Facile enantioselective ring-opening reaction of meso epoxides with anilines using (S)-(-)-BINOL-Ti complex as a catalyst

Article abstract of DOI:10.1002/ejoc.200500765

The catalytic enantioselective ring-opening reaction of meso-stilbene oxide and cyclohexene oxide with anilines was catalyzed by (S)-(-)-BINOL-Ti complexes at ambient temperature to obtain β-amino alcohols in high yield (95%) and enantio-selectivity (ee,

Full text of DOI:10.1002/ejoc.200500765

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DOI: 10.1002/ejoc.200500765
Facile Enantioselective Ring-Opening Reaction of meso Epoxides with Anilines
Using (S)-(–)-BINOL-Ti Complex as a Catalyst
Rukhsana I. Kureshy,*[a] Surendra Singh,[a] Noor-ul H. Khan,[a] Sayed H. R. Abdi,[a]
Eringathodi Suresh,[b] and Raksh V. Jasra[a]
Keywords: Asymmetric ring opening / Catalysis / Epoxides / Anilines
The catalytic enantioselective ring-opening reaction of meso-
stilbene oxide and cyclohexene oxide with anilines was cata-
lyzed by (S)-(–)-BINOL-Ti complexes at ambient temperature
to obtain β-amino alcohols in high yield (95%) and enantio-
selectivity (ee, 78%). The enantiomeric excess (ee) of the
zation step. The absolute configuration of representative β-
amino alcohols was determined by single-crystal X-ray dif-
fraction analysis. The catalyst recovered after first use was
recycled four times with retention in its performance.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
product was further improved to 98% by a single recrystalli- Germany, 2006)
lyst was recovered after the first use and was recycled four
times with the retention in its performance.
Introduction
The catalytic enantioselective ring-opening reaction of
epoxides is an attractive and powerful method in asymmet-
ric synthesis.[1,2] A number of valuable products could be
synthesized when reagents such as trialkylsilyl azide,[3–6] tri-
methylsilyl cyanide,[7–10] aryllithium,[11] halides[12–14] and
alkylamines,[15] alcohols/phenols,[16,17] thiols,[18,19] as well as
carboxylic acid[20] were used as nucleophiles for ring-open-
ing reactions of epoxides. A catalytic asymmetric ring open-
ing of meso-epoxide with aromatic amines is of particular
interest because it has wider applications in the synthesis of
pharmaceutically active compounds.[21] However, until now,
this area has been scarcely studied.[15] Nevertheless, various
lanthanides[21,22–25] with (R)/(S)-BINOL, Cr(Salen)[26] and
Sc(bipyridine)[27] have been employed as catalysts for ring-
opening of meso epoxide with alkyl/arylamines to generate
β-amino alcohols. Herein, we report the opening of meso-
stilbene oxide and cyclohexene oxide with aniline and sub-
stituted anilines, catalyzed by the recoverable (S)-BINOL-
Ti complex to get enantio-enriched syn-β-amino alcohols
and trans-β-amino alcohols in high yield (up to 95%) with
78% enantiomeric excess at ambient temperature. The cata-
Results and Discussion
The enantioselective ring-opening reaction of meso-stil-
bene oxide with aniline was carried out by using complexes
1–4 generated in situ by the interaction of equimolar quan-
tities of (S)-BINOL and an appropriate Ti source such as
Ti(OiPr)4, Ti(OC2H5)4, TiBr4 and TiCl4 in toluene
(Scheme 1). NMR and MS data for these complexes suggest
the existence of catalytically active dimeric species, which
are in equilibrium with the corresponding monomeric spe-
cies. This observation is in agreement with previous re-
ports.[28,29] The complexes 1 and 2 were found to be better
catalysts to yield syn-β-amino alcohol in excellent yields
(85–90%) with good enantioselectivity (ee, 63–67%)
(Table 1, Entries 1, 2) than the complexes 3 and 4 (yield,
20–40%; ee, 35–51%) (Table 1, Entries 3, 4). The use of
complexes 3 and 4 affected the rearrangement of the epox-
ide into 2-phenylacetophenone, which further decomposes
to give benzaldehyde as major side product.
The complex 1 was further explored for carrying out the
ring-opening reaction of meso-stilbene oxide with substi-
tuted anilines under identical reaction conditions. The re-
sult was 72–95% isolated yield of respective syn-β-amino
alcohols with ee in the range of 64–78% (Table 2, Entries
5, 7–11). The product 7a was recrystallized from toluene/
hexane solvent mixture where the racemic product (Fig-
ure 1) preferentiallycrystallized out first leaving behind a
solution with 98% ee for (1R,2R)-1,2-diphenyl-2-(phen-
ylamino)ethanol. The above solution was treated with di-
[a] Silicates and Catalysis Discipline, Central Salt and Marine
Chemicals Research Institute (CSMCRI),
Bhavnagar 364 002, Gujarat, India
Fax: +91-0278-2566970
E-mail: rukhsana93@yahoo.co.in
[b] Analytical Science Division, Central Salt and Marine Chemi-
cals Research Institute (CSMCRI),
Bhavnagar 364 002, Gujarat, India
Fax: +91-0278-2566970
Eur. J. Org. Chem. 2006, 1303–1309
© 2006 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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R. I. Kureshy, S. Singh, N. H. Khan, S. H. R. Abdi, E. Suresh, R. V. Jasra
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Scheme 1. Synthesis of catalyst 1–4.
Table 1. Asymmetric catalytic ring opening of meso-stilbene oxide diphenylphosphanylbutane and triphenylphosphane exhib-
with aniline using complexes 1–4.
ited the best enantioselectivity (71% and 78% ee, respec-
tively) (Entries 16, 17), which is significantly higher than
the ee obtained for the reaction conducted in the absence
of an additive (Table 1, Entry 1). However, other additives
adversely affected the activity and selectivity (Table 3, En-
tries 12–15).
Furthermore, ring-opening reaction of epoxides has been
reported to be solvent-dependent.[15,21] The ring opening of
Entry Catalyst
Time [h]
Yield of 7a [%][a]
ee [%][b]
meso-stilbene oxide with aniline using (S)-(BINOL)-Ti in
the presence of different solvents suggests that toluene
(Table 4, Entry 18) is the solvent of choice. In case of other
solvents CH2Cl2 (Entry 19) worked better than solvents
having a heteroatom such as THF (Entry 20) and CH3CN
(Entry 21).[15,21]
1
2
3
4
1
2
3
4
7
8
5
5
90
67
63
35
51
85
20[c]
40[c]
[a] Isolated yield after chromatographic separation. [b] Determined
by HPLC. [c] Epoxide was completely consumed and rest of the
material was benzaldehyde.
We have also used the catalyst 1 for the ring opening of
cyclohexene oxide (8) with different anilines 6a–c, where
lute HCl, and the solid obtained was recrystallized from trans-amino alcohols were obtained in excellent yields with
methanol/water (1:1) to yield crystals of 7a·HCl with moderate enantioselectivity (Table 5). The catalyst 1 was
(1R,2R) configuration (Figure 2).
found to be very active for the ring opening of cyclohexene
Further, it has been reported in the literature[21] that the oxide with aniline in the presence of triphenylphosphane
use of additives improves the ee of amino alcohols. There- (TPP) (Table 5, Entry 23) giving 92% isolated yield and
fore, we next examined the influence of N-, O- and P-coor- 39% ee in 2 h. These results are significantly superior as
dinated additives such as triethylamine, pyridine, pyridine compared to the report where lanthanide iodobinapthol-
N-oxide, 4-(phenylpropyl)pyridine N-oxide, 1,4-bis(diphen- ate[25] was used as a catalyst for a similar reaction which
ylphosphanyl)butane and triphenylphosphane on the enan- gave 55% yield with 20% ee in 18 h. The absolute configu-
tioselective ring opening of meso-stilbene oxide with aniline ration was determined by comparing the optical rotation
under identical reaction conditions, and the results are and the HPLC profile with literature. Details are given in
given in Table 3. Of all additives used, P-containing 1,4- the Experimental Section.
1304
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Ring-Opening of meso Epoxides with Anilines Using (S)-(–)-BINOL-Ti
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Table 2. Asymmetric catalytic ring-opening of meso-stilbene oxide with anilines using complex 1.
Entry
Amines
Time [h]
Isolated yield 7a–f [%][a]
ee [%][b]
5 (6)
7
8
9
10
11
6a
6b
6c
6d
6e
6f
7
20
8
5
5
90
72
90
95
95
80
67 (98)[c]
78
64
65
67
71
10
[a] Isolated yield after chromatographic separation. [b] Determined by HPLC. [c] Value in parenthesis refers to ee after recrystallization.
Table 3. Effect of additives on catalytic asymmetric ring opening of meso-stilbene oxide with aniline using complex 1.
Entry Additives
Time (h)
Isolated yield 7a [%][a]
ee [%][b]
12
13
14
15
16
17
triethylamine
pyridine
pyridine N-oxide
4-(phenylpropyl)pyridine N-oxide
1,4-bis(diphenylphosphanyl)butane
triphenylphosphane
24
24
24
20
7
10
30
10
30
90
90
0
27
23
30
71
78
7
[a] Isolated yield after chromatographic separation. [b] Determined by HPLC.
Figure 2. ORTEP diagram (40% probability factor for the thermal
ellipsoid) of the cationic part of compound (1R,2R)-diphenyl-2-
(phenylamino)ethanol hydrochloride with atom-numbering
scheme.
Figure 1. ORTEP diagram (40% probability factor for the thermal
ellipsoid) with atom-numbering scheme for racemic 1,2-diphenyl-
2-(phenylamino)ethanol.
Table 4. Effect of different solvent on asymmetric ring opening of
meso-stilbene oxide with aniline using complex 1.
The recycling experiments were conducted with the (S)-
BINOL-Ti complex 1. The recovered catalyst was charac-
terized by MS, NMR and elemental analysis, and the data
correspond to the fresh complex. The recovered catalyst
was used for subsequent catalytic runs for the ring opening
of meso-stilbene oxide with aniline that showed essentially
the same performance for four catalytic runs (Table 6).
Entry Solvent
Time [h] Isolated yield 7a [%][a]
ee [%][b]
18
19
20
21
toluene
CH2Cl2
THF
7
7
90
80
75
15
67
50
29
13
7
20
CH3CN
[a] Isolated yield after chromatographic separation. [b] Determined
by HPLC.
Eur. J. Org. Chem. 2006, 1303–1309
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R. I. Kureshy, S. Singh, N. H. Khan, S. H. R. Abdi, E. Suresh, R. V. Jasra
FULL PAPER
Table 5. Effect of additives on catalytic asymmetric ring opening of cyclohexene oxide with aniline.
Entry
Temp. (°C)
Additive
Amine
Time [h]
Isolated yield 9a–c [%][a]
ee [%][b]
22
23
24
25
25
25
25
25
–
6a
6a
6b
6c
3 h
2 h
3 h
4 h
90
92
93
95
21
39
48
63
TPP
TPP
TPP
[a] Isolated yield after chromatographic separation. [b] Determined by HPLC.
Table 6. Asymmetric catalytic aminolysis of meso-stilbene oxide by stilbene oxide with anilines at room temperature catalyzed
aniline with recycled complex 1.
by the recyclable (S)-(–)-(BINOL)-Ti complex to give the
respective syn-β-amino alcohols in 95% isolated yield with
78% ee. The commercial availability of the BINOL ligand
and Ti(OiPr)4 as well as the recycling of the catalyst (4 runs)
make this protocol suitable for industrial use.
Run
1
2
3
4
Time (h)
Isolated yield
ee
7
85
67
7
75
65
7
70
64
7
60
64
Determination of the Absolute Configuration of β-Amino
Alcohols
Experimental Section
General: The solvents were dried by standard procedures, distilled
and stored under nitrogen. All melting points reported are uncor-
rected. NMR spectra were obtained with a Bruker F113V spec-
As there is no X-ray crystal structure determination of
the absolute configuration of 7a available in the literature,
an attempt was made to get suitable crystals for X-ray dif-
fraction studies of the product 7a (Table 2, Entry 6). A
plate-like crystal of 7a was obtained from toluene/hexane
(1:1) solution. This compound crystallized in the centro-
symmetric space group P21/c, and the established crystal
structure of the compound showed the presence of a race-
mic mixture with equimolar amounts of R,R and S,S with
respect to the chiral center C7 and C8, thus confirming rac-
1,2-diphenyl-2-(phenylamino)ethanol. An ORTEP[30] dia-
gram of the compound with atom-numbering scheme is
shown in Figure 1. Block crystals with different mor-
phology were obtained from the same crystallization experi-
ment, as a second crop after three days. In an attempt to
derive the absolute configuration at the C7 and C8 asym-
metric carbon atom, we converted the compound (1R,2R)-
1,2-diphenyl-2-(phenylamino)ethanol to its hydrochloride
salt. The ORTEP diagram of the cationic part of the com-
pound with an atom-numbering scheme is depicted in Fig-
ure 2. This compound crystallizes in the chiral space group
P21, and the established crystal structure revealed the con-
figuration as (1R,2R) with respect to the chiral carbon
atoms C7 and C8, respectively.
1
trometer (200 MHz and 50 MHz for H and 13C, respectively) and
are referenced internally with TMS. FTIR spectra were recorded
with a Perkin–Elmer Spectrum GX spectrophotometer in KBr win-
dow. High-resolution mass spectra were obtained with a LC-MS
(Q-TOFF) LC (Waters), MS (Micromass) instruments. Product pu-
rification was performed by flash chromatography using silica gel
60–200 mesh purchased from s. d. Fine-Chem. Limited Mumbai
(India). Enantiomeric excesses (ee) were determined by HPLC (Shi-
madzu SCL-10AVP) using Daicel Chiralpak AD, OD and OJ chiral
columns (wavelengths 243 nm) with 2-propanol/hexane as eluent.
Optical rotations were measured with a Digipol 781 Automatic
Polarimeter Rudolph Instruments. TiCl4, TiBr4, Ti(OEt)4,
Ti(OiPr)4, aniline, 2-methoxyaniline, 4-methoxyaniline, 2-chloro-
aniline, 4-chloroaniline and 4-methylaniline as well as meso-stilbene
oxide were purchased from Aldrich Chemicals and were used as
received.
General Procedure for Asymmetric Catalytic Aminolysis of meso-
Stilbene Oxide: To a 5-mL round-bottom flask fitted with a rubber
septum and equipped with a magnetic stirring bar, S-BINOL
(0.025 mmol) and Ti(OiPr)4 (0.025 mmol) were added in dry tolu-
ene (0.5 mL) at room temperature (27 °C). The reaction mixture
was stirred at 27 °C for 30 min. To the above mixture, were added
meso-stilbene oxide and anilines all at once in equimolar amount
(0.25 mmol), and the reaction was stirred for the specified time.
The progress of the reaction was checked by TLC using hexane/
ethyl acetate (8:2) as mobile phase. The reaction mixture was con-
centrated and hexane/diethyl ether (9:1) was used for the precipi-
tation of the catalyst. The catalyst was filtered off, dried under
Conclusion
In conclusion, we have developed a highly regio-, dia-
stereo-, and enantioselective ring-opening reaction of meso- vacuum and kept for further use. The filtrate containing the prod-
1306 Eur. J. Org. Chem. 2006, 1303–1309
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