FICA, a new chiral derivatizing agent for determining the absolute configuration of secondary alcohols by 19F and 1H NMR spectroscopies

Article abstract of DOI:10.1016/j.tetasy.2013.06.012

Optically active 1-fluoroindan-1-carboxylic acid (FICA) was designed and prepared as its methyl ester for determining the absolute configuration of chiral molecules by both ¹H and ¹⁹F NMR spectroscopies. Enantiomerically pure isomers of FICA methyl esters (FICA Me esters) were obtained by chromatographic separation using HPLC with a Daicel Chiralcel OJ-H column. The absolute configuration of the (+)-FICA Me ester was deduced to be (S) by X-ray crystallographic analysis of the (+)-FICA amide of (R)-α-phenethylamine. Both enantiomers were derived to the diastereomeric esters of chiral secondary alcohols by an ester exchange reaction. In the ¹H NMR spectra, the signs of Δδ_H (δ_R - δ_S) were consistent on each side of the FICA molecular plane. Therefore, the concept of the modified Mosher's method could be successfully applied to the FICA-based procedure. Moreover, the consistency in the signs of Δδ_F (δ_R - δ_S) values suggests that the FICA method would be reliable in assigning the absolute configurations of secondary alcohols based on ¹⁹F NMR spectroscopy.

Full text of DOI:10.1016/j.tetasy.2013.06.012

Tetrahedron: Asymmetry 24 (2013) 1001–1009
Contents lists available at SciVerse ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
FICA, a new chiral derivatizing agent for determining the absolute
1
configuration of secondary alcohols by 19F and H NMR
spectroscopies
b
a
a
c
Tamiko Takahashi a,b, , Hiroaki Kameda , Tomoyo Kamei , Jyunichi Koyanagi , Fabio Pichierri ,
⇑
Kenji Omata d, Miyuki Ishizaki a, Hiroshi Nakamura a
a Faculty of Pharmaceutical Sciences, Josai International University, 1 Gumyo, Togane, Chiba 283-8555, Japan
b Division of Chemistry, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan
c Department of Applied Chemistry, Graduate School of Engineering, Tohoku University, Aoba-yama 6-6-07, Sendai 980-8579, Japan
d Department of Chemistry, Graduate School of Science, Tohoku University, 6-3 Aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
Optically active 1-fluoroindan-1-carboxylic acid (FICA) was designed and prepared as its methyl ester for
determining the absolute configuration of chiral molecules by both 1H and 19F NMR spectroscopies.
Enantiomerically pure isomers of FICA methyl esters (FICA Me esters) were obtained by chromatographic
separation using HPLC with a Daicel Chiralcel OJ-H column. The absolute configuration of the (+)-FICA Me
Received 20 May 2013
Accepted 11 June 2013
Available online 12 August 2013
ester was deduced to be (S) by X-ray crystallographic analysis of the (+)-FICA amide of (R)-
amine. Both enantiomers were derived to the diastereomeric esters of chiral secondary alcohols by an
ester exchange reaction. In the 1H NMR spectra, the signs of
dH (dR ꢀ dS) were consistent on each side
of the FICA molecular plane. Therefore, the concept of the modified Mosher’s method could be success-
fully applied to the FICA-based procedure. Moreover, the consistency in the signs of
a-phenethyl-
D
D
dF (dR ꢀ dS) values
suggests that the FICA method would be reliable in assigning the absolute configurations of secondary
alcohols based on 19F NMR spectroscopy.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
CF3
C
F
COOH
Ph
COOH
Techniques for assigning the absolute configuration of chiral
molecules have progressed considerably with the development of
asymmetric synthesis. Among the available methods that require
both reliability and simplicity, 1H NMR-based methods employing
a chiral derivatizing agent (CDA) represented by the modified
Mosher’s method have been widespread because of the simple
NMR operations, the small amount of analyzed sample, and their
applicability to different types of samples.1 Among the many CDAs,
OCH3
2
1
Figure 1. Chemical structures of 1 and 2.
a
-methoxy-a
-(trifluoromethyl) phenylacetic acid (MTPA) 12 (Fig. 1)
to the predominance of one NMR-significant conformer, character-
ized by the fixed orientation of the aromatic ring and restriction of
is one of the most widely available agents. However, the 1H NMR
spectra of the corresponding diastereomers indicate poor resolu-
tion, which was attributed to the presence of three dominant con-
formers.3 Moreover, the 19F chemical shifts cannot be generally
used for configuration assignments because of inconsistencies in
rotation about the C –CO bond. We previously reported on the
a
synthesis of racemic FICA methyl esters and suggested that FICA sur-
passes MTPA as a CDA in all 19F NMR analyses examined with nine
alcohols.4 In particular, the magnitude of
DdF values of FICA esters
the signs of
D
dF.2
was larger than that of the corresponding MTPA esters. Furthermore,
it is noteworthy that the concept of the modified Mosher’s method
was successfully applied to a (R)-(ꢀ)-8-phenylmethyl ester in the
1H NMR analyses. Due to the potential interest in using FICA as a
CDA, we extended our investigation. Herein we report on the prep-
aration of the FICA methyl ester in enantiomerically pure form and
the estimation of its ability as a CDA for the determination of the
In order to develop a CDA that surpasses the capabilities of MTPA,
we designed a fluorine-containing CDA, 1-fluoroindan-1-carboxylic
acid (FICA) 2 (Fig. 1). This was expected to give larger
Dd values due
⇑
Corresponding author. Tel.: +81 475 53 4596; fax: +81 475 53 4556.
E-mail address: tamikot@jiu.ac.jp (T. Takahashi).
0957-4166/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetasy.2013.06.012

1002
T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
absolute configuration of secondary alcohols by both 1H and 19F
NMR spectroscopies.
R*OH + n-BuLi
COOMe
COOR*
F
F
R*OLi
*
*
2. Results and discussion
–5 ºC
(R)-3
(S)-3
(R)a-5
(S)a-5
2.1. Resolution of ( )-FICA methyl ester ( )-3
Scheme 2. a(R) or (S) shows the absolute configuration of 3.
The ( )-FICA methyl ester ( )-3 was synthesized according to
the reported procedure.4 The resolution of racemic ester ( )-3
was performed by HPLC using a Daicel Chiralcel OJ-H column (/
1 ꢁ 25 cm, Daicel Co., Japan) (eluent: n-hexane/EtOH = 95:5, flow
rate: 4.7 mL/min, temp: 25 °C). The first eluted fraction with a
retention time of 7 min gave the (ꢀ)-FICA methyl ester (ꢀ)-3, while
the second with a retention time of 11 min gave the (+)-isomer (+)-
3 both of which are shown in Scheme 1.
According to the modified Mosher’s method, the chemical shift
differences between the corresponding protons in the two diaste-
reomers,
D
dH (dR ꢀ dS) for the FICA esters and
D
dH (dS ꢀ dR) for
the MTPA esters,6 are shown in Fig. 3 and Fig. 4, respectively.
For all of FICA esters examined here, similar magnitudes of
D
dH
values and the systematic distributions for the signs of
DdH values
to those of the corresponding MTPA esters were obtained. How-
F
ever, in the case of isomenthol 5m, the FICA ester showed a
COOMe
systematic distribution of the signs of
DdH values while the MTPA
(R)
ester did not. This result indicates that the concept of the modified
F
COOMe
(–)-3 t = 7 min
chiralcel OJ-H
(φ 1 x 25cm)
+0.01
H
hexane/EtOH = 95 : 5
flow rate 4.7 mL/min
-0.02
-0.08
+0.04
+0.05
+0.05
+0.08
F
H
COOMe
-0.07
5a
5b
+0.11
( )-3
(S)
(S)
+0.15
FICA
(S)
O
O
MTPA
(+)-3 t = 11 min
-0.01
H
+0.01
H
-0.05
-0.07
-0.05
-0.06
-0.09
-0.06
+0.07
+0.09
Scheme 1.
(R)
(R)
-0.17
-0.14
O
FICA
O
MTPA
2.2. Determination of the absolute configuration of (+) and (ꢀ)-
FICA methyl ester
-0.01
-0.06
-0.09
+0.02
H
-0.05
-0.07
H
-0.11
-0.09
+0.06
-0.07
-0.06
+0.09
5c
5d
The absolute configuration of (+)-FICA methyl ester (+)-3 was
determined to be (S) by single-crystal X-ray crystallographic anal-
(R)
(R)
-0.20
-0.16
O
FICA
O
MTPA
ysis of (R)-a-phenethylamide 4 prepared from (+)-FICA methyl
ester (+)-3.5 The unit cell of the crystal contains two crystallo-
graphically independent molecules, one of which is shown in
Figure 2. Therefore, on the basis of this result, the (ꢀ)-FICA methyl
ester (ꢀ)-3 was confirmed to have an (R)-configuration.
+0.01
-0.06
-0.02
-0.07
+0.06
+0.09
+0.05
H
+0.07
H
+0.04
+0.05
(S)
(S)
+0.10
+0.16
FICA
+0.09
O
MTPA
O
-0.01
H
-0.07
-0.09
+0.01
-0.01
-0.08
H
-0.06
+0.06
+0.08
5e
5f
(R)
(R)
-0.02
-0.02
-0.01
-0.06
-0.11
-0.15
-0.14
O
FICA
O
MTPA
-0.01
H
+0.01
H
-0.06
-0.09
-0.05
-0.07
-0.01
+0.06
+0.08
(R)
(R)
-0.03
O
FICA
O
MTPA
+0.15
+0.08
+0.03
-0.09
-0.01
-0.08
H
H
H
H +0.03
+0.07
+0.09
+0.15
5g
5h
(S)
(S)
Figure 2. ORTEP drawing for the (+)-FICA amide of (R)-a-phenethylamine 4.
O
FICA
O
MTPA
2.3.
DdH values for the FICA and MTPA esters of chiral secondary
+0.03
alcohols
+0.02
+0.04
-0.06
H
H
-0.05
The obtained enantiomers (R)-3 and (S)-3 were transformed
into their respective diastereomeric esters via an ester exchange
reaction4 where commercially available chiral secondary alcohols
with known configurations 5a–m were employed (Scheme 2).
(S)
(S)
O
FICA
O
MTPA
Figure 3.
D
dH values of the FICA and MTPA1f esters of chain alcohols.

T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
1003
+0.06
H
of the FICA esters was relatively constant. Accordingly, the FICA-
based procedure based on 19F NMR spectroscopy was reliable in
assigning the absolute configurations of the secondary alcohols.
+0.01
H
+0.17
+0.10
H
0
-0.004
H
+0.04
H
+0.03
0
0
-0.06 H
H
H
CH3
CH3
CH3
CH3
-0.01
H
H
+0.01
H
-0.06
5i
0
2.5. DFT calculations on a model of FICA methyl ester
H
H
-0.08
H3C
-0.02
H3C
-0.15
H
(R)
(R)
+0.13
+0.10
In order to explain the assignment of the absolute configura-
tions, we performed density functional theory (DFT) calculations
on the simple FICA methyl ester molecule (Fig. 5). Two molecular
O
O
H
H
+0.04
+0.04
FICA
MTPA
+0.01
H
models arise upon rotation about the C –CO bond: synperiplanar
-0.01
H
+0.03
+0.02
a
0
-0.13
H
H
(sp), with the C–F and C@O bonds oriented in the same direction,
and antiperiplanar (ap), with these same bonds oriented in oppos-
ing directions. The geometry optimizations performed at the
B3LYP/6-31G(d,p) level of theory7,8 predicted that the ap rotamer
is more stable than the sp rotamer by 0.67 kcal/mol while the
dihedral angle \(F–C–C–O) is +18° for the sp rotamer and ꢀ149°
for the ap rotamer. The sp rotamer displays a folded form and
the ap rotamer an extended one. In the sp rotamer, the aromatic
ring is favorably positioned so as to exert a shielding effect on
the protons of both the R1 and R2 groups of the alcohol, whereas
this does not occur in the ap rotamer. Therefore, the 1H NMR signif-
icant conformer is likely to be mainly the sp one. Although the ori-
entation of the aromatic ring was fixed, the comparatively small
+0.03
+0.01
H
-0.02
H
H
-0.06
H
H
H
+0.02
+0.06
-0.07
H
H3C
0
CH3
H
CH3
H
H
5j
-0.20
-0.16
H3C
(R)
(R)
+0.08
+0.28
H
H
+0.09
+0.31
-0.14
O
O
CH3
-0.22
CH3
-0.28
H
H
-0.05
MTPA
FICA
+0.02
H
-0.01
H
+0.02
+0.02
0
-0.05
H
H
+0.01
H
H
0
-0.02
-0.03
H
H
H
H
+0.03
+0.03
-0.04
H
-0.09
H
H3C
CH3
H
CH3
-0.10
-0.15
5k
(R)
(R)
H3C
H
H
D
dH values were due to the smaller population of the sp rotamer.
+0.06
+0.07
-0.34
H
-0.46
H
H
H3C
-0.12
O
+0.14
O
+0.14
H3C
H
H
+0.02
-0.05
MTPA
FICA
-0.18
-0.09
H
-0.1
-0.06
H
-0.17
-0.68
-0.24
H
H
H
H
0
+0.05
H
H
H3C
-0.21
H3C
+0.02
-0.09
H
H
H
5l
H
+0.26
(S)
(S)
CH3
CH3
-0.20
-0.03
H
-0.11
H
H
H
CH
+0.65
+0.1
3
H
H
-0.07
CH3
+0.01
+0.06
O
O
H
H
+0.23
+0.08
+0.06
+0.06
FICA
MTPA
Figure 5. DFT calculations on FICA model (R = Me).
+0.1
H
-0.05
H
-0.04
H
-0.05
-0.15
-0.24
H
H
H
+0.1
+0.12
Furthermore, we calculated the differences in 19F chemical
H
H
H3C
-0.07
H
H3C
-0.05
+0.12
shifts differences (dF) between the sp and the ap rotamers at the
GIAO-B3LYP/6-31+G(2d,p) level of theory.9 For the ap rotamer we
obtained dF = ꢀ162.1 ppm while for the sp one we calculated dF = -
H
H
+0.09
H
+0.05
H
5m
CH3
CH3
(S)
-0.19
(S)
H
H
H
+0.15
CH3
+0.07
+0.19
H
H
-0.04
-0.21
CH3
+0.25
+0.03
ꢀ157.5 ppm which corresponds to
DdF (syn–anti) = 5 ppm. The DFT
O
O
H
H
results nicely explain the 19F chemical shift differences experimen-
tally observed (see Table 1).
+0.09
+0.01
+0.03
FICA
MTPA
Figure 4.
D
dH values of the FICA and MTPA1f esters of cyclic alcohols.
3. Conclusions
Mosher’s method could be successfully applied to the FICA-based
procedure. While FICA and MTPA showed similar performances
for acyclic alcohols (Fig. 3), FICA was superior to MTPA when ap-
plied to cyclic alcohols (Fig. 4).
The FICA-based method is reliable in assigning the absolute
configurations of secondary alcohols based on both 1H and 19F
NMR spectroscopies. The ap rotamer was found to be energetically
more stable than the sp rotamer. However, due to the shielding of
the protons by the aromatic moiety of FICA, the NMR-significant
conformer is mainly the sp one. Despite the fixed orientation of
2.4.
DdF values for the FICA and MTPA esters of chiral secondary
alcohols
the aromatic ring, the comparatively small
DdH values are due to
the small population of the sp rotamer. The non-equivalence in
the measured 19F NMR shifts could be rationalized by the bias
associated with the existence of the sp and ap rotamers.
In order to elucidate the applicability of the FICA-based proce-
dure by 19F NMR, we examined the chemical shift differences
dF
between the diastereomers. Table 1 reports the consistent relation-
ship between the signs of dF values and the absolute configuration
D
D
for the FICA esters of the chiral secondary alcohols. In other words,
the signs of the (S)-alcohols were all positive and those of (R)-alco-
hols were all negative. However, such a correlation does not appear
4. Experimental
4.1. General
among the MTPA esters. Furthermore, the magnitude of the
ues of the FICA esters was much larger than that of the MTPA esters.
Independent of the size of alcohols, the magnitude of the dF values
DdF val-
Melting points were measured with a Yanaco micro melting point
apparatus and are uncorrected. Microanalyses were performed by
D

1004
T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
Table 1
D
dF values obtained for the FICA and MTPA esters
R1
R1
R2
R2
F3C CO2
C
F
CO2
∗
C
∗
H
H
OMe
FICA esters
MTPA esters
MicroanalysisCenterofToyamaMedical&PharmaceuticalUniversity
and Microanalysis Center of Josai University. Spectroscopic measure-
ments were carried out with the following instruments: optical rota-
tions, JASCO P1020 and JASCO DIP-1000 digital polarimeter; IR,
Perkin–Elmer 1600 Series FT-IR, JASCO FT/IR-7300 and JASCO FT/IR-
4200; mass (MS), JEOL JMS-700 and JEOL JMS-GCmate; high resolu-
tion mass spectra (HRMS), JEOL JMS-700 and JEOL JMS-AX505HAD;
1H NMR, JEOL ECA 500 (500 MHz), Varian Unity 500 (500 MHz) and
Varian Gemini 300 (300 MHz) for solutions in CDCl3 with Me4Si as
an internal standard; 13C NMR, JEOL ECA 500 (125.8 MHz) and Varian
Gemini 300 (75.46 MHz) for solutionsin CDCl3 with CDCl3 as an inter-
nal standard (77.2 ppm); 19F NMR, JEOL ECA 500 (470.6 MHz), and
JEOL JNM-GX 270 (254 MHz) for solutions in CDCl3 with CFCl3 as an
internal standard. Column chromatography, flash column chroma-
tography, and preparative TLC (PLC) were performed on Kieselgel
60 (Merck Art. 7734, Art. 9385, and 7748, respectively). Quantum
chemical calculations were performed with Gaussian 037 on a
Linux-based workstation at Tohoku University.
HPLC (DAICEL CHIRALCEL OJ-H, / 0.46 ꢁ 25 cm, Daicel Co., Japan; n-
hexane/EtOH = 95/5, 1.0 mL/min, 254 nm), t1 = 9.83 min, k0 = 2.23,
1
a
= 1.80, Rs = 1.45.
The second fraction to be eluted (retention time t2 = 11 min) was a
colorless oil of (+)-1-fluoroindan-1-carboxylic acid methyl ester
(348 mg, 1.79 mmol, 43%, ee >99% by HPLC); ½a D27
¼ þ38:9 (c 1.56,
ꢂ
CHCl3); IR (neat) 2955 (CH), 1757 (C@O) cmꢀ1; 1H NMR (300 MHz) d
2.49 (dddd, 1H, J = 5.0, 8.5, 14.3, 23.4 Hz, 2-H), 2.84 (dddd, 1H, J = 5.7,
8.5, 14.3, 20.0 Hz, 2-H), 3.03–3.12 (m, 1H, 3-H), 3.13–3.23 (m, 1H, 3-
H), 3.81 (s, 3H, OCH3), 7.24–7.42 (m, 4H, 4–7-H); 13C NMR
(75.46 MHz) d 30.4 (s, CH2, 3-C), 36.5 (d, J = 23.2 Hz, CH2, 2-C), 53.0
(s, CH3, OCH3), 102.3 (d, J = 190.4 Hz, C, 1-C), 124.3 (s, CH, 7-C), 125.3
(s, CH, 4-C), 127.2 (d, J = 2.4 Hz, CH, 6-C), 130.6 (d, J = 2.4 Hz, CH, 5-
C), 139.3 (d, J = 20.7 Hz, C, 7a-C), 145.0 (d, J = 4.8 Hz, C, 3a-C), 171.1
(d, J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ139.02 (t, J =
22.2 Hz); MS m/z: 194 (M+), 174 ([MꢀHF]+), 135 ([MꢀCOOMe]+), 115
(indenyl cation); HRMS calcd for C11H11O2F (M+): 194.0743, found:
194.0745; HPLC (DAICEL CHIRALCEL OJ-H, / 0.46 ꢁ 25 cm, Daicel
Co., Japan; n-hexane/EtOH = 95/5, 1.0 mL/min, 254 nm), t2 =
15.27 min, k02 = 4.02,
a = 1.80, Rs = 1.45.
4.2. Chromatographic separation of ( )-1-fluoroindan-1-
carboxylic acid methyl ester (FICA Me ester) (+)-3 and (ꢀ)-3
4.3. N-(R)-1-Phenylethyl-(S)-1-fluoroindan-1-carboxamide 4
Chromatographic separation of ( )-34 (804 mg, 4.14 mmol) was
carried out by HPLC with a Daicel Chiralcel OJ-H column (/
1.0 ꢁ 25 cm, Daicel Co., Japan) (eluent: n-hexane/EtOH = 95:5, flow
rate 4.7 mL/min, temp: 25 °C). The first fraction to be eluted (reten-
tion time t1 = 7 min) was a colorless oil of (ꢀ)-1-fluoroindan-1-car-
boxylic acid methyl ester (353 mg, 1.82 mmol, 44%, ee >99% by
Colorless needles; mp 84 °C; ½a D26
ꢂ
¼ þ167:2 (c 0.80, CHCl3); IR
;
1H NMR (500 MHz) d 1.59
(neat) 2928 (CH), 1661 (C@O) cmꢀ1
(d, 3H, J = 7.5 Hz, CH3), 2.44 (dddd, 1H, J = 3.4, 8.0, 14.3, 23.5 Hz,
CH2), 2.90 (dddd, 1H, J = 6.9, 8.6, 14.3, 27.5 Hz, CH2), 3.09 (m, 1H,
CH2), 3.19 (m, 1H, CH2), 5.24 (qd, 1H, J = 1.2, 6.9 Hz, CH), 7.30
(s, 1H, NH), 7.11–7.41 (m, 9H, Ph, Ph0-H); 13C NMR (125.8 MHz) d
21.7 (s, CH3), 30.2 (s, CH2), 36.0 (d, J = 24.0 Hz, CH2), 48.7 (s, CH),
105.2 (d, J = 193.2 Hz, C), 123.7 (s, CH), 125.1 (s, CH), 126.1 (s,
CH), 127.0 (s, CH), 127.5 (s, CH), 128.7 (s, CH), 130.4 (s, CH),
139.8 (d, J = 19.2 Hz, CH), 142.9 (s, CH), 145.6 (s, C), 170.0 (d,
J = 26.4 Hz, CO); 19F NMR (470.6 MHz) d ꢀ136.54 (t, J = 25.2 Hz);
MS m/z: 283 (M+), 263 ([MꢀHF]+), 135 ([MꢀCONHR⁄]+); HRMS
calcd for C18H18NOF (M+): 283.1372, found: 283.1362; Anal. Calcd
for C18H18NOF: C, 76.30; H, 6.40; N, 4.94. Found: C, 76.23; H, 6.42;
N, 4.70.
HPLC); ½a 2D6
¼ ꢀ39:1 (c 1.58, CHCl3); IR (neat) 2955 (CH), 1756
ꢂ
(C@O) cmꢀ1; 1H NMR (300 MHz) d 2.49 (dddd, 1H, J = 5.0, 8.5, 14.3,
23.4 Hz, 2-H), 2.84 (dddd, 1H, J = 5.7, 8.5, 14.3, 20.0 Hz, 2-H), 3.03–
3.12 (m, 1H, 3-H), 3.13–3.23 (m, 1H, 3-H), 3.81 (s, 3H, OCH3), 7.24–
7.42 (m, 4H, 4–7-H); 13C NMR (75.46 MHz) d 30.4 (s, CH2, 3-C),
36.5 (d, J = 23.2 Hz, CH2, 2-C), 53.0 (s, CH3, OCH3), 102.3
(d, J = 190.4 Hz, C, 1-C), 124.3 (s, CH, 7-C), 125.3 (s, CH, 4-C), 127.2
(d, J = 2.4 Hz, CH, 6-C), 130.6 (d, J = 2.4 Hz, CH, 5-C), 139.3 (d,
J = 20.7 Hz, C, 7a-C), 145.0 (d, J = 4.8 Hz, C, 3a-C), 171.1 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ139.02 (t, J = 22.2 Hz);
MS m/z: 194 (M+), 174 ([MꢀHF]+), 135 ([MꢀCOOMe]+), 115 (indenyl
cation); HRMS calcd for C11H11O2F (M+): 194.0743, found:194.0736;
X-ray crystallographic data: C18H18NOF, monoclinic, space group
C121, a = 19.660 (10) Å, b = 8.206 (4) Å, c = 18.516 (9) Å, V = 2928

T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
1005
(2) Å3, Z = 8, size = 0.25 ꢁ 0.20 ꢁ 0.15 mm,
l
(MoK
a
) = 0.088 cmꢀ1
,
4.4.3. (R)-2-Pentyl (R)-1-fluoroindan-1-carboxylate (R)-5b
T = 173 K, total data = 21448, unique data = 6712 (Rint = 0.042), 416
76%; Colorless oil; ½a D27
ꢂ
¼ ꢀ36:2 (c 2.21, CHCl3); IR (neat) 2961
parameters, R (5707 data with I >2.0
r
(I)) = 0.0349, wR (all reflec-
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.82 (t, 3H,
tions) = 0.0485, GOF = 0.973. The authors have deposited atomic
coordinates for the amide with the Cambridge Crystallographic Data
Centre, CCDC number 946714. The coordinates can be obtained, on
request, from the Director, Cambridge Crystallographic Data Centre,
12 Union Road, Cambridge, CB2 1EZ (UK).
J = 7.3 Hz, 50-H), 1.19 (m, 2H, 40-H), 1.26 (d, 3H, J = 6.4 Hz, 10-H),
1.44 (dddd, 1H, J = 5.6, 6.4, 9.8, 13.7 Hz, 30-H), 1.56 (dddd, 1H,
J = 5.6, 8.1, 9.8, 13.7 Hz, 30-H), 2.48 (dddd, 1H, J = 5.1, 8.5, 14.1,
22.6 Hz, 2-H), 2.82 (dddd, 1H, J = 5.6, 8.5, 14.1, 19.7 Hz, 2-H), 3.07
(m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.04 (qdd, 1H, J = 6.4, 5.1, 6.4 Hz,
20-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H), 7.31 (d, 1H, J = 7.3 Hz, 4-H),
7.37 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.42 (d, 1H, J = 8.1 Hz, 7-H);
13C NMR (75.46 MHz) d 14.0 (s, CH3, 50-C), 18.6 (s, CH2, 40-C),
20.2 (s, CH3, 10-C), 30.4 (s, CH2, 3-C), 36.4 (d, J = 23.2 Hz, CH2, 2-
C), 38.0 (s, CH2, 30-C), 72.7 (s, CH, 20-C), 102.0 (d, J = 199.0 Hz, C,
1-C), 124.1 (s, CH, 7-C), 125.1 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH,
6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C), 139.6 (d, J = 19.5 Hz, C, 7a-C),
144.9 (d, J = 4.9 Hz, C, 3a-C), 170.3 (d, J = 33.0 Hz, C, COO); 19F
NMR (254 MHz) d ꢀ139.45 (t, J = 23.1 Hz); MS m/z: 250 (M+), 230
([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd
for C15H19O2F (M+): 250.1369, found: 250.1382.
4.4. General procedure for the ester exchange reaction of 1-
fluoroindan-1-carboxylic acid methyl ester with a secondary
alcohol
To a solution of a secondary alcohol (0.177 mmol) in dry THF
(0.5 mL) was added dropwise n-BuLi (1.59 mol/L in hexane,
0.1 mL, 0.159 mmol, at ꢀ5 °C) under a nitrogen atmosphere. After
being stirred for 30 min, a solution of (R)-3 or (S)-3 (34.3 mg,
0.177 mmol) was added slowly to the mixture. After 15 min, the
reaction was quenched with a saturated aqueous NH4Cl solution
(1 mL), and then water (5 mL) and Et2O (10 mL) were added to
the reaction mixture. The organic layer was separated, washed
with 2% HCl (5 mL), water (5 mL), and a saturated aqueous NaHCO3
solution (5 mL), and dried over MgSO4. The solvent was evaporated
and the residue was purified by column chromatography (hexane/
AcOEt = 19:1) to give 1-fluoroindan-1-carboxylic acid ester with a
secondary alcohol.
4.4.4. (R)-2-Pentyl (S)-1-fluoroindan-1-carboxylate (S)-5b
71%; Colorless oil; ½a D27
ꢂ
¼ þ3:5 (c 2.01, CHCl3); IR (neat) 2961
(CH), 1751 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.92 (t, 3H,
J = 7.3 Hz, 50-H), 1.20 (d, 3H, J = 6.0 Hz, 10-H), 1.35 (m, 2H, 40-H),
1.49 (dddd, 1H, J = 5.6, 6.0, 9.4, 13.7 Hz, 30-H), 1.63 (dddd, 1H,
J = 5.6, 7.7, 9.8, 13.7 Hz, 30-H), 2.48 (dddd, 1H, J = 4.7, 8.5, 14.1,
22.6 Hz, 2-H), 2.82 (dddd, 1H, J = 5.6, 8.5, 14.1, 20.1 Hz, 2-H), 3.07
(m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.05 (qdd, 1H, J = 6.0, 6.4, 6.8 Hz,
20-H), 7.27 (t, 1H, J = 7.7 Hz, 6-H), 7.32 (d, 1H, J = 7.7 Hz, 4-H),
7.37 (tt, 1H, J = 1.3, 7.3 Hz, 5-H), 7.40 (d, 1H, J = 8.1 Hz, 7-H); 13C
NMR (75.46 MHz) d 14.1 (s, CH3, 50-C), 19.0 (s, CH2, 40-C), 20.0
(s, CH3, 10-C), 30.5 (s, CH2, 3-C), 36.5 (d, J = 23.2 Hz, CH2, 2-C),
38.1 (s, CH2, 30-C), 72.9 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C, 1-
C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.2 (d, J = 2.4 Hz, CH,
6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C), 139.6 (d, J = 20.8 Hz, C, 7a-C),
145.0 (d, J = 4.9 Hz, C, 3a-C), 170.3 (d, J = 31.7 Hz, C, COO); 19F
NMR (254 MHz) d ꢀ139.11 (t, J = 22.2 Hz); MS m/z: 250 (M+), 230
([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd
for C15H19O2F (M+): 250.1369, found: 250.1352.
4.4.1. (S)-2-Butyl (R)-1-fluoroindan-1-carboxylate (R)-5a
84%; Colorless oil; ½a D26
ꢂ
¼ ꢀ6:8 (c 2.29, CHCl3); IR (neat) 2975
(CH), 1751 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.92 (t, 3H,
J = 7.3 Hz, 40-H), 1.19 (d, 3H, J = 6.4 Hz, 10-H), 1.58 (qdd, 1H,
J = 7.3, 5.6, 15.0 Hz, 30-H), 1.65 (qdd, 1H, J = 7.3, 6.8, 14.1 Hz,
30-H), 2.48 (dddd, 1H, J = 5.1, 8.5, 14.1, 22.6 Hz, 2-H), 2.83 (dddd,
1H, J = 5.6, 8.5, 14.1, 19.7 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m,
1H, 3-H), 4.98 (qdd, 1H, J = 6.4, 6.4, 6.4 Hz, 20-H), 7.27 (t, 1H,
J = 7.7 Hz, 6-H), 7.32 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (t, 1H, J = 7.7 Hz,
5-H), 7.41 (d, 1H, J = 7.7 Hz, 7-H); 13C NMR (75.46 MHz) d 10.1
(s, CH3, 40-C), 19.5 (s, CH3, 10-C), 28.9 (s, CH2, 30-C), 30.4 (s, CH2,
3-C), 36.5 (d, J = 24.4 Hz, CH2, 2-C), 74.3 (s, CH, 20-C), 102.1 (d,
J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1
(d, J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C), 139.6
(d, J = 20.8 Hz, C, 7a-C), 145.0 (d, J = 4.9 Hz, C, 3a-C), 170.3
4.4.5. (R)-2-Hexyl (R)-1-fluoroindan-1-carboxylate (R)-5c
75%; Colorless oil; ½a D28
ꢂ
¼ ꢀ38:0 (c 2.31, CHCl3); IR (neat) 2957
(d, J = 31.7 Hz, C, COO); 19F NMR (254 MHz)
d
ꢀ139.18 (t,
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.81 (t, 3H,
J = 23.1 Hz); MS m/z: 236 (M+), 216 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+),
115 (indenyl cation); HRMS calcd for C14H17O2F (M+): 236.1212,
found: 236.1167.
J = 7.3 Hz, 60-H), 1.11 (m, 2H, 40-H), 1.20 (qt, 2H, J = 7.3, 6.8 Hz 50-
H), 1.26 (d, 3H, J = 6.0 Hz, 10-H), 1.46 (dddd, 1H, J = 5.2, 6.8, 8.5,
15.4 Hz, 30-H), 1.55 (dddd, 1H, J = 6.0, 7.7, 9.0, 13.7 Hz, 30-H), 2.47
(dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd, 1H, J = 5.1,
8.5, 14.1, 19.2 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.02
(qdd, 1H, J = 6.0, 6.4, 6.8 Hz, 20-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H),
7.31 (d, 1H, J = 7.7 Hz, 4-H) 7.37 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.41
4.4.2. (S)-2-Butyl (S)-1-fluoroindan-1-carboxylate (S)-5a
68%; Colorless oil; ½a D27
ꢂ
¼ þ35:6 (c 1.80, CHCl3); IR (neat) 2975
(CH), 1751 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.77 (t, 3H,
13
J = 7.3 Hz, 40-H), 1.26 (d, 3H, J = 6.4 Hz, 10-H), 1.52 (qdd, 1H,
J = 7.3, 5.6, 15.0 Hz, 30-H), 1.57 (qdd, 1H, J = 7.3, 6.8, 14.1 Hz, 30-
H), 2.48 (dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd,
1H, J = 5.6, 8.5, 14.1, 19.7 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m,
1H, 3-H), 4.97 (qdd, 1H, J = 6.4, 6.0, 6.4 Hz, 20-H), 7.26 (t, 1H,
J = 7.7 Hz, 6-H), 7.31 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (tt, 1H, J = 1.3,
7.7 Hz, 5-H), 7.42 (d, 1H, J = 7.7 Hz, 7-H); 13C NMR (75.46 MHz) d
9.8 (s, CH3, 40-C), 19.7 (s, CH3, 10-C), 28.9 (s, CH2, 30-C), 30.5 (s,
CH2, 3-C), 36.4 (d, J = 23.2 Hz, CH2, 2-C), 74.2 (s, CH, 20-C), 102.1
(d, J = 189.2 Hz, C, 1-C), 124.2 (s, CH, 7-C), 125.2 (s, CH, 4-C),
127.1 (d, J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C), 139.7
(d, J = 20.8 Hz, C, 7a-C), 144.9 (d, J = 4.9 Hz, C, 3a-C), 170.3
(d, 1H, J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 14.2 (s, CH3, 60-C),
20.2 (s, CH3, 10-C), 22.6 (s, CH2, 50-C), 27.5 (s, CH2, 40-C), 30.5 (s,
CH2, 3-C), 35.6 (s, CH2, 30-C), 36.4 (d, J = 23.2 Hz, CH2, 2-C), 73.0
(s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C),
125.2 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH, 6-C), 130.4
(d, J = 2.4 Hz, CH, 5-C), 139.7 (d, J = 20.8 Hz, C, 7a-C), 144.9 (d,
J = 4.9 Hz, C, 3a-C), 170.3 (d, J = 31.7 Hz, C, COO); 19F NMR
(254 MHz) d ꢀ139.62 (t, J = 23.1 Hz); MS m/z: 264 (M+), 244
([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd
for C16H22O2F ([M+H]+): 265.1604, found: 265.1622.
4.4.6. (R)-2-Hexyl (S)-1-fluoroindan-1-carboxylate (S)-5c
(d, J = 33.0 Hz, C, COO); 19F NMR (254 MHz)
d
ꢀ139.41 (t,
62%; Colorless oil; ½a D27
¼ þ2:9 (c 1.84, CHCl3); IR (neat) 2957
ꢂ
J = 23.1 Hz); MS m/z: 236 (M+), 216 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+),
115 (indenyl cation); HRMS calcd for C14H17O2F (M+): 236.1212,
found: 236.1241.
(CH), 1751 (C@O) cmꢀ1 1H NMR (500 MHz)
; d 0.89 (t, 3H,
J = 6.8 Hz, 60-H), 1.19 (d, 3H, J = 6.4 Hz, 10-H), 1.31 (m, 4H,
40,50-H), 1.52 (m, 1H, 30-H), 1.64 (m, 1H, 30-H), 2.48 (dddd, 1H,

1006
T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
13
J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd, 1H, J = 5.5, 8.5, 14.1,
20.1 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.03 (qdd, 1H,
J = 6.0, 6.4, 6.8 Hz, 20-H), 7.26 (t, 1H, J = 7.3 Hz, 6-H), 7.32 (d, 1H,
J = 7.7 Hz, 4-H), 7.37 (tt, 1H, J = 1.3, 7.3 Hz, 5-H), 7.40 (d, 1H,
(d, 1H, J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 14.4 (s, CH3, 80-C),
20.2 (s, CH3, 10-C), 22.8 (s, CH2, 70-C), 25.3 (s, CH2, 40-C), 29.1 (s,
CH2, 50-C), 30.5 (s, CH2, 3-C), 31.9 (s, CH2, 60-C), 35.9 (s, CH2, 30-
C), 36.4 (d, J = 23.2 Hz, CH2, 2-C), 73.0 (s, CH, 20-C), 102.1 (d,
J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1
(d, J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 3.6 Hz, CH, 5-C), 139.7 (d,
J = 22.0 Hz, C, 7a-C), 144.9 (d, J = 4.9 Hz, C, 3a-C), 170.3 (d,
13
J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 14.2 (s, CH3, 60-C), 20.2
(s, CH3, 10-C), 22.7 (s, CH2, 50-C), 27.8 (s, CH2, 40-C), 30.5 (s, CH2,
3-C), 35.6 (s, CH2, 30-C), 36.5 (d, J = 23.2 Hz, CH2, 2-C), 73.1 (s, CH,
20-C), 102.1 (d, J = 190.4 Hz, C, 1-C), 124.2 (s, CH, 7-C), 125.2
(s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 3.7 Hz, CH,
5-C), 139.6 (d, J = 20.8 Hz, C, 7a-C), 145.0 (d, J = 4.9 Hz, C, 3a-C),
170.3 (d, J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ139.20
(t, J = 23.1 Hz); MS m/z: 264 (M+), 244 ([MꢀHF]+), 135
([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd for C16H21O2F
(M+): 264.1526, found: 264.1492.
J = 31.7 Hz, C, COO); 19F NMR (254 MHz)
d
ꢀ139.54 (t,
J = 23.1 Hz); MS m/z: 292 (M+), 272 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+),
115 (indenyl cation); HRMS calcd for C18H25O2F (M+): 292.1839,
found: 292.1844.
4.4.10. (R)-2-Octyl (S)-1-fluoroindan-1-carboxylate (S)-5e
59%; Colorless oil; ½a D27
ꢂ
¼ þ1:9 (c 1.98, CHCl3); IR (neat) 2932
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.88 (t, 3H,
4.4.7. (S)-2-Heptyl (R)-1-fluoroindan-1-carboxylate (R)-5d
J = 6.8 Hz, 80-H), 1.20 (d, 3H, J = 6.4 Hz, 10-H), 1.22–1.36 (m, 8H,
40–70-H), 1.52 (m, 1H, 30-H), 1.63 (m, 1H, 30-H), 2.48 (dddd, 1H,
J = 4.7, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd, 1H, J = 5.6, 8.5, 14.1,
20.1 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.03 (qdd, 1H,
J = 6.4, 6.0, 7.3 Hz, 20-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H), 7.32 (d, 1H,
J = 7.7 Hz, 4-H), 7.37 (tt, 1H, J = 1.3, 7.6 Hz, 5-H), 7.40 (d, 1H,
55%; Colorless oil; ½a D26
ꢂ
¼ ꢀ2:4 (c 1.80, CHCl3); IR (neat) 2934
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.88 (t, 3H,
J = 6.8 Hz, 70-H), 1.20 (d, 3H, J = 6.4 Hz, 10-H), 1.25–1.38 (m, 6H,
40–60-H), 1.52 (m, 1H, 30-H), 1.63 (m, 1H, 30-H), 2.48 (dddd, 1H,
J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd, 1H, J = 5.5, 8.5, 14.1,
19.7 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.20 (m, 1H, 3-H), 5.03 (qdd,
1H, J = 6.4, 6.0, 7.3 Hz, 20-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H), 7.32 (d,
1H, J = 7.7 Hz, 4-H), 7.37 (t, 1H, J = 7.7 Hz, 5-H), 7.40 (d, 1H,
13
J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 14.4 (s, CH3, 80-C), 20.2 (s,
CH3, 10-C), 22.8 (s, CH2, 70-C), 25.6 (s, CH2, 40-C), 29.3 (s, CH2, 50-C),
30.5 (s, CH2, 3-C), 32.0 (s, CH2, 60-C), 36.0 (s, CH2, 30-C), 36.5 (d,
J = 23.2 Hz, CH2, 2-C), 73.1 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C,
1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH,
6-C), 130.4 (d, J = 3.6 Hz, CH, 5-C), 139.6 (d, J = 20.8 Hz, C, 7a-C),
145.0 (d, J = 4.9 Hz, C, 3a-C), 170.3 (d, J = 33.0 Hz, C, COO); 19F NMR
(254 MHz) d ꢀ139.21 (t, J = 23.1 Hz); MS m/z: 292 (M+), 272
([MꢀHF]+), 135 ([MꢀCOOR⁄]+); HRMS calcd for C18H25O2F (M+):
292.1838, found: 292.1845.
13
J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 14.3 (s, CH3, 70-C), 20.2
(s, CH3, 10-C), 22.8 (s, CH2, 60-C), 25.3 (s, CH2, 40-C), 30.4 (s, CH2,
3-C), 31.8 (s, CH2, 50-C), 35.9 (s, CH2, 30-C), 36.5 (d, J = 23.2 Hz,
CH2, 2-C), 73.1 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C, 1-C), 124.1
(s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH, 6-C), 130.4
(d, J = 3.7 Hz, CH, 5-C), 139.6 (d, J = 20.8 Hz, C, 7a-C), 145.0 (d,
J = 4.9 Hz, C, 3a-C), 170.2 (d, J = 33.0 Hz, C, COO); 19F NMR
(254 MHz) d ꢀ139.21 (t, J = 20.4 Hz); MS m/z: 278 (M+), 258
([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd
for C17H23O2F (M+): 278.1682, found: 278.1644.
4.4.11. (R)-2-Nonyl (R)-1-fluoroindan-1-carboxylate (R)-5f
57%; Colorless oil; ½a D27
ꢂ
¼ ꢀ34:4 (c 2.06, CHCl3); IR (neat) 2930
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.87 (t, 3H,
4.4.8. (S)-2-Heptyl (S)-1-fluoroindan-1-carboxylate (S)-5d
J = 7.2 Hz, 90-H), 1.08–1.22 (m, 8H, 40–70-H), 1.26 (m, 2H, 80-H),
1.26 (d, 3H, J = 6.4 Hz, 10-H), 1.45 (m, 1H, 30-H), 1.54 (m, 1H, 30-
H), 2.48 (dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd,
1H, J = 5.1, 8.5, 14.1, 19.2 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m,
1H, 3-H), 5.02 (qdd, 1H, J = 6.0, 6.0, 6.4 Hz, 20-H), 7.26 (t, 1H,
J = 7.5 Hz, 6-H), 7.31 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (t, 1H, J = 7.6 Hz,
5-H), 7.41 (d, 1H, J = 7.7 Hz, 7-H); 13C NMR (75.46 MHz) d 14.4 (s,
CH3, 90-C), 20.2 (s, CH3, 10-C), 22.9 (s, CH2, 80-C), 25.3 (s, CH2, 40-
C), 29.4 (s, CH2, 60-C), 29.4 (s, CH2, 50-C), 30.5 (s, CH2, 3-C), 31.9
(s, CH2, 70-C), 35.9 (s, CH2, 30-C), 36.4 (d, J = 23.2 Hz, CH2, 2-C),
73.0 (s, CH, 20-C), 102.1 (d, J = 191.7 Hz, C, 1-C), 124.2 (s, CH, 7-
C), 125.2 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH, 6-C), 130.4 (d,
J = 2.4 Hz, CH, 5-C), 139.7 (d, J = 20.8 Hz, C, 7a-C), 144.9 (d,
J = 4.9 Hz, C, 3a-C), 170.3 (d, J = 31.7 Hz, C, COO); 19F NMR
(254 MHz) d ꢀ139.54 (t, J = 23.1 Hz); MS m/z: 306 (M+), 286
([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd
for C19H27O2F (M+): 306.1995, found: 306.2004.
56%; Colorless oil; ½a D26
ꢂ
¼ þ36:0 (c 1.79, CHCl3); IR (neat) 2934
(CH), 1751 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.82 (t, 3H,
J = 6.8 Hz, 70-H), 1.14 (m, 4H, 40,50-H), 1.20 (m, 2H, 60-H), 1.26 (d,
3H, J = 6.0 Hz, 10-H), 1.46 (m, 1H, 30-H), 1.54 (m, 1H, 30-H), 2.48
(dddd, 1H, J = 5.1, 8.5, 14.1, 22.6 Hz, 2-H), 2.82 (dddd, 1H, J = 5.1,
8.5, 14.1, 19.2 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.02
(qdd, 1H, J = 6.0, 6.0, 7.7 Hz, 20-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H),
7.31 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (t, 1H, J = 7.3 Hz, 5-H), 7.41 (d,
13
1H, J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 14.2 (s, CH3, 70-C),
20.2 (s, CH3, 10-C), 22.7 (s, CH2, 60-C), 25.0 (s, CH2, 40-C), 30.5 (s,
CH2, 3-C), 31.7 (s, CH2, 50-C), 35.9 (s, CH2, 30-C), 36.4
(d, J = 23.2 Hz, CH2, 2-C), 73.0 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz,
C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz,
CH, 6-C), 130.4 (d, J = 2.4 Hz, CH, 5-C), 139.7 (d, J = 20.8 Hz, C, 7a-
C), 144.9 (d, J = 4.9 Hz, C, 3a-C), 170.3 (d, J = 33.0 Hz, C, COO); 19F
NMR (254 MHz) d ꢀ139.54 (t, J = 23.1 Hz); MS m/z: 278 (M+), 258
([MꢀHF]+), 135 ([MꢀCOOR⁄]+); HRMS calcd for C17H24O2F
([M+H]+): 279.1760, found: 279.1739.
4.4.12. (R)-2-Nonyl (S)-1-fluoroindan-1-carboxylate (S)-5f
73%; Colorless oil; ½a D27
ꢂ
¼ þ1:7 (c 2.56, CHCl3); IR (neat) 2930
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.88 (t, 3H,
4.4.9. (R)-2-Octyl (R)-1-fluoroindan-1-carboxylate (R)-5e
65%; Colorless oil; ½a D27
ꢂ
¼ ꢀ36:5 (c 2.23, CHCl3); IR (neat) 2932
J = 7.3 Hz, 90-H), 1.20 (d, 3H, J = 6.4 Hz, 10-H), 1.21–1.37 (m, 8H,
40–70-H), 1.24–1.34 (m, 2H, 80-H), 1.51 (m, 1H, 30-H), 1.63 (m, 1H,
30-H), 2.48 (dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.83 (dddd,
1H, J = 5.1, 8.5, 14.1, 19.7 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m,
1H, 3-H), 5.03 (qdd, 1H, J = 6.4, 6.0, 7.3 Hz, 20-H), 7.26 (t, 1H,
J = 7.7 Hz, 6-H), 7.32 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (t, 1H, J = 7.6 Hz,
5-H), 7.40 (d, 1H, J = 8.1 Hz, 7-H); 13C NMR (75.46 MHz) d 14.4 (s,
CH3, 90-C), 20.0 (s, CH3, 10-C), 22.9 (s, CH2, 80-C), 25.7 (s, CH2,
40-C), 29.4 (s, CH2, 60-C), 29.5 (s, CH2, 50-C), 30.4 (s, CH2, 3-C),
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.86 (t, 3H,
J = 6.8 Hz, 80-H), 1.08–1.20 (m, 6H, 40 60-H), 1.23 (m, 2H, 70-H),
1.26 (d, 3H, J = 6.4 Hz, 10-H), 1.45 (dddd, 1H, J = 5.1, 6.4, 9.4,
13.7 Hz, 30-H), 1.54 (dddd, 1H, J = 5.5, 7.7, 9.0, 13.2 Hz, 30-H), 2.47
(dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H), 2.82 (dddd, 1H, J = 5.1,
8.5, 14.1, 19.2 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.02
(qdd, 1H, J = 6.4, 5.1, 7.7 Hz, 20-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H),
7.31 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (tt, 1H, J = 1.3, 7.6 Hz, 5-H), 7.41

T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
1007
32.0 (s, CH2, 70-C), 36.0 (s, CH2, 30-C), 36.5 (d, J = 23.2 Hz, CH2, 2-C),
73.1 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C),
125.2 (s, CH, 4-C), 127.1 (s, CH, 6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C),
139.6 (d, J = 19.5 Hz, C, 7a-C), 145.0 (d, J = 3.7 Hz, C, 3a-C), 170.3
4.4.16. (S)-1-Phenylethyl (S)-1-fluoroindan-1-carboxylate (S)-5h
18%; Colorless solid; mp 41 °C; ½a D27
ꢂ
¼ ꢀ17 (c 0.58, CHCl3); IR
(neat) 2982 (CH), 1751 (C@O) cmꢀ1
;
1H NMR (500 MHz) d 1.58
(d, 3H, J = 6.8 Hz, 10-H), 2.49 (dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz,
2-H), 2.85 (dddd, 1H, J = 5.6, 8.5, 14.1, 19.7 Hz, 2-H), 3.09 (m, 1H,
3-H), 3.20 (m, 1H, 3-H), 5.99 (q, 1H, J = 6.8 Hz, 20-H), 7.17–7.39
(d, J = 33.0 Hz, C, COO); 19F NMR (254 MHz)
d
ꢀ139.21 (t,
J = 21.3 Hz); MS m/z: 306 (M+), 286 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+);
HRMS calcd for C19H27O2F (M+): 306.1995, found: 306.2007.
(m, 9H, Ph, Ph0-H); C NMR (75.46 MHz) d 22.6 (s, 10-C), 30.5 (s,
13
3-C), 36.4 (d, J = 23.2 Hz, 2-C), 73.9 (s, 20-C), 102.1 (d, J = 191.7 Hz,
1-H), 124.4 (s, 7-C), 125.2 (s, 4-C), 125.8 (s, 60-C), 127.1 (s, 6-C),
128.0, 128.5 (s, 40,50-C), 130.5 (d, J = 3.7 Hz, 5-C), 139.4 (d,
J = 20.8 Hz, 7a-C), 141.0 (s, 30-C) 145.0 (d, J = 4.9 Hz, 3a-C), 169.8
4.4.13. (S)-3-Methyl-2-butyl (R)-1-fluoroindan-1-carboxylate
(R)-5g
71%; Colorless oil; ½a D27
ꢂ
¼ ꢀ8:0 (c 2.09, CHCl3); IR (neat) 2968
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.91 (d, 3H,
(d, J = 33.0 Hz, COO); 19F NMR (254 MHz)
d
ꢀ139.35 (t,
J = 6.8 Hz, 40-H), 0.91 (d, 3H, J = 6.8 Hz, 40-H), 1.12 (d, 3H,
J = 6.4 Hz, 10-H), 1.82 (qqd, 1H, J = 6.8, 6.8, 6.0 Hz, 30-H), 2.49 (dddd,
1H, J = 5.1, 8.5, 14.1, 22.6 Hz, 2-H), 2.82 (dddd, 1H, J = 5.1, 8.5, 14.1,
19.2 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 4.86 (qd,
1H, J = 6.4, 6.0 Hz, 20-H), 7.27 (t, 1H, J = 7.7 Hz, 6-H), 7.32 (dd, 1H,
J = 0.9, 7.7 Hz, 4-H), 7.37 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.40 (d, 1H,
J = 20.3 Hz); MS m/z: 284 (M+), 264 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+),
115 (indenyl cation); HRMS calcd for C18H17O2F (M+): 284.1212,
found: 284.1209.
4.4.17. (1S,2R,4S)-Bornyl (R)-1-fluoroindan-1-carboxylate (R)-5i
100%; Colorless oil; ½a D26
¼ ꢀ39:8 (c 3.85, CHCl3); IR (neat) 2955
ꢂ
13
J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 16.7 (s, CH3, 10-C), 18.2
(CH), 1754 (C@O) cmꢀ1 1H NMR (500 MHz) d 0.70 (s, 3H, 100-H),
;
(s, CH3, 40-C), 18.4 (s, CH3, 40-C), 30.5 (s, CH2, 3-C), 32.8 (s, CH2,
30-C), 36.6 (d, J = 23.2 Hz, CH2, 2-C), 77.2 (s, CH, 20-C), 102.1 (d,
J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.0
(d, J = 3.7 Hz, CH, 6-C), 130.4 (d, J = 2.4 Hz, CH, 5-C), 139.7 (d,
J = 20.8 Hz, C, 7a-C), 144.9 (d, J = 4.9 Hz, C, 3a-C), 170.2 (d,
0.84 (s, 3H, 90-H), 0.89 (s, 3H, 80-H), 0.99 (dd, 1H, J = 3.4, 13.7 Hz,
30aq-H), 1.19 (m, 2H, 50aq, 60aq-H), 1.67 (m, 1H, 60eq-H), 1.68 (dd,
1H, J = 4.7, 4.7 Hz, 40-H), 1.73 (m, 1H, 50eq-H), 2.37 (dddd, 1H,
J = 3.4, 4.7, 9.8, 13.7 Hz, 30eq-H), 2.48 (dddd, 1H, J = 5.6, 8.5, 14.1,
23.5 Hz, 2-H), 2.84 (dddd, 1H, J = 5.1, 8.5, 14.1, 16.7 Hz, 2-H), 3.09
(m, 1H, 3-H), 3.20 (m, 1H, 3-H), 5.01 (ddd, 1H, J = 2.1, 3.4, 9.8 Hz,
20eq-H), 7.27 (t, 1H, J = 7.7 Hz, 6-H), 7.32 (dd, 1H, J = 0.9, 7.7 Hz,
4-H), 7.37 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.43 (d, 1H, J = 7.7 Hz,
J = 31.7 Hz, C, COO); 19F NMR (254 MHz)
d
ꢀ139.43 (t,
J = 23.1 Hz); MS m/z: 250 (M+), 230 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+),
115 (indenyl cation); HRMS calcd for C15H19O2F (M+): 250.1369,
found: 250.1383.
13
7-H); C NMR (75.46 MHz) d 13.6 (s, CH3, 100-C), 19.1 (s, CH3, 90-
C), 19.9 (s, CH3, 80-C), 27.2 (s, CH2, 60-C), 28.3 (s, CH2, 50-C), 30.5
(s, CH2, 3-C), 36.4 (d, J = 23.2 Hz, CH2, 2-C), 36.9 (s, CH2, 30-C),
45.0 (s, CH, 40-C), 48.1 (s, C, 70-C), 49.3 (s, C, 10-C), 81.4 (s, CH, 20-
C), 102.1 (d, J = 191.7 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH,
4-C), 127.2 (s, CH, 6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C), 139.8 (d,
J = 22.0 Hz, C, 7a-C), 144.7 (d, J = 4.9 Hz, C, 3a-C), 170.8 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ140.37 (ddd, J = 5.5,
16.7, 24.0 Hz); MS m/z: 316 (M+), 296 ([MꢀHF]+), 135
([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd for C20H25O2F
(M+): 316.1839, found: 316.1799.
4.4.14. (S)-3-Methyl-2-butyl (S)-1-fluoroindan-1-carboxylate
(S)-5g
48%; Colorless oil; ½a D27
ꢂ
¼ þ35:3 (c 1.39, CHCl3); IR (neat) 2967
(CH), 1752 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.76 (d, 3H,
J = 6.8 Hz, 40-H), 0.76 (d, 3H, J = 6.8 Hz, 40-H), 1.22 (d, 3H, J = 6.0 Hz,
10-H), 1.73 (qqd, 1H, J = 6.8, 6.8, 6.4 Hz, 30-H), 2.48 (dddd, 1H,
J = 5.6, 8.5, 14.1, 23.1 Hz, 2-H), 2.81 (dddd, 1H, J = 5.1, 8.5, 14.1,
17.5 Hz, 2-H), 3.07 (m, 1H, 3-H), 3.20 (m, 1H, 3-H), 4.83 (qd, 1H,
J = 6.0, 6.4 Hz, 20-H), 7.26 (t, 1H, J = 7.3 Hz, 6-H), 7.31 (d, 1H,
J = 7.7 Hz, 4-H), 7.36 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.42 (d, 1H,
13
J = 7.7 Hz, 7-H); C NMR (75.46 MHz) d 17.1 (s, CH3, 10-C), 17.9 (s,
4.4.18. (1S,2R,4S)-Bornyl (S)-1-fluoroindan-1-carboxylate (S)-5i
CH3, 40-C), 18.3 (s, CH3, 40-C), 30.5 (s, CH2, 3-C), 32.9 (s, CH2, 30-C),
36.4 (d, J = 23.2 Hz, CH2, 2-C), 77.1 (s, CH, 20-C), 102.1 (d,
J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.1 (s, CH, 4-C), 127.1 (d,
J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 2.4 Hz, CH, 5-C), 139.7 (d,
J = 20.8 Hz, C, 7a-C), 144.8 (d, J = 4.9 Hz, C, 3a-C), 170.2 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ140.00 (t, J = 23.1 Hz);
MS m/z: 250 (M+), 230 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl
cation); HRMS calcd for C15H19O2F (M+): 250.1369, found: 250.1326.
55%; Pale yellow oil; ½a D25
¼ ꢀ5:6 (c 2.00, CHCl3); IR (neat) 2955
ꢂ
(CH), 1752 (C@O) cmꢀ1 1H NMR (500 MHz) d 0.85 (s, 3H, 100-H),
;
0.86 (s, 3H, 90-H), 0.86 (dd, 1H, J = 3.0, 13.7 Hz, 30aq-H), 0.90 (s,
3H, 80-H), 1.03 (ddd, 1H, J = 4.7, 9.4, 11.1 Hz, 50aq,-H), 1.26 (m,
1H, 60aq-H), 1.65 (dd, 1H, J = 3.8, 3.8 Hz, 40-H), 1.67 (m, 1H, 50eq-
H), 1.73 (m, 1H, 60eq-H), 2.36 (dddd, 1H, J = 3.8, 4.3, 9.8, 14.1 Hz,
30eq-H), 2.49 (dddd, 1H, J = 5.6, 8.5, 14.1, 23.5 Hz, 2-H), 2.83 (dddd,
1H, J = 4.7, 8.5, 14.1, 17.5 Hz, 2-H), 3.09 (m, 1H, 3-H), 3.20 (m, 1H,
3-H), 4.97 (ddd, 1H, J = 2.6, 3.0, 9.8 Hz, 20eq-H), 7.27 (t, 1H,
J = 7.3 Hz, 6-H), 7.32 (d, 1H, J = 7.7 Hz, 4-H), 7.37 (t, 1H, J = 7.7 Hz,
5-H), 7.42 (d, 1H, J = 7.2 Hz, 7-H); 13C NMR (75.46 MHz) d 13.9 (s,
CH3, 100-C), 19.1 (s, CH3, 90-C), 19.9 (s, CH3, 80-C), 27.3 (s, CH2,
60-C), 28.1 (s, CH2, 50-C), 30.5 (s, CH2, 3-C), 36.5 (d, J = 23.2 Hz,
CH2, 2-C), 36.8 (s, CH2, 30-C), 45.0 (s, CH, 40-C), 48.1 (s, C, 70-C),
49.1 (s, C, 10-C), 81.7 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C, 1-C),
124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1 (d, J = 2.4 Hz, CH, 6-C),
130.4 (d, J = 2.4 Hz, CH, 5-C), 139.7 (d, J = 20.8 Hz, C, 7a-C), 144.7
(d, J = 4.9 Hz, C, 3a-C), 170.8 (d, J = 33.0 Hz, C, COO); 19F NMR
(254 MHz) d ꢀ140.33 (t, J = 23.1 Hz); MS m/z: 316 (M+), 296
([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS calcd
for C20H25O2F (M+): 316.1839, found: 316.1848.
4.4.15. (S)-1-Phenylethyl (R)-1-fluoroindan-1-carboxylate (R)-
5h
22%; Colorless oil; ½a D26
ꢂ
¼ ꢀ50:8 (c 0.74, CHCl3); IR (neat) 2983
1H NMR (500 MHz)
1.53 (d, 3H,
(CH), 1751 (C@O) cmꢀ1
;
d
J = 6.8 Hz, 10-H), 2.47 (dddd, 1H, J = 5.1, 8.5, 14.1, 23.1 Hz, 2-H),
2.81 (dddd, 1H, J = 5.6, 8.5, 14.1, 20.1 Hz, 2-H), 3.07 (m, 1H, 3-H),
3.19 (m, 1H, 3-H), 6.01 (q, 1H, J = 6.8 Hz, 20-H), 7.23 (t, 1H,
J = 7.7 Hz, 6-H), 7.28–7.38 (m, 8H, Ph, Ph0-H); 13C NMR
(75.46 MHz) d 22.3 (s, CH3, 10-C), 30.5 (s, CH2, 3-C), 36.4 (d,
J = 23.2 Hz, CH2, 2-C), 74.2 (s, CH, 20-C), 102.1 (d, J = 190.4 Hz, C,
1-C), 124.2 (s, CH, 7-C), 125.2 (s, CH, 4-C), 126.2 (s, CH, 60-C),
127.2 (d, J = 2.4 Hz, CH, 6-C), 128.2, 128.6 (s, CH, 40,50-C), 130.5
(d, J = 2.4 Hz, CH, 5-C), 139.5 (d, J = 20.8 Hz, C, 7a-C), 140.9 (s, C,
30-C) 145.0 (d, J = 4.9 Hz, C, 3a-C), 169.9 (d, J = 33.0 Hz, C, COO);
19F NMR (254 MHz) d ꢀ139.35 (t, J = 21.3 Hz); MS m/z: 284 (M+),
264 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl cation); HRMS
calcd for C18H17O2F (M+): 284.1213, found: 284.1216.
4.4.19. (1R,2S,5R)-8-Phenylmenthyl (R)-1-fluoroindan-1-
carboxylate (R)-5j
58%; Colorless oil; ½a D27
ꢂ
¼ ꢀ33:2 (c 2.69, CHCl3); IR (neat) 2954
(CH), 1732 (C@O) cmꢀ1
;
1H NMR (500 MHz) d 0.78 (dddd, 1H,

1008
T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
J = 3.4, 12.0, 12.8, 12.8 Hz, 40aq-H), 0.86 (d, 3H, J = 6.4 Hz, 100-H), 0.96
(dddd, 1H, J = 3.4, 12.8, 12.8, 13.2 Hz, 30aq-H), 1.05 (s, 3H, 90-H), 1.08
(ddd, 1H, J = 10.7, 12.0, 12.0 Hz, 60aq-H), 1.16 (s, 3H, 80-H), 1.37
(dddd, 1H, J = 3.4, 3.4, 3.8, 13.7 Hz, 30eq-H), 1.45 (m, 1H, 50aq-H),
1.53 (ddddd, 1H, J = 2.1, 3.4, 3.4, 3.8, 12.8 Hz, 40eq-H), 1.92 (ddd,
1H, J = 3.4, 10.7, 12.4 Hz, 20aq-H), 2.01 (dddddd, 1H, J = 1.7, 1.7, 1.7,
2.1, 2.6, 12.0 Hz, 60eq-H), 2.39 (dddd, 1H, J = 5.6, 8.5, 14.1, 23.5 Hz,
2-H), 2.69 (dddd, 1H, J = 5.1, 8.5, 14.1, 17.9 Hz, 2-H), 3.04 (m, 1H,
3-H), 3.16 (m, 1H, 3-H), 4.87 (ddd, 1H, J = 4.3, 10.7, 10.7 Hz, 10aq-
H), 7.12 (tt, 1H, J = 1.3, 7.3 Hz, p0-H), 7.15–7.23 (m, 4H, Ph0-H), 7.26
(t, 1H, J = 7.7 Hz, 6-H), 7.29 (d, 1H, J = 6.8 Hz, 4-H), 7.35 (tt, 1H,
J = 1.3, 7.7 Hz, 5-H), 7.43 (d, 1H, J = 7.7 Hz, 7-H); 13C NMR
(75.46 MHz) d 22.0 (s, CH3, 100-C), 24.6(s, CH3, 80-C), 27.4 (s, CH2,
30-C), 29.3 (s, CH3, 90-C), 30.5 (s, CH2, 3-C), 31.6 (s, CH, 50-C), 34.7
(s, CH2, 40-C), 36.1 (d, J = 23.2 Hz, CH2, 2-C), 40.3 (s, C, 70-C), 41.7 (s,
CH2, 60-C), 50.7 (s, CH, 20-C), 77.1 (s, CH, 10-C), 102.0 (d,
J = 191.7 Hz, C, 1-C), 124.3 (s, CH, 7-C), 125.2 (s, CH, 4-C), 125.4 (s,
CH, p0-C), 125.7 (s, CH, o0 or m0-C), 127.1 (s, CH, 6-C), 128.0 (s, CH,
o0 or m0-C), 130.5 (d, J = 3.7 Hz, CH, 5-C), 139.3 (d, J = 22.0 Hz, C,
7a-C), 145.0 (d, J = 3.7 Hz, C, 3a-C), 150.2 (s, C, ipso0-C), 169.8
11.1, 11.1 Hz, 10aq-H), 7.25 (t, 1H, J = 7.7 Hz, 6-H), 7.30 (dd, 1H,
J = 0.9, 7.7 Hz, 4-H), 7.36 (tt, 1H, J = 1.3, 7.3 Hz, 5-H), 7.40 (d, 1H,
13
J = 7.3 Hz, 7-H); C NMR (75.46 MHz) d 16.3 (s, CH3, 90-C), 20.8 (s,
CH3, 80-C), 22.3 (s, CH3, 100-C), 23.5 (s, CH2, 30-C), 26.2 (s, CH, 70-C),
30.5 (s, CH2, 3-C), 31.6 (s, CH, 50-C), 34.4 (s, CH2, 40-C), 35.4 (d,
J = 22.0 Hz, CH2, 2-C), 40.9 (s, CH2, 60-C), 47.2 (s, CH, 20-C), 76.1 (s,
CH, 10-C), 102.0 (d, J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.1 (s,
CH, 4-C), 127.0 (d, J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 2.4 Hz, CH, 5-C),
139.6 (d, J = 20.8 Hz, C, 7a-C), 144.8 (d, J = 4.9 Hz, C, 3a-C), 170.2 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ139.83 (t, J = 23.1 Hz);
MS m/z: 318 (M+), 298 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115
(indenyl cation); HRMS calcd for C20H27O2F (M+): 318.1995, found:
318.2028.
4.4.22. (1R,2S,5R)-Menthyl (S)-1-fluoroindan-1-carboxylate (S)-
5k
94%; Colorless oil; ½a D28
ꢂ
¼ ꢀ32:5 (c 3.45, CHCl3); IR (neat) 2956
1H NMR (500 MHz)
0.77 (d, 3H,
(CH), 1750 (C@O) cmꢀ1
;
d
J = 6.8 Hz, 90-H), 0.83 (dddd, 1H, J = 3.4, 12.8, 12.8, 12.8 Hz, 40aq-H),
0.88 (d, 3H, J = 6.8 Hz, 100-H), 0.91 (ddd, 1H, J = 11.7, 11.7, 11.7 Hz,
60aq-H), 0.90 (d, 3H, J = 6.8 Hz, 80-H), 1.05 (dddd, 1H, J = 3.4, 12.4,
12.8, 13.7 Hz, 30aq-H), 1.42 (dddd, 1H, J = 3.0, 3.4, 11.5, 11.5 Hz,
20aq-H), 1.49 (m, 1H, 50aq-H), 1.64–1.70 (m, 2H, 30eq, 40eq-H), 1.91
(qqd, 1H, J = 6.8, 7.3, 2.6 Hz, 70-H), 1.96 (br d, 1H, J = 12.0 Hz, 60eq-
H), 2.49 (dddd, 1H, J = 4.7, 8.5, 14.1, 23.1 Hz, 2-H), 2.79 (dddd, 1H,
J = 5.5, 8.5, 14.1, 20.1 Hz, 2-H), 3.06 (m, 1H, 3-H), 3.20 (m, 1H, 3-H),
4.81 (ddd, 1H, J = 4.2, 11.1, 11.1 Hz, 10aq-H), 7.27 (t, 1H, J = 7.7 Hz,
6-H), 7.32 (d, 1H, J = 7.3 Hz, 4-H), 7.35–7.39 (m, 2H, 5, 7-H); 13C
NMR (75.46 MHz) d 16.3 (s, CH3, 90-C), 21.1 (s, CH3, 80-C), 22.2 (s,
CH3, 100-C), 23.3 (s, CH2, 30-C), 26.5 (s, CH, 70-C), 30.5 (s, CH2, 3-C),
31.6 (s, CH, 50-C), 34.3 (s, CH2, 40-C), 36.6 (d, J = 23.2 Hz, CH2, 2-C),
40.5 (s, CH2, 60-C), 47.0 (s, CH, 20-C), 76.1 (s, CH, 10-C), 102.1 (d,
J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1 (d,
J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 2.4 Hz, CH, 5-C), 139.7 (d,
J = 20.8 Hz, C, 7a-C), 145.0 (d, J = 4.9 Hz, C, 3a-C), 170.2 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ138.81 (t, J = 22.2 Hz);
MS m/z: 318 (M+), 298 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+); HRMS calcd
for C20H27O2F (M+): 318.1995, found: 318.1953.
(d, J = 31.7 Hz, C, COO); 19F NMR (254 MHz)
d
ꢀ139.13 (t,
J = 23.1 Hz); MS m/z: 394 (M+), 374 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+),
115 (indenyl cation); HRMS calcd for C26H31O2F (M+): 394.2308,
found: 394.2266.
4.4.20. (1R,2S,5R)-8-Phenylmenthyl (S)-1-fluoroindan-1-
carboxylate (S)-5j
25%; Colorless solid; mp 88 °C; ½a D27
ꢂ
¼ þ1:0 (c 1.13, CHCl3); IR
(neat) 2957 (CH), 1745 (C@O) cmꢀ1
;
1H NMR (500 MHz) d 0.75
(dddd, 1H, J = 3.0, 12.4, 12.4, 12.4 Hz, 40aq-H), 0.77 (ddd, 1H,
J = 12.4, 12.4, 12.4 Hz, 60aq-H), 0.80 (d, 3H, J = 6.4 Hz, 100-H), 1.03
(dddd, 1H, J = 3.4, 12.8, 12.8, 13.2 Hz, 30aq-H), 1.25 (s, 3H, 90-H),
1.38 (s, 3H, 80-H), 1.41 (m, 1H, 50aq-H), 1.50 (dddd, 1H, J = 3.4, 3.4,
3.4, 13.7 Hz, 30eq-H), 1.54 (ddddd, 1H, J = 3.0, 3.4, 3.8, 3.8, 12.8 Hz,
40eq-H), 1.73 (dddddd, 1H, J = 1.7, 2.1, 2.1, 2.1, 2.1, 12.0 Hz, 60eq-
H), 1.99 (ddd, 1H, J = 3.4, 10.7, 12.4 Hz, 20aq-H), 2.14–2.21 (m, 2H,
2-H), 2.87 (m, 1H, 3-H), 3.07 (m, 1H, 3-H), 5.01 (ddd, 1H, J = 4.3,
10.7, 10.7 Hz, 10aq-H), 7.14–7.17 (m, 1H, p0-H), 7.25 (t, 1H,
J = 7.7 Hz, 6-H), 7.27-7.29 (m, 5H, 4, o0, m0-H), 7.34–7.37 (m, 2H, 5,
13
7-H); C NMR (75.46 MHz) d 22.0 (s, CH3, 100-C), 26.6(s, CH3, 90-
4.4.23. (1S,2S,5R)-Neomenthyl (R)-1-fluoroindan-1-carboxylate
(R)-5l
C), 27.2 (s, CH2, 30-C), 27.8 (s, CH3, 80-C), 30.4 (s, CH2, 3-C), 31.5 (s,
CH, 50-C), 34.5 (s, CH2, 40-C), 35.5 (d, J = 23.2 Hz, CH2, 2-C), 40.3 (s,
C, 70-C), 41.3 (s, CH2, 60-C), 50.0 (s, CH, 20-C), 76.8 (s, CH, 10-C),
102.0 (d, J = 189.2 Hz, C, 1-C), 124.2 (s, CH, 7-C), 125.1 (s, CH, 4-C),
125.4 (s, CH, p0-C), 125.6 (s, CH, o0 or m0-C), 127.0 (d, J = 2.4 Hz, CH,
6-C), 128.2 (s, CH, o0 or m0-C), 130.3 (d, J = 3.7 Hz, CH, 5-C), 139.5
(d, J = 20.8 Hz, C, 7a-C), 145.1 (d, J = 3.7 Hz, C, 3a-C), 150.9 (s, C,
ipso0-C), 169.8 (d, J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d
ꢀ138.77 (t, J = 22.2 Hz); MS m/z: 394 (M+), 374 ([MꢀHF]+); HRMS
calcd for C26H31O2F (M+): 394.2308, found: 394.2269.
62%; Colorless solid; mp 67 °C; ½a D27
¼ ꢀ8:7 (c 2.32, CHCl3); IR
ꢂ
(neat) 2950 (CH), 1752 (C@O) cmꢀ1 1H NMR (500 MHz) d 0.67 (d,
;
3H, J = 6.4 Hz, 100-H), 0.79 (dddd, 1H, J = 3.4, 11.5, 11.5, 12.8 Hz,
40aq-H), 0.88 (d, 3H, J = 6.8 Hz, 90-H), 0.89 (m, 1H, 50aq-H), 0.90 (d,
3H, J = 6.8 Hz, 80-H), 0.95 (m, 1H, 20aq-H), 0.96 (m, 1H, 60aq-H),
1.10 (dddd, 1H, J = 3.8, 12.8, 12.8, 12.8 Hz, 30aq-H), 1.41 (qqd, 1H,
J = 6.4, 6.8, 9.0 Hz, 70-H), 1.56 (ddddd, 1H, J = 3.0, 3.0, 3.4, 3.4,
12.4 Hz, 40eq-H), 1.69 (dddd, 1H, J = 3.0, 3.4, 3.4, 12.8 Hz, 30eq-H),
1.82 (dddd, 1H, J = 2.6, 2.6, 3.4, 13.2 Hz, 60eq-H), 2.48 (dddd, 1H,
J = 6.0, 8.5, 14.1, 23.9 Hz, 2-H), 2.79 (dddd, 1H, J = 4.7, 8.5, 14.1,
15.4 Hz, 2-H), 3.08 (m, 1H, 3-H), 3.20 (m, 1H, 3-H), 5.28 (br ddd,
1H, J = 1.7 Hz, 10aq-H), 7.25 (t, 1H, J = 7.7 Hz, 6-H), 7.31 (d, 1H,
J = 6.8 Hz, 4-H), 7.36 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.38 (d, 1H,
4.4.21. (1R,2S,5R)-Menthyl (R)-1-fluoroindan-1-carboxylate (R)-
5k
89%; Colorless oil; ½a D27
ꢂ
¼ ꢀ64:5 (c 3.19, CHCl3); IR (neat) 2956
1H NMR (500 MHz)
0.62 (d, 3H,
(CH), 1751 (C@O) cmꢀ1
;
d
J = 8.1 Hz, 7-H); C NMR (75.46 MHz) d 20.9 (s, CH3, 80-C), 21.3 (s,
13
J = 6.8 Hz, 90-H), 0.72 (d, 3H, J = 6.8 Hz, 80-H), 0.85 (dddd, 1H,
J = 3.4, 11.3, 12.8, 12.8 Hz, 40aq-H), 0.91 (d, 3H, J = 6.4 Hz, 100-H),
1.02 (dddd, 1H, J = 3.4, 12.4, 12.8, 13.2 Hz, 30aq-H), 1.04 (ddd, 1H,
J = 11.1, 12.0, 12.4 Hz, 60aq-H), 1.33 (dddd, 1H, J = 3.0, 3.4, 11.1,
12.4 Hz, 20aq-H), 1.44 (qqd, 1H, J = 6.8, 7.3, 3.0 Hz, 70-H), 1.50 (m,
1H, 50aq-H), 1.63 (dddd, 1H, J = 3.0, 3.4, 3.4, 13.2 Hz, 30eq-H), 1.67
(ddddd, 1H, J = 2.1, 3.0, 3.4, 3.9, 12.8 Hz, 40eq-H), 2.03 (dddddd, 1H,
J = 1.3, 2.3, 2.3, 2.3, 2.3, 12.0 Hz, 60eq-H), 2.47 (dddd, 1H, J = 5.6,
8.5, 14.1, 23.5 Hz, 2-H), 2.81 (dddd, 1H, J = 5.1, 8.5, 14.1, 17.9 Hz,
2-H), 3.06 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 4.76 (ddd, 1H, J = 4.3,
CH3, 90-C), 22.2 (s, CH3, 100-C), 25.6 (s, CH2, 30-C), 26.4 (s, CH, 70-C),
29.6 (s, CH, 50-C), 30.5 (s, CH2, 3-C), 34.7 (s, CH2, 40-C), 36.4 (d,
J = 22.0 Hz, CH2, 2-C), 39.0 (s, CH2, 60-C), 46.8 (s, CH, 20-C), 73.0 (s,
CH, 10-C), 102.0 (d, J = 189.2 Hz, C, 1-C), 123.8 (s, CH, 7-C), 125.2 (s,
CH, 4-C), 127.0 (d, J = 2.4 Hz, CH, 6-C), 130.3 (d, J = 3.7 Hz, CH, 5-C),
139.8 (d, J = 20.8 Hz, C, 7a-C), 144.5 (d, J = 4.9 Hz, C, 3a-C), 170.1 (d,
J = 34.2 Hz, C, COO); 19F NMR (254 MHz) d ꢀ141.18 (ddd, J = 6.5,
15.7, 23.1 Hz); MS m/z: 319 ([M + 1]+), 298 ([MꢀHF]+), 135
([MꢀCOOR⁄]+); HRMS calcd for C20H28O2F ([M+H]+): 319.2074,
found: 319.2045.

T. Takahashi et al. / Tetrahedron: Asymmetry 24 (2013) 1001–1009
1009
4.4.24. (1S,2S,5R)-Neomenthyl (S)-1-fluoroindan-1-carboxylate
(S)-5l
J = 6.8 Hz, 90-H), 0.86 (d, 3H, J = 6.8 Hz, 80-H), 0.93 (d, 3H, J = 6.8 Hz,
100-H), 1.21 (m, 1H, 40aq-H), 1.27 (m, 1H, 40eq), 1.40 (m, 3H, 30aq,
30eq, 40eq-H), 1.55 (m, 2H, 60aq, 70-H), 1.64 (ddd, 1H, J = 4.3, 6.8,
13.7 Hz, 60eq-H), 1.86 (m, 1H, 50eq-H), 2.47 (dddd, 1H, J = 5.6, 9.0,
14.1, 23.1 Hz, 2-H), 2.82 (dddd, 1H, J = 5.1, 8.5, 14.1, 17.5 Hz, 2-H),
3.08 (m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.12 (ddd, 1H, J = 3.4, 6.8,
6.8 Hz, 10aq-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H), 7.31 (d, 1H, J = 7.7 Hz,
4-H), 7.36 (t, 1H, J = 7.2 Hz, 5-H), 7.41 (d, 1H, J = 7.7 Hz, 7-H); 13C
NMR (75.46 MHz) d 19.1 (s, CH3, 100-C), 20.7 (s, CH3, 90-C), 20.8 (s,
CH2, 30-C), 21.0 (s, CH3, 80-C), 26.4 (s, CH, 70-C), 27.9 (s, CH, 50-C),
30.1 (s, CH2, 40-C), 30.5 (s, CH2, 3-C), 36.0 (s, CH2, 60-C), 36.5 (d,
J = 23.2 Hz, CH2, 2-C), 45.8 (s, CH, 20-C), 73.7 (s, CH, 10-C), 102.1 (d,
J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1 (s,
CH, 6-C), 130.4 (d, J = 2.4 Hz, CH, 5-C), 139.7 (d, J = 20.8 Hz, C, 7a-
C), 144.8 (d, J = 4.9 Hz, C, 3a-C), 170.0 (d, J = 33.0 Hz, C, COO); 19F
NMR (254 MHz) d ꢀ140.16 (t, J = 23.1 Hz); MS m/z: 318 (M+), 298
([MꢀHF]+), 135 ([MꢀCOOR⁄]+); HRMS calcd for C20H27O2F (M+):
318.1995, found: 318.1996.
100%; Colorless solid; mp 75 °C; ½a D28
¼ þ49:3 (c 2.32, CHCl3); IR
ꢂ
(neat) 2920 (CH), 1746 (C@O) cmꢀ1 1H NMR (500 MHz) d 0.62 (d,
;
3H, J = 6.4 Hz, 90-H), 0.67 (d, 3H, J = 6.4 Hz, 80-H), 0.76 (qqd, 1H,
J = 6.4, 6.8, 9.0 Hz, 70-H), 0.87 (d, 3H, J = 6.4 Hz, 100-H), 0.88 (m, 1H,
40aq-H), 0.89 (m, 1H, 20aq-H), 1.07 (m, 1H, 60aq-H), 1.08 (m, 1H,
30aq-H), 1.57 (m, 1H, 50aq-H), 1.64 (dddd, 1H, J = 3.4, 3.4, 3.4,
12.8 Hz, 30eq-H), 1.73 (ddddd, 1H, J = 3.0, 3.0, 3.0, 3.0, 14.5 Hz,
40eq-H), 2.02 (dddd, 1H, J = 2.6, 3.4, 3.4, 14.5 Hz, 60eq-H), 2.48 (dddd,
1H, J = 6.4, 9.0, 14.1, 23.9 Hz, 2-H), 2.81 (dddd, 1H, J = 4.3, 8.5, 13.7,
14.1 Hz, 2-H), 3.09 (m, 1H, 3-H), 3.20 (m, 1H, 3-H), 5.22 (br ddd,
1H, J = 1.7 Hz, 10aq-H), 7.25 (t, 1H, J = 7.7 Hz, 6-H), 7.30 (d, 1H,
J = 7.7 Hz, 4-H), 7.35 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.40 (d, 1H,
J = 7.7 Hz, 7-H); 13C NMR (75.46 MHz) d 20.7 (s, CH3, 80-C), 21.0 (s,
CH3, 90-C), 22.4 (s, CH3, 100-C), 25.5 (s, CH2, 30-C), 27.1 (s, CH, 70-C),
29.1 (s, CH, 50-C), 30.6 (s, CH2, 3-C), 34.8 (s, CH2, 40-C), 36.6 (d,
J = 22.0 Hz, CH2, 2-C), 39.2 (s, CH2, 60-C), 46.8 (s, CH, 20-C), 73.1 (s,
CH, 10-C), 101.9 (d, J = 190.4 Hz, C, 1-C), 123.9, (s, CH, 7-C) 125.1 (s,
CH, 4-C), 127.0 (d, J = 2.4 Hz, CH, 6-C), 130.3 (d, J = 3.7 Hz, CH, 5-C),
139.7 (d, J = 22.0 Hz, C, 7a-C), 144.3 (d, J = 4.9 Hz, C, 3a-C), 170.1 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ141.32 (ddd, J = 6.5,
13.9, 24.0 Hz); MS m/z: 318 (M+), 298 ([MꢀHF]+), 135
([MꢀCOOR⁄]+); HRMS calcd for C20H27O2F (M+): 318.1995, found:
318.1987.
Acknowledgments
We thank Mr. Atsushi Ohnishi of the Daicel Corporation for the
investigation on the HPLC conditions. This work was partly sup-
ported by a grant from The First Bank of Toyama Foundation
(T.T.). F.P. thanks the Department of Applied Chemistry (Tohoku
University) for the financial support.
4.4.25. (1R,2S,5S)-Isomenthyl (R)-1-fluoroindan-1-carboxylate
(R)-5m
References
55%; Colorless oil; ½a D27
ꢂ
¼ ꢀ9:4 (c 2.03, CHCl3); IR (neat) 2957
(CH), 1750 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.86 (d, 3H,
1. (a) Kusumi, T. Synth. Org. Chem. Jpn. 1993, 51, 462–470; (b) Takeuchi, Y.;
Takahashi, T. In Enantiocontrolled Synthesis of Fluoro-organic Compounds;
Soloshonok, V. A., Ed.; Wiley: Chichester, 1999. Chapter 16; (c) Seco, J. M.;
Quinoa, E.; Riguera, R. Chem. Rev. 2004, 104, 17–117; (d) Kasai, Y.; Naito, J.;
Kuwahara, S.; Watanabe, M.; Ichikawa, A.; Harada, N. Synth. Org. Chem. Jpn.
2004, 62, 1114–1127; (e) Kusumi, T.; Yabuuchi, T.; Takahashi, H.; Ooi, T. Synth.
Org. Chem. Jpn. 2005, 63, 1102–1114; (f) Takahashi, T.; Fukushima, A.; Tanaka, Y.;
Takeuchi, Y.; Kabuto, K.; Kabuto, C. Chem. Commun. 2000, 788–789; (g) Pe´rez-
Estrada, S.; Joseph-Nathan, P.; Jime´nez-Va´zquez, H. A.; Medina-Lo´pez, M. E.;
Ayala-Mata, F.; Zepeda, L. G. J. Org. Chem. 2012, 77, 1640–1652; (h) Seco, J. M.;
Quinoa, E.; Riguera, R. Chem. Rev. 2012, 112, 4603–4641; (i) Sungsuwan, S.;
Ruangsupapichart, N.; Prabpai, S.; Kongsaeree, P.; Thongpanchang, T.
Tetrahedron Lett. 2010, 51, 4965–4967; (j) Iwamoto, H.; Kobayashi, Y.;
Kawatani, T.; Suzuki, M.; Fukazawa, Y. Tetrahedron Lett. 2006, 47, 1519–1523;
(k) Fukui, H.; Fukushi, Y.; Tahara, S. Tetrahedron Lett. 2005, 46, 5089–5093.
2. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem. Soc. 1991, 113,
4092–4096.
J = 6.8 Hz, 100-H), 0.86 (d, 3H, J = 6.8 Hz, 90-H), 0.95 (d, 3H,
J = 6.4 Hz, 80-H), 1.16 (dddd, 1H, J = 4.7, 8.5, 8.5, 12.8 Hz, 40aq-H),
1.37 (m, 2H, 40eq, 60aq-H), 1.42 (ddd, 1H, J = 3.0, 8.1, 13.7 Hz, 60eq-
H), 1.52 (m, 3H, 20aq, 30aq, 30eq-H), 1.62 (m, 1H, 50eq-H), 1.74 (qqd,
1H, J = 6.8, 6.8, 7.3 Hz, 70-H), 2.48 (dddd, 1H, J = 5.6, 8.5, 14.1,
23.1 Hz, 2-H), 2.83 (dddd, 1H, J = 5.1, 8.5, 14.1, 17.9 Hz, 2-H), 3.08
(m, 1H, 3-H), 3.19 (m, 1H, 3-H), 5.16 (ddd, 1H, J = 3.4, 6.4, 6.4 Hz,
10aq-H), 7.26 (t, 1H, J = 7.7 Hz, 6-H), 7.32 (dd, 1H, J = 0.9, 7.7 Hz, 4-
H), 7.37 (tt, 1H, J = 1.3, 7.7 Hz, 5-H), 7.40 (d, 1H, J = 7.7 Hz, 7-H);
13C NMR (75.46 MHz) d 19.4 (s, CH3, 100-C), 20.9 (s, CH3, 90-C), 21.2
(s, CH3, 80-C), 21.2 (s, CH2, 30-C), 26.5 (s, CH, 70-C), 27.6 (s, CH, 50-C),
29.9 (s, CH2, 40-C), 30.5 (s, CH2, 3-C), 35.5 (s, CH2, 60-C), 36.5
(d, J = 22.0 Hz, CH2, 2-C), 45.5 (s, CH, 20-C), 73.9 (s, CH, 10-C), 102.1
(d, J = 190.4 Hz, C, 1-C), 124.1 (s, CH, 7-C), 125.2 (s, CH, 4-C), 127.1
(d, J = 2.4 Hz, CH, 6-C), 130.4 (d, J = 3.7 Hz, CH, 5-C), 139.8 (d,
J = 20.8 Hz, C, 7a-C), 144.8 (d, J = 4.9 Hz, C, 3a-C), 170.0 (d,
J = 33.0 Hz, C, COO); 19F NMR (254 MHz) d ꢀ139.91 (t, J = 23.1 Hz);
MS m/z: 318 (M+), 298 ([MꢀHF]+), 135 ([MꢀCOOR⁄]+), 115 (indenyl
cation); HRMS calcd for C20H27O2F (M+): 318.1995, found: 318.2011.
3. Latypov, Sh. K.; Seco, J. M.; Quinoa, E.; Riguera, R. J. Org. Chem. 1996, 61,
8569–8577.
4. Takahashi, T.; Kameda, H.; Kamei, T.; Ishizaki, M. J. Fluorine Chem. 2006, 127,
760–768.
5. Synthesis of (R)-a-phenethylamide from (+)-FICA methyl ester will be reported
in the following paper.
6. When Ph, COOH, and F or CF3 groups are arranged similarly on the stereocenters,
the absolute configurations of FICA and MTPA is opposite because of the priority
of the substituents.
7. Frisch, M. J. et al Gaussian 03, Revision C.02; Gaussian Inc.: Wallingford CT, 2004.
8. Becke, A. D. J. Chem. Phys. 1993, 98, 5648–5652.
9. Cheeseman, J. R.; Trucks, G. W.; Keith, T. A.; Frisch, M. J. J. Chem. Phys. 1996, 104,
5497–5509.
4.4.26. (1R,2S,5S)-Isomenthyl (S)-1-fluoroindan-1-carboxylate
(S)-5m
66%; Colorless oil; ½a D28
ꢂ
¼ þ39:3 (c 2.39, CHCl3); IR (neat) 2958
(CH), 1749 (C@O) cmꢀ1
;
1H NMR (500 MHz)
d
0.77 (d, 3H,