Molecularly enlarged S,S-BnTsDPEN ligands for iron-catalyzed asymmetric olefin epoxidation reactions using hydrogen peroxide

Article abstract of DOI:10.1039/c3cy00484h

A convenient approach for the anchoring of S,S-BnTsDPEN ligands (S,S-N-tosyl-1,2-diphenylethylenediamine) to branched carbosilane scaffolds was investigated. It is based on a high-yielding reductive amination reaction between commercially available S,S-TsDPEN and readily accessible carbosilanes furnished with benzaldehyde terminal fragments. These molecularly enlarged ligands, bearing four S,S-BnTsDPEN units, and their simplified monomeric and "dimeric" analogues were evaluated in iron(iii)-catalyzed asymmetric trans-stilbene epoxidation reactions using hydrogen peroxide as an environmentally benign oxidant. The catalytic investigations showed a large degree of variation in the activity and stereoselectivity of the series of DPEN catalysts. In combination with ESI-MS investigations, these data revealed an important role of the ligand orientation in determining the overall activity of the catalyst system. Accordingly, a suitable design of the molecularly enlarged ligands resulted in fully retained activity and selectivity in catalysis. Finally, a number of strategies for the recovery and reuse of the best performing carbosilane-tethered DPEN ligands were explored.

Full text of DOI:10.1039/c3cy00484h

View Article Online
View Journal
Catalysis
Science&Technology
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: V. Yazerski, A. Orue, T. Evers, H. Kleijn
and B. Klein Gebbink, Catal. Sci. Technol., 2013, DOI: 10.1039/C3CY00484H.
This is an Accepted Manuscript, which has been through the RSC Publishing peer
review process and has been accepted for publication.
Catalysis
Science&Technology
Accepted Manuscripts are published online shortly after acceptance, which is prior
www.rsc.org/catalysis
Volume 1 | Number 1 | 2011 | Pages 0001–0100
to technical editing, formatting and proof reading. This free service from RSC
Publishing allows authors to make their results available to the community, in
citable form, before publication of the edited article. This Accepted Manuscript will
be replaced by the edited and formatted Advance Article as soon as this is available.
To cite this manuscript please use its permanent Digital Object Identifier (DOI®),
which is identical for all formats of publication.
More information about Accepted Manuscripts can be found in the
Information for Authors.
Please note that technical editing may introduce minor changes to the text and/or
graphics contained in the manuscript submitted by the author(s) which may alter
content, and that the standard Terms & Conditions and the ethical guidelines
that apply to the journal are still applicable. In no event shall the RSC be held
responsible for any errors or omissions in these Accepted Manuscript manuscripts or
any consequences arising from the use of any information contained in them.
ISSN 2044-4753
www.rsc.org/catalysis
Registered Charity Number 207890

Catalysis Science & Technology
Page 1 of 9Journal Name
Dynamic Article Links ►
View Article Online
DOI: 10.1039/C3CY00484H
Cite this: DOI: 10.1039/c0xx00000x
www.rsc.org/xxxxxx
ARTICLE TYPE
Molecularly enlarged S,S-BnTsDPEN ligands for iron-catalyzed
asymmetric olefin epoxidation reactions using hydrogen peroxide
Vital A. Yazerski,a Ane Orue,a Tim Evers,a Henk Kleijna and Robertus J.M. Klein Gebbink*a
Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX
5
DOI: 10.1039/b000000x
A
convenient approach for the anchoring of S,SꢀBnTsDPEN ligands (S,SꢀNꢀtosylꢀ1,2ꢀ
diphenylethylenediamine)to branched carbosilane scaffolds was investigated. It is based on a highꢀ
yielding reductive amination reaction between commercially available S,SꢀTsDPEN and readily
accessible carbosilanes furnished with benzaldehyde terminal fragments. These molecularly enlarged
10 ligands, bearing four S,SꢀBnTsDPEN units, and their simplified monomeric and “dimeric” analogues
were evaluated in iron(III)ꢀcatalyzed asymmetric transꢀstilbene epoxidation reactions using hydrogen
peroxide as an environmentally benign oxidant. The catalytic investigations showed a large degree of
variation in the activity and stereoselectivity of the series of DPEN catalysts. In combination with ESIꢀ
MS investigations, these data revealed an important role for the ligand orientation in determining the
15 overall activity of the catalyst system. Accordingly, a proper deign of the molecularly enlarged ligands
resulted in a fully retained activity and selectivity in catalysis. Finally, a number of strategies for the
recovery and reuse of the best performing carbosilaneꢀtethered DPEN ligands were explored.
mmol of substrate.
We envisioned that the ability to recycle the S,Sꢀ1 ligand would
Introduction
significantly improve the overall practical use of the catalytic
protocol. Most common methodologies aimed at the recycling
45 and reuse of a homogeneous catalyst are associated with the
20 Enantiopure epoxides have found a wide application in organic
synthesis.[1] For instance, they are key precursors and
intermediates in the preparation of vicinal diols, aminoalcohols,
and diamines, each of which are found abundantly in chiral
auxiliaries, ligands, and organocatalysts.[2] Among the general
25 strategies[1ꢀ5] for the assembly of an oxirane ring, a direct olefin
oxidation[5] is economically appealing and it might have the least
negative ecological impact, utilizing air or hydrogen peroxide as
the terminal oxidant.
Recently, Beller et al. reported on the application of the S,Sꢀ
30 BnTsDPEN ligand (S,Sꢀ1), a benzylated derivative of S,Sꢀ
TsDPEN, in the high yielding and enantioselective iron(III)ꢀ
catalyzed epoxidation of aromatic alkenes with hydrogen
peroxide.[6] The overall catalytic protocol is easy to apply at
ambient conditions, but requires column chromatography to
35 separate the epoxide product from substantial sacrificial amounts
of catalyst residue (ca. 10ꢀ20 mol%). More importantly, the most
expensive part of the catalytic system is the optically pure ligand,
whereas the total value of the other components, i.e. hydrated
ferric chloride, 2,6ꢀpyridinedicarboxylic acid (H2PDC) and tertꢀ
40 amyl alcohol as the reaction solvent, does not exceed €2 per
immobilization of the catalyst on
a
solid support.[7] The
separation of such insoluble, heterogenized catalysts from
reaction media is straightforward, e.g. by filtration, yet most often
such catalysts show a decreased activity and selectivity.[8] Soluble
50 polymeric supports have been shown to be a viable alternative to
solid supports, allowing for the immobilized catalysts to maintain
their singleꢀsite characteristics.[9,10,11aꢀd] Such molecularly
enlarged catalysts are recoverable from reaction solutions by
means of precipitation using an antiꢀsolvent or via any size
55 discriminative method (e.g. membrane nanofiltration).[12]
Information on the parent catalyst composition, structure,
reaction and deactivation pathways are key hints aiding to choose
a proper immobilization strategy. For epoxidations using S,Sꢀ1,
the reported ratio of catalyst components Fe/S,Sꢀ1/H2PDC 1:2.4:1
60 (i.e. overꢀstoichiometric ligand loading) and the available spectral
data suggest that the formation of [FeIIICl2(S,Sꢀ1)2(H2PDPC)]+
ions is of importance.[6] Accordingly, it was decided to explore
soluble symmetric molecules bearing multiple S,SꢀTsDPEN units.
The application of such structures in catalysis could be beneficial,
65 because of ligand preꢀorientation and preꢀconcentration
phenomena in oligomeric entities, which can facilitate the
formation of active species with a 2:1 Fe/L ratio.
a
Organic Chemistry & Catalysis, Debye Institute for Nanomaterials
Science, Utrecht University, Universiteitsweg 99, 3584 CG Utrecht, The
Netherlands; Fax: +31 30 2523615; Tel: +31 30 2531889; E-mail:
r.j.m.kleingebbink@uu.nl
† Electronic Supplementary Information (ESI) available: Experimental
procedures and characterization data. For ESI data see DOI: 10.1039/
b000000x/
A number of molecularlyꢀenlarged DPENꢀbased catalysts have
been reported to date.[11eꢀh] All of them were developed
This journal is © The Royal Society of Chemistry [year]
[journal], [year], [vol], 00–00 | 1

Catalysis Science & Technology
Page 2 of 9
View Article Online
DOI: 10.1039/C3CY00484H
exclusively for hydrogenation or hydrogen transfer processes and,
chemoselectivity around 80%.
unfortunately, contain fragments that are vulnerable to oxidation
or hydrolysis, or that can potentially coordinate to a metal center.
Examples include Fréchetꢀtype benzylic dendrons, PEGꢀmoieties,
and Newcomeꢀtype polyamides. Herein, we report on a detailed
study on the design and preparation of molecularly enlarged
carbosilane analogues of S,Sꢀ1 and on their use in asymmetric
O
O
Si
5
Si
alkene epoxidation reactions. In addition, we provide
a
Si
Si
prospective on the recovery and reuse of these ligands in
10 catalysis.
Si
Results and Discussion
O
O
The carbosilaneꢀlinked chiral ligand CSꢀS,Sꢀ1 bearing four S,Sꢀ
BnTsDPEN units was prepared via a quantitative oneꢀpot
reductive amination reaction[13] between the branched aldehyde
15 reported by Van Koten et al.[14] and commercially available S,Sꢀ
TsDPEN (Scheme 1). Characteristic signals of the
carboxaldehyde support in IR (ν(C=O) 1701 cmꢀ1), 1Hꢀ
(δ(C(O)H) 10.00 ppm) and 13CꢀNMR (δ(CO) 192.5 ppm)
disappeared within 24 h, indicating the completion of the
20 reaction. The isolated material was efficiently purified using
passive membrane dialysis.[15] Size exclusion chromatography
(SEC) confirmed the monodispersity (PDI 1.02) of the obtained
polymeric material (Page 43 in Supporting Info). In ESIꢀMS, CSꢀ
S,Sꢀ1 predominantly appeared as a doubly charged ion with m/z
25 1126.4945 (calcd. for [M+2H]2+ 1126.4985).
S,S-TsDPEN
NaBH(OAc)3
DCM, 24 h
O
O
O
S
O
S
N
HN
HN
H
HN
Si
Si
CSꢀS,Sꢀ1 was investigated in the epoxidation of several transꢀ
stilbenes (2a-d) under conditions previously developed and
optimized for the parent S,Sꢀ1 ligand by Beller et al. (Scheme
2).[6] The loading of CSꢀS,Sꢀ1 was adjusted taking into account
30 the total number of DPEN units (see Supporting Information).
The results of independently reproduced oxidation experiments
with S,Sꢀ1 were consistent with previously reported data (Table
1). However, in some cases the isolated epoxide yields were
higher than the ones previously estimated using GC analysis. This
35 can be attributed to a moderate stability of certain epoxides under
flame ionisation detection conditions. For that reason the main
Si
Si
Si
NH
H
NH
NH
N
S
O
S
O
O
O
(CS-S,S-1)
epoxide products were also carefully isolated and their 60 Scheme 1. Synthesis of optically pure ligand CSꢀS,Sꢀ1.
composition monitored by NMR. Moreover, no alkene cleavage
or epoxide isomerization products were observed by 1HꢀNMR
40 analysis of crude product mixtures in reactions with transꢀ
stilbenes 2a-c. In contrast, while no essential byꢀproducts were
detected by GC in the case of 2d oxidation with S,Sꢀ1, the same
crude sample subjected to 1HꢀNMR analysis appeared to be a
complex mixture of products. In addition, the corresponding
45 epoxide 3d was found to be prone towards degradation upon its
purification on silica gel.
In contrast, epoxide 3d was only isolated in a modest yield of
8.7%, whereas 59% of the substrate 2d was consumed. Such a
low chemoselectivity (15%) most likely relates to product
stability issues, which have been encountered as well when
65 oxidizing 2d with the parent S,Sꢀ1 ligand.
H2O2 (2 eq.) over 1 h
L (12/n mol%)
.
FeCl3 6H2O (5 mol%)
R2
R2
Surprisingly, a very low catalytic activity within the normal
reaction time of 1 h was observed using CSꢀS,Sꢀ1 for the
oxidation of 2a-d. Only upon extending the reaction time to 24 h,
50 a substrate conversion of 67% was achieved without extra
oxidant addition for transꢀstilbene (2a). The corresponding
epoxide (3a) was isolated in 23% yield only. CSꢀS,Sꢀ1
demonstrated a moderate chemoselectivity in the epoxidation of
substituted stilbenes over a longer reaction time. For instance, the
55 epoxides 3b and 3c derived from 4,4’ꢀdisubstituted transꢀ
stilbenes 2b and 2c were isolated in satisfactory 53 and 34%
yields, respectively, which corresponds to a reasonable reaction
H2PDC (5 mol%)
tert-amyl alcohol, RT
R1
O
R1
2
3
n:
L:
CSꢀS,Sꢀ1
S,Sꢀ1
S,Sꢀ4aꢀc
S,Sꢀ4d
CSꢀS,Sꢀ5
CSꢀS,Sꢀ6
2a, 3a: R1 = R2 = ꢀPh
4
1
1
2
4
1
2b, 3b: R1 = R2 = ꢀpꢀtol
2c, 3c: R1 = R2 = ꢀpꢀtBuPh
2d, 3d: R1 = ꢀpꢀtBuPh, R2 = ꢀ2ꢀnaphtyl
Scheme 2. transꢀStilbene epoxidation with DPEN ligands.
2
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 3 of 9
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C3CY00484H
The enantioselectivities of epoxidations carried out with CSꢀS,Sꢀ1
were essentially lower than with the parent monomeric ligand
detected at all for the substituted stilbenes 2b-d in the presence of
S,Sꢀ4c, and only 11% of 2a was consumed. In the latter case, the
S,Sꢀ1. Transꢀstilbene oxide (3a) was obtained with only 7.7% ee. 50 epoxide R,Rꢀ3a was isolated in 11% yield and low ee of 12%.
The highest enantiomeric enrichment of the epoxide product
obtained with CSꢀS,Sꢀ1 was found for the epoxidation of 2c and
2d (36% in both cases), which is roughly two times lower than
the values obtained with the original ligand (71 and 73%,
respectively). Hence, tetramer CSꢀS,Sꢀ1 can in general be
considered as a poor ligand for the epoxidation of the selected
ESIꢀMS analysis of a catalyst mixture based on S,Sꢀ4c only
revealed the protonated ligand and its numerous clusters [X(S,Sꢀ
4c)n(HCl)mꢀ1]+ (where {n, m} = 1, 2, 3 and X = H or Na), whereas
no ironꢀcontaining ions were observed.
5
10 substrates, showing neither good activity nor good
enantioselectivity.
O
O
N
H
NH HN
S
Table 1. Stilbenes epoxidation with S,Sꢀ1 and CSꢀS,Sꢀ1.a)
O
NH
Yield [%]b)
/
ee [%]d,e)
O
S
Entry
Substrate
Ligand
Conv. [%]c)
87c)/99
95/99
R
1f)
2
2a
2a
2a
2b
2b
2b
2c
2c
2c
2d
2d
2d
S,Sꢀ1
S,Sꢀ1
CSꢀS,Sꢀ1
S,Sꢀ1
S,Sꢀ1
CSꢀS,Sꢀ1
S,Sꢀ1
S,Sꢀ1
CSꢀS,Sꢀ1
S,Sꢀ1
S,Sꢀ1
CSꢀS,Sꢀ1
42
41
7.7
64
61
12
81
71
36
91
73
36
Si
3g)
23/67
4f)
92c)/99
86/99
5
6g)
53/63
(S,S-4d)
7f)
82c)/99
85/99
R = -H
(S,S-1)
HN
-p-TMS (S,S-4a)
-m-TMS (S,S-4b)
-o-TMS (S,S-4c)
8
9g)
10f,h)
11
12g)
34/43
HN
46c)/99
46/99
S
O
O
8.7/59
55
.
a) Reaction conditions: stilbene (0.5 mmol), H2O2 (1.0 mmol), FeCl3 6H2O
Figure 1. TMSꢀdecorated ligands S,Sꢀ4a-c and the „dimer“ S,Sꢀ4d.
(5.0 mol%), H2PDC (5.0 mol%), S,Sꢀligand (12 mol%), tertꢀamyl alcohol
b)
c)
15 (9 mL), RT, 1 h. Isolated yield. Determined by GC using PhNO2 or
PhBr as internal standard. d) Determined by chiral HPLC. e) Absolute (+)ꢀ
2R,3R configuration determined by comparing the sign of the optical
100
f)
g)
rotation of the isolated product with literature data. Literature data.[2]
80
S,Sꢀ4a
S,Sꢀ4b
Reaction time 24 h, 3 mol% tetramer ligand. h) Double loading of the iron
20 catalyst and oxidant.
60
S,Sꢀ1
40
To find out the reasons for such a distinctive catalytic behaviour
of the DPEN ligands before and after immobilization, several
model ligands were designed (Figure 1). These ligands are
represented by three isomeric trimethylsilyl (TMS) appended
25 DPEN ligands (S,Sꢀ4a-c) and a dimeric ligand (S,Sꢀ4d) formed by
two S,SꢀBnTsDPEN fragments tethered via the shortest possible
carbosilane linker (see Supporting Info for details on synthesis
and characterization).
No induction periods were observed in the kinetic profiles of the
30 oxidation reaction of transꢀstilbene using either the paraꢀ or
metaꢀTMSꢀappended DPEN ligands S,Sꢀ4a and S,Sꢀ4b, while the
parent S,Sꢀ1 ligand demonstrated at least a 10 min lag time. Full
substrate consumption was achieved within 45 min, i.e. 15 min
prior to complete delivery of 2.0 equiv. of the oxidant (Figure
35 2A). S,Sꢀ4a and S,Sꢀ4b also demonstrated a marginal effect on
the chemoꢀ and enantioꢀselectivity of the reaction. Catalytic
epoxidations carried out with these ligands yielded quite
consistent amounts of transꢀstilbene oxide (R,Rꢀ3a) of 86, 83 and
95% with corresponding ee values of 38, 42 and 41%, using S,Sꢀ
40 4a, S,Sꢀ4b and S,Sꢀ1, respectively (Table 2). Further screening of
the substituted transꢀstilbenes 2b-d also did not reveal a great
difference in chemoselectivity between these ligands, however,
the optical purity of the substituted stilbene oxides 3c and 3d
produced by S,Sꢀ4b was somewhat lower than those obtained
45 with the ligands S,Sꢀ4a and S,Sꢀ1.
S,Sꢀ4c
20
0
0
20
40
60
80
Reaction time, min
100
80
60
40
20
0
CSꢀS,Sꢀ6
CSꢀS,Sꢀ5
S,Sꢀ4d
CSꢀS,Sꢀ1
0
20
40
60
80
Reaction time, min
Figure 2. Transꢀstilbene conversion vs time plots for A) S,Sꢀ1, S,Sꢀ4a-c
60 and B) S,Sꢀ4d, CSꢀS,Sꢀ1, CSꢀS,Sꢀ5 and CSꢀS,Sꢀ6 ligands.
Probably, the orthoꢀpositioning of the carbosilane moiety
interferes with the formation of the catalytically active
[FeIIICl2(L)2(H2PDC)]+ species, resulting in a lower activity, in
particular with sterically demanding substrates such as 2b-d.
65 While the orthoꢀpositioning of
detrimental effects on the overall performance of the DPEN
a carbosilane moiety has
Positioning the TMSꢀgroup in the orthoꢀposition (S,Sꢀ4c) had a
dramatic effect on the DPEN catalyst activity. No conversion was
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 3

Catalysis Science & Technology
Page 4 of 9
View Article Online
DOI: 10.1039/C3CY00484H
ligand in catalysis, positioning the carbosilane moiety at either
the metaꢀ or in particular the paraꢀposition, like in CSꢀS,Sꢀ1,
case of S,Sꢀ1 and S,Sꢀ4d will be different. Where in the case of
S,Sꢀ1 coordination of two DPEN ligands to the iron centre is
seems to exert a minor steric or electronic effect on the catalytic 45 likely to result in a complex in which two identical Nꢀdonors are
performance.
positioned trans with respect to each other, the connectivity
within S,Sꢀ4d will force these donors to be cis to each other. Yet,
a more specific explanation cannot be given because of the need
for further structural information required to build a more
50 detailed model for the active species in this catalytic system.
5
Table 2. Olefin epoxidation with S,Sꢀ4a-d ligands.a)
Entry
Substrate
Ligand
Yield [%]b)
/
ee [%]d,e)
Conv. [%]c)
86/99
83/99
11/11
54/69
88/99
79/99
0/0
1
2
2a
2a
2a
2a
2b
2b
2b
2b
2c
2c
2c
2c
2d
2d
2d
2d
S,Sꢀ4a
S,Sꢀ4b
S,Sꢀ4c
S,Sꢀ4d
S,Sꢀ4a
S,Sꢀ4b
S,Sꢀ4c
S,Sꢀ4d
S,Sꢀ4a
S,Sꢀ4b
S,Sꢀ4c
S,Sꢀ4d
S,Sꢀ4a
S,Sꢀ4b
S,Sꢀ4c
S,Sꢀ4d
38
42
12
21
54
nd
ꢀ
18
76
60
ꢀ
3
4f)
5
O
O
O
O
6
S
S
N
H
7
HN
HN
8f)
9
49/58
85/99
77/99
0/0
42/45
39/99
32/99
0/0
HN
10
11
12f)
13
14
15
16f)
Si
48
71
63
ꢀ
Si
Si
Si
24/41
55
Si
aꢀe) See Table 1. f) 6 mol% of ligand S,Sꢀ4d.
Si
In turn, the S,Sꢀ4dꢀbased catalytic system demonstrated only a
moderate oxidative activity (Figure 2B, Table 2). The best
substrate conversion within 1 h was achieved with transꢀstilbene
Si
Si
Si
10 2a (69%). The reaction chemoselectivity with S,Sꢀ4d and S,Sꢀ1
did not differ that much in the epoxidation of substrates 2a-c (78ꢀ
93 and 86ꢀ96%, respectively). Moreover, oxidation of 2d using
the S,Sꢀ4d ligand proceeded with 59% selectivity towards the
epoxide, while S,Sꢀ1 ligand was less chemoselective (46%). This
15 variation can be attributed to different substrate conversion levels
reached with S,Sꢀ4d (41ꢀ69%) and S,Sꢀ1 (over 99%) catalysts.
Unfortunately, not only was the activity of the S,Sꢀ4d catalyst
lower compared to that of S,Sꢀ1, the epoxidation stereoselectivity
with S,Sꢀ4d decreased as well. For instance, R,Rꢀ3a was obtained
20 with 21% ee using S,Sꢀ4d, against 41% using the parent S,Sꢀ1
ligand. Using S,Sꢀ4d, a maximum ee value of 55% was achieved
in the epoxidation of 2d, while epoxidation of 2b gave the lowest
ee value of 18% for the R,Rꢀ3b oxide.
These observations for the ‘dimeric’ ligand S,Sꢀ4d contrast the
25 fact that the use of an excess of monomeric ligand S,Sꢀ1 with
respect to the iron salt (L/Fe = 2.4/1) positively affects the
oxidation rate and, to a lesser extent, product stereoselectivity.[6]
In addition, ESIꢀMS analysis of the S,Sꢀ1ꢀbased catalytic system
showed the ironꢀcontaining ions [FeIIICl2(S,Sꢀ1)2(H2PDC)]+
30 (previously reported)[6] and [FeIII(PDC)(S,Sꢀ1)2(H2PDC)]+ (this
work) with m/z values of 1205.2715 (calcd. 1205.2690) and
1300.3287 (calcd. 1300.3373), respectively, in which the 2:1
L/Fe ratio supports the necessity of a high ligand loading over the
iron precursor for successful catalysis. In the case of catalytic
35 mixtures containing the dimeric ligand S,Sꢀ4d, ESIꢀMS analysis
revealed the analogously composed ion [FeIIICl2(S,Sꢀ
4d)(H2PDC)]+ with m/z 1261.2788 (calcd. 1261.2770). If these
similar species, containing two DPEN ligands combined with one
Fe ion, indeed participate in the catalytic cycle, it is not their
40 composition that determines their catalytic properties.
Considering the respective ligand structures, both the overall
geometry and the electronics of the active species formed in the
NH
NH
H
N
NH
S
S
O
O
O
O
Figure 3. Optically pure elongated carbosilaneꢀlinked CSꢀS,Sꢀ5 ligand.
Further inspection of ESIꢀMS data of the S,Sꢀ4dꢀbased system
showed a complex ion with m/z 1168.2155, which can be
55 assigned to an ion of overall formula [FeIIICl2(S,Sꢀ4d)(HCl)2]+
(calcd. 1261.2056). Such an ion can correspond to
a
tetrachloroferrate salt of S,Sꢀ4d ([(S,Sꢀ4d)H]+[FeCl4]ꢀ or [(S,Sꢀ
4d)H2]2+Xꢀ[FeCl4]ꢀ, where X = chloride or tetrachloroferrate).
Related ions in the case of monomeric DPEN ligands, e.g. [(S,Sꢀ
60 1)H]+ [FeCl4]ꢀ, would appear as [(S,Sꢀ1)H]+ in ESIꢀMS and would
be indistinguishable from the singly protonated S,Sꢀ1 ligand.
Importantly, carrying out the catalytic reaction with these ligands
in the absence of H2PDC showed no conversion.
ESIꢀMS spectra of CSꢀS,Sꢀ1 premixed with ferric chloride and
65 H2PDC in tertꢀamyl alcohol were more complex. A number of
anticipated ironꢀcontaining doubly charged ions with m/z
1272.9475 (calcd. 1272.9414) and 1225.9098 (calcd. 1225.9185)
were observed, which correspond to partially metallated CSꢀS,Sꢀ1
species of the formula [HFeIIICl2(CSꢀS,Sꢀ1)(H2PDC)]2+ and
70 [HFeIIICl2(CSꢀS,Sꢀ1)(HCl)2]2+, respectively. The species derived
from the exhaustively metallated CSꢀS,Sꢀ1 molecule,
[(FeIIICl2)2(CSꢀS,Sꢀ1)(H2PDC)2]2+ with calcd. m/z 1418.8835, was
observed at a very low intensity.
Keeping in mind that CSꢀS,Sꢀ1 bears four DPEN units per
75 molecule, these species are characterized by DPEN/Fe ratios of
4/1 and 2/1, respectively. The low abundance of dimetallated
4
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 5 of 9
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C3CY00484H
species and the presence of H2PDCꢀfree complexes might explain
spectrum of the CSꢀS,Sꢀ5 catalyst mixture at m/z 1473.5658
the observed lower catalytic activity of the carbosilaneꢀlinked 50 (calcd. 1473.5833), corresponding to [HFeIIICl2(CSꢀS,Sꢀ
ligand CSꢀS,Sꢀ1. The oxidation stereoselectivity in this case,
presumably, is affected by the distorted geometry of immobilized
active sites enforced by the carbosilane support structure.
Tentatively, the molecules with a higher concentration of
5)(H2PDC)]2+. Besides this ion with an L/Fe ratio of 4/1, no
exhaustively metallated or H2PDCꢀfree species were found in this
case. This observation suggests that the enlarged carbosilane
support does not hamper interactions between CSꢀS,Sꢀ5, ferric
5
TsDPEN units at their periphery than in CSꢀS,Sꢀ1 will be even 55 chloride and, especially, H2PDC, and that the reactivity of the
less active in catalysis.[16]
In order to overcome the ligand proximity and orientation issue it
10 was decided to anchor the S,Sꢀ1 ligand to a more elongated
carbosilane molecule and to a carbosilane wedge (Figure 3 and
catalyst sites located at partially metallated carbosilaneꢀlinked
ligands (with L/Fe = 4) is only slightly affected by neighbouring
peripheral DPEN fragments. Accordingly, the preꢀorientation of
DPEN fragments on the carbosilane support is more crucial for
4). These organic supports were prepared following general 60 catalysis than the peripheral ligand concentration. On the other
protocols for carbosilane tetramer preparation and modification,
reported by Van Koten,[14] and Van Leeuwen[17,18]. Subsequently
15 these compounds were treated with S,SꢀTsDPEN and sodium
triacetoxyborohydride to accomplish the reductive amination
hand, the relatively restricted mobility of the anchored DPEN
ligands within the CSꢀS,Sꢀ5 structure results in lower
stereoselectivity of the epoxidation reaction than demonstrated by
a
S,Sꢀ1.
1
coupling. The immobilization progress was monitored by IR, H
and 13CꢀNMR. Approximately after 24 h all starting materials and
intermediates had disappeared. Purification of CSꢀS,Sꢀ5 bearing
20 four DPEN units was achieved using passive membrane dialysis,
whereas the monomeric ligand CSꢀS,Sꢀ6 was subjected to column
chromatography. Purity of these molecularly enlarged ligands
was confirmed by NMR, ESIꢀMS, and SEC (PDI 1.03 and 1.02
for CSꢀS,Sꢀ5 and CSꢀS,Sꢀ6, respectively; Page 45 and 46 in
25 Supporting Info). In ESIꢀMS, CSꢀS,Sꢀ5 appeared predominantly
as the corresponding doubly charged ion with m/z 1326.6398
(calcd. for M+2H+ 1326.6400). The CSꢀS,Sꢀ6 ligand appeared as
an ion with m/z 929.5128 (calcd. for M+H+ 929.5161).
The CSꢀS,Sꢀ5 ligand comprises enlarged carbosilane branches
30 compared to CSꢀS,Sꢀ1 and, hence, the anchored DPEN units are
more mobile in space. As it turned out, this modification of the
carbosilane support structure completely restored the initial
catalytic activity of the S,Sꢀ1 system. The epoxidation of transꢀ
stilbene reached 98% conversion within 1 h and yielded 79% of
35 the R,Rꢀ3a epoxide (Table 3). In this reaction, CSꢀS,Sꢀ5 also
demonstrated an improved stereoselectivity compared to CSꢀS,Sꢀ
1, i.e. the R,Rꢀ3a epoxide was formed with an increased ee of
25% (which is still lower than the value obtained using the parent
S,Sꢀ1 ligand, see Table 1). Epoxidation of the substituted
40 stilbenes 2b-d with CSꢀS,Sꢀ5 proceeded smoothly as well,
reaching nearly complete substrate conversion. The R,Rꢀ3b and
3c products were isolated with good yields above 80% and ee’s
of 38 and 63%, respectively. R,Rꢀ3d was also obtained with 63%
ee, whereas the low chemoselectivity (35%) is inherent to the
45 epoxidation of this particular substrate.
65
Figure 5. Catalyst mixtures with CSꢀS,Sꢀ6 (left), S,Sꢀ1 (middle) and CSꢀ
S,Sꢀ5 (right).
In turn, the activity, chemoꢀ and enantioselectivity of CSꢀS,Sꢀ6
closely resembled that of the parent catalyst (Table 3). For
70 example, transꢀstilbene 2a was quantitatively converted within 45
min into R,Rꢀ3a with an ee of 38% using CSꢀS,Sꢀ6. Like in the
case of the original S,Sꢀ1 ligand, even the crude reaction mixture
1
analysed by HꢀNMR was free of byꢀproducts. With CSꢀS,Sꢀ6, a
complex product mixture was obtained only in the epoxidation of
75 2d. The R,Rꢀ3d epoxide was isolated in 41% yield and 73% ee,
nearly reproducing the original S,Sꢀ1ꢀcatalyzed reaction outcome.
The highest epoxide ee 80% and almost quantitative yield 92%
were observed when oxidizing 2c in the presence of CSꢀS,Sꢀ6.
Table 3. Olefin epoxidation with CSꢀS,Sꢀ5 and CSꢀS,Sꢀ6 ligands.a)
Entry
Substrate
Ligand
Yield [%]b)
/
ee [%]d,e)
Conv. [%]c)
79/98
1f)
2
2a
2b
2c
2d
CSꢀS,Sꢀ5
CSꢀS,Sꢀ6
CSꢀS,Sꢀ5
CSꢀS,Sꢀ6
CSꢀS,Sꢀ5
CSꢀS,Sꢀ6
CSꢀS,Sꢀ5
CSꢀS,Sꢀ6
25
38
38
55
63
80
63
73
99/99
80/95
95/99
83/99
92/99
35/99
41/99
3f)
4
Si
5f)
6
Si
N
7f)
8
H
O
NH
O
S
Si
Si
Si
80 aꢀe) See Table 1. f) 3 mol% of ligand CSꢀS,Sꢀ5.
While all other DPEN ligands described here, including S,Sꢀ1,
formed highly turbid solutions upon mixing with ferric chloride
and H2PDC, the CSꢀS,Sꢀ6 catalyst mixture remained completely
transparent (Figure 5). Transꢀstilbene and the other tested
85 substrates are moderately soluble in the reaction solvent (tertꢀ
Figure 4. Optically pure CSꢀS,Sꢀ6 ligand.
Only one ironꢀcontaining ion was identified in the ESIꢀMS
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 5

Catalysis Science & Technology
Page 6 of 9
View Article Online
DOI: 10.1039/C3CY00484H
amyl alcohol), while the epoxide products possess a fair
solubility, allowing for the oxidation progress using CSꢀS,Sꢀ6 to
be monitored visually as the reaction medium gradually turned
clear and transparent.
most of the 2c substrate (59%) remained unreacted. The
corresponding epoxide R,Rꢀ3c was isolated in 34% yield and only
25% ee.
55 It was previously observed while optimizing the conditions for
transꢀstilbene oxidation with the parent S,Sꢀ1 ligand that the
reaction stereoselectivity remained unchanged in a broad L/Fe
ratio from 0.5/1 to 2.4/1 at a constant concentration of iron.[6] In
addition, the oxidation rate was found to be rather low under
60 ligandꢀdeficient conditions and an essential loss of the reaction
stereoselectivity was found under ironꢀdeficient conditions. The
recycling of CSꢀS,Sꢀ5 catalyst is likely to be accompanied by a
significant iron leaching from the catalytically active species, due
to processes related to ferric chloride hydrolysis and further
65 condensation of iron hydroxides. These sideꢀreactions will shift
the actual reaction conditions towards ironꢀdeficient, i.e. low
stereoselective, conditions upon catalyst recycling. The drop in
substrate conversion in the third catalyst run along with the
further decrease of the product ee point at an extremely low
70 concentration of catalytically active species and a high L/Fe ratio.
ESIꢀMS analysis of the recovered CSꢀS,Sꢀ5 containing catalyst
mixture showed the presence of the initial ligand and of several
new and, so far, unidentified ions, but did not show previously
assigned ironꢀcontaining species.
5
Catalyst recycling studies
It was found that the carbosilaneꢀappended DPEN ligands are
fairly soluble in common organic solvents (DCM, CHCl3, EtOAc,
THF, MeOH, Et2O, toluene and acetone), however, their
solubility in hexanes varies. For instance, the parent ligand S,Sꢀ1
10 and the other monomeric ligands 4a-c are partially soluble, the
“dimer” 4d and the “tetramers” CSꢀS,Sꢀ1 and CSꢀS,Sꢀ5 are
hardlyꢀsoluble, while CSꢀS,Sꢀ6 is completely soluble in hexanes.
Basing on this observation we attempted the separation of the
catalyst CSꢀS,Sꢀ5 from the reaction medium via precipitation
15 using hexanes. Ferric chloride and 2,6ꢀpyridinedicarboxylic acid
are also known to have a poor solubility in hexanes, while all the
obtained epoxides 3a-d and the corresponding transꢀstilbenes,
except for 2b, easily go into solution in hexanes. By selecting 2c
as a model substrate for the epoxidation with CSꢀS,Sꢀ5 it was
20 envisioned to separate the catalyst and the reaction products using
their drastic solubility difference in hexanes.
In order to investigate the recycling of the CSꢀS,Sꢀ5 catalyst, the
epoxidation of 2c was performed as usual in a batchꢀwise mode.
After oxidant addition was completed, the reaction mixture was
25 concentrated under reduced pressure at RT until most of the tertꢀ
amyl alcohol solvent was removed and a very viscous brownish
residue was obtained. Some hexanes were added to this and the
mixture was thoroughly shaken. The obtained suspension was
centrifuged to form a dense solid phase and a transparent product
30 solution in hexanes. The organic supernatant was decanted from
solids and concentrated under reduced pressure yielding a
brownish oil, which solidified upon standing. The resulting
75 In order to compensate for iron loss during catalysis and
recycling, the same recycling experiment was carried out with the
addition of ca. 20% of the initially introduced amount of
.
FeCl3 6H2O and H2PDC in every subsequent reaction run. In
doing so, complete substrate conversion was reached in the
80 second catalytic run and 96% of R,Rꢀ3c was isolated, which is
comparable to the value obtained in the initial recycling
experiment. At the same time, the stereoselectivity in the second
run improved from 42 to 51% ee, confirming that iron depletion
was the main issue affecting the enantiomeric product outcome.
85 Extra ferric chloride and H2PDC were added again to the
precipitate obtained in this experiment and the obtained mixture
was used in the epoxidation of 2c for the third time. Incomplete
substrate consumption of 78% was observed in this case and 69%
of 3c was isolated. This is roughly two times more than the yield
90 in the initial recycling experiment. The recovered catalyst
stereoselectivity was also higher; it rose slightly from 25 to 30%
ee of the R,Rꢀ3c product. Overall this protocol, involving batchꢀ
wise catalyst recovery and reuse combined with an extra feed of
iron(III) chloride and H2PDC, allowed us to obtain three times
95 more of the 3c epoxide, compared to the conventional reaction
workꢀup. Nevertheless, the average ee of R,Rꢀ3c was 49% against
62% after the first reaction cycle.
1
epoxide product was essentially pure according to GC and Hꢀ
NMR analysis. It was further decolorized by passing it through a
35 short column of silica gel with EtOAc to give 92% of the R,Rꢀ3c
product with 62% ee (Table 4).
Table 4. Study of the CSꢀS,Sꢀ5 catalyst recycling via precipitation and
reuse in batch mode with 2c as a substrate.a)
Entry
1
Run
1
2
3
1
Yield [%]b)
Conv. [%]c)
ee [%]d,e)
92
95
34
95
96
69
99
99
41
99
99
78
62
42
25
63
51
30
2f)
3f)
4
5f,g)
6f,g)
2
3
.
a) Reaction conditions: 2c (1.0 mmol), H2O2 (2.0 mmol), FeCl3 6H2O (5.0
While CSꢀS,Sꢀ5 was recycled based on its poor solubility in
hexanes, recovery and reuse of the carbosilaneꢀlinked monomeric
100 CSꢀS,Sꢀ6 ligand were carried out using its high affinity to apolar
solvents. In this case a hexanesꢀacetonitrile biphasic solvent
system was considered to separate the ligand and the reaction
products. It was found that both trans-stilbene 2a and its epoxide
3a preferably (above 80%) reside in the MeCN phase allowing
105 for their effective extraction. Thus, 2a was oxidized following a
standard catalytic protocol and using the CSꢀS,Sꢀ6 ligand. The
reaction mixture was dried at the end and, subsequently,
partitioned between MeCN and hexanes. The top layer was
40 mol%), H2PDC (5.0 mol%), CSꢀS,Sꢀ5 (3.0 mol%), tertꢀamyl alcohol (18
bꢀe)
f)
mL), RT, 1 h.
See Table 1. A precipitate from the former reaction
cycle was used as a catalyst instead of the ligand, ferric chloride and
g)
.
H2PDC. In addition FeCl3 6H2O (1.0 mol%), H2PDC (1.0 mol%) were
introduced.
45 The solid precipitate was used in the next oxidation run as a
replacement for the ligand, ferric chloride and 2,6ꢀ
pyridinedicarboxylic acid, and only fresh solvent, substrate, and
oxidant were added. A full substrate conversion was achieved in
the second reaction cycle and the epoxide R,Rꢀ3c was isolated in
50 95% yield. The recovered CSꢀS,Sꢀ5 catalyst demonstrated a lower
enantioselectivity (42% ee) in this run. In the third catalyst run
further
washed
with
acetonitrile,
water
containing
6
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 7 of 9
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C3CY00484H
ethylenediamine to scavenge iron and H2PDC, and dried. The 55 for an efficient catalyst reuse, avoiding, for instance, superfluous
isolated material, according to 1HꢀNMR, consisted of mainly
stilbene oxide and carbosilane wedge residues. However, the
characteristic pattern of the chiral DPEN backbone in the 1Hꢀ
NMR spectrum drastically changed (See supporting information
solvent exchange steps, required for precipitation. Most of the
relevant publications in the field emphasize on the fact that the
commercial membranes are often not compatible with organic
solvents required for the reported catalytic transformations (olefin
5
for the details). A new group of multiplets with 1:1 integral ratio 60 metathesis, crossꢀcoupling etc.)[19,20] and in some cases the
appeared at 5.1 and 4.4 ppm. The observed NMR shift to the
weak field may be caused by ligand oxidation; however, no
assignment to any definite structure has been made.
membrane material interacts with
deactivation.[14] Especially when using hydrogen peroxide the
membrane choice is limited. We selected MILLIPORE
Ultrafiltration Membrane made of regenerated cellulose with
from 2.0 to 0.6 equiv. in order to avoid ligand oxidation by the 65 molecular weight cutꢀoff (MWCO) of 1000 Da and of 47 mm in
a catalyst, causing its
a
10 In the next step, the amount of hydrogen peroxide was reduced
excess of oxidant. Also the oxidant addition time was scaled to 30
min instead of 1 h. Under these oxidant limiting conditions
conversion of 2a reached 57% and the epoxide R,Rꢀ3a (in the
15 MeCN layer) was isolated in a 48% substrateꢀbased yield and
diameter. In the case of solvents like CH2Cl2 and EtOAc a stable
flow rate of 25ꢀ45 mL/h was observed under an external pressure
of 3ꢀ4 atm. Pure methanol often caused this membrane to
suddenly leak, while the preferred reaction solvent (tertꢀamyl
40% ee (Table 5). The apolar phase contained the unchanged CSꢀ 70 alcohol) even under 4.5 atm. of external pressure oozed through
S,Sꢀ6 ligand and 3a and 3b as impurities (in total ca. 5ꢀ10% by
weight). After the first reaction run CSꢀS,Sꢀ6 was recovered in
approx. a 75% yield as a slightly turbid colourless oil. In the next
20 run, the substrate, ferric chloride and H2PDC loading were
this membrane with only 0.3ꢀ0.7 mL/h.
Accordingly, the retention of CSꢀS,Sꢀ5 by the membrane was
tested using CH2Cl2 as a solvent and it was estimated to be above
99.90%, as 400/400 mg of CSꢀS,Sꢀ5 stayed behind the membrane
complimentary decreased to maintain the right proportions with 75 and no ligand was found in the permeate. Then, the oxidation of
respect to the recovered ligand. In this case, the epoxide was
isolated in 53% yield and 37% ee; ca. 80% of the CSꢀS,Sꢀ6 ligand
was recovered. The third catalyst cycle provided 46% of R,Rꢀ
25 stilbene oxide with 38% ee and 83% of the ligand was isolated.
2c was carried out as usual with CSꢀS,Sꢀ5 and the reaction
mixture was concentrated to remove tertꢀamyl alcohol. The
residue was dissolved in CH2Cl2, passed through a paper filter
first and then filtered through the MILLIPORE membrane. This
The ESIꢀMS analysis of this recovered ligand revealed except for 80 filtration was repeated three times to wash out the epoxide
the anticipated m/z 929.5195 [M+H]+ also a monoꢀcharged ion of
a low intensity with a 16 units higher m/z value of 945.5385,
which could be attributed to a [M+O+H]+ ion (calcd. m/z
30 945.5128), i.e. a hydroxylation product of CSꢀS,Sꢀ6.
product entirely. After drying the epoxide R,Rꢀ3c was obtained in
96% yield with ee 64% and was shown to be analytically pure.
Conclusions
Table 5. Study of the CSꢀS,Sꢀ6 catalyst recycling via phase separation
and reuse in batch mode with 2a as a substrate.a)
We have presented the immobilization of S,SꢀDPENꢀderived
85 ligands for the homogeneous epoxidation of stilbenes and
demonstrated a determining role of the structure of the soluble
carbosilane support on the catalytic behaviour. This study
emphasizes, once more, that even when having a perfectly
operating and optimized homogeneous catalytic system, along
90 with a large number of catalyst heterogenization strategies at
hand, it is still not a trivial task to transfer the single site
properties of the parent homogeneous catalyst onto its
immobilized and, in this case, molecularly enlarged version. The
initially selected carbosilane support turned out to be
95 inappropriate and lead to a devastating activity of the linked S,Sꢀ
DPEN ligand. In order to understand this observation, several
aspects of the support structure were investigated.
Catalytic stilbene epoxidation experiments with the TMSꢀ
substituted ligands S,Sꢀ4a-c showed that linking of the DPEN
100 ligand to the carbosilane support through the paraꢀposition (as in
S,Sꢀ4a) had a minor impact on catalyst activity, chemoꢀ and
stereoselectivity in transꢀstilbene epoxidation. The diminished
catalytic activity of the “dimeric” ligand S,Sꢀ4d pointed to the
importance of the formation of the proper single site active
105 species. The enlarged carbosilaneꢀlinked CSꢀS,Sꢀ5 was then
studied in order to investigate the preorientation of the peripheral
S,SꢀDPEN ligands by adjusting the flexibility of the support,
which showed that ligand preorientation has a more pronounced
influence on the epoxidation reaction outcome than the proximity
110 of the neighbouring DPEN units.
Run
Ligand
Yield [%]b)
Conv. [%]c)
ee [%]d,e)
recovered, %
1
75
80
83
48
53
45
57
60
55
40
37
38
2f)
3f)
.
a) Reaction conditions: 2a (1.0 equiv.), H2O2 (0.6 equiv.), FeCl3 6H2O (5.0
mol%), H2PDC (5.0 mol%), CSꢀS,Sꢀ6 (12 mol%), tertꢀamyl alcohol, RT,
bꢀe)
f)
35 30 min.
See Table 1. The ligand isolated in the previous run was
.
used; the substrate, FeCl3 6H2O and H2PDC amounts were adjusted in
proportion to the recovered ligand quantity.
Overall, the carbosilane wedge in CSꢀS,Sꢀ6 was shown to be quite
oxidatively robust under oxidant limiting conditions. Moreover,
40 by introducing it into the parent ligand structure, the solubility of
catalyst species was immensely increased, allowing for the
epoxidation to occur faster compared to the parent S,Sꢀ1 catalyst
without sacrificing the stereoselectivity in epoxidations.
Furthermore, the lipophilic nature of the CSꢀS,Sꢀ6 ligand allowed
45 for a simple recovery and reuse of the expensive DPEN ligand. In
addition, by isolating the CSꢀS,Sꢀ6 ligand after its use in catalysis
confirmed its stability during catalytic stilbene epoxidations. This
feature is not obvious for nitrogen ligands used in ironꢀmediated
oxidations and has not been documented before for the DPEN
50 ligand framework.
Finally, ultrafiltration can be considered as an appealing
technique that allows for the (continuous) separation of sizeꢀ
enlarged molecules from a reaction medium. Within our study its
application could further simplify product purification and allow
The recovery and reuse of the carbosilaneꢀappended DPEN
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 7

Catalysis Science & Technology
Page 8 of 9
View Article Online
DOI: 10.1039/C3CY00484H
117, 2675–2676; b) M. L. Clarke, S. D. Phillips, J. A. Fuentes, Chem.
Eur. J. 2010, 16, 8002ꢀ8005; c) I. Carpenter, S. C. Eckelmann, M. T.
Kuntz, J. A. Fuentes, M. B. France and M. L. Clarke, Dalton Trans.
2012, 41, 10136ꢀ10140.
ligands was investigated next. The catalytic system derived from
CSꢀS,Sꢀ5 can be efficiently separated from product mixtures via
precipitation with hexanes or ultrafiltration. Both approaches
facilitate epoxide synthesis and raise the isolated product yield to
near quantitative in the initial run. Moreover, the recovered CSꢀ
S,Sꢀ5 catalyst was shown to be active in three subsequent batch
oxidation experiments, where feeding the system with fresh ferric
chloride and H2PDC lead to better results. A gradual loss of the
catalyst stereoselectivity and, to a lesser extent, activity was still
10 observed though. This can be attributed to a partial catalyst
deactivation as well as catalyst loss due to the required
manipulations in between catalytic runs. In order to overcome
these problems, the application of CSꢀS,Sꢀ5 in a continuous flow
membrane reactor is currently under investigation.
15 The carbosilane wedge linked DPEN ligand CSꢀS,Sꢀ6 has shown
the best performance in epoxidation reactions of the transꢀ
stilbenes 2a-d. This molecularly enlarged ligand closely mimics
the catalytic properties of the parent S,Sꢀ1 ligand by providing
full flexibility to the ligand. Moreover, this ligand has superior
20 solubility properties and remains entirely in solution upon mixing
with the other vital reaction ingredients ferric chloride and
H2PDC, allowing for its potential application in microꢀreactors.
In contrast to the parent S,Sꢀ1 ligand, CSꢀS,Sꢀ6 can be efficiently
recovered unchanged from the reaction medium and reused
25 afterwards. Still, the applied ligand recovery strategy in a
biphasic acetonitrileꢀhexanes system is accompanied by about
20% ligand loss per reaction run and requires the oxidation to be
carried out at moderate substrate conversion levels. Although it
was not exhaustively explored in this study, the size of this
30 molecularly enlarged ligand would allow for its separation from
reaction mixture by means of nanofiltration using a membrane
with MWCO lower than 1000 Da.[20]
Overall, this study has shown the delicacy in designing the proper
soluble supporting material for singleꢀsite homogeneous
35 catalysts. Where earlier we had shown that proximity effects can
be detrimental for the catalytic activity of preformed catalysts,[16b]
the current study has shown that care should be taken in the
immobilization of chiral ligands used for the in-situ formation of
catalysts. These and other considerations are currently employed
40 in the design of advanced supported versions of homogeneous
oxidation catalysts based on iron, where reuse of precious ligands
is more important than reuse of the metal.
60
65
70
75
80
[3] B. Koppenhoefer, V. Schurig, Org. Synth. 1993, 8, 434ꢀ441.
[4] a) A. W. Johnson, R. B. LaCount, J. Am. Chem. Soc. 1961, 83, 417–
423; b) V. K. Aggarwal, J. Richardson, Chem. Commun. 2003, 2644ꢀ
2651; c) V. K. Aggarwal and C. L. Winn, Acc. Chem. Res. 2004, 37,
611ꢀ620.
[5] a) G. De Faveri, G. Ilyashenko and M. Watkinson, Chem. Soc. Rev.
2011, 40, 1722–1760; b) R. W. Murray and M. Singh, Org. Synth.
1997, 74, 91ꢀ95; c) S. Colonna, N. Gaggero, L. Casella, G. Carrea,
and P. Pasta, Tetrahedron: Asymmetry 1993, 4, 1325ꢀ1330; d) T.
Katsuki, K. B. Sharpless, J. Am. Chem. Soc. 1980, 102, 5974ꢀ5976;
e) Z.ꢀX. Wang, Y. Tu, M. Frohn, J.ꢀR. Zhang, and Y. Shi. J. Am.
Chem. Soc. 1997, 119, 11224ꢀ11235.
[6] a) F. G. Gelalcha, B. Bitterlich, G. Anilkumar, M. K. Tse, and M.
Beller, Angew. Chem. Int. Ed. 2007, 46, 7293 –7296; b) F. G.
Gelalcha, G. Anilkumar, M. K. Tse, A. Bruckner, and M. Beller,
Chem. Eur. J. 2008, 14, 7687 – 7698.
[7] a) J. M. Fraile, Jo. I. García, J. A. Mayoral, and E. Pires in
Heterogenized Homogeneous Catalysts for Fine Chemicals
Production (Eds.: P. Barbaro and F. Liguori), Springer, London,
2010, pp. 65ꢀ121; b) N. Baig and R. S. Varma Chem. Commun.,
2012, Accepted Manuscript; c) H. L. Xie, Y. X. Fan, C. H. Zhou, Z.
X. Du, E. Z. Min, Z. H. Ge, and X. N. Li, Chem. Biochem. Eng. Q.
2008, 22, 25ꢀ39.
5
85 [8] For a specific example on the immobilization of DPEN ligands, see
C.ꢀF. Nie, J.ꢀS. Suo, Chin. J. Chem. 2005, 23, 315—320.
[9] a) T. J. Dickerson, N. N. Reed, K. D. Janda, Chem. Rev. 2002, 102,
3325–3344; b) J. K. Kassube, L. H. Gade, Top. Organomet. Chem.
2006, 20, 61ꢀ96; c) D. Astruc, F. Chardac, Chem. Rev. 2001, 101,
90
95
2991ꢀ3023; d) B. Helms and J. M. J. Frechet, Adv. Synth. Catal.
2006, 348, 1125ꢀ1148; e) R. van Heerbeek, P. C. J. Kamer, P. W. N.
M. van Leeuwen, and J. N. H. Reek, Chem. Rev. 2002, 102, 3717ꢀ
3756.
[10] a) V. A. Yazerski and R. J. M. Klein Gebbink in Heterogenized
Homogeneous Catalysts for Fine Chemicals Production (Eds.: P.
Barbaro and F. Liguori), Springer, London, 2010, pp. 171ꢀ201; b) R.
Haag, S. Roller in Polymeric Materials in Organic Synthesis and
Catalysis (Ed.: M.R. Buchmeiser), WileyꢀVCH, Weinheim, 2003, pp.
305ꢀ344.
100 [11] a) N. J. M. Pijnenburg, H. P. Dijkstra, G. van Koten and R. J. M.
Klein Gebbink, Dalton Trans. 2011, 40, 8896ꢀ8905; b) N. J. M.
Pijnenburg, M. Lutz, M. A. Siegler, A. Spek, G. van Koten, R. J. M.
Klein Gebbink, New J. Chem. 2011, 35, 2356ꢀ2365; c) M. A. N.
Virboul, M. Lutz, M. A. Siegler, A. L. Spek, G. van Koten, R. J. M.
105
Klein Gebbink., Eur. J. Chem. 2009, 15, 9981ꢀ9986, d) D. J. M.
Snelders, M. A. N. Virboul, R. Kreiter, C. Versluis, G. van Koten and
R. J. M. Klein Gebbink, Dalton Trans. 2012, 41, 2354ꢀ2359; e) A. V.
Gaikwad, V. Boffa, J.E. ten Elshof, G. Rothenberg, Angew. Chem.
Int. Ed. 2008, 47, 5407ꢀ5410; f) Y.ꢀC. Chen, T.ꢀF. Wu, J.ꢀG. Deng,
H. Liu, X. Cui, J. Zhou, Y.ꢀZ. Jiang, M. C. K. Choi, and A. S. C.
Chan, J. Org. Chem. 2002, 67, 5301ꢀ5306; g) J. Liu, Y. Zhou, Y. Wu,
X. Li and A. S. C. Chan, Tetrahedron: Asymmetry 2008, 19, 832ꢀ
837; h) W. Wang and Q. Wang, Chem. Commun. 2010, 46, 4616ꢀ
4618.
110
Acknowledgements
This work was supported by 7PCRD EU funds from the Marieꢀ
45 Curie Initial Training Network NANOꢀHOST (grant agreement
ITN 215193). The national research school combination catalysis
(NRSCC) is acknowledged for further financial support.
115 [12] A. Berger, R. J. M. Klein Gebbink, and G. van Koten, Top.
Organomet. Chem. 2006, 20, 1ꢀ37.
[13] A. F. AbdelꢀMagid, K. G. Carson, B. D. Harris, C. A. Maryanoff, R.
D. Shah, J. Org. Chem. 1996, 61, 3849ꢀ3862.
[14] P. Wijkens, J. T. B. H. Jastrzebski, P. A. van der Schaaf, R. Kolly, A.
Hafner, G. van Koten, Org. Lett. 2000, 11, 1621ꢀ1624.
References
[1] a) L. P. C. Nielsen and E. N. Jacobsen in Aziridines and Epoxides in 120
50
55
Organic Synthesis (Ed.: A. K. Yudin), WileyꢀVCH, Weinheim, 2006,
pp. 229ꢀ269; b) P. Crotti and M. Pineschi in Aziridines and Epoxides
in Organic Synthesis (Ed.: A. K. Yudin), WileyꢀVCH, Weinheim,
2006, pp. 271ꢀ313; c) V. V. Fokin and P. Wu in Aziridines and
Epoxides in Organic Synthesis (Ed.: A. K. Yudin), WileyꢀVCH, 125
Weinheim, 2006, pp. 443ꢀ477.
[15] J. Le Notre, J. J. Firet, L. A. Sliedregt, B. J. van Steen, G. van Koten,
R. J. M. Klein Gebbink, Org. Lett. 2005, 7, 363ꢀ366.
[16] a) A. W. Kleij, R. A. Gossage, J. T. B. H.Jastrzebski, J. Boersma, G.
van Koten, Angew. Chem. Int. Ed. 2000, 39, 176–178; b) A. W. Kleij,
R. A. Gossage, R. J. M. Klein Gebbink, N. Brinkmann, E. J. Reijerse,
U. Kragl, M. Lutz, A. L. Spek, G. van Koten, J. Am. Chem. Soc.
2000, 122, 12112–12124.
[2] Diols, aminoalcohols and diamines in catalysis: a) T. Ohkuma, H.
Ooka, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1995,
8
|
Journal Name, [year], [vol], 00–00
This journal is © The Royal Society of Chemistry [year]

Page 9 of 9
Catalysis Science & Technology
View Article Online
DOI: 10.1039/C3CY00484H
[17] G. E. Oosterom, R. J. van Haaren, J. N. H. Reek, P.C.J. Kamer, P.
W. N. M. van Leeuwen, Chem. Commun. 1999, 1119–1120.
[18] A. W. van der Made, P. W. N. M. van Leeuwen, Chem. Soc. Chem.
Commun. 1992, 1400ꢀ1401.
5
[19] a) A. Kajetanowicz, J. Czaban, G. R. Krishnan, M. Malinska, K.
Wozniak, H. Siddique, L. G. Peeva, A. G. Livingston, and K. Grela
Chem. Sus. Chem. DOI: 10.1002/cssc.201200466; b) M. Janssen, J.
Wilting, C. Müller, and D. Vogt, Angew. Chem. Int. Ed. 2010, 49,
7738ꢀ7741.
10 [20] A. M. Arink, R. van de Coevering, B. Wieczorek, J. J. Firet, J. T. B.
H. Jastrzebski, R. J. M. Klein Gebbink, G. van Koten, J. Organomet.
Chem. 2004, 689, 3813ꢀ3819.
This journal is © The Royal Society of Chemistry [year]
Journal Name, [year], [vol], 00–00 | 9