Catalytic asymmetric ring-opening reaction of meso-epoxides with aryl selenols and thiols catalyzed by a heterobimetallic gallium-titanium-salen complex

Article abstract of DOI:10.1002/adsc.200800767

A chiral heterobimetallic Lewis acid complex has been developed as an efficient catalyst. The enantioselective desymmetrization of meso-epoxides with aryl selenols and thiols catalyzed by the heterobimetallic complex has been optimized. The optically active β-arylseleno alcohols and β-hydroxy sulfides were obtained in good yields and high enantioselec- tivities (up to 97% ee and 92% ee, respectively). A strong synergistic effect between different Lewis acids was exhibited in the catalytic process. & copy; 2009 Wiley-VCH Verlag GmbH & Co. KGaA.

Full text of DOI:10.1002/adsc.200800767

FULL PAPERS
DOI: 10.1002/adsc.200800767
Catalytic Asymmetric Ring-Opening Reaction of meso-Epoxides
with Aryl Selenols and Thiols Catalyzed by a Heterobimetallic
Gallium-Titanium-Salen Complex
Jiangtao Sun,a Minghua Yang,a Fang Yuan,a Xuefeng Jia,a Xia Yang,a Yi Pan,a
and Chengjian Zhua,b,*
a
State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University,
Nanjing 210093, Peopleꢀs Republic of China
Fax : (+86)-25-8331-7761; phone: (+86)-25-8359-4886; e-mail: cjzhu@nju.edu.cn
State Key Laboratory of Organometallic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of
b
Science, Shanghai, 200032, Peopleꢀs Republic of China
Received: December 10, 2008; Revised: March 12, 2009; Published online: April 6, 2009
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/adsc.200800767.
Abstract: A chiral heterobimetallic Lewis acid com- tivities (up to 97% ee and 92% ee, respectively). A
plex has been developed as an efficient catalyst. The strong synergistic effect between different Lewis
enantioselective desymmetrization of meso-epoxides acids was exhibited in the catalytic process.
with aryl selenols and thiols catalyzed by the hetero-
bimetallic complex has been optimized. The optically
active b-arylseleno alcohols and b-hydroxy sulfides Keywords: asymmetric catalysis; catalyst design; ep-
were obtained in good yields and high enantioselec- oxides; gallium; synthetic methods
Introduction
metric reactions over the past several decades. Until
now, many efforts have been devoted to developing
The design and use of bimetallic complexes for asym- new catalysts based on the salen framework. Quite re-
metric catalysis have seen significant progress and is cently, Shibasaki and co-workers reported the discov-
emerging as a rapidly developing area. Inspired by ery and utility of a new type of salen complex – the
the advantages of enzymes containing two or more dinucleated Schiff base complex 1 as efficient cata-
active sites, and in the assumption that the potential lysts in asymmetric aza-Henry reactions and nitroal-
well-organized spatial arrangement of the bimetallic dol reactions (Figure 1).[5] This N2O4 Schiff base selec-
or multimetallic complex would make the reaction tively incorporated M1 into the inner N2O2 cavity and
more reactive and selective, chemists have succeeded an oxophilic rare earth metal (M2), into the outer O4
in developing several kinds of multifunctional cata- cavity. They found that the cooperative function of
lysts for asymmetric reactions.[1] In the 1990s, Shibasa- the two metals was the key factor to achieving high
ki and co-workers reported their first investigations diastereo- and enantioselectivity in the reactions.
using a chiral heterobimetallic complex in asymmetric
The broad applicability of salen ligands makes fur-
reactions with good enantioselectivities.[2] Subsequent- ther developments possible by serving as useful plat-
ly, they developed a series of bimetallic Lewis acid– forms for the discovery of new catalysts.[6b] For tradi-
Brønsted base, Lewis acid–Lewis acid catalytic sys- tional metal-salen complexes, the tetradentate motif
tems for use in various asymmetric reactions with ex- incorporates a metal into the N2O2 cavity to form a
cellent results.[3] Recently, several other groups have “closed” structure (Figure 1, previous work). Thus,
also reported the successful applications of chiral bi- many of the applications associated with these cata-
or multimetallic complexes in asymmetric reactions lysts rely upon this arrangement and the predomi-
with high catalytic reactivities and enantioselectivi- nance of the chelate effect.[6] In some cases, however,
ties.[4]
metal-salen complexes have been shown to support
Metal complexes of the salen ligand, classified as a monometallic or bimetallic formulations of metals
“privileged catalyst”, have been widely used in asym- with a “open” mode. The fact that the monometallic
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Adv. Synth. Catal. 2009, 351, 920 – 930

Catalytic Asymmetric Ring-Opening Reaction of meso-Epoxides
FULL PAPERS
Figure 1. Different metal-ligand complexes.
“open” complex still contains an uncoordinated NO Scheme 1).[9] The reaction of 1 equivalent of GaMe3
moiety makes it possible to incorporate another metal with salen gave the “open” complex 6 not 5, subse-
(M2) into the N2O2 cavity, resulting in the formation quent reaction with another 1 equivalent of GaMe3
of heterobimetallic complex 2 (Figure 1, our work). In furnished the “open” homobimetallic complex 7
addition, the design of this type of catalyst has also (Scheme 1).
been governed by the hypothetical existence of coop-
In the present work we report the reaction of mon-
erative effects between the two metal centers under ometallic chiral complexes (salen-GaMe2) with anoth-
the same chiral template, which may lead to better er metal source (M2) to form the heterobimetallic
asymmetric induction in the reaction transition state. complexes (salen-Ga-M2) and their applications in the
Furthermore, as it is well known that even if a small enantioselective ring-opening reactions of meso-epox-
change in the structure of the catalyst may exert a tre- ides with aryl selenols and thiols.
mendous influence on the catalytic reactivity and se-
lectivity, this also prompted us to explore the applica-
tions of the heterobimetallic salen-M1–M2 complexes Results and Discussion
in asymmetric reactions.
Compared with transition metals, the combination The enantioselective desymmetrization of meso-epox-
of group 13 elements with chiral salen ligands has at- ides with nucleophiles has proven to be a valuable
tracted less attention in asymmetric reactions, except tool for the straightforward synthesis of enantiomeri-
for salen-Al.[7] In general, group 13-salen complexes cally highly enriched 1,2-difunctionalized organic
can be prepared by combining the ligand with trialkyl compounds.[10] Although ring-opening reactions of
group 13 reagents in non-oxygenated solvents.[8] The meso-epoxides with different nucleophiles have been
reaction of AlMe3 with a chiral salen ligand afforded described,[11] up to now, only a few reports have been
the monometallic chelate salen-AlMe and we found concerned with the use of thiols as nucleophiles[12]
the same situation with indium (Scheme 1). Mean- and much less with selenols.[13]
while, the metal, Al or In, is coordinated by all of the
Our preliminary experiments showed that 5 mol%
four heteroatoms of the ligand in a planar arrange- of Ga-Ti-salen complex effectively catalyzed the sele-
ment. However, some investigations have reported nolysis of various meso-epoxides in excellent yields
and what we have discovered, is that gallium readily and enantioselectivities.[13a] Herein, we wish to report
forms open structures with salen ligands (complex 6, our further investigations on the optimizations of var-
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Scheme 1. Reactions of salen ligand with different trimethyl group 13 reagents.
ious reaction parameters in the ring-opening reactions groups at two positions on the phenol rings in the
with aryl selenols and thiols. ring-opening reactions. As shown in Scheme 2, treat-
In order to avoid solubility problems, we firstly in- ment of 3 with one equivalent of GaMe3 provided
vestigated salen(t-Bu)-3 which possesses tert-butyl monometallic “open” complex 6. Subsequent reaction
ACHTUNGTRENNUNG
Scheme 2. Reagents and conditions: a) GaMe3, hexane, 0–258C, 4 h; b) Ti
Pr)4, hexane, 08C, 1 h.
ACHUTGTNRENNUG(O-i-Pr)4 (1 equiv.), hexane, 08C, 1 h; c) TiACHTUNGTRENNUNG(O-i-
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Catalytic Asymmetric Ring-Opening Reaction of meso-Epoxides
FULL PAPERS
Table 1. Asymmetric ring-opening of cyclohexene oxide with
Table 2. Asymmetric ring-opening of cyclohexene oxide with
selenophenol.[a]
selenophenol.[a]
Entry Amount
[mol%]
Solvent Temp. Time Yield
ee
Entry Catalyst
Yield
[%][b]
ee
[oC]
[h]
[%][b]
[%][c]
[%][c]
1
2
3
4
5
6
7
8
10
10
10
10
10
10
10
10
5
2
1
0.5
5
Et2O
20
2
2
2
2
3
5
5
5
5
5
5
5
5
96
90
93
96
96
94
94
83
93
92
85
62
92
69
35
83
85
90
95
97
91
97
95
92
89
94
1
2
3
4
3+GaMe3 (6)
3+2 equivalent GaMe3 (7)
3+Ti(O-i-Pr)4 (9)
75
75
85
85
32
35
59
50
CH2Cl2 20
toluene 20
hexane 20
AHCTUNGTRENNUNG
3+GaMe3 +Ti
(1:1:0.5)
ACHTUNGTNER(NUNG O-i-Pr)4
hexane 0
hexane À20
hexane À40
hexane À78
hexane À40
hexane À40
hexane À40
hexane À40
Hexane À40
5
6
3+GaMe3 +Ti
A
80
76
3+GaMe3 +TiACHTUNGTRENNNUG
[a]
Reaction conditions: cyclohexene oxide (1.0 mmol),
PhSeH (1.1 mmol), catalyst (5 mol%), hexane (3 mL).
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H
column.
9
10
11
12
13[d]
[b]
[c]
[a]
Unless otherwise noted, all reactions were conducted
under the following conditions: cyclohexene oxide
(1.0 mmol), PhSeH (1.1 mmol), catalyst 8 (10 mol%), sol-
vent (3 mL).
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H
column.
er, further decreasing the catalyst loading to
0.5 mol% resulted in a moderate yield and a slight
lower enantioselectivity (89% ee) (entry 12). Howev-
er, the addition of 4 ꢂ molecular sieves did not gave
any positive effect (entry 13). So we chose 5 mol%
catalyst loading, hexane as solvent and À408C as pre-
ferred reaction temperature for further optimization.
For comparison, the mono- and homobigallium cat-
alysts 6, 7 and monotitanium complex 9 have also
[b]
[c]
[d]
4 ꢂ molecular sieves were added as additives.
with one equivalent of Ti
metallic complex 8 (Scheme 2), which was directly conditions. However, we found that when 6 and 7
used as chiral catalyst in the reaction. were used, moderate yields and low selectivities were
ACHTUNGRTEN(NUNG O-i-Pr)4 gave the heterobi- been investigated under the above optimized reaction
Using the in situ prepared complex 8 (10 mol%) as obtained. In particular, 6 and 7 displayed similar reac-
catalyst, we initially tested the asymmetric ring-open- tivity and selectivity (Table 2, entries 1 and 2). The
ing of cyclohexene oxide with selenophenol as a use of cyclic titanium complex 9 provided high yield
model reaction in different solvents at 208C. From but moderate selectivity (entry 3). The molar ratio of
the summarized results (Table 1) we found that the Ga/Ti/3 was also critical for the selectivity. Changing
solvents toluene and hexane gave the ring-opening the molar ratio of GaMe3/Ti
products in good yields and high enantioselectivities or lower avlues resulted in a decreased enantioselec-
(Table 1, entries 3 and 4), while diethyl ether dis- tivity. Meanwhile, changing the ratio of GaMe3/Ti(O-
ACHTUNGTERN(NUNG O-i-Pr)4 to either higher
ACHTUNGTRENNUNG
played good reactivity but moderate selectivity (en- i-Pr)4 to 1:0.5 gave a much lower enantioselectivity.
tries 1). The use of CH2Cl2 led to good yield but a So this optimization demonstrated that the combina-
very low ee value. Among the solvents tested, hexane tion of Ga-Ti-salen heterobimetallic complex in a
was proven to be the best one in terms of yield and ratio of 1:1:1 was essential for the high enantioselec-
selectivity. A variation of the reaction temperature tivity.
from 20 to À408C caused a significant increase in the
The selection of the chiral ligand is an important
enantioselectivity (up to 97%, entry 7), but a slight factor in the asymmetric reaction. A suitable chiral
decrease was observed when the reaction was carried ligand would offer an optimal chiral environment in
out at À788C (entry 8). Using hexane as solvent, dif- the asymmetric induction process. Under the opti-
ferent catalyst loadings were then investigated at mized reaction conditions (5 mol% catalyst loading,
À408C. The results showed there was no significant À408C, hexane as solvent), we initiated the optimiza-
change in reactivity and selectivity when the catalyst tion by investigating the steric and electron effects of
loading was decreased to 5 mol% (entry 9). The reac- the substituents on the phenyl ring of the salen li-
tions still showed good results even with 2 mol% cata- gands (Figure 2).[14] All chiral complexes were used
lyst loading (entry 10), and 1 mol% still provided the with in situ formation. The results revealed that the
product in 92% ee and 85% yield (entry 11). Howev- bulky ortho-substitution on the phenyl ring of the
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Figure 2. List of chiral ligands investigated in the ring-opening reaction.
Schiff base part was necessary for high enantioselec- the ligand structure was the change to the macrocycle
tivity (Table 3, entries 3 and 5 vs. the others). Howev- Schiff-base ligand (15),[19] with the expectation that
er, the utilization of Kozlowskiꢀs modular bifunctional this multidentate N4O2-coordination compartment
salen ligands,[15] which contain both Lewis acid and could bind the two metals in a planar mode. Unfortu-
Lewis base activating groups, did not improve but nately, the enantioselectivity obtained was still far
rather decreased the reactivity and selectivity (en- from satisfying (entry 16). The optimization of the
tries 7 and 8). Secondly, we attempted to change the ligand structure revealed that ligand 3 remained the
chiral backbone from cyclohexane-1,2-diamine to 1,2- best one when combined with Ga and Ti species in
diphenylethane-1,2-diamine and 2,5-dimethylcyclo- this ring-opening reaction.
hexane-1,4-diamine,[16] but these changes did not
As the chiral complex Ga-Ti-3 worked very well in
make any improvements either on reactivity or on se- the enantioselective ring-opening reaction of meso-
lectivity. Next, we chose salan [N,N’-alkylbis(salicyl- epoxides with selenophenol, a further investigation on
ACHTUNGTRENNUNGamine)] ligands as chiral sources. Compared with the combination of GaMe3-3 with different Lewis
salen, salan ligands have increased basicity due to 2 acids was performed. All reactions were conducted
À
N H groups and a more flexible framework, these with 5 mol% chiral complexes in hexane at À408C.
properties make possible the salan ligand and the The results are summarized in Table 4. From the re-
metal atom binding in a non-planar arrangement sults we can see that the combination of Ga-TiCl4-3
which afforded superior asymmetric induction to caused
metal-salen in several reactions.[17] However, the het- (entry 1). Compared with Ti
erobimetallic complex Ga-Ti-13 gave inferior selectiv- relatively weaker Lewis acid VO
ity and inverse configuration compared with the cor- lower reactivity and selectivity (entry 2). Similar phe-
responding salen ligands (entries 13 and 14). A fur- nomena were observed with CrCl3 and Cu(OAc)2 (en-
a
slight decrease in enantioselectivity
(O-i-Pr)4, the use of the
(O-i-Pr)3 led to both
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ther modification towards an increase of the ligandꢀs tries 3 and 4). Also, the introduction of another tri-
coordination sites[18] was performed, in the expecta- methyl group 13 reagent, AlMe3 or InMe3, gave mod-
tion that this hexadentate chiral ligand (14) could co- erate reactivity but pretty low selectivity (entries 5
ordinate more easily with two metals to afford favora- and 6). Screening of two rare earth metals indicated
ble stereochemical control in the asymmetric induc- that both of them gave poor reactivities and low se-
tion process. It turned out, however, that Ga-Ti-14 lectivities (entries 7 and 8). Inspection of different
gave poor results (entry 15). The last modification of Lewis acids revealed that TiACTHNUTRGNEN(UG O-i-Pr)4 was the best
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Catalytic Asymmetric Ring-Opening Reaction of meso-Epoxides
Table 3. Optimization of ligands in the ring-opening reac-
FULL PAPERS
Lewis acid when combined with Ga species and 3
under the same reaction conditions.
ACHTUNGTRENNUNG
tion.[a]
Under the optimized reaction conditions, asymmet-
ric ring-openings of a variety of meso-epoxides with
selenophenol and 1-selenonaphthol were investigated.
The results are summarized in Table 5. It can be seen
that all reactions proceeded smoothly to afford the b-
arylseleno alcohols in high yields for both cyclic and
acyclic meso-epoxides. In general, the cyclic epoxides
gave the ring-opening products in better selectivities
than the acyclic ones when reacted with the same se-
lenol (entries 1, 3 and 9 vs. 5 and 7). When reacted
with the same epoxide substrate, selenophenol gave
better enantioselectivity than 1-selenonaphthol in all
of the cases (entries 1, 3, 5, 7 vs. 2, 4, 6, 8. respective-
ly).
Based on the results obtained when aryl selenols
were utilized in the ring-opening reaction, we next
studied the use of thiols as nucleophiles for further in-
vestigations. For comparison, complexes 6, 7 and Ga-
Ti-13b were also examined in the reaction. Choosing
cyclohexene oxide as substrate and thiophenol as nu-
cleophile, the reaction conditions were firstly opti-
mized and the results are summarized in Table 6.
Among the solvents investigated, hexane was proved
to be the best one in terms of reactivity and selectivi-
ty. A variation of the reaction temperature from 0 to
À208C caused a significant increase in the ee value
(Table 6, entry 5), but a slight decrease was observed
when the reaction was carried out at À408C (entry 6).
Further investigation revealed that there was no sig-
nificant change when the amount of 8 was decreased
to 5 mol% (entry 7). The reaction still showed good
reactivity and selectivity even with only 2 mol% cata-
lyst loading (entry 8). However, the monometallic
complex 6 and homobimetallic complex 7 gave both
low selectivities and moderate reactivities (entries 9
and 10). When Ga-Ti-13b was utilized in the reaction,
the product was obtained in moderate reactivity and
selectivity in the (R,R) configuration (entry 11).
Entry Ligand Yield[b] [%] ee[c] [%] Configuration[d]
1
2
3
4
5
6
7
8
10a
10b
10c
10d
10e
10f
10g
10h
11a
11b
12a
12b
13a
13b
14
85
84
93
78
73
82
81
83
92
73
64
76
83
87
65
86
32
39
72
12
55
23
36
8
47
55
28
46
30
66
25
72
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
9
10
11
12
13
14
15
16
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
15
ACHTUNGTRENNUNG
[a]
Reaction conditions: cyclohexene oxide (1.0 mmol),
PhSeH (1.1 mmol), catalyst (5 mol%), hexane (3 mL),
À408C, 5 h.
[b]
[c]
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H
column.
Absolute configurations of the major products were as-
signed by comparison of CD spectroscopy with that of
sulfur anologue with known absolute configuration.
[d]
Table 4. Optimization of Lewis acid in the ring-opening re-
action.[a]
Entry MLn
Yield [%][b] ee [%][c] Configuration[d]
Under the optimized reaction conditions (5 mol%
complex 8, À208C, hexane as solvent), we next inves-
tigated the scope of a variety of meso-epoxides and
different thiols in the reaction. As shown in Table 7,
the results revealed that most of reactions proceeded
smoothly to furnish the corresponding b-hydroxy sul-
fides in high yields and moderate to high enantiomer-
ic excesses (65–92% ee), except for epoxide 16f. We
also found that cyclic meso-epoxides provided the cor-
responding products with better enantioselectivity
than acyclic ones under the same reaction conditions.
Unfortunately, for the more sterically hindered epox-
ide 16f, the reaction proceeded very sluggishly, afford-
ing the ring-opening product in low yield and moder-
ate ee value even with a longer reaction time (en-
tries 12). Cyclooctene oxide 16g, which had been
found to entirely unrecative with thiophenol catalyzed
1
2
3
4
5
6
7
8
TiCl4
VO(O-i-Pr)3 66
CrCl3
Cu(OAc)2
AlMe3
InMe3
93
88
34
15
36
28
43
52
37
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
N
84
63
75
78
62
56
N
Yb
A
Sm
A
[a]
Reaction conditions: cyclohexene oxide (1.0 mmol),
PhSeH (1.1 mmol), catalyst (5 mol%), n-hexane (3 mL),
À408C, 5 h.
[b]
[c]
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H
column.
Absolute configurations of the major products were as-
signed by comparison of CD spectroscopy with that of
sulfur anologue with known absolute configuration.
[d]
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Jiangtao Sun et al.
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Table 5. Asymmetric addition of ArSeH to meso-epoxides catalyzed by 8.[a]
Entry
1
Epoxide
Ar
Product
Yield[b] [%]
94
ee[c] [%]
Configuration[d]
(1S,2S)
16a
16a
17a
18a
97
ACHTUNGTRENNUNG
2
17b
18b
93
78
ACHTUNGTRENNUNG
3
4
16b
16b
17a
17b
18c
18d
85
80
94
70
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
5
6
16c
16c
17a
17b
18e
18f
70
70
72
55
–
–
7
8
16d
16d
16e
17a
17b
17a
18g
18h
18i
87
73
92
87
75
90
–
–
–
9
[a]
Reaction conditions: epoxide (1.0 mmol), ArSeH (1.1 mmol), catalyst (5 mol%), hexane (3 mL), À408C, 5 h.
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H column.
Absolute configurations of the major products were assigned by comparison of CD spectroscopy with that of sulfur ana-
logue with known absolute configuration.
[b]
[c]
[d]
by complex 9, gave the ring-opening product 20m in heterobimetallic catalyst appears to act as multifunc-
moderate yield and 80% ee in our case. The addition tional catalyst, with a lithium binaphthoxide moiety
of 4-chlorothiophenol to epoxide 16h gave good reac- functioning as a Brønsted base, activating thiol and a
tivity and high selectivity (entry 14). The results also gallium metal functioning as a Lewis acid, activating
revealed that the para-chloro- or para-methyl-substi- and also controlling the orientation of epoxide, with
tuted thiophenols gave better reactivity and selectivity the result that a high asymmetric induction was realiz-
than thiophenol. However, benzylthiol (19d) dis- ed.
played lower reactivity and selectivity compared with
In our case, the current catalyst system has two dif-
aryl thiols (entry 15). It is also worth noting that the ferent Lewis acid centers. Considering that the bimet-
results represent a considerable improvement compa- allic complex salen-Ga2 (7) and the monometallic
rable to the results catalyzed by complex 9.[12c]
complex (6) gave similar results, we think this proba-
The X-ray crystal structures of the above men- bly attributes to the structure characteristic of the
tioned Ga-Ti-salen complexes have never been deter- complex. So there is probably no cooperative effect
mined, and this restricted the mechanistic investiga- between the two gallium atoms. As a result, homobi-
tions aimed at further improving the catalytic reactivi- metallic complex 7 gave similar reactivity and selec-
ty and enantioselectivity. So it is not easily to identify tivity as the monometallic complex salen-Ga (6). The
the active species that contribute to the overall reac- high catalytic activity of Ga-Ti-salen (8) can be ac-
tion rate. As mentioned in Shibasakiꢀs report on the counted for by the existence of synergistic coopera-
ring-opening reaction of epoxides with thiols,[2] the tion between the two different Lewis acids. Consider-
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Catalytic Asymmetric Ring-Opening Reaction of meso-Epoxides
FULL PAPERS
Table 6. Asymmetric ring-opening of cyclohexene oxide with thiophenol.[a]
Entry
Catalyst
Solvent
Temp. [oC]
Yield [%][b]
ee [%][c]
Configuration[d]
1
2
3
4
5
6
8
8
8
8
8
8
8
8
hexane
Toluene
Et2O
0
0
0
0
À20
À40
À20
À20
À20
À20
À20
96
93
92
90
96
93
95
88
70
72
76
76
70
63
45
87
86
87
86
22
22
63
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
CH2Cl2
hexane
hexane
hexane
hexane
hexane
hexane
hexane
7[e]
8[f]
9[g]
10[g]
11
6
7
Ga+Ti +13b
ACHTUNGTRENNUNG
[a]
Unless otherwise noted, the reactions were carried out under the following conditions: cyclohexene oxide (1 mmol),
PhSH (1.2 mmol), catalyst (10 mol%).
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H column.
Absolute configurations of the major enantiomer was assigned by comparison with literature reports.
5 mol% of 8.
2 mol% of 8.
Reaction time is 4 h.
[b]
[c]
[d]
[e]
[f]
[g]
ing that a fully chelated titanium derivative would be Conclusions
six-coordinate and salen-Ti displaying a “closed”
structure, we think it is possible that the reaction of In summary, we have succeeded in developing a
complex 6 with TiACTHUNTGRENUNG(O-i-Pr)4 would favor the formation highly efficient heterobimetallic catalytic system in
of a heterobimetallic complex with a partly “closed” the enantioselective ring-opening reactions and a
structure (Figure 3). And the shorter distance be- strong synergistic cooperation between the different
tween the two metal centers enables the existence of Lewis acids was exhibited in the catalysis process. The
the synergistic effect between metals Ti and Ga.
enantioselective ring-opening reaction of meso-epox-
Also, it is likely that the harder Lewis acid titanium ides with aryl selenols and thiols gave optically active
is apt to coordinate with epoxide (hard Lewis base), b-arylseleno alcohols and b-hydroxy sulfides in good
while the soft Lewis base nucleophile selenophenol yields and high enantioselectivities. Further applica-
tends to coordinate with the relatively soft gallium tions of this kind of heterobimetallic catalytic system
(trimethylgallium was also classified as a hard Lewis in other reactions are under study.
acid),[20] which directs the attack of the nucleophile to
the epoxide (Figure 3). The possible existence of rela-
tively independent coordination modes makes the re-
Experimental Section
action proceed more effectively and selectively. Also,
1
as mentioned in our previous report, a H NMR study
General Procedure for the Asymmetric Ring-
Opening of meso-Epoxides by Aryl Selenols
showed that the chemical shifts of the dimethylgalli-
um hydrogens of complex 8 appear at a higher field
(d=À0.25 and À0.36 ppm) in comparison with those GaMe3 (0.05 mmol, 0.5M in hexane) was added dropwise to
3 mL of a hexane solution of ligand (R,R)-3 (28 mg,
of complex 6 (d=À0.22 and À0.31 ppm), which
0.05 mmol) under an argon atmosphere at 08C. After the so-
lution had been stirred for 1 h at room temperature, a solu-
tion of TiACTHNURGTNEUNG(O-i-Pr)4 (0.05 mmol, 0.2M in hexane) was then
added and stirring was continued for another 1 h to form
the Ti-Ga-salen complex. The resulting yellow solution was
cooled to À408C. The epoxide (1.0 mmol) and aryl selenol
(1.2 mmol) were added successively. The mixture was stirred
for 5 h at the same temperature before being quenched with
a saturated NH4Cl solution and extracted with ether. The or-
ganic phase was dried over Na2SO4, and the solvent re-
maybe due to the coordination of the oxygen in the
isopropoxy group to the gallium, with the result of a
change in the bond angle between the Lewis acids
and the substrates, which is probably the crucial
factor.
Adv. Synth. Catal. 2009, 351, 920 – 930
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Jiangtao Sun et al.
FULL PAPERS
Table 7. Asymmetric thiolysis of meso-epoxides catalyzed by 8.[a]
Entry
1
Epoxide
R’SH
Product
Yield[b] [%]
95
ee[c] [%]
84
16a
Ph
20a
2
3
16a
16a
4-Me-C6H4
4-Cl-C6H4
20b
20c
95
97
87
92
4
5
16b
16b
Ph
20d
20e
96
95
71
82
4-Me-C6H4
6
7
8
16c
16c
16c
Ph
20f
20g
20h
91
95
90
74
84
85
4-Me-C6H4
4-Cl-C6H4
9
16d
16d
16e
16f
Ph
20i
20j
20k
20l
88
92
83
23
72
81
65
53
10
11
12[d]
4-Me-C6H4
Ph
Ph
13[d]
14[d]
16g
Ph
20m
50
80
16h
16a
4-Cl-C6H4
-CH2Ph
20n
20o
85
74
82
76
15
[a]
Unless otherwise noted, all reactions were carried out under such conditions: epoxide (1.0 mmol), thiol (1.2 mmol), com-
plex 8 (5 mol%), hexane (3 mL), À208C, 1 h.
[b]
[c]
Isolated yields.
Determined by HPLC with a Daicel Chiralcel OD-H or OB-H column. Absolute configurations of the major enantio-
mers (1S,2S) were assigned by comparison of the rotation values in the literature or by analogy.
Reaction was carried out at À208C for 24 h.
[d]
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Catalytic Asymmetric Ring-Opening Reaction of meso-Epoxides
FULL PAPERS
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General Procedure for the Asymmetric Ring-
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GaMe3 (0.05 mmol, 0.5M in hexane) was added dropwisely
to 3 mL of a hexane solution of ligand (R,R)-8 (28 mg,
0.05 mmol) under argon at 08C. After the solution had been
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was continued for another 1 h to form the Ga-Ti-8 complex.
The resulting yellow solution was cooled to À208C. Then
epoxide (1.0 mmol) and thiol (1.2 mmol) were added succes-
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column.
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Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (20672053, 20832001) and the National
Basic Research Program of China (2007CB925103) for their
financial support. The Program for new Century Excellent
Talents in the University of China (NCET-06-0425) is also ac-
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