Supporting Information
Wiley-VCH 2011
69451 Weinheim, Germany
Asymmetric Autocatalysis: Triggered by Chiral Isotopomer Arising
from Oxygen Isotope Substitution**
Tsuneomi Kawasaki,* Yasushi Okano, Etsuharu Suzuki, Shizuka Takano, Shotaro Oji, and
Kenso Soai*
anie_201102263_sm_miscellaneous_information.pdf
1. General Comments.
All reactions were performed under an argon atmosphere unless otherwise noted. NMR
spectra were recorded on a BRUKER AV600 spectrometer (operating at 600 MHz for 1H
and 150 MHz for
13
C acquisitions). Multiplicities are classified by the following
abbreviations: s = singlet, d = doublet, m = multiplet signal. Infrared (IR) data were
recorded on a Horiba FT-200 FT-IR spectrometer. Optical rotations were measured using a
Jasco P-1030 digital polarimeter using 5 cm cells. High-resolution mass spectra were
recorded using a ESI-TOF mass spectrometers (Bruker Daltonics micrOTOF focus).
2. Synthetic methods and characterization data of oxygen-18 substituted
meso-hydrobenzoin 1.
Scheme S1. Synthesis of 18O-labeled hydrobenzoin 1 with oxygen isotope chirality (Table 1
and Table S1 series I). (i) Daicel Chiralpak IA (10 ! 250 mm), 20% 2-propanol in hexane,
flow rate: 2.0 mL/min, 254 nm, r.t., retention time: 10.3 min for (R,R)-4, 16.1 min for (S,S)-4.
(ii) Na18OH, H218O, 2-methoxyethanol (46% yield, dr = 100:0).
Ph O
(S)
(ii)
(S)
O Ph
Ph
Racemic transstilbene oxide (4)
Ph
(S,S)-4
(>99.5% ee)
(i) HPLC resolution
using chiral
stationary phase
(R)
H2
18O
O Ph
(R)
Ph
(R,R)-4
(>99.5% ee)
H18O
(S)
Ph
Ph
(R)-1-18O
HO
(ii)
OH
(R)
18OH
(R)
(S)
Ph
Ph
(R)-1-18O
(R)-1-18O: To 2-methoxyethanol (5.0 mL), sodium metal (115 mg, 5 mmol) was added at
0 °C and the mixture was stirred for 30 min. To water-18 (18O: 97%, 1.0 mL), the above
solution (1.0 mL) and (S,S)-4 (98.2 mg, 0.5 mmol) were added. The reaction mixture was
stirred for 2 d at 95 °C. After finishing the reaction, the mixture was extracted using ether.
The organic layer was dried over anhydrous magnesium sulfate and concentrated under
reduced pressure. The residue was purified using silica gel thin layer chromatography
(CHCl3:MeOH = 50:1, v/v) to give (R)-1-18O (49.9 mg) in 46% yield. Once more, the
S1
compound was purified using silica gel column chromatography (hexane:ethyl acetate = 1:1,
v/v).
Analytical data for (R)-1-18O: Colorless crystal; Mp. 133.5–135.0 ℃; [!]D22 –0.08 (c 0.5,
CHCl3).; 1H-NMR (600 MHz, CDCl3) ! (ppm) 2.16 (2H, s), 4.84 (2H, s), 7.25–7.34 (10H,
m); 13C-NMR (150 MHz, CDCl3) ! 78.1, 127.1, 128.1 128.3, 139.8; IR (KBr) " (cm–1) 1011,
1279, 3364; HRMS : Calcd. for C14H14O18ONa+ [M+Na+]: 239.0928, found : 239.0894.
Analytical data for (S)-1-18O: Colorless crystal; Mp. 133.5-135.0 ℃; [!]D22 –0.20 (c 0.5,
CHCl3); HRMS: Calcd. for C14H14O18ONa+ [M+Na+]: 239.0928, found : 239.0885.
Scheme S2. Synthesis of chiral meso-hydrobenzoin 1 with the oxygen isotope substitution
(Table 1 and Table S1 series II). (i) Ph2POCl, pyridine, r.t.; (ii) K2 CO3, MeOH, r.t.
HO
OH
(S)
(S)
Ph
Ph
(i)–(ii)
OH
(R)
(R)
Ph
Ph
(R,R)-1
(S)
(R)-1-18O
(S)
Ph
(S,S)-4
(S,S)-1
HO
Ph O
H218O
(R)
(i)–(ii)
O Ph
(R)-1-18O
(R)
Ph
(R,R)-4
The (S,S) and (R,R)-4 were prepared from (S,S) and (R,R)-1, purchased from Tokyo
Chemical Industry Co., Ltd, by using a reported method.[S1]
[S1] Fox, D. J.; Pedersen, D. S.; Peterson, A. B.; Warren, S. Org. Biomol. Chem. 2006, 4,
3117–3119.
S2
3. Characterization data for bis-(S)-MTPA esters 6 and 7.
Scheme S3. Synthesis of bis-(S)-MTPA ester of
18
O-substituted hydrobenzoin 1. (i) (R)-(–)-
!-methoxy-!-(trifluoromethyl)phenylacetyl chloride, DMAP, pyridine (99%).
(R)/(S)-1-18O
(i)
Ph
OMe
F3C (S)
18O
O
Ph
MeO
O
Ph
(S)
CF3
O
Ph
6/7
Bis-(S)-MTPA ester 6: To a pyridine (0.5 mL) solution of (R)-1-18O (5.3 mg, 0.025 mmol)
and 4-dimethylaminopyridine (DMAP) (3.1 mg, 0.025 mmol) was added (R)-(–)-!methoxy-!-(trifluoromethyl)phenylacetyl chloride (14 µL, 0.75 mmol). After stirring for 18
h at r.t., the reaction mixture was quenched with water and extracted with ether. The organic
layer was dried over anhydrous sodium sulfate. After filtration followed by evaporation in
vacuo, the crude residue was purified by silica gel column chromatography (hexane:ethyl
acetate = 7:1, v/v) to give product 6 (16.0 mg) in 99% yield.
Analytical data for 6: Colorless solid; [!]D24 –31.2 (c 0.45, CHCl3); Mp. 123.0–124.0 °C;
1
H-NMR (600 MHz, CDCl3) ! (ppm) 3.16 (3H, s), 3.21 (3H, s), 6.20 (1H, d, J = 7.8 Hz),
6.32 (1H, d, J = 7.8 Hz), 7.02–7.39 (20H, m);
13
C-NMR (150 MHz, CDCl3) ! (ppm) 55.91,
78.77, 79.12, 85.34, 85.52, 123.40, 125.28, 127.98, 128.05, 128.98, 129.03, 129.12, 129.14,
129.39, 129.57, 129.78, 130.15, 130.21, 130.24, 133.21, 133.31, 135.85, 136.32, 165.42,
165.72; IR (nujol) " (cm–1) 1750, 1455, 1292, 1017.
Analytical data for 7: Colorless solid; [!]D24 –32.1 (c 0.46, CHCl3); Mp. 123.0–124.0 °C;
1
H-NMR (600 MHz, CDCl3) ! (ppm) 3.13 (3H, s), 3.20 (3H, s), 6.19 (1H, d, J = 7.8 Hz),
6.30 (1H, d, J = 7.8 Hz), 7.01–7.35 (20H, m);
13
C-NMR (150 MHz, CDCl3) ! (ppm) 55.91,
78.81, 79.10, 85.34, 85.52, 123.39, 125.31, 127.99, 128.06, 128.98, 129.04, 129.12, 129.15,
129.39, 129.58, 129.78, 130.15, 130.21, 130.24, 133.22, 133.32, 135.86, 136.33, 165.42,
165.74; IR (nujol) " (cm–1) 1750, 1455, 1291, 1025.
S3
4. Additional results of asymmetric autocatalysis triggered by chiral
hydrobenzoin 1 due to oxygen-18 substitution.
Table S1.
Entry[a]
[f]
Chiral trigger 1[b]
Sample #[c]
5-Pyrimidyl alkanol 2
Yield[d]
ee[e]
config
Series I
1
#1
(S)-1-18O
94
91
R
18
2
#2
(R)-1- O
95
82
S
3
#1
(S)-1-18O
94
97
R
4
#2
(R)-1-18O
95
79
S
18
5
#3
(S)-1- O
96
83
R
6
#4
(R)-1-18O
97
84
S
18
7
#3
(S)-1- O
90
88
R
8
#4
(R)-1-18O
90
78
S
18
9
#5
(S)-1- O
95
90
R
10
#6
(R)-1-18O
97
93
S
18
11
#7
(S)-1- O
92
89
R
12
#8
(R)-1-18O
93
88
S
13
#7
(S)-1-18O
87
79
R
18
14
#8
(R)-1- O
92
89
S
Series II[g]
15
#11
(S)-1-18O
89
97
R
16
#12
(R)-1-18O
90
96
S
18
17
#11
(S)-1- O
99
69
R
18
#12
(R)-1-18O
79
97
S
18
19
#13
(S)-1- O
92
91
R
20
#14
(R)-1-18O
88
88
S
18
21
#13
(S)-1- O
91
93
R
22
#14
(R)-1-18O
86
73
S
23
#15
(S)-1-18O
93
93
R
18
24
#16
(R)-1- O
85
83
S
25
#15
(S)-1-18O
91
91
R
18
26
#16
(R)-1- O
93
89
S
27
#15
(S)-1-18O
85
94
R
18
28
#17
(S)-1- O
90
88
R
29
#18
(R)-1-18O
87
95
S
18
30
#17
(S)-1- O
94
75
R
31
#18
(R)-1-18O
86
78
S
32
#17
(S)-1-18O
88
86
R
18
33
#18
(R)-1- O
88
83
S
18
[a] The molar ratios used were 1- O:2:iPr2Zn = 0.05:1.05:2.2. [b] The ee of 1 was >95% ee.
See also Figure 2. [c] Each sample of isotopically chiral hydrobenzoin 1 was prepared in a
different reaction batch using different apparatus. [d] Isolated yield. [e] The ee value was
determined by HPLC using a chiral stationary phase. [f] Chiral initiators 1 were prepared
S4
from resolved 4 using HPLC with a chiral stationary phase. [g] Chiral triggers 1 were
prepared via hydrolysis of 4, derived from commercial (S,S) and (R,R)-hydrobenzoin.
5. The reaction of Et2Zn with meso-hydrobenzoin.
Scheme S4
Et
Zn
HO
OH
Et2Zn (excess)
HO
O
Ph
Ph
toluene
Ph
Ph
meso-hydrobenzoin
(1 eq.)
+
EtH
(ca. 1 eq.)
mono-ethylzinc
alkoxide
The reaction was performed using reaction vessel having 60 mL volume under atmospheric
pressure (1010!102 Pa) at room temperature (294.9 K). A 1.0 mol/L toluene solution of
Et2Zn (3.6 mL, 3.6 mmol) was added dropwise to toluene (2.5 mL) solution of mesohydrobenzoin (97.9 mg, 0.457 mmol). The reaction readily proceeded to observe the
generation of ethane (8.3 mL).
The molar amount of 8.3 mL of generating ethane gas is 0.342 mmol at 294.9 K under
1010!102 Pa. In addition, ethane should be dissolved in the solvent. Based on the literature
values,[S2] the solubility of ethane in toluene is approximated to be 0.151 mol/L at 294.9 K.
Considering the partial pressure of ethane in this reaction vessel (air: 60 mL, ethane 8.3 mL),
the molar amount of ethane dissolved in 6.1 mL of toluene is 0.112 mmol. Therefore, total
molar amount of generated ethane is calculated to be 0.454 mmol.
[S2] J. A. Waters, G. A. Mortimer, H. E. Clements, J. Chem. Eng. Data 1970, 15, 174–176.
S5