Kinetic Resolution of Racemic and Branched Monosubstituted Allylic Acetates by a Ruthenium-Catalyzed Regioselective Allylic Etherification

Article abstract of DOI:10.1021/acs.joc.6b00939

We demonstrated the kinetic resolution of racemic and branched monosubstituted allylic acetates by a ruthenium-catalyzed regioselective allylic etherification. The reaction was effectively catalyzed by the chiral ruthenium catalyst, which was generated by [RuCl₂(p-cymene)]₂ and (S,S)-iPr-pybox and a catalytic amount of TFA, and both the allylic etherification product and recovered allylic acetate were obtained as an enantiomerically enriched form with up to a 103 s value.

Full text of DOI:10.1021/acs.joc.6b00939

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Note
Kinetic Resolution of Racemic and Branched Monosubstituted Allylic
Acetates by a Ruthenium-Catalyzed Regioselective Allylic Etherification
Toru Shinozawa, Shou Terasaki, Shota Mizuno, and Motoi Kawatsura
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.6b00939 • Publication Date (Web): 08 Jun 2016
Downloaded from http://pubs.acs.org on June 14, 2016
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Kinetic Resolution of Racemic and Branched Monosubstituted Allylic
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Acetates by
Etherification
a
Ruthenium-Catalyzed Regioselective Allylic
Toru Shinozawa, Shou Terasaki, Shota Mizuno, and Motoi Kawatsura*
Department of Chemistry, College of Humanities & Sciences, Nihon University,
Sakurajosui, Setagaya-ku, Tokyo 156-8550, Japan
ABSTRACT: We demonstrated the kinetic resolution of racemic and branched
monosubstituted allylic acetates by a ruthenium-catalyzed regioselective allylic
etherification. The reaction was effectively catalyzed by the chiral ruthenium catalyst,
which was generated by [RuCl2(p-cymene)]2 and (S,S)-iPr-pybox, catalytic amount of
TFA, and both the allylic etherification product and recovered allylic acetate were
obtained as an enantiomerically enriched form with up to a 103 s value.
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The synthesis of enantiomerically-enriched organic compounds is an
important topic in the field of synthetic organic chemistry, and the transition metal
catalyzed asymmetric allylic substitution of the allylic substrate, which possesses a
leaving group at the allylic position, has been recognized as one of the most powerful
methods to construct chiral carbon-carbon or chiral carbon-heteroatom bonds.1 For
example, the reaction of allylic substrates with the oxygen nucleophiles effectively
provides the allylic ethers,2-4 and those asymmetric reactions were also realized by
several transition metal catalysts.5,6 Especially, there are several types of asymmetric
allylic etherfications of monosubstituted allylic compounds, but the reaction of the
racemic and branched monosubstituted allylic substrates, which are easy to prepare, is a
still challenging reaction system compared to the reaction of linear-type
monosubstituted allylic substrates.7 To the best our knowledge, there are only limited
examples of asymmetric allylic etherification of racemic and branched monosubstituted
allylic substrates. For example, Carreira6h,7b and Hartwig7c realized those asymmetric
reactions by the kinetic resolution using chiral iridium catalysts. On the other hand,
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the ruthenium catalyzed asymmetric allylic substitutions of monosubstituted allylic
compounds,8,9 which include the allylic etherification,10 have been developed by several
groups over the last decade. However, these reactions were conducted using
linear-type monosubstituted allylic substrates, and there is still no report about the
asymmetric allylic etherification of racemic and branched monosubstituted allylic
substrates. Recently, we studied several types of stereoselective ruthenium-catalyzed
allylic substitutions,9i,11 and succeeded in the intermolecular asymmetric allylic
substitution of racemic and branched monosubstituted allylic substrates with amines.
During the course of those ruthenium-catalyzed reactions of the racemic and branched
monosubstituted allylic substrates, we examined the reaction with alcohols and revealed
that the reaction provides both the starting allylic substrate and allylic etherification
product with a high % ee and s value. We now report the kinetic resolution6h,7b-c,12-14
of racemic and branched monosubstituted allylic acetates by a ruthenium-catalyzed
allylic etherification.
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We first examined the reaction of the racemic and branched allylic acetate 1a
with benzyl alcohol (2a) (2.0 equiv to 1a) in the presence of 5 mol% of
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11b,11d,15
[RuCl2(p-cymene)]2
and 10 mol% of (S,S)-iPr-pybox (L*), but the intended
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reaction did not proceed (Table 1, entry 1). However, when 0.5 equivalent of
trifluoroacetic acid (TFA) was added to the reaction system, the intended regioselective
reaction proceeded and the desired branched etherification product 3aa was obtained in
47% isolated yield with 72% ee (R) (entry 2).16 Based on this reaction, we also
confirmed that the enantiomeric excess of the unreacted and recovered substrate 1a is
92% ee (S), and we are convinced that kinetic resolution (s = 17) took place in this
ruthenium-catalyzed reaction. To progress the reaction with a higher s value, we
optimized the reaction conditions, then we found that the amounts and the ratio of
ruthenium and iPr-pybox are important for determining the s value. For example, the
reaction by two equivalents of chiral ligands to ruthenium decreased the conversion
and % ee of recovered allylic substrate, but the higher s value was observed (entry 3).
We also confirmed that a reduced amount of the ruthenium/ligand catalyst increased the
s value (entries 3 and 4). Furthermore, the present reaction is also very sensitive to the
amount of TFA and 2a, and we confirmed that the use of 0.8 equivalent of TFA and 2.5
equivalents of 2a produced the highest s value (s = 99) (entries 4-8).17 We also
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demonstrated the reaction with 1 mmol of 1a and confirmed that the reaction proceeds
without loosing s value (entry 9).
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Table 1. Ruthenium-catalyzed Allylic Etherification of Racemic Allylic Acetate
1a with Benzylalcohol (2a)a
OAc
Ph
(S)-1a
OAc
[Ru/L*]
+
+
BnOH
Ph
TFA
THF
OBn
2a
1a
25˚C, 19 h
Ph
[Ru] = [RuCl2(p-cymene)]2
(R)-3aa
O
O
N
N
N
iPr
iPr
L* = (S,S)-iPr-pybox
entry
[Ru]
L*
TFA
conversionb
% eec of
yieldd (%)
% eec of
se
(mol%)
(mol%)
(equiv)
(%) of 1a
recovered
of (R)-3aa
(R)-3aa
(S)-1a
––
1
2
5.0
5.0
5.0
2.5
2.5
2.5
2.5
2.5
2.5
10
10
20
10
10
10
10
10
10
––
0.5
0.5
0.5
1.0
0.7
0.7
0.8
0.8
0
0
––
72
90
95
88
94
94
90
90
––
17
31
57
45
63
77
99
99
55
35
29
50
40
45
52
53
92
47
27
25
44
36
40
44
48
3
46
4
40
5
85
6
66
7f
8f
9g
73
99
95
a
Reaction conditions: 1a (0.14 mmol), 2a (0.28 mmol), [RuCl2(p-cymene)]2, L*, and TFA in THF at 25
b
˚C for 19 h.
Conversion (c) was calculated by the following formula: c = (NMR yield1a)/[(NMR
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yield1a) + (NMR yield3aa)]. See Ref. 18. c Determined by chiral HPLC analysis. d Determined by 1H
7
8
e
NMR of crude materials.
Calculated by % ee of 3aa (eeP) and conversion (c). s = ln[1-c(1 +
9
f
g
eeP)]/ln[1-c(1-eeP)], here c means conversion. See Ref. 12, and 19.
0.35 mmol of 2a was used.
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Reaction conditions: 1a (1.0 mmol), 2a (2.5 equiv), [RuCl2(p-cymene)]2 (2.5 mol%), L* (10 mol%), and
TFA (0.8 equiv) in THF (1.1 mL) at 25 ˚C for 19 h.
With the optimized conditions in hand, the scope of the substrates and
alcohols of this kinetic resolution system was explored. We initially examined the
reaction of 1a with several alcohols, and the results are summarized in Table 2. The
reactions with primary alcohols (2b and 2c) provided good s values (entries 1 and 2).
For example, the reaction with 2c provided (R)-3ac in 41% yield with a 90% ee and
recovered (S)-1a with an 85% ee (s = 52) (entry 1). The reaction with the secondary
alcohol 2d also exhibited a similar result (entry 3), but the reaction with cyclohexanol
(2e) resulted in a lower s value (entry 4). Based on the result with 2a, we further
examined the reactions with several arylmethanols 2f-o, and revealed that most of the
reactions proceeded with an acceptable s value (entries 5-14). Especially, the reactions
with 2j, 2n, and 2o exhibited high s values (entries 9, 13, and 14), and the highest s
value (s = 103) was obtained for the reaction using 1-naphthalenemethanol (2o) (entry
14).
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Table 2. Kinetic Resolution for the Reaction of 1a with Several Alcohols 2b-oa
OAc
Ph
2.5 mol% [Ru]
(S)-1a
10 mol% L*
+
+
1a
ROH
TFA (0.8 equiv)
THF
OR
2b-o
25 ˚C, 19 h
Ph
(R)-3ab-ao
[Ru] = [RuCl2(p-cymene)]2
L* = (S,S)-iPr-pybox
entry
2
conversionb
% eec of
yieldd (%)
%eec of
se
(%) of 1a
recovered
(S)-1a
84
of (R)-3aa
(R)-3
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48
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26
41
39
25
39
91
90
92
87
92
57
52
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32
55
OH
2b
85
78
83
77
OH
MeO
2c
OH
2d
OH
2e
F
OH
2f
F
6
50
93
45
89
51
OH
2g
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OH
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9
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85
77
93
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92
92
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67
85
F
2h
OH
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Cl
2i
Me
OH
2j
Me
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79
88
93
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38
74
OH
2k
OH
Me
2l
OH
75
MeO
2m
OH
O
94
2n
103
OH
2o
a Reaction conditions: 1a (0.14 mmol), 2b-o (0.35 mmol), 2.5 mol% of [RuCl2(p-cymene)]2, 10 mol% of
b
L*, and TFA (0.11 mmol) in THF at 25 ˚C for 19 h.
Conversion (c) was calculated by the following
c
formula: c = (NMR yield1a)/[(NMR yield1a) + (NMR yield3aa)]. See Ref. 18.
Determined by chiral
d
1
e
HPLC analysis.
Determined by H NMR of crude materials.
Calculated by % ee of 3aa (eeP) and
conversion (c). s = ln[1-c(1 + eeP)]/ln[1-c(1-eeP)], here c means conversion. See Ref. 12 and 19.
We next demonstrated the reaction of several racemic and branched allylic
acetates with 1-naphthalenemethanol (2o). As shown in Table 3, although the
reactions requires a small modification, the reactions of the allylic acetates 1b-e with 2o
using a decreased amount of TFA to 0.5 equiv provided both the recovered allylic
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acetates (S)-1 and allylic substituted product (R)-3 with a good enantiomeric excess and
moderate to good s value (entries 1-4). On the other hand, we confirmed that the
reactions of allylic acetates 1f-i, which contained an electron-withdrawing group on the
phenyl group, were slow and exhibited reduced s values even when the reaction was
conducted at 40 ˚C (entries 5, 7, 9 and 11). However, better results were obtained
when the leaving group of allylic esters was changed from acetates to methyl carbonates
(entried 6, 8 and 10). Unfortunately, the reaction of 1j, which possessed the
para-methoxyphenyl group, under optimized reaction conditions was also unsuccessful;
the reaction provided (R)-3jo in 24% yield with a high enantiomeric excess (94% ee),
but only a trace amount of 1j was recovered (entry 12).20
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Table 3. Kinetic Resolution for the Reaction of Several Allylic Acetates 1b-i with
2oa
OAc
Ar
2.5 mol% [Ru]
(S)-1a
OAc
10 mol% L*
+
+
2o
Ar
TFA (0.8 equiv)
THF
1-Napthyl
1b-i
25 ˚C, 19 h
O
[Ru] = [RuCl2(p-cymene)]2
L* = (S,S)-iPr-pybox
Ar
(R)-3bo-io
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entry
1
conversionb
% eec of
recovered
(S)-1
yieldd (%)
%eec of
se
(%) of 1
of (R)-3
(R)-3
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1f
50
52
50
53
80
46
40
41
42
93
80
89
88
94
25
51
67
OAc
1b
2f
98
90
96
OAc
1c
3f
Me OAc
1d
4f
OAc
Me
1e
Cl
LG
5g,h
6i
11
25
24
28
8
84
93
13
37
22
1f: LG = OAc
1f': LG = OCO2Me
LG
7g,j
8k
11
38
30
63
8
93
96
31
88
Cl
32
1g: LG = OAc
1g': LG = OCO2Me
LG
9g,l
52
51
86
39
46
45
82
86
31
38
10m
Cl
1h: LG = OAc
1h': LG = OCO2Me
OAc
11
12
45
––
49
––
32
24
92
94
55
––
Br
1i
OAc
MeO
1j
a
Reaction conditions: 1b-j (0.14 mmol), 2o (0.35 mmol), 2.5 mol% of [RuCl2(p-cymene)]2, 10 mol% of
b
L*, and TFA (0.11 mmol) in THF at 25 ˚C for 19 h.
Conversion (c) was calculated by the following
c
formula: c = (NMR yield1a)/[(NMR yield1a) + (NMR yield3aa)]. See Ref. 18.
Determined by chiral
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d
1
e
HPLC analysis.
Determined by H NMR of crude materials.
Calculated by % ee of 3aa (eeP) and
7
8
f
conversion (c). s = ln[1-c(1 + eeP)]/ln[1-c(1-eeP)], here c means conversion. See Ref. 12 and 19.
9
g
h
i
0.5 equiv of TFA was used.
Reaction was conducted at 40 ˚C.
Reaction of 1f.
Reaction of 1f’.
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j Reaction of 1g. k Reaction of 1g’. l Reaction of 1h. m Reaction of 1h’.
In conclusion, we have demonstrated the kinetic resolution of racemic and
branched monosubstituted allylic acetates by the ruthenium-catalyzed regioselective
allylic etherification.
The reaction was effectively catalyzed by the
[RuCl2(p-cymene)]2/(S,S)-iPr-pybox catalyst with catalytic amount of TFA, and
provided both the enantiomerically enriched allylic etherification product and the
recovered branched monosubstituted allylic acetate with a high enantiomeric excess and
high s value.
EXPERIMENTAL SECTION
General Information. All manipulations were carried out under a nitrogen
1
13
atmosphere. NMR spectra were recorded on a 500 MHz (for H), 125 MHz (for C),
and 470 MHz (for 19F). Chemical shifts are reported in δ ppm referenced to an
1
internal SiMe4 standard for H NMR and an internal C6F6 standard for 19F NMR.
Residual chloroform (δ 77.0 for 13C) was used as internal reference for C NMR. 1H
13
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and C NMR spectra were recorded in CDCl3 at 25 ˚C unless otherwise noted. The
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NMR yields were determined by H NMR using an internal standard (phenanthrene).
HRMS were obtained on an ESI mass spectrometer. Allylic acetates 1a-i were
prepared according to the literature, or by the reaction of corresponding allylic alcohols
with acetic anhydride, in the presence of pyridine and DMAP.21 (S,S)-iPr-pybox22 was
prepared according to the literature.
All other chemicals, including
[RuCl2(p-cymene)]2 and trifluoroacetic acid, were purchased from commercial sources
and used without further purification.
General procedure for the kinetic resolution in the ruthenium-catalyzed
asymmetric allylic etherification of racemic 1-arylallyl esters with alcohols. The
reaction conditions and results are shown in Tables. A Typical procedure is given for
the reaction of rac-1a with 2a (Table 1, Entry 8). To a solution of rac-1a (25 mg, 0.14
mmol), [RuCl2(p-cymene)]2 (2.1 mg, 0.004 mmol), (S,S)-iPr-pybox (4.2 mg, 0.014
mmol), and TFA (12.5 mg, 0.11 mmol) in anhydrous THF (0.15 mL) was added alcohol
2a (38 mg, 0.35 mmol). The reaction mixture was stirred at 25 ˚C for 19 h, then
quenched with H2O, and extracted with ethyl acetate (3 x 2 mL). The combined
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organic layers were dried over MgSO4 and concentrated in vacuo. The NMR yield
(phenanthrene as an internal standard) of (R)-3aa was determined to be 44% by 270
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MHz H NMR of the crude materials. The crude material was chromatographed on
silica gel (hexane/ethyl acetate/Et3N = 96/4/1) to give 12 mg (38%) of (R)-3aa and 7.4
mg (30%) of (S)-1a, then enantiomeric purities were determined by HPLC using a
chiral stationary phase column.
(R)-Benzyloxy allylbenzene ((R)-3aa).6h Colorless oil. 1H NMR (270
MHz, CDCl3): δ 4.52 (s, 2H), 4.83 (d, J = 7.0 Hz, 1H), 5.22 (dt, J = 10.3, 1.4 Hz, 1H),
5.29 (dt, J = 17.0, 1.4 Hz, 1H), 5.99 (ddd, J = 17.0, 10.3, 7.0 Hz, 1H), 7.23–7.39 (m,
10H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 70.0, 81.9, 116.4, 126.9, 127.5, 127.6,
127.7, 128.3, 128.4, 138.4, 138.8, 140.9. IR (neat) 3063, 3030, 2859, 1496, 1454,
1388, 1304, 1199, 1065, 1028, 991, 927, 844, 737, 418 cm–1. [α]D +48 (c 0.29,
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CHCl3) (90% ee). Enantiomeric purity was determined by chiral HPLC using a Daicel
CHIRALCEL OJ-H (hexane/2-propanol = 499/1, flow: 1.0 mL/min, 220 nm, rt, tR 22.8
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min (minor); tR 25.5 min (major)). (S)-1a: [α]D +38 (c 0.16, CHCl3) (99% ee).
Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
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OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 10.3 min (minor); tR
11.4 min (major)).
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(R)-Butoxy allylbenzene ((R)-3ab).23 Colorless oil (26% NMR yield, and
3.8 mg (20% isolated yield) after silica gel chromatography). 1H NMR (270 MHz,
CDCl3): δ 0.90 (t, J = 7.4 Hz, 3H), 1.32–1.46 (m, 2H), 1.54–1.65 (m, 2H), 3.32–3.51 (m,
2H), 4.72 (d, J = 6.8 Hz, 1H), 5.18 (dt, J = 10.3, 1.4 Hz 1H), 5.25 (dt, J = 17.0, 1.4 Hz,
1H), 5.94 (ddd, J = 17.0, 10.3, 6.8 Hz, 1H), 7.23–7.40 (m, 5H). 13C{1H} NMR (67.5
MHz, CDCl3): δ 13.9, 19.4, 31.9, 68.4, 82.9, 115.9, 126.8, 127.5, 128.4, 139.3, 141.4.
IR (neat) 3029, 2958, 2931, 1455, 1092, 924, 745, 700 cm–1. [α]D –77 (c 0.03,
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CHCl3) (91% ee). Enantiomeric purity was determined by chiral HPLC using a Daicel
CHIRALCEL OJ-H (hexane/2-propanol = 499/1, flow: 1.0 mL/min, 220 nm, rt, tR 6.0
min (minor); tR 6.5 min (major)). (S)-1a: Enantiomeric purity was determined by
chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0
mL/min, 220 nm, rt, tR 10.3 min (minor); tR 11.2 min (major)).
(R)-2-Methoxyethoxy allylbenzene ((R)-3ac). Colorless oil (41% NMR
yield, and 6.4 mg (23% isolated yield) after silica gel chromatography). 1H NMR (270
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MHz, CDCl3): δ 3.38 (s, 3H), 3.51–3.67 (m, 4H), 4.79 (d, J = 6.5 Hz, 1H), 5.19 (d, J =
10.3 Hz, 1H), 5.26 (d, J = 17.0 Hz, 1H), 5.97 (ddd, J = 17.0, 10.3, 6.5 Hz, 1H),
7.23–7.41 (m, 5H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 59.1, 67.8, 72.0, 83.5, 116.4,
126.9, 127.6, 128.4, 138.9, 140.9. IR (neat) 2874, 1492, 1452, 1307, 1199, 1093, 1030,
990, 927, 844, 759, 701, 522 cm–1. HRMS (ESI): m/z: calcd for C12H16O2 [M]
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192.1150, found 192.1122. [α]D –4.8 (c 0.42, CHCl3) (90% ee). Enantiomeric
purity was determined by chiral HPLC using a Daicel CHIRALCEL OJ-H
(hexane/2-propanol = 499/1, flow: 1.0 mL/min, 220 nm, rt, tR 13.5 min (minor); tR 14.1
min (major)). (S)-1a: Enantiomeric purity was determined by chiral HPLC using a
Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR
10.2 min (minor); tR 11.1 min (major)).
(R)-isoPropoxy allylbenzene ((R)-3ad).6h Colorless oil (39% NMR yield,
and 7.0 mg (28% isolated yield) after silica gel chromatography). 1H NMR (270 MHz,
CDCl3): δ 1.15 (d, J = 5.9 Hz, 3H), 1.20 (d, J = 5.9 Hz, 3H), 3.67 (sep, J = 5.9 Hz, 1H),
4.86 (d, J = 6.8 Hz, 1H), 5.15 (d, J = 10.3 Hz, 1H), 5.23 (d, J = 17.0 Hz, 1H), 5.95 (ddd,
J = 17.0, 10.3, 6.8 Hz, 1H), 7.22–7.41 (m, 5H). 13C{1H} NMR (67.5 MHz, CDCl3): δ
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22.1, 22.4, 68.7, 79.9, 115.6, 126.8, 127.4, 128.3, 139.7, 141.8. IR (neat) 3063, 3028,
2972, 2931, 2872, 1493, 1452, 1372, 1303, 1174, 1122, 1081, 1056, 1028, 991, 923,
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755, 700 cm–1. [α]D –18 (c 0.33, CHCl3) (92% ee). Enantiomeric purity was
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determined by chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol =
499/1, flow: 0.8 mL/min, 220 nm, rt, tR 7.4 min (minor); tR 7.9 min (major)). (S)-1a:
Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 9.8 min (minor); tR
10.8 min (major)).
(R)-Cyclohexyloxy allylbenzene ((R)-3ae).6f Colorless oil (25% NMR
yield, and 6.7 mg (22% isolated yield) after silica gel chromatography). 1H NMR (270
MHz, CDCl3): δ 1.16–1.96 (m, 10H), 3.30–3.39 (m, 1H), 4.92 (d, J = 6.5Hz, 1H), 5.15
(dt, J = 10.3, 1.5 Hz, 1H), 5.23 (dt, J = 17.3, 1.5 Hz, 1H), 5.95 (ddd, J = 17.3, 10.3, 6.5
Hz, 1H), 7.23–7.41 (m, 5H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 24.1, 24.2, 25.8,
32.3, 32.6, 74.7, 79.5, 115.5, 126.8, 127.3, 128.3, 139.9, 142.0. IR (neat) 3062, 3028,
2931, 2856, 1639, 1493, 1450, 1341, 1302, 1259, 1198, 1080, 1027, 990, 964, 922, 844,
758, 700, 520 cm–1. [α]D +19 (c 0.43, CHCl3) (87% ee). Enantiomeric purity was
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determined by chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol =
499/1, flow: 0.5 mL/min, 210 nm, rt, tR 14.2 min (minor); tR 14.8 min (major)).
(S)-1a: Enantiomeric purity was determined by chiral HPLC using a Daicel
CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 11.5
min (minor); tR 12.8 min (major)).
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(R)-1-Fluoro-2-((1-phenylallyloxy)methyl)benzene ((R)-3af).
Colorless
oil (39% NMR yield, and 12 mg (35% isolated yield) after silica gel chromatography).
1H NMR (270 MHz, CDCl3): δ 4.59 (d, J = 4.6 Hz, 2H), 4.86 (d, J = 6.5 Hz, 1H), 5.24
(dt, J = 10.3, 1.4 Hz, 1H), 5.32 (dt, J = 17.0, 1.4 Hz, 1H), 5.99 (ddd, J = 17.0, 10.3, 6.5
Hz, 1H), 6.98–7.51 (m, 9H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 63.8 (d, JCF = 3.9
Hz), 82.5, 115.1 (d, JCF = 21.1 Hz), 116.6, 124.0 (d, JCF = 3.9 Hz), 125.6 (d, JCF = 14.4
Hz), 126.9, 127.7, 128.5, 129.0, 129.2, 129.9 (d, JCF = 4.5 Hz), 139.7 (d, JCF = 143.2
Hz), 158.8. 19F NMR (470 MHz, CDCl3): δ 42.89–42.94 (m). IR(neat) 3030, 2859,
1619, 1587, 1492, 1455, 1390, 1231, 1194, 1111, 1069, 991, 928, 836, 757, 701, 516
cm–1. HRMS (ESI): m/z: calcd for C16H15FNaO+ [M+Na]+ 265.0999, found 265.1009.
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[α]D +23 (c 0.44, CHCl3) (92% ee). Enantiomeric purity was determined by chiral
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HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 499/1, flow: 0.5
mL/min, 220 nm, rt, tR 28.4 min (major); tR 29.5 min (minor)). (S)-1a: Enantiomeric
purity was determined by chiral HPLC using a Daicel CHIRALCEL OJ-H
(hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 9.5 min (minor); tR 10.4
min (major)).
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(R)-1-Fluoro-3-((1-phenylallyloxy)methyl)benzene ((R)-3ag). Colorless
oil (45% NMR yield, and 14 mg (40% isolated yield) after silica gel chromatography).
1H NMR (270 MHz, CDCl3): δ 4.51 (s, 2H), 4.83 (d, J = 6.8Hz, 1H), 5.23 (dt, J = 10.3,
1.4 Hz, 1H), 5.30 (dt, J = 17.3, 1.4 Hz, 1H), 5.99 (ddd, J = 17.3, 10.3, 6.8 Hz, 1H),
6.92–7.40 (m, 9H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 69.3 (d, JCF = 1.7 Hz), 82.3,
114.1 (d, JCF = 2.2 Hz), 114.4 (d, JCF = 2.8 Hz), 116.6, 122.9 (d, JCF = 2.8 Hz), 126.9,
127.8, 128.5, 129.8 (d, JCF = 8.4 Hz), 138.6, 140.7, 141.2 (d, JCF = 7.2 Hz), 162.9 (d, JCF
= 245.4 Hz). 19F NMR (470 MHz, CDCl3): δ 48.3–48.4 (m). IR (neat) 3030, 2860,
1618, 1592, 1489, 1451, 1388, 1255, 1197, 1138, 1092, 1065, 991, 928, 867, 784, 757,
701, 522, 442 cm–1. HRMS (ESI): m/z: calcd for C16H16FO+ [M+H]+ 243.1180, found
243.1190. [α]D24 +22 (c 0.55, CHCl3) (89% ee). Enantiomeric purity was determined
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by chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow:
1.0 mL/min, 220 nm, rt, tR 8.0 min (minor); tR 8.8 min (major)). (S)-1a: Enantiomeric
purity was determined by chiral HPLC using a Daicel CHIRALCEL OJ-H
(hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 10.5 min (minor); tR 11.2
min (major)).
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(R)-1-Fluoro-4-((1-phenylallyloxy)methyl)benzene ((R)-3ah).5e Colorless
oil (46% NMR yield, and 15 mg (45% isolated yield) after silica gel chromatography).
1H NMR (270 MHz, CDCl3): δ 4.47 (s, 2H), 4.81 (d, J = 7.0 Hz, 1H), 5.22 (dt, J = 10.3,
1.4 Hz, 1H), 5.28 (dt, J = 17.3, 1.4 Hz, 1H), 5.98 (ddd, J = 17.3, 10.3, 7.0 Hz, 1H),
6.97–7.08 (m, 2H), 7.24–7.37 (m, 7H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 69.4,
82.1, 115.2 (d, JCF = 21.1 Hz), 116.5, 126.9, 127.7, 128.5, 129.4 (d, JCF = 8.3 Hz), 134.1
(d, JCF = 3.3 Hz), 138.7, 140.8, 162.3 (d, JCF = 244.8 Hz). 19F NMR (470 MHz,
CDCl3): δ 46.58–46.64 (m). IR (neat) 3030, 2862, 1604, 1510, 1452, 1224, 1156,
1067, 991, 927, 824, 762, 701, 499 cm–1. [α]D –31 (c 0.59, CHCl3) (89% ee).
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Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 11.2 min (minor); tR
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14.7 min (major)). (S)-1a: Enantiomeric purity was determined by chiral HPLC using
a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt,
tR 10.5 min (minor); tR 11.5 min (major)).
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(R)-1-Chloro-4-((1-phenylallyloxy)methyl)benzene ((R)-3ai).5e Colorless
oil (44% NMR yield, and 15 mg (41% isolated yield) after silica gel chromatography).
1H NMR (270 MHz, CDCl3): δ 4.47 (s, 2H), 4.80 (d, J = 6.8 Hz, 1H), 5.22 (dt, J = 10.3,
1.4, Hz 1H), 5.29 (dt, J = 17.0, 1.4 Hz, 1H), 5.97 (ddd, J = 17.0, 10.3, 6.8 Hz, 1H),
7.22–7.43 (m, 9H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 69.3, 82.1, 116.6, 126.9,
127.8, 128.4, 128.5, 128.9, 133.2, 136.9, 138.6, 140.7. IR (neat) 3063, 3029, 2858,
1640, 1600, 1492, 1452, 1408, 1383, 1341, 1295, 1199, 1088, 1015, 990, 927, 806, 761,
701, 518 cm–1. [α]D +31 (c 0.59, CHCl3) (92% ee). Enantiomeric purity was
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determined by chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol =
499/1, flow: 1.0 mL/min, 220 nm, rt, tR 31.4 min (minor); tR 37.7 min (major)).
(S)-1a: Enantiomeric purity was determined by chiral HPLC using a Daicel
CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 10.5
min (minor); tR 11.5 min (major)).
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(R)-1-Methyl-2-((1-phenylallyloxy)methyl)benzene ((R)-3aj). Colorless
oil (46% NMR yield, and 14 mg (42% isolated yield) after silica gel chromatography).
1H NMR (270 MHz, CDCl3): δ 2.30 (s, 3H), 4.50 (d, J = 3.5 Hz, 2H), 4.83 (d, J = 6.5
Hz, 1H), 5.22 (dt, J = 10.3, 1.4 Hz, 1H), 5.30 (dt, J = 17.0, 1.4 Hz, 1H), 5.99 (ddd, J =
17.0, 10.3, 6.5 Hz, 1H), 7.11–7.42 (m, 9H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 18.9,
68.6, 82.1, 116.3, 125.7, 126.9, 127.6, 127.7, 128.4, 128.5, 130.1, 136.3, 136.7, 138.9,
141.0. IR (neat) 3063, 3027, 2861, 1639, 1604, 1493, 1453, 1379, 1287, 1196, 1119,
1065, 991, 926, 842, 745, 701, 522, 434 cm–1. HRMS (ESI): m/z: calcd for
C17H18NaO+ [M+Na]+ 261.1250, found 261.1226. [α]D23 +9 (c 0.64, CHCl3) (92% ee).
Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 8.9 min (minor); tR
11.3 min (major)). (S)-1a: Enantiomeric purity was determined by chiral HPLC using
a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt,
tR 9.8 min (minor); tR 10.7 min (major)).
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(R)-1-Methyl-3-((1-phenylallyloxy)methyl)benzene ((R)-3ak). Colorless
oil (35% NMR yield, and 10 mg (30% isolated yield) after silica gel chromatography).
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1H NMR (270 MHz, CDCl3): δ 2.34 (s, 3H), 4.48 (s, 2H), 4.83 (d, J = 6.5 Hz, 1H), 5.22
(dt, J = 10.3, 1.4 Hz, 1H), 5.29 (dt, J = 17.0, 1.4 Hz, 1H), 5.99 (ddd, J = 17.0, 10.3, 6.5
Hz, 1H), 7.07–7.42 (m, 9H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 21.4, 70.1, 82.0,
116.4, 124.7, 127.0, 127.6, 128.22, 128.23, 128.41, 128.43, 137.9, 138.3, 138.9, 141.0.
IR (neat) 3028, 2922, 2860, 1640, 1609, 1491, 1452, 1384, 1305, 1197, 1156, 1067, 990,
926, 843, 759, 700, 522, 431 cm–1. HRMS (ESI): m/z: calcd for C17H18NaO+ [M+Na]+
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261.1250, found 261.1248. [α]D +13 (c 0.62, CHCl3) (91% ee). Enantiomeric
purity was determined by chiral HPLC using a Daicel CHIRALCEL OJ-H
(hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 8.9 min (minor); tR 11.0
min (major)). (S)-1a: Enantiomeric purity was determined by chiral HPLC using a
Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR
9.8 min (minor); tR 10.7 min (major)).
(R)-1-Methyl-4-((1-phenylallyloxy)methyl)benzene ((R)-3al).5e Colorless
oil (44% NMR yield, and 14 mg (42% isolated yield) after silica gel chromatography).
1H NMR (270 MHz, CDCl3): δ 2.34 (s, 3H), 4.48 (s, 2H), 4.81 (d, J = 6.8Hz, 1H), 5.21
(dt, J = 10.3, 1.4 Hz, 1H), 5.27 (dt, J = 17.8, 1.4 Hz, 1H), 5.97 (ddd, J = 17.8, 10.3, 6.8
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Hz, 1H), 7.13–7.36 (m, 9H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 21.1, 69.9, 81.7,
116.3, 126.9, 127.6, 127.8, 128.4, 129.0, 135.3, 137.1, 138.9, 141.0. IR (neat) 3027,
2860, 1517, 1492, 1452, 1385, 1304, 1200, 1066, 1021, 991, 926, 840, 802, 759, 701,
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49
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484 cm–1. [α]D +6 (c 0.65, CHCl3) (92% ee). Enantiomeric purity was determined
33
by chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow:
1.0 mL/min, 220 nm, rt, tR 11.7 min (minor); tR 16.0 min (major)). (S)-1a:
Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 10.3 min (minor); tR
11.2 min (major)).
(R)-1-Methoxy-4-((1-phenylallyloxy)methyl)benzene
((R)-3am).5e
Colorless oil (44% NMR yield, and 14 mg (39% isolated yield) after silica gel
chromatography). 1H NMR (270 MHz, CDCl3): δ 3.80 (s, 3H), 4.45 (s, 2H), 4.81 (d, J
= 7.0 Hz, 1H), 5.21 (dt, J = 10.5, 1.4 Hz, 1H), 5.27 (dt, J = 17.0, 1.4 Hz, 1H), 5.98 (ddd,
J = 17.0, 10.5, 7.0 Hz, 1H), 6.87 (d, J = 8.6 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H), 7.31–7.42
(m, 5H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 55.3, 69.7, 81.6, 113.7, 116.4, 127.0,
127.6, 128.4, 129.3, 130.5, 138.9, 141.0, 159.1. IR (neat) 3029, 2934, 2836, 1613,
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1586, 1514, 1454, 1419, 1387, 1302, 1248, 1173, 1063, 1036, 991, 926, 821, 759, 701,
517 cm–1. [α]D24 +8 (c 0.49, CHCl3) (93% ee). Enantiomeric purity was determined by
chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0
mL/min, 220 nm, rt, tR 23.6 min (minor); tR 30.9 min (major)). (S)-1a: Enantiomeric
purity was determined by chiral HPLC using a Daicel CHIRALCEL OJ-H
(hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 10.2 min (minor); tR 11.1
min (major)).
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(R)-2-(((Phenylallyl)oxy)methyl)furan ((R)-3an).
Colorless oil (31%
NMR yield, and 9.3 mg (31% isolated yield) after silica gel chromatography). 1H
NMR (270 MHz, CDCl3): δ 4.46 (s, 2H), 4.84 (d, J = 7.0 Hz, 1H), 5.23 (d, J = 10.0 Hz,
1H), 5.28 (d, J = 16.7 Hz, 1H), 5.97 (ddd, J = 16.7, 10.0, 7.0 Hz, 1H), 6.28–6.34 (m,
2H), 7.25–7.42 (m, 6H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 62.1, 81.7, 109.3, 110.2,
116.8, 127.0, 127.7, 128.5, 138.5, 140.6, 142.7, 151.8. IR (neat) 3029, 2857, 1503,
1452, 1341, 1225, 1150, 1060, 1015, 993, 923, 885, 813, 740, 701, 600 cm–1. HRMS
33
(ESI): m/z: calcd for C14H14O2 [M] 214.0994, found 214.1015. [α]D –44 (c 0.18,
CHCl3) (93% ee). Enantiomeric purity was determined by chiral HPLC using a Daicel
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CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 14.1
min (minor); tR 15.9 min (major)). (S)-1a: Enantiomeric purity was determined by
chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0
mL/min, 220 nm, rt, tR 12.0 min (minor); tR 12.6 min (major)).
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(R)-2-(((Phenylallyl)oxy)methyl)naphthalene ((R)-3ao).
Colorless oil
(48% NMR yield, and 17 mg (44% isolated yield) after silica gel chromatography). 1H
NMR (270 MHz, CDCl3): δ 4.92 (d, J = 6.8 Hz, 1H), 4.96 (s, 2H), 5.25 (d, J = 10.5 Hz,
1H), 5.31 (d, J = 17.0 Hz, 1H), 6.03 (ddd, J = 17.0, 10.5, 6.8 Hz, 1H), 7.27–7.51 (m,
9H), 7.79–7.87 (m, 2H), 8.07–8.10 (m, 1H). 13C{1H} NMR (67.5 MHz, CDCl3): δ
68.6, 82.1, 116.7, 124.0, 125.2, 125.7, 126.1, 126.3, 127.0, 127.7, 128.4, 128.5, 131.7,
133.7, 133.8, 138.8, 140.9. IR (neat) 3060, 2857, 1598, 1509, 1452, 1387, 1231, 1167,
1064, 927, 793, 776, 701 cm–1. HRMS (ESI): m/z: calcd for C20H18NaO+ [M+Na]+
297.1250, found 297.1271. [α]D27 +8 (c 0.48, CHCl3) (93% ee). Enantiomeric purity
was determined by chiral HPLC using
a
Daicel CHIRALCEL AD-H
(hexane/2-propanol = 499/1, flow: 1.0 mL/min, 220 nm, rt, tR 7.7 min (minor); tR 8.2
min (major)). (S)-1a: Enantiomeric purity was determined by chiral HPLC using a
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Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR
10.5 min (minor); tR 11.5 min (major)).
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(R)-1-(((1-(Naphthalen-2-yl)allyl)oxy)methyl)naphthalene
((R)-3bo).
Colorless oil (46% NMR yield, and 19 mg (42% isolated yield) after silica gel
chromatography). 1H NMR (270 MHz, CDCl3): δ 5.00 (s, 2H), 5.09 (d, J = 6.5 Hz,
1H), 5.28 (d, J = 10.3 Hz, 1H), 5.36 (d, J = 17.0 Hz, 1H), 6.10 (ddd, J = 17.0, 10.3, 6.5
Hz, 1H), 7.41–7.53 (m, 7H), 7.80–7.87 (m, 6H), 8.09–8.12 (m, 1H). 13C{1H} NMR
(67.5 MHz, CDCl3): δ 68.7, 82.1, 116.8, 124.1, 125.0, 125.2, 125.7, 125.9, 126.0,
126.09, 126.1 126.4, 127.7, 127.9, 128.0, 128.3, 128.5, 128.51, 133.1, 133.3, 133.7,
133.8, 138.3, 138.8. IR (neat) 3047, 2998, 2923, 2872, 1931, 1734, 1636, 1598, 1509,
1481, 1441, 1421, 1381, 1365, 1307, 1291, 1278, 1268, 1244, 1227, 1171, 1156, 1124,
1083, 1036, 990, 948, 933, 901, 863, 822, 803, 781, 752, 700, 648, 624, 603, 548, 515,
504, 476, 434, 418, 402 cm–1. HRMS (ESI): m/z: calcd for C24H20NaO+ [M+Na]+
30
347.1406, found 347.1435. [α]D –44 (c 0.09, CHCl3) (93% ee). Enantiomeric
purity was determined by chiral HPLC using a Daicel CHIRALCEL AD-H
(hexane/2-propanol = 499/1, flow: 1.0 mL/min, 220 nm, rt, tR 6.4 min (minor); tR 6.8
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min (major)). (S)-1b: [α]D23 +62 (c 0.29, CHCl3) (80% ee). Enantiomeric purity was
determined by chiral HPLC using a Daicel CHIRALPAK AD-H (hexane/2-propanol =
499/1, flow: 1.0 mL/min, 220 nm, rt, tR 16.5 min (minor); tR 19.9 min (major)).
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(R)-1-(((1-(Naphthalen-1-yl)allyl)oxy)methyl)naphthalene
((R)-3co).
Colorless oil (48% NMR yield, and 17 mg (37% isolated yield) after silica gel
chromatography). 1H NMR (270 MHz, CDCl3): δ 5.00 (d, J = 5.7 Hz, 2H), 5.24 (d, J
= 10.3 Hz, 1H), 5.35 (d, J = 17.3 Hz, 1H), 5.60 (d, J = 5.7 Hz, 1H), 6.22 (ddd, J = 17.3,
10.3, 5.7 Hz, 1H), 7.39–7.52 (m, 7H), 7.65 (d, J = 6.8 Hz, 1H), 7.79–7.94 (m, 4H),
8.06–8.08 (m, 1H), 8.18 (d, J = 8.1 Hz, 1H). 13C{1H} NMR (67.5 MHz, CDCl3): δ
68.8, 80.3, 116.7, 124.1, 124.2, 125.2, 125.3, 125.4, 125.5, 125.6, 125.7, 125.8, 126.0,
126.4, 128.4, 128.5, 128.7, 131.0, 131.7, 133.7, 133.8, 134.0, 136.2, 138.3. IR (neat)
3048, 2857, 1597, 1509, 1395, 1167, 1063, 926, 777, 418 cm–1. HRMS (ESI): m/z:
calcd for C24H20NaO+ [M+Na]+ 347.1406, found 347.1435. [α]D30 +28 (c 0.58, CHCl3)
(84% ee). Enantiomeric purity was determined by chiral HPLC using a Daicel
CHIRALPAK AD-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min, 220 nm, rt, tR 5.5
24
min (minor); tR 6.7 min (major)). (S)-1c: [α]D –18 (c 0.22, CHCl3) (98% ee).
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Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
AD-H (hexane/2-propanol = 499/1, flow: 1.0 mL/min, 220 nm, rt, tR 14.7 min (minor);
tR 16.0 min (major)).
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(R)-1-(((1-(o-Tolyl)allyl)oxy)methyl)naphthalene ((R)-3do). Colorless oil
(54% NMR yield, and 21 mg (52% isolated yield) after silica gel chromatography). 1H
NMR (270 MHz, CDCl3): δ 2.26 (s, 3H), 4.94 (s, 2H), 5.11 (d, J = 6.2 Hz, 1H), 5.21 (d,
J = 9.5 Hz, 1H), 5.23 (d, J = 17.0 Hz, 1H), 6.00 (ddd, J = 17.0, 9.5, 6.2 Hz, 1H),
7.14–7.27 (m, 3H), 7.39–7.53 (m, 5H), 7.78–7.87 (m, 2H), 8.07–8.10 (m, 1H).
13C{1H} NMR (67.5 MHz, CDCl3): δ 19.2, 68.5, 79.1, 116.5, 124.0, 125.2, 125.7, 126.0,
126.2, 126.3, 126.8, 127.5, 128.4, 128.5, 130.5, 131.7, 133.7, 133.9, 135.8, 137.9, 138.6.
IR (neat) 3048, 2862, 1598, 1510, 1488, 1459, 1384, 1231, 1166, 1065, 991, 927, 793,
777, 756, 727, 456 cm–1. HRMS (ESI): m/z: calcd for C21H21O+ [M+H]+ 289.1587,
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found 289.1589. [α]D +55 (c 0.55, CHCl3) (89% ee). Enantiomeric purity was
determined by chiral HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol =
9/1, flow: 0.5 mL/min, 220 nm, rt, tR 13.2 min (minor); tR 14.9 min (major)). (S)-1d:
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[α]D –129 (c 0.14, CHCl3) (96% ee). Enantiomeric purity was determined by chiral
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HPLC using a Daicel CHIRALCEL OJ-H (hexane/2-propanol = 49/1, flow: 1.0 mL/min,
220 nm, rt, tR 6.6 min (minor); tR 7.6 min (major)).
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(R)-1-(((1-(p-Tolyl)allyl)oxy)methyl)naphthalene ((R)-3eo). Colorless oil
(59% NMR yield, and 21 mg (52% isolated yield) after silica gel chromatography). 1H
NMR (270 MHz, CDCl3): δ 2.35 (s, 3H), 4.89 (d, J = 6.2 Hz, 1H), 4.94 (s, 2H), 5.22 (d,
J = 10.0 Hz, 1H), 5.30 (d, J = 17.3 Hz, 1H), 6.02 (ddd, J = 17.3, 10.0, 6.2 Hz, 1H), 7.17
(d, J = 7.8 Hz, 2H), 7.27 (m, 2H), 7.40–7.51 (m, 4H), 7.79–7.87 (m, 2H), 8.07–8.10 (m,
1H). 13C{1H} NMR (67.5 MHz, CDCl3): δ 21.2, 68.5, 82.0, 116.4, 124.1, 125.2, 125.7,
126.0, 126.3, 127.0, 128.4, 128.5, 129.2, 131.7, 133.7, 133.9, 137.4, 137.9, 139.0. IR
(neat) 3048, 2923, 2859, 1511, 1065, 926, 793, 776, 527 cm–1. [α]D +61 (c 0.36,
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CHCl3) (88% ee). HRMS (ESI): m/z: calcd for C21H21O+ [M+H]+ 289.1587, found
289.1594. Enantiomeric purity was determined by chiral HPLC using a Daicel
CHIRALCEL OJ-H (hexane/2-propanol = 9/1, flow: 0.5 mL/min, 220 nm, rt, tR 18.1
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min (minor); tR 19.3 min (major)). (S)-1e: [α]D –224 (c 0.17, CHCl3) (97% ee).
Enantiomeric purity was determined by chiral HPLC using a Daicel CHIRALCEL
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