhoubt, Chem. Rev. 1994, 94, 279–
299; b) G. Mezei, C. M. Zaleski, V. L. Pecoraro, Chem. Rev.
2007, 107, 4933–5003.
[2] For selected examples of metallacrown ethers, see: a) D. C.
Smith Jr., C. H. Lake, G. M. Gray, Chem. Commun. 1998,
2771–2772; b) D. C. Smith Jr., G. M. Gray, Inorg. Chem. 1998,
37, 1791–1797; c) J. M. Butler, M. J. Jablonsky, G. M. Gray,
[8] D. Nicholls, M. Szwarc, J. Phys. Chem. 1967, 71, 2727–2730.
[9] P. Thordarson, Chem. Soc. Rev. 2011, 40, 1305–1323.
[10] a) A. Bianchi, A. Bernardi, J. Org. Chem. 2006, 71, 4565–4577;
b) N. Priyadarshani, J. Suriboot, D. E. Bergbreiter, Green
Chem. 2013, 15, 1361–1367.
[11] M. Bollini, K. M. Frey, J. A. Cisneros, K. A. Spasov, K. Das,
J. D. Bauman, E. Arnold, K. S. Anderson, W. L. Jorgensen,
Bioorg. Med. Chem. Lett. 2013, 23, 5209–5212.
Organometallics 2003, 22, 1081–1088; d) S. B. Owens Jr., G. M. [12] B. M. Trost, D. A. Thaisrivongs, E. J. Donckele, Angew. Chem.
Gray, Organometallics 2008, 27, 4282–4287; e) M. E. Kelly, A.
Dietrich, S. Gómez-Ruiz, B. Kalinowski, G. N. Kaluderovic´, T.
Müller, R. Paschke, J. Schmidt, D. Steinborn, C. Wagner, H.
Schmidt, Organometallics 2008, 27, 4917–4927; f) X. Zhang, Y.
Qiu, B. Rao, M. Luo, Organometallics 2009, 28, 3093–3099; g)
Y. Li, B. Ma, Y. He, F. Zhang, Q.-H. Fan, Chem. Asian J. 2010,
Int. Ed. 2013, 52, 1523–1526; Angew. Chem. 2013, 125, 1563–
1566.
[13] Q.-S. Wang, J.-H. Xie, W. Li, S.-F. Zhu, L.-X. Wang, Q.-L.
Zhou, Org. Lett. 2011, 13, 3388–3391.
Received: June 10, 2014
Published Online: September 8, 2014
Eur. J. Org. Chem. 2014, 6713–6719
© 2014 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
6719