Heterogeneous simplified Maruoka phase-transfer catalyst tethered on poly(styrene-co-acrylamide) microsphere: Structure-activity relationship in enantioselective Α-alkylation

Article abstract of DOI:10.1016/j.catcom.2017.06.002

The covalent immobilization of valuable simplified Maruoka catalyst onto poly(styrene-co-acrylamide)microsphere at different locations was developed for the first time through the copolymerization of Maruoka catalyst-functionalized styrene with styrene an

Full text of DOI:10.1016/j.catcom.2017.06.002

Accepted Manuscript
Heterogeneous simplified Maruoka phase-transfer catalyst
tethered on poly(styrene-co-acrylamide) microsphere: Structure-
activity relationship in enantioselective α-alkylation
Dandan Feng, Jingwei Wan, Fei Teng, Xuebing Ma
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DOI:
Reference:
S1566-7367(17)30233-9
doi: 10.1016/j.catcom.2017.06.002
CATCOM 5068
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Catalysis Communications
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1 April 2017
4 June 2017
6 June 2017
Please cite this article as: Dandan Feng, Jingwei Wan, Fei Teng, Xuebing Ma ,
Heterogeneous simplified Maruoka phase-transfer catalyst tethered on poly(styrene-co-
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ACCEPTED MANUSCRIPT
Heterogeneous simplified Maruoka phase-transfer catalyst tethered on poly(styrene-co-acrylamide)
microsphere: structure -activity relationship in enantioselective α-alkylation
Dandan Feng,a Jingwei Wan,b Fei Teng,a and Xuebing Ma*a
a Key Laboratory of Applied Chemistry of Chongqing Municipality, College of Chemistry and Chemical Engineering, Southwest
University, Chongqing, 400715, P. R. China; b Railway Police College, Henan, 450053, P. R. China
* Corresponding author. Tel.: +86-23-68252360;
fax: +86-23-68254000.
E-mail addresses: zcj123@swu.edu.cn (X.B. Ma),

ACCEPTED MANUSCRIPT
Abstract
The covalent immobilization of valuable simplified Maruokacatalyst onto poly(styrene-co-acrylamide)microsphereat different
locations was developed for the first time through the copolymerization of Maruokacatalyst-functionalized styrenewith styreneand
acrylamide cross-linked by EGDMA. It was found the morphology, porous feature of microsphere and the anchor location of Maruoka
catalyst were mainly responsible for the catalyticperformance in heterogeneous α- alkylation. Thecatalyst poly[St-co-AA-co-(R)-11]
with a rigid framework, where homogeneous (R)-11 was anchored at the 6, 6’-positions of binaphthylskeleton, possessed therelatively
-1
larger surface area (33.5 m2 g ) and porevolume (1.27 cc g-1) and displayed high yields (81–96%) and excellent enantioselectivities
(96–97 %ee) in enantioselective α-alkylation.
Keywords: Simplified Maruokacatalyst; Heterogeneous catalysis; Poly(styrene-co-acrylamide) microsphere; Structure-activity
relationship; Asymmetric α-alkylation

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1. Introduction
Asymmetric phase-transfer catalysis (PTC) by means of a chiral quaternary ammonium salt has been recognized as
one of the most practical methodologies in the enantioselective synthesis of highly valuable and optically active natural
and non-natural organic compounds through carbon-carbon or carbon-heteroatom bond-forming reactions under mild
biphasic conditions [1, 2]. Owing to the importance of PTC in enantioselective synthesis, the various categories of chiral
phase-transfer catalysts (PTCs), especially well-known representatives such as cinchona alkaloid and binaphthyl-derived
PTCs, had been well developed for organic synthesis in both industry and academia [3]. Up to now these privileged chiral
PTCs were efficiently utilized for a wide variety of asymmetric transformations such as α-alkylation [4–7], conjugate ad-
dition [8, 9], Mannich reaction [10], Michael addition [11], aldol reaction [12] and cascade reaction [13]. From the view-
point of green sustainable chemistry, it was well known that homogeneous catalyst could be generally heterogenized onto
solid supports (e.g., inorganic material or polymer) to achieve the sustainability via (i) covalent bonding, (ii) adsorption
or ion-pair formation, (iii) encapsulation and (iv) entrapment [14, 15]. To achieve the reusability of homogeneous PTCs,
several reports focused on polymeric [16–20] and inorganic material [21, 22]-supported cinchona alkaloid-derived PTCs
had been investigated in detail. However, there were the limited reports on the recovery and reusability of versatile and
extraordinarily expensive Maruoka PTCs owing to the difficult functionalization of binaphthyl skeleton [23–26]. Early in
2004, K. Maruoka developed a fluorous chiral binaphthyl-modified spiro-type quaternary ammonium salt attached with
the 4, 4´, 6, 6´-tetra-substituted C8F17CH2CH2SiMe2 groups, which could be recovered though liquid/liquid biphasic
separation by using fluorous perfluorohexane (FC-72) as an extractant in the asymmetric synthesis of α-amino acids [27].
In 2008, S. Itsuno et al. immobilized Maruoka PTCs onto sulfonated polymer through the ionic bond interaction between
quarternary ammonium cation and sulfonate anion [28].
Despite their excellent catalytic performances of reusable Maruoka PTCs, these two strategies actually still had the
drawbacks of the laborious fluorous liquid/liquid separation and less stability of PTCs against leaching of cationic species

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in catalytic medium, respectively. Generally, the covalent immobilization of homogeneous chiral catalyst onto solid sup-
port via covalent bond is the most often employed method to heterogenize stereoselective catalyst in view of enhanced
stability in reuse [29–32]. To our knowledge, the covalent linkage of well-known Maruoka PTCs onto whatever inorganic
or polymeric materials was never reported up to now, possibly owing to the difficult functionalization of the inert skele-
ton of Maruoka PTCs. In this work, we endeavoured to introduce two anchorage points of carbon-carbon double bond in
styrene moiety into the skeleton of simplified Maruoka catalyst through two routes, in which one of the rigid binaphthyl
moieties in Maruoka PTCs was replaced by flexible straight-chain alkyl groups to furnish new simplified Maruoka PTCs
[33]. This is the first example of the immobilization of simplified Maruoka PTCs into polystyrene microspheres through
the covalent immobilization (Scheme 1).
Scheme 1 The routes to the covalent immobilization of simplified Maruoka PTCs onto polystyrene microspheres
2. Experimental

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2.1. Materials
Styrene (St) was pre-treated with aqueous NaOH solution (10 %) and distilled under reduced pressure to remove po-
lymerization inhibitor completely. The initiator azobisisobutyronitrile (AIBN) was further purified by ethanol recrystalli-
zation. The intermediates (R)-8 [33, 34], (R)-11, (R)-12 and bis(4-(4-vinylphenyl)butyl)amine were synthesized according
1
to the procedure shown in ESI† and their structures were evidenced by H and 13C NMR.
2.2. Preparation of microsphere-supported Maruoka catalysts
Suspension polymerization: To the well-stirred solution of acrylamide (AA) (53.3 mg, 0.75 mmol) and poly(vinyl
alcohol) (PVA, 20.0 mg, 0.4 wt%) in DI water (5.0 mL) was added a mixture of (R)-11 (53.0 mg, 0.05 mmol), styrene (St,
312.4 mg, 3.0 mmol), initiator AIBN (21.3 mg, 0.13 mmol) and ethyleneglycol dimethacrylate (EGDMA, 75.3 mg, 0.38
mmol) by syringe under Ar atmosphere and well stirred for 2 h. Then the resulting emulsion was stirred at 70 °C for ano-
ther 24 h and diluted with ethanol (15 mL). The yellow granules were filtered, washed with ethanol (5 mL × 3), toluene
(5 mL × 3) and dried in vacuo at 60 °C to afford supported simplified Maruoka catalyst poly[St-co-AA-co-(R)-11] (318.5
mg).
According to the above-mentioned procedure, the other supported simplified Maruoka catalysts were also prepared
and designated as a control poly[St-co-AA] (232.3 mg) in the absence of (R)-11, poly[St-co-AA-co-(R)-11]′ (233.9 mg)
and poly[St-co-AA-co-(R)-11]′′ (230.5 mg) upon the added amount of PVA set to 1.0 wt% and 4.0 wt%, poly[St-co-(R)-
11] (281.5 mg) in the absence of AA, poly[St-co-(AA)-co-(R)-11] (275.9 mg) upon the decreased St (234.3 mg, 2.3 mmol)
and increased AA (106.6 mg, 1.5 mmol), and poly[St-co-AA-co-(R)-12] (261.8 mg) instead of (R)-11 with (R)-12.
Emulsion polymerization:Instead of initiator AIBN and emulsifier PVA with potassiumpersulfate (KPS) and sodi-
um dodecyl sulfate (SDS), poly{St-co-AA-co-(R)-11} (210.4 mg) was prepared through emulsion polymerization accord-
ing to the same procedure as poly[St-co-AA-co-(R)-11].
2.3. General enantioselective α-alkylation reaction

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To a mixture of poly[St-co-AA-co-(R)-11] (40.0 mg, 5.6 mol%), N-(diphenylmethylene)glycine tert-butylester
(28.5 mg, 0.1 mmol), aqueous KOH solution (50wt%, 0.45 mL,8.0mmol) and toluene (1.0 mL) was added various
substituted benzylbromides (0.5 mmol), cooled to -20 °C and vigorously stirred for 72 h. the resulting reaction mixture
was diluted with DI water (5 mL) and ether (5 mL). The catalyst poly[St-co-AA-co-(R)-11] was recovered by filtration.
The filtrate was extracted with ether (5 mL × 2). The combined organic phases were dried over anhydrous Na2SO4 and
concentrated underreduced pressure to afford the crude α-alkylation product,which was purified by gradient column
chromatography on alumina gel using petroleum ether/ethylacetate (v/v = 60/1 → 40/1) as eluents to afford pure
α-alkylation products.
3. Results and discussion
3.1. Immobilization and loading capacity of PTCs
The conformationally rigid spiro-type structure of binaphthyl-modified chiral PTCs imposes a limitation on the co-
valent immobilization of Maruoka PTCs owing to the lack of active reaction site. In this communication, we endeavoured
to introduce styrene moieties as anchorage points at the different locations in the framework of simplified Maruoka PTCs
through two routes to achieve the covalent immobilization of Maruoka PTCs (Scheme 1). The first route was the bromi-
nation of (R)-9 and then Suzuki coupling of p-styrylboronic acid with (R)-10 to afford (R)-11 with two styrene-attached
moieties at the 6, 6’-positions of binaphthyl skeleton. The second route provided a direct method for the simultaneous
generation of quaternary ammonium catalytic site and styrene anchorage points by the nucleophilic substitution of (R) -8
with bis(4-(4-vinylphenyl)butyl)amine to afford (R)-12. Subsequently, in PVA-emulsified aqueous system, the as-synthe-
sized (R)-11 and (R)-12 were covalently immobilized into the polymeric backbone of poly[St-co-AA-co-(R)-11] and
poly[St-co-AA-co-(R)-12] by the suspension polymerization of (R)-11 and (R)-12 with AA and St monomers cross-linked
by EGDMA, respectively. The distinct difference in the structure between poly[St-co-AA-co-(R)-11] and poly[St-co-AA-
co-(R)-12] was the different distance of polystyrene backbone to the quaternary ammonium catalytic site. The quaternary

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ammonium catalytic sites in poly[St-co-AA-co-(R)-11] were located in the rooms far away from the polymer chain and
remained the original structure feature of simplified Maruoka PTCs to a great extent owing to the rigid styrene anchorage
points. In the other hand, the quaternary ammonium catalytic sites in poly[St-co-AA-co-(R)-12] were linked to polymeric
primary chain though the flexible alkyl chains, which resulted in the less rigidity of poly[St-co-AA-co-(R)-12] than that of
poly[St-co-AA-co-(R)-11]. Fromthe SEM images (Fig.1), both poly[St-co-AA-co-(R)-11] and poly[St-co-AA-co-(R)-12]
showed the similar microsphere morphology in the range of 40–200 um. Based on the contents of nitrogen determined by
elemental analysis, poly[St-co-AA-co-(R)-11] and poly[St-co-AA-co-(R)-12] also possessed the same loading capacity of
(R)-11 and (R)-12 (0.14 mmol g-1). However, the utilization of (R)-12 (73%) in the preparation process was lower than
that of (R)-11 (89%), possibly due to the steric hindrance of binaphthyl moieties near to styrene anchorage points in
poly[St-co-AA-co-(R)-12] .
Fig. 1 The SEM images of poly[St-co-AA-co-(R)-11] (c) and poly[St-co-AA-co-(R)-12].
The covalent attachment of simplified Maruoka catalyst (R)-11 to the microsphere poly[St-co-AA-co-(R)-11] via the
copolymerization of C=C double bonds was clearly corroborated by FT-IR spectroscopy (Fig. S2). The loading capacities
of (R)-11 in various polymer-supported PTCs were calculated according to the contents of nitrogen obtained from
elemental analysis, and the utilization of (R)-11 was evaluated by the mass ratios of loaded (R)-11 to added (R)-11 (Table
1). First of all, the control polymer poly[St-co-AA] possessed the low loading capacity of AA (0.16 mmol g-1) with only
5% utilization of added AA based on 0.23% of nitrogen. Secondly, upon increasing the added amount of emulsifier PVA
from 0.4 wt% to 4.0 wt%, the loading capacities of (R)-11 in poly[St-co-AA-co-(R)-11]′ (0.19 mmol g-1) and poly[St-co-
AA-co-(R)-11]′′ (0.20 mmol g-1) with the good utilizations of (R)-11 (89–92%) were slightly improved owing to the

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better emulsified effect. Thirdly, the added amount of AA, whatever decreased or increased, had no significant influence
on the loading capacity of (R)-11 with the good utilizations of (R)-11 (83–90%). It was noticeable that the as-synthesized
poly{St-co-AA-co-(R)-11} via emulsion polymerization exhibited the slightly higher loading capacity (0.18 mmol g-1)
and lower utilization (76%) of (R)-11 than poly[St-co-AA-co-(R)-11] via suspension polymerization.
Table 1 The loading capacities and efficient utilizations of (R)-11 and (R)-12 determined by elemental analysis
Entry
Sample
N content
Loading capacity
Utilization of Cat.
a
b
c
(%)
(mmol g-1)
(%)
1
2
3
4
5
6
7
8
poly[St-co-AA]
0.23
0.42
0.43
0.49
0.51
0.22
0.41
0.48
0.16 c
0.14
0.14
0.19
0.20
0.16
0.15
0.18
5 c
73
89
89
92
90
83
76
poly[St-co-AA-co-(R)-12]
poly[St-co-AA-co-(R)-11]
poly[St-co-AA-co-(R)-11]′
poly[St-co-AA-co-(R)-11]′′
poly[St-co-(R)-11]
poly[St-co-(AA)-co-(R)-11]
poly{St-co-AA-co-(R)-11}
b
a Determined by elemental analysis. Based on the content of nitrogen. c The mass ratio of loaded PTCs to added PTCs.
3.2. Surface morphology of supported simplified Maruoka PTCs
The preparation conditions played an important role in surface morphology of supported Maruoka PTCs (Fig. S7).
The catalyst poly[St-co-AA-co-(R)-11] presented the spherical microsphere in the range of 40–200 um centered at 120–
140 um. Upon increasing the added PVA from 0.4 wt% to 1.0 wt% and 4.0 wt%, poly[St-co-AA-co-(R) -11]′ and poly[St-
co-AA-co-(R)-11]′′ became smaller, especially for poly[St-co-AA-co-(R)-11]′′ with the 3–21 um diameters centered at 4–
8 um owing to the improved emulsification at high PVA concentration. Furthermore, poly[St-co-(R)-11] (60–110 um)
containing no AA possessed the relatively smaller diameter than the poly[St-co-AA-co-(R)-11] and poly[St-co-(AA)-co-
(R)-11] with increased AA exhibited a slight variation in the diameter (80–160 um), which implied that AA monomer had
an influence in the diameter of supported Maruoka PTCs to a certain degree. By contrast, poly{St-co-AA-co-(R)-11} by
emulsion polymerization showed the submicron size and irregular shape (<2 um) accumulated from mutually adherent
nanoparticles (<50 nm) (Fig. S5).

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3.3. Porous structure feature
The porous structures and surface areas of polymer-supported simplified Maruoka PTCs were illustrated by N2
adsorption–desorption isotherms obtained at 77 K (Fig. S3), and their BET-specific surface areas, average pore diameters
and pore volumes were listed in Table S2. The microsphere poly[St-co-AA-co-(R)-11] possessed the largest surface area
(33.5 m2 g-1), average pore diameter (75.8 nm) and pore volumes (1.27 cc g-1), which favoured the mass transfer of reac-
tants and products into and out from the heterogeneous matrix. When the added PVA increased from 0.4 wt% to 1.0 wt%
and 4.0 wt% respectively, poly[St-co-AA-co-(R)-11]′ and poly [St-co-AA-co-(R)-11]′′ exhibited the decreased surface
areas, pore diameters and pore volumes. Whatever no added AA or increased AA monomer, both poly[St-co-(R)-11] and
poly[St-co-(AA)-co-(R)-11] gave the disappointing average pore diameters and pore volumes. It was concluded that
poly[St-co-AA-co-(R)-11] with the molar ratio of St/AA = 4/1 could construct the optimal porous structure for polymer-
supported Maruoka PTCs. Furthermore, the poly{St-co-AA-co-(R)-11} with the poor surface area (7.6 m2 g-1), average
pore diameter (4.6 nm) and pore volume (0.017 cc g-1) indicated that emulsion polymerization could not construct a fine
porous structure suitable for heterogeneous catalysis. Moreover, poly[St-co-AA-co-(R)-12] with the styrene anchorage
point near to the quaternary ammonium bromide catalytic site displayed the poor porous feature.
The pore size distributions (PSDs) of various Maruoka PTCs possessed the similar micro/mesoporous cavities cen-
tered at 0.8, 1.3, 1.9, 2.7 and 5.8 nm (Fig. S4). Under the improved emulsion system, some characteristic pores disappear-
ed and the irregular PSDs were observed for poly[St-co-AA-co-(R) -11]′ and poly[St-co-AA-co-(R)-11]′′, accompanied
by the low adsorption Dv(r) (0–20 × 10-4 cc Å-1 g-1). Especially, it was worthwhile to note that poly[St-co-AA-co-(R)-11]
afforded the highest nitrogen adsorption Dv(r) (0–10 × 10-3 cc Å-1 g-1) among the as-prepared supported PTCs. Therefore,
It was concluded that the suspension polymerization in 0.4 wt% PVA -emulsified aqueous solution with the molar ratio of
(R)-11/AA/EGDMA/St = 1/7.5/15/60 could construct the microsphere poly[St-co-AA-co-(R)-11] with fine porous struct-
ure and large surface area.

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3.4. Structure-activity relationship in asymmetric α-alkylation
In the previous literatures, seldom was reported on the structure/activity relationship between the surface morpho-
logy, porous feature of polymer-supported catalysts and catalytic performance [35]. In this work, it was found that the str-
uctures such as surface morphology, porous feature and anchorage location of Maruoka PTCs played an important role in
the catalytic performance of polymer-supported Maruoka PTCs in enantioselective α-alkylation.
Table 2 The enantioselective α-alkylation of N-(diphenylmethylene)glycine tert-butyl ester catalyzed by various supported Maruoka
PTCs a
Entry
Cat.
Yield (%) b
(%ee) c
1
2
3
4
5
6
7
poly[St-co-AA-co-(R)-11]
poly[St-co-AA-co-(R)-11]′
poly[St-co-AA-co-(R)-11]′′
poly[St-co-(R)-11]
67
60
52
51
56
26
58
96
94
89
94
96
84
94
poly[St-co-(AA)-co-(R)-11]
poly{St-co-AA-co-(R)-11}
poly[St-co-AA-co-(R)-12]
a Reaction conditions: Cat. (5.0 mol%), BnBr (85.5 mg, 0.5 mmol), N-(diphenylmethylene)glycine tert-butyl ester (29.5 mg, 0.1
b
mmol), KOH (50 wt%, 0.15 mL, 2.7 mmol), toluene (1.0 mL), 0 °C, 48 h. Isolated yield. c Determined by HPLC on
Phenomenex Lux 5u Amylose-2 chiral column.
Under the same catalytic reactions at 0 °C for 48 h, the catalytic performances of supported Maruoka PTCs were
listed in Table 2. It was found that the surface morphology, porous feature and anchorage location of Maruoka PTCs
were responsible for the yield and enantioselectivity in enantioselective α-alkylation. First of all, due to the fine porous
feature with the large surface area (33.5 m2 g-1), average pore diameter (75.8 nm) and pore volume (1.27 cc g-1), poly[St-
co-AA-co-(R)-11] via suspension polymerization exhibited the higher catalytic performances (67%, 96 %ee) than poly{St
-co-AA-co-(R)-11} via emulsion polymerization (26%, 84 %ee), even though poly{St-co-AA-co-(R)-11} possessed the
smaller submicron size and higher loading capacity of (R)-11. Secondly, under the improved emulsification at 4.0 wt%
PVA concentration, poly[St-co-AA-co-(R)-11]′′ with the smaller diameter (3–21 um) showed the sharply reduced surface

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area (16.1 m2 g-1), average pore diameter (11.9 nm) and pore volume (9.6 × 10-2 cc g-1), which ultimately resulted in the
disappointed catalytic performances (52%, 89 %ee). When the used amounts of AA were further screened, both poly[St-
co-(R)-11] and poly[St-co-(AA)-co-(R)-11] afforded α-alkylation products in the inferior yields to poly[St-co-AA-co-(R)-
11] due to the reduced surface area, average pore diameter and pore volume . Especially, the anchorage location of homo-
geneous Maruoka PTCs had a great influence on catalytic performances including activity and steroselectivity. It was
found that poly[St-co-AA-co-(R)-12] with styrene anchorage points through flexible alkyl chain connected to quarternary
ammoniumcatalytic site exhibited the lower yield (58%) and slightly poorer enantioselectivity (94 %ee) than poly[St-co-
AA-co-(R)-11]. The low surface area and poor porous feature were responsible for the lower yield, whereas the poorer
enantioselectivity was attributed to the rigidity of polymeric framework. For poly[St-co-AA-co-(R)-11], (R)-11 was cova-
lently bonded to the polymeric chain through phenyl with π-π conjugation effect. It was easier for poly[St-co-AA-co-
(R)-11] with a good rigidity to remain the original conformation of homogeneous Maruoka PTCs. However, (R)-12 was
covalently bonded to the polymeric chain through the flexible alkyl group, which would result in the subtle change in the
conformation of quaternary ammoniumcatalytic site. In the catalytic process, this subtle change in conformation affect ed
the interaction of ammonium catalytic site with the incoming substrates and the decreasing in enantioselectivity was ob-
tained.
It was worthwhile to note that the really catalyst's porous structure in α - alkylation was more complex than the mea-
sured values owing to the swelling of polymer backbone in reaction medium. Owing to the complete insolubility in vari-
ous polar and non-polar solvents, the different chiral subtle microenvironments in polymer-supported Maruoka PTCs are
difficult to be clarified by CD spectrometry. As an alternative to elucidate the different subtle microenvironments, the
solid state 13C MAS NMR spectra of poly{St-co-AA-co-(R)-11} with the inferior enantioselectivity (84 %ee) displayed
no peaks of aromatic ring at 166.5 ppm and 136.4 ppm (Fig. S8), which implied that the binaphthyl moiety in poly{St-co-
AA-co-(R)-11} possessed the different subtle microenvironments. Furthermore, under the improved emulsification at 4.0

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wt% PVA, the obtained poly[St-co-AA-co-(R)-11]′′ showed the same absorption peaks of binaphthyl moiety as poly[St-
co-AA-co-(R)-11] in the 100–250 ppm range and different absorption peaks of alkyl carbon in the 10–80 ppm range,
which illustrated that the emulsification played an important role on the subtle microenvironments of alkyl chain near to
the catalytic site of quaternary ammonium. On the whole, the subtle microenvironments under different polymerizations
were the major sources of catalytic performances including activity and enantioselectivity.
3.5. Heterogeneous enantioselective α-alkylation
After the α-alkylation catalytic conditions such as temperature, used amount of poly[St-co- AA-co-(R)-11] and base
were further optimized, the heterogeneous α-alkylation of N-(diphenylmethylene)glycine tert-butyl ester with benzyl bro-
mide, catalyzed by 5.6 mol% of poly[St-co-AA-co-(R)-11] at -20 °C in toluene (1.0 mL) for 72 h, gave the product in
high yield (96%) with excellent enanotioselectivity (97 %ee) (Table 3, Entry 1). With the optimized conditions at hand,
the effect of styrene anchorage location on α-alkylation of N-(diphenylmethylene)glycine tert-butyl ester with o, m, p-
methylbenzyl bromides was further investigated in detail. Just as above- mentioned experimental phenomena (Table 2,
Entry 7), the microsphere poly[St-co-AA-co-(R)-11] displayed the superior yields and enantioselectivities (81–96 %, 96
–97 %ee) to poly[St-co-AA-co-(R)-12] (78–88%, 88–95 %ee). Encouraged by the remarkable catalytic results under the
optimal catalytic conditions, the substrate scope of electrophiles was extended to various o, m, p-CH3, F, CF3 and NO2-
substituted benzyl bromides, allyl bromides and propargyl bromide. It was found that the various benzyl bromides, both
with electron-withdrawing (–F, –CF3 and –NO2) and electron-donating (–CH3) groups, could produce the corresponding
α-alkylation products with good to excellent yields (76–96%) and enantioselectivities (88–97 %ee). In particular, comp-
ared with benzyl bromides bearing the m, p-CF3, F, CH3 and NO2 substituents, the electrophiles bearing o-CF3, F, CH3
and NO2 substituents exhibited the poor yields owing to the steric hindrance resulted from the confined interaction be-
tween the benzyl bromides with o-CF3, F, CH3 and NO2 substituents and glycine tert-butyl ester in heterogeneous
α-alkylation (Entries 2, 5, 8, 11, Table 3). Moreover, unlike other heterogeneous PTCs [25], the allyl and propargyl

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bromides could afford the corresponding α-alkylation products in good yields (77–91%) with satisfactory enantioselec-
tivities (93–97 %ee) (Entries 14–16, Table 3). However, due to the mass transfer limitation of reactants and embedding
active catalytic sites in heterogeneous phase, poly[St-co-AA-co-(R)-11] displayed the lower catalytic activities and requi-
red significantly prolonged reaction times to achieve the similar yields as homogeneous (R)-11.
Table 3 Enantioselective phase-transfer α-alkylation of N-(diphenylmethylene)glycine tert-butyl ester using different
electrophilesa
Entry
1
RBr
Time (h)
Yield (%) b
(%ee) c
72
4 e
72 f
10 g
72
96
96
86
95
81
96
78
95
93
96
84
94
93
96
88
93
85
96
97
97
93
96
96
97
95
98
97
97
88
96
96
97
90
96
96
97
2
3
4
7 e
72 f
10 g
72
3 e
72 f
10 g
72
3 e
72 f
10 g
72
5
6
7
10 e
72
3 e
90
96
97
97
72
7 e
96
96
97
97

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8
72
3 e
76
96
97
97
9
72
8 e
90
96
96 d
96 d
10
11
12
13
14
15
16
72
3 e
76
96
96
96
72
89
95
89
91
12 e
60
3 e
93
95
88
95
72
3 e
90
95
89
96
72
3 e
77
92
97
97
72
3 e
91
93
95
96
72
3 e
82
92
93
90
a Reaction conditions: poly[St-co-AA-co-(R)-11] (40 mg, 5.6 mol%), benzylbromide derivatives (0.5 mmol), N-(diphenylmethylene)
glycine tert-butyl ester (28.5 mg, 0.1 mmol), KOH aq. (50 wt%, 0.45 mL, 8.0 mmol), toluene (1.0 mL), -20 °C. b Isolated yield. c
Determined by chiral HPLC with Phenomenex Lux 5u Amylose-2 chiral column. d Daicel Chiralpak OD-H column. e Homogeneous
(R)-11. f poly[St-co-AA-co-(R)-12]. g Homogeneous (R)-12.
3.6. Reusability
After the completion of α-alkylation, the microsphere poly[St-co-AA-co-(R)-11] could be recovered by filtration and
reused directly for the next run without further treatment. The recovered poly[St-co-AA-co-(R)-11] in the third reuse ex-
hibited the significantly enhanced catalytic activity and afforded α-alkylation product in high yield (96%) within the

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shortened 48 h. Unfortunately, the reduced enantioselectivities from 97 %ee to 91 %ee were observed in the fifth run. In
order to clarify the reason for the change in catalytic performances of α-alkylation, the 5th-recycled poly[St-co-AA-co-(R)
-11] was characterized by N2 adsorption–desorption isotherm, SEM, elemental analysis and IR spectra. It was found that
the nitrogen content increased from 0.43% to 0.48%, and the surface area, average pore size and pore volume decreased
from 33.5 m2 g-1, 75.8 nm and 1.27 cm3 g-1 to 6.8 m2 g-1, 8.4 nm and 0.13 cm3 g-1 respectively, which elucidated that some
nitrogen-containing compounds such as N-(diphenylmethylene)glycine tert-butyl ester and its product were adsorbed in
the porous backbone of poly[St-co-AA-co-(R)-11]. Furthermore, the pore size distribution of 5th-recycled poly[St-co-AA-
co-(R)-11] showed that the five characteristic diameters of the original micropores at 0.28, 1.26, 1.87, 2.72 and 5.75 nm
disappeared and the new pores at 1.77, 2.82, 4.47, 7.47 and 19.02 nm emerged. The same phenomenon was observed for
poly[St-co-AA-co-(R)-12] (Fig.S27). These enlarged pore diameters were mainly responsible for the enhanced catalytic
activity of α-alkylation. Due to the enlarged pores in the reused sample, the weakened confinement effect of the enlarged
pores on the enantioselectivity was essentially a consequence of subtle change in the transition state induced by the weak-
er interaction among these pores and reactants. Moreover, the change in the surface morphology of poly[St-co-AA-co-(R)
-11] and poly[St-co-AA-co-(R)-12] in the catalytic process was also monitored by SEM. It was observed that more and
more particle defects on the surfaces with the prolonging of reaction time within 108 h (Fig.S28), which may be the other
reason for the enhanced catalytic activity of α-alkylation. At the fifth time, no enormous deformation and massive colla-
pse were observed for the SEM image of 5th-recycled poly[St- co-AA-co-(R)-11] (Fig.S25a), which stated clearly that
poly[St-co-AA-co-(R)-11] possessed the good mechanical stability in the reused process.
4. Conclusions
In this work, the covalent immobilization of simplified Maruoka PTCs onto the framework of polymeric microsph-
ere was developed for the first time to achieve the good reusability of homogeneous simplified Maruoka PTCs. It was of
special importance to substantiate that the surface morphology and porous feature of polymer-supported Maruoka PTCs

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had a significant influence on the catalytic performance including yield and enantioselectivity in the heterogeneous enan-
tioselective α-alkylation. The immobilization of Maruoka PTCs at the 6, 6´-positions of binaphthyl skeleton afforded the
superior catalytic results to that of Maruoka PTCs at the close location to quaternary ammonium catalytic site. Moreover,
the recovered Maruoka PTCs with good mechanical stability displayed a significantly improved catalytic activity and a
little loss in enantioselectivity, which resulted from the improved mass transfer and weakened confinement effect due to
the enlarged pores and defects of supported Maruoka PTCs, respectively.
Acknowledgements
We are grateful to the Fundamental Research Funds for the Central Universities [XDJK2015D028] and the National
Science Foundation of China [21071116].
Supplementary data
IR, N2 adsorption–desorption isotherms and SEM of supported PTCs, 1H and 13C NMR and HPLC spectra of
products can be found, in the online version, at…...
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Graphical abstract
The covalent immobilization of valuable Maruoka catalyst onto poly(styrene-co-acrylamide) microsphere was
developed for the first time through the copolymerization of styrene-functionalized Maruoka catalyst with styrene
and acrylamide by means of suspension polymerization.

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Highlights



The covalentimmobilization of Maruoka PTCs onto microspherefor the firsttime.
The porous feature of microsphere was responsiblefor catalytic performance in α-alkylation.
Good reusability was achieved without significantloss of catalytic performances.