Biaryl-bridged salalen ligands and their application in titanium-catalyzed asymmetric epoxidation of olefins with aqueous H2O2

Article abstract of DOI:10.1002/ejoc.201100512

A series of biaryl-bridged salalen ligands together with their titanium complexes have been designed and synthesized. The Ti complexes could serve as highly efficient catalysts for the asymmetric epoxidation of a wide range of olefins, giving the corresponding epoxides with high ee values. A biaryl-bridged salalen titanium complex was developed and used in the enantioselective epoxidation of a range of olefins with aqueous hydrogen peroxide as the oxidant. Notably, the intramolecular dinuclear Ti catalyst possessing a biaryl bridge is highly efficient for the reaction, especially using terminal aromatic olefins as substrates.

Full text of DOI:10.1002/ejoc.201100512

SHORT COMMUNICATION
DOI: 10.1002/ejoc.201100512
Biaryl-Bridged Salalen Ligands and Their Application in Titanium-Catalyzed
Asymmetric Epoxidation of Olefins with Aqueous H2O2
Donglu Xiong,[a,b] Xiaoxue Hu,[a] Shoufeng Wang,[a] Cheng-Xia Miao,[a] Chungu Xia,[a] and
Wei Sun*[a]
Keywords: O ligands / Asymmetric catalysis / Epoxidation / Alkenes / Titanium
A series of biaryl-bridged salalen ligands together with their
titanium complexes have been designed and synthesized.
The Ti complexes could serve as highly efficient catalysts for
the asymmetric epoxidation of a wide range of olefins, giving
the corresponding epoxides with high ee values.
ation reaction.[24,28,29] As for another breakthrough in
designing new ligands for asymmetry reaction, Ding and
co-workers developed binuclear Ti–salen catalysts con-
nected through organic linkages to dramatically enhance
the catalytic activity and enantioselectivity for the cyan-
ation of aldehydes.[40]
Inspired by this pioneering work and our early work in
asymmetric reactions,[30,41] we decided to bridge two salalen
ligands with a biaryl linker and to synthesize their corre-
sponding di-μ-oxotitanium complexes. Delightedly, the di-
nuclear Ti complexes are found to serve as effective cata-
lysts for the asymmetric epoxidation of a variety of olefins
with high enantioselectivities.
Introduction
Optically active epoxides are very important molecules
in a broad range of chemical transformations; these com-
pounds are mainly produced by a critical process involving
catalyzed enantioselective epoxidation reactions of ole-
fins.[1–3] Over the past three decades, many efforts have been
devoted to the development of efficient catalysts for the
enantioselective epoxidation of olefins. Many catalyst sys-
tems including chiral metal complexes[3–9] and organocat-
alysts[10–15] have been successfully established. Indeed, high
asymmetric induction for the asymmetric epoxidation of
olefins clearly depends on the used oxidant. For example,
NaOCl or PhIO was generally employed as oxidant in epox-
idation reactions catalyzed by salen–MnIII complexes.[16–18]
However, in terms of sustainability and atom efficiency,
aqueous hydrogen peroxide is a desired choice of oxidant,
only producing water as a byproduct.[19] In this context, the
recent catalyst systems reported by Katsuki et al. are very
successful, as they are able to catalyze the asymmetric epox-
idation of olefins in high yield with high enantioselectivity
by using titanium salalen or salan complexes as cata-
lysts.[20–30] Moreover, other metal complexes based on sal-
alen or salan ligands are effective catalysts in a number of
asymmetric reactions.[31–39] The feature of these titanium
complexes (salan or salalen) is that two Ti complex units
are connected by two oxygen bridges. Based on their find-
ings, Katsuki and Berkessel favored a mononuclear tita-
nium complex as the real species responsible for the epoxid-
Results and Discussion
The synthetic route is illustrated in Scheme 1. The biaryl-
bridged salalen ligands could be easily prepared from
monoalkylated diamine II and 3,3Ј-diformyl-2,2-dihydroxy-
1,1Ј-biphenyl or 3,3Ј-diformyl-2,2-dihydroxy-(R)-1,1Ј-bi-
naphthyl according to the procedures for the synthesis of
monomeric salalen ligands.[28,29] Based on this strategy, bi-
aryl-bridged salalen ligands 1–4 were readily synthesized
(Figure 1). A desired di-μ-oxotitanium complex could be
formed with a standard procedure reported by Katsuki et
al., which was confirmed by ESI-TOF MS (Figure 2). In
[a] State Key Laboratory for Oxo Synthesis and Selective
Oxidation, Lanzhou Institute of Chemical Physics, Chinese
Academy of Sciences,
Lanzhou 730000, China
Fax: +86-931-496-8129
E-mail: wsun@licp.cas.cn
[b] Graduate School of the Chinese Academy of Sciences,
Beijing 100039, China
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201100512.
Scheme 1. The synthetic route for biaryl-bridge salalen ligands.
© 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 4289
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D. Xiong, X. Hu, S. Wang, C.-X. Miao, C. Xia, W. Sun
SHORT COMMUNICATION
Figure 1. Chiral salalen ligands 1–4.
addition, partial 16O exchange with H218O also demon-
With these Ti complexes in hand, their performance in
strates the existence of the oxygen bridge (Figure 3; Fig- the asymmetric epoxidation of styrene were initially evalu-
ures S4 and S5, Supporting Information).
ated by using H2O2 as the oxidant and dichloromethane as
the solvent. When 1 mol-% of complex Ti-1 was used as the
catalyst, 88%ee was observed with 1 equiv. of H2O2
(Table 1, Entry 1). Styrene oxide was obtained in 70% yield
and 90%ee after increasing the amount of H2O2 to 2 equiv.
(Table 1, Entry 3). With complex Ti-2 as the catalyst, only
77%ee was achieved under the same conditions (Table 1,
Entry 5). Unfortunately, complex Ti-3 was an inefficient
catalyst, resulting in a trace amount of the product (Table 1,
Entry 6). Complex Ti-4, derived from (1R,2R)-1,2-cyclo-
hexanediamine and (R)-BINOL, provided considerable
enantioselectivity, albeit with a low yield (Table 1, En-
tries 7 & 8). Interestingly, in situ generation of complex Ti-
1 from ligand 1 and Ti(OiPr)4 showed comparable activity
compared with pre-prepared complex Ti-1 (Table 1, Entry 4
vs. 3). Then the in situ generation of the active catalyst
would be more practical and convenient.
Figure 2. Chiral salalen-Ti complexes.
Table 1. Screening of the catalysts and reaction conditions.
Entry
Complex (mol-%) H2O2 Yield
ee
Config.[c]
[equiv.] [%][a] [%][b]
1
2
3
Ti-1 (1)
Ti-1 (1)
Ti-1 (1)
1.0
1.5
2.0
2.0
2.0
2.0
2.0
2.0
61
62
70
73
67
trace
17
50
88
90
90
88
77
–
S
S
S
S
R
–
4[d]
5
1 and Ti(OiPr)4 (1)
Ti-2 (1)
6
7
8
Ti-3 (1)
Ti-4 (1)
Ti-4 (2)
81
88
S
S
[a] Determined by GC with n-nonane as internal standard. [b] De-
termined by GC with a CP-Chirasil-Dex CB chiral column (25 m
ϫ0.25 mm). [c] The absolute configurations were assigned by com-
paring GC elution order with known literature data. [d] Reaction
conditions: To a CH2Cl2 (0.5 mL) solution of ligand 1 and Ti-
(OiPr)4 (1 mol-%) stirred initially for 1 h was added one drop of
H2O. The mixture was then stirred for 30 min, and styrene
(0.1 mmol) and n-nonane (as internal standard) were added. Then,
30% aqueous hydrogen peroxide (0.2 mmol) was added into the
mixture over 100 min. Finally, the mixture was stirred for 9 h.
Figure 3. HRMS of C52H51N4O6Ti2 with partial 16O exchange with
H218O. Testing conditions: 20 equiv. of H218O was added to the
mixture of C52H51N4O6Ti2 (0.9 mg) and CH2Cl2, and then the mix-
ture was stirred for 1 h.
Having established the optimal reaction system, a variety
of olefins with different structures were explored with com-
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Eur. J. Org. Chem. 2011, 4289–4292

Ti-Catalyzed Asymmetric Epoxidation of Olefins with Aqueous H2O2
plex Ti-1 as the catalyst, and the results are summarized in phenylpent-2-en-3-yne underwent the epoxidation with 97,
Table 2. To our delight, various styrene derivatives could 96, and 92%ee, respectively (Table 2, Entries 9, 11 and 13).
be smoothly transformed into their epoxide derivatives in Besides, a comparison experiment for the epoxidation of
satisfactory yields and with Ͼ90%ee (Table 2, Entries 1–3). a mixture of cis-β-methylstyrene and trans-β-methylstyrene
Substitution of styrene with electron-withdrawing groups (cis/trans = 57:43) was also conducted, and the reaction of
such as chloride and bromide resulted in higher enantio- trans-β-methylstyrene proved to be very sluggish (see the
selectivity than that observed with styrene. It is noteworthy Supporting Information). The reaction of vinylcyclohexane
that epoxidation of 2-vinylnaphthalene gave the corre- proceeded with 78%ee, but the reaction was very slow
sponding epoxide in high enantioselectivity (99%ee; (Table 2, Entry 15). The epoxidation of 1-octene gave
Table 2, Entry 4). Next, two 2,2-disubstituted chromene de- 61%ee with 3 mol-% of complex Ti-2 as catalyst (Table 2,
rivatives were examined in the asymmetric epoxidation with Entry 17).
complex Ti-1 as catalyst. The epoxidation reactions pro-
Comparison experiments between biaryl-bridged com-
ceeded smoothly with good chemical yield and high plex Ti-1 and nonbridged complex Ti-5 reported by Berkes-
enantioselectivity (Table 2, Entries 6 & 8). Moreover, the sel were performed under the same reaction conditions. In
catalytic system was also successfully applied to cis-olefins. the case of 2-vinylnaphthalene, complex Ti-1 led to a 93%
1,2-Dihydronaphthalene, cis-β-methylstyrene, and (Z)-5- yield and 99%ee (Table 2, Entry 4). However, only 66%ee
was observed with complex Ti-5 (Table 2, Entry 5).[42] For
the epoxidation of 2,2-disubstituted chromene derivatives
and 1,2-dihydronaphthalene, both catalysts showed similar
activity and enantioselectivity (Table 2, Entries 6 & 7 and
Table 2. Asymmetric epoxidation of various olefins catalyzed by Ti
complex Ti-1 and Ti-5.
9 & 10). When complexes Ti-1 and Ti-5 were used to cata-
lyze the epoxidation of cis-β-methylstyrene or (Z)-5-phen-
ylpent-2-en-3-yne, the ee values were 96 and 69% or 92 and
76%, respectively (Table 2, Entries 11 & 12 and 13 & 14).
We also tested nonconjugated olefins such as vinylcyclohex-
ane, and the epoxide yield was quite low with both catalysts
(Table 2, Entries 15 & 16). Based on the above results, com-
plex Ti-1 has great advantages in the epoxidation of ter-
minal aromatic olefins such as 2-vinylnaphthalene. It can
also efficiently catalyze the asymmetric epoxidation of cis-
β-methylstyrene, affording the enantioenriched epoxide in
96%ee. As for the improvement in the ee values in some
examples, the reason may be ascribed to the larger steric
hindrance of complex Ti-1 at the biaryl substituent site
compared with the Ph group of Ti-5.
Conclusions
In conclusion, we have developed a biaryl-bridged sal-
alen titanium complex that exhibited high enantioselectivity
in the epoxidation of a range of olefins with aqueous hydro-
gen peroxide as the oxidant. The intramolecular dinuclear
Ti catalyst possessing a biaryl bridge is highly efficient for
the reaction of terminal aromatic olefins. Further studies
on asymmetric catalysis and the mechanism of metal com-
plexes bearing the biaryl-bridged salalen or salan ligands
are in progress.
Experimental Section
Procedure for the Synthesis of Ligands 1–4: Under an argon
atmosphere, 3,3Ј-diformyl-2,2Ј-dihydroxy-1,1Ј-biphenyl (121 mg,
0.5 mmol) and N-(3-phenyl-2-hydroxybenzyl)-(1R,2R)-1,2-diami-
nocyclohexane (296 mg, 1 mmol) were dissolved in ethanol
[a] Determined by GC analysis with n-nonane as internal standard.
(15 mL), and the mixture was heated at reflux overnight. The mix-
[b] Determined by GC with a CP-Chirasil-Dex CB chiral column
ture was cooled and filtered. Then the residue was washed with
(25 m ϫ0.25 mm) or HPLC with a Daicel chiral column. [c] The
cooled ethanol and dried under vacuum at 40 °C. Ligand 1 was
absolute configurations were assigned by comparing optical rota-
obtained as a yellow powder (203 mg, 51% yield). Data for ligand
1: [α]2D0 = –135.7 (c = 0.47, CH2Cl2). 1H NMR (400 MHz, CDCl3):
δ = 13.57 (s, 2 H), 8.45 (s, 2 H), 7.57–6.80 (m, 22 H), 4.08 (d, J =
tions and/or GC & HPLC elution order with known literature data.
[d] Isolated yield. [e] Reaction at r.t. for 4 h. [f] Ti-2 (3 mol-%) as
catalyst.
Eur. J. Org. Chem. 2011, 4289–4292
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D. Xiong, X. Hu, S. Wang, C.-X. Miao, C. Xia, W. Sun
SHORT COMMUNICATION
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2.71 (m, 2 H), 2.21–2.18 (m, 2 H), 1.79–1.20 (m, 14 H) ppm. 13C
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Procedure for the Synthesis of Complex Ti-1: Ti(OiPr)4 (2.6 mmol)
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dichloromethane (3.5 mL) under an argon atmosphere, and the
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General Procedure for the Asymmetric Epoxidation of the Olefins:
To a stirred solution of catalyst Ti-1 (0.9 mg, 1 mol-%) in dichloro-
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Acknowledgments
Financial support from the Chinese Academy of Sciences and
National Natural Science Foundation of China (20873166,
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Received: April 12, 2011
Published Online: June 6, 2011
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Eur. J. Org. Chem. 2011, 4289–4292