Acylative kinetic resolution of racemic heterocyclic amines with (R)-2-phenoxypropionyl chloride

Article abstract of DOI:10.1016/j.tetasy.2016.10.004

The acylative kinetic resolution of racemic heterocyclic amines such as 3,4-dihydro-3-methyl-2H-[1,4]benzoxazines, 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine, 2-methyl-1,2,3,4-tetrahydro-quinolines and 2-methylindoline with enantiopure (R)-2-phenoxypropionyl chloride has been studied. It has been found that acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine proceeds with the best stereoselectively when compared with other racemic amines. An efficient method for the preparation of (S)-3,4-dihydro-3-methyl-2H-[1,4]benzothiazine (99.4% ee) via a kinetic resolution protocol was developed. The possibility of recycling (R)-2-phenoxypropionic acid has been demonstrated.

Full text of DOI:10.1016/j.tetasy.2016.10.004

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Acylative kinetic resolution of racemic heterocyclic amines
with (R)-2-phenoxypropionyl chloride
Sergey A. Vakarov a, Dmitry A. Gruzdev a, Evgeny N. Chulakov a, Liliya Sh. Sadretdinova a,
Andrey A. Tumashov a, Marina G. Pervova a, Marina A. Ezhikova a, Mikhail I. Kodess a,b, Galina L. Levit a,
Victor P. Krasnov a, Valery N. Charushin a,b
⇑
,
a Postovsky Institute of Organic Synthesis of RAS (Ural Branch), 22/20 S. Kovalevskoy/Akademicheskaya St., Ekaterinburg 620990, Russia
b Ural Federal University, 19 Mira St., Ekaterinburg 620002, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The acylative kinetic resolution of racemic heterocyclic amines such as 3,4-dihydro-3-methyl-2H-[1,4]
benzoxazines, 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine, 2-methyl-1,2,3,4-tetrahydro-quinolines
and 2-methylindoline with enantiopure (R)-2-phenoxypropionyl chloride has been studied. It has been
found that acylation of 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine proceeds with the best stereoselec-
tively when compared with other racemic amines. An efficient method for the preparation of (S)-3,4-
dihydro-3-methyl-2H-[1,4]benzothiazine (99.4% ee) via a kinetic resolution protocol was developed.
The possibility of recycling (R)-2-phenoxypropionic acid has been demonstrated.
Received 31 August 2016
Accepted 7 October 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
noxypropionyl chloride 2a, the derivative of L-lactic acid, is the
most easily available in enantiomerically pure form among the
studied 2-phenoxy carbonyl chlorides.
The development of efficient methods for the synthesis of enan-
tiopure amines is one of the priorities of modern organic synthesis.
In order to obtain individual enantiomers, the kinetic resolution of
a racemate is often used. Kinetic resolution is based on the differ-
ence in the reaction rates of individual enantiomers with a chiral
non-racemic agent.1 This approach allows for stereoisomerically
enriched reaction products and an unreacted substrate to be
obtained. The kinetic resolution of racemic amines is most fre-
quently carried out by acylation in the presence of enzymes and
synthetic acyl-transfer catalysts, as well as under the action of chi-
ral acylating agents.2
Over the last few years, we have performed a detailed study on
the acylative kinetic resolution of racemic amines over the course
of diastereoselective acylation with acyl chlorides of chiral acids,
such as 2-arylpropionic acids3 and N-protected amino acids.4
Recently, we have demonstrated that the acylation of racemic ami-
nes 1a and 1b with racemic 2-phenoxy carbonyl chlorides 2a–c
(Scheme 1) proceeds with high diastereoselectivity,5 exceeding
that in the acylation of the studied amines with 2-arylpropionyl
chlorides. Thus, the diastereoisomeric ratio (dr) of the amide
formed reached 499 in the acylation of racemic amine 1a with acyl
chloride 2b in toluene at ꢀ20 °C.5 It should be noted that 2-phe-
Herein our aim was to study the kinetic resolution of racemic
heterocyclic amines 1a–f with enantiopure (R)-2-phenoxypropi-
onyl chloride (R)-2a, as well as the possibility of the preparation
of some enantiomerically pure amines via a kinetic resolution pro-
tocol with acyl chloride (R)-2a (Scheme 1).
2. Results and discussion
In order to obtain enantiopure amines (ee >99%) via kinetic res-
olution with chiral resolving agents, the latter are required to be of
a particularly high enantiomeric purity, therefore, we have devel-
oped a process for the preparation of enantiopure (R)-2-phe-
noxypropionic acid (R)-5 (Scheme 2).
Commercially available enantiomerically pure ethyl L-lactate
(S)-3 was used as the starting material; the interaction of com-
pound (S)-3 with phenol in the presence of diisopropyl azodicar-
boxylate (DIAD) and triphenylphosphine by the Mitsunobu
reaction (Scheme 2) resulted in ethyl (R)-2-phenoxypropionate
(R)-4. It is known that this approach allows for the esters of
(R)-2-aryloxy carboxylic acids to be obtained with high
enantiomeric purity.6 The alkaline hydrolysis of compound
(R)-4 afforded acid (R)-5 with 95.6% ee according to the chiral HPLC
(Chiralpak AD column). Thus, minor racemization was observed
⇑
Corresponding author.
E-mail address: ca512@ios.uran.ru (G.L. Levit).
over the course of the Mitsunobu reaction between ethyl L-lactate
http://dx.doi.org/10.1016/j.tetasy.2016.10.004
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
Please cite this article in press as: Vakarov, S. A.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.004

2
S. A. Vakarov et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
F
F
F
NH
Me
NH
Me
NH
Me
NH
NH
Me
NH
O
O
S
Me
Me
O
1d
1a
1c
1b
1e
1f
2a: R = Me
2b
PhO
Cl
2a-c
: R = iPr
2c: R = Bn
R
Scheme 1. Racemic amines 1a–f and 2-phenoxy carbonyl chlorides 2a–c.
O
O
O
O
(i)
64%
(ii)
(iii)
PhO
HO
PhO
PhO
OEt
Cl
OEt
OH
89%
99%
Me
Me
Me
Me
(S)-3
(R)-4
(R)-5
95.6% ee
(R)-2a
95.6% ee
F
F
O
O
(iv), (v)
76%
OPh
PhO
+
N
OH
O
Me
Me
Me
6a
(R)-5
99.6% ee
Reagents and conditions: (i) PhOH, DIAD, PPh3, toluene; (ii) 2M NaOH, EtOH, 4 oC, 24 h; (iii) (COCl)2, CH2Cl2, rt;
(iv) rac-1a (0.15 equiv.), PhNEt2 (0.15 equiv.), toluene, rt; (v) Na2CO3, H2O-MeOH
Scheme 2. Preparation of enantiopure (R)-2-phenoxypropionic acid (R)-5.
and phenol and subsequent alkaline hydrolysis of the ester group.
Therefore, we studied the possibility of enantiomeric enrichment
of scalemic acid (R)-5. We examined two methods. The first con-
sisted of the double recrystallization of sodium salt of acid (R)-5
from acetone similar to the described procedure.7 As a result, enan-
tiopure acid (R)-5 (99.4% ee) was isolated in low yield (17%).
The second approach was based on the reaction of acyl chloride
(R)-2a [obtained from acid (R)-5 (95.6% ee)] with a lack of racemic
amine 1a (0.15 equiv) in the presence of N,N-diethylaniline
(PhNEt2, 0.15 equiv) as an acceptor of HCl (Scheme 2). A theoretical
rationale of the possibility of increasing the ee value of an enan-
tioimpure substance using a racemic reagent in kinetic resolution
(R)-2a from the reaction mixture and subsequent treatment with
aqueous solution of Na2CO3, we obtained acid (R)-5 (99.6% ee,
76% yield), which was further used as a chiral resolving agent.
The acylation of racemic amines 1a–f with acyl chloride (R)-2a
was carried out in a 2:1 amine:acyl chloride molar ratio at +20 °C
for 6 h (Scheme 3). The initial concentration of racemic amine
was 0.1 M. Each experiment was carried out in two parallel runs.
Previously we have shown that toluene is the solvent of choice
for the kinetic resolution of racemic methylbenzoxazines 1a and
1b with 2-phenoxy carbonyl chlorides;5 hence the acylation was
carried out in that solvent. After the appropriate treatment, mix-
tures of diastereoisomeric amides 6a–f and unreacted enantiomer-
ically enriched amines 1a–f were isolated from the reaction
mixture. The diastereomeric excess (de) of the resulting amides
was determined by GC or reversed-phase HPLC; the enantiomeric
was provided.8 In our case, the formation of
a mixture of
diastereoisomeric amides 6a occurred, and acyl chloride (R)-2a
taken in an excess remained unreacted. After isolation of unreacted
Z
Y
Z
Y
Z
Y
Z
Y
Me
Me
Me
OPh
OPh
toluene
N
+
+
+
NH
Me
N
NH
Me
PhO
(R)-2a
COCl
+20 oC, 6 h
X
O
X
X
X
O
Me
Me
rac-1a-f
(2 equiv.)
(R,R)-6a-f
(R)-1a-f
unreacted
(S,R)-6a-f
major
de up to 94.2%
1a, 6a: X = OCH2, Y = Z = F
1b, 6b: X = OCH2, Y = Z = H
ee up to 91.5%
1c 6c
,
: X = SCH2, Y = Z = H
1d, 6d: X = (CH2)2, Y = Z = H
1e, 6e: X = (CH2)2, Y = H, Z = F
1f 6f
,
: X = CH2, Y = Z = H
Scheme 3. Kinetic resolution of racemic amines 1a–f with enantiopure acyl chloride (R)-2a.
Please cite this article in press as: Vakarov, S. A.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.004

S. A. Vakarov et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
Table 1
Stereoselectivity results of the kinetic resolution of racemic amines 1a–f with acyl chloride (R)-2a in toluene at +20 °Ca
Entry
Amine
(S,R)-Amide, de (%)b
(R)-Amine, ee (%)c
Conversion C (%)d
Selectivity factor se
1
2
3
4
5
7
8
1a
1b
1c
1c
1d
1e
1f
6a, 91.8
6b, 84.1
6c, 94.2
6c, 95.5
6d, 74.0
6e, 60.4
6f, 8.8g
87.4
69.8
91.6
87.4
66.7
53.0
4.6
49
45
49
48
47
48
34
67
24
111
135f
13
6.1
1.3
a
b
c
d
e
f
Average values for two parallel runs are presented.
Determined by GC (see Section 4).
Determined by chiral HPLC (see Section 4).
C = eeamine/(eeamine + deamide).1
Selectivity factor, s = kfast/kslow = ln[(1 ꢀ C)(1 ꢀ eeamine)]/ln[(1 ꢀ C)(1 + eeamine)].1
Reaction temperature ꢀ20 °C.
g
Determined by RP-HPLC (see Section 4).
excess (ee) of unreacted amines was determined by chiral HPLC on
a Chiralcel OD-H column (Table 1). Based on these data, we calcu-
lated the conversion of the starting racemate (C, %) and the selec-
tivity factor s (Kagan’s factor), i.e., the ratio of the rate constants
of the enantiomers. As a result of the acylation, the predominant
formation of diastereomerically enriched amides 6a–f and unre-
acted enantiomerically enriched amines 1a–f occurred. As shown
by chiral HPLC, the (R)-amines were prevailed in the isolated unre-
acted amines 1a–f. From this it follows that acyl chloride (R)-2a
reacted faster with (S)-amines, and amides 6a–f were enriched in
(S,R)-diastereomers.
The predominant diastereoisomeric amides (S,R)-6a–e
(Scheme 3) were isolated from the reaction mixtures by recrystal-
lization or flash column chromatography. We also managed to iso-
late the minor amide (R,R)-6f from the reaction mixture by flash
column chromatography. In the case of crystalline amides (S,R)-
6c and (S,R)-6e, the absolute configuration was confirmed by X-
ray diffraction from the known configuration of the acyl fragment
(Figs. 1 and 2).
As can be seen from the data presented in Table 1, acylation of
racemic 3-methylbenzoxazines 1a and 1b with acyl chloride (R)-2a
proceeded with high stereoselectivity (selectivity factor s 67 and
24, respectively), with the acylation of amine 1a being more selec-
tive. These data are comparable to the previously published stere-
ochemical results of acylation of racemic amines 1a and 1b with
Figure 2. Structure of amide (S,R)-6e (thermal ellipsoids of 50% probability).
racemic acyl chloride 2a under the same conditions (selectivity
factor s was 55 and 35, respectively).5
Replacement of the oxygen atom in the amine molecule 1b by
the sulfur atom (amine 1c) significantly increased the stereoselec-
tivity of acylation. Thus, the kinetic resolution of 3-methyl-dihy-
drobenzothiazine 1c with acyl chloride (R)-2a at +20 °C led to
amide (S,R)-6c with 94.2% de (selectivity factor s 111).
Acylation of racemic quinoline derivatives 1d and 1e took place
with substantially lower selectivity than the acylation of amines
1a–c: the selectivity factor s did not exceed 13. The kinetic resolu-
tion of racemic 2-methylindoline 1f with acyl chloride (R)-2a was
inefficient (de of (S,R)-6f was 8.8%, s 1.3). In the case of acylation of
racemic amine 1c with acyl chloride (R)-2a, lowering the reaction
temperature to ꢀ20 °C made it possible to increase the stereoselec-
tivity of the process (de of (S,R)-6c 95.5%, s 135). These kinetic res-
olution conditions were selected to develop a preparative method
for the (S)-enantiomer of amine 1c.
Thus, in order to obtain amine (S)-1c, we carried out the kinetic
resolution of racemic 3,4-dihydro-3-methyl-2H-[1,4]benzothiazine
1c with acyl chloride (R)-2a in toluene at ꢀ20 °C for 24 h, which
resulted in amide (S,R)-6c with 94.8% de and unreacted amine
(R)-1c (91.0% ee) (Scheme 4). The subsequent recrystallization of
amide (S,R)-6c from a hexane–EtOAc mixture gave diastereomeri-
cally pure amide (S,R)-6c (>99.9% de) in 73% yield. Acidic hydrolysis
Figure 1. Structure of amide (S,R)-6c (thermal ellipsoids of 50% probability).
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4
S. A. Vakarov et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
O
Me
toluene
OPh
+
NH
Me
(R)-1c
91.0% ee
+
NH
Me
rac-1c
(2 equiv.)
N
-20 oC, 24 h
PhO
COCl
S
S
S
Me
Me
(S,R)-6c
94.8% de
92% yield
(R)-2a
recrystallization
(i) HCl / AcOH, 90-95 oC, 20 h
(ii) Na2CO3
Me
NH
Me
(S,R)-6c
>99% de
73% yield
+
PhO
COOH
S
(S)-1c
>99% ee
34% overall yield
(relative to rac-1c)
(R)-5
99.6% ee
94% yield
Scheme 4. Preparation of amine (S)-1c via kinetic resolution with acyl chloride (R)-2a.
of the latter in a mixture of glacial AcOH and concentrated HCl
(1:1) was carried out at 90–95 °C for 20 h resulted in enantiopure
amine (S)-1c (according to chiral HPLC) in 34% overall yield (rela-
tive to the starting racemate). In addition, the (R)-enantiomer of
2-phenoxypropionic acid 5 was isolated in 94% yield from the
hydrolysis products. Chiral HPLC of acid (R)-5 (99.6% ee) showed
that there was no racemization of the acyl fragment either during
the acylation of amine 1c or the hydrolysis of amide 6c. Hence, the
isolated acid (R)-5 can be recycled to obtain enantiopure acyl chlo-
ride (R)-2a.
NMR spectra of other compounds, at ambient temperature.
Elemental analysis was performed using Perkin Elmer 2400 II or
EuroVector EA3000 analyzers. The high-resolution mass spectra
of amides (S,R)-6d, (S,R)-6f, (R,R)-6f and amine (S)-1c were
obtained on a Bruker maXis Impact HD mass spectrometer, electro-
spray ionization with direct sample inlet (flow rate 4 L/min).
GC analyses of amides 6a–e were performed using a Shimadzu
GC-2010 instrument with
a ZB-5 quartz capillary column
(30 m ꢁ 0.25 mm ꢁ 0.25 m); initial column temperature 40 °C
l
(3 min), programming with a rate of 10 K/min up to 280 °C
(30 min); oven temperature 250 °C, detector temperature 300 °C;
nitrogen as a carrier gas, flow rate 1.0 mL/min, split ratio 1:30.
Analytical chiral HPLC of amines 1a–f was performed on a
Knauer Smartline-1100 instrument using a Chiralcel OD-H column
(250 ꢁ 4.6 mm), detection at 220 nm; 0.6 mL/min flow rate, n-hex-
ane–iPrOH 40:1 for amine 1a (s(R)-1a 12.3–12.5 min, s(S)-1a 16.3–
16.5 min); 1.0 mL/min flow rate, n-hexane–iPrOH–MeOH 100:1:1
for amines 1b, d, e (s(R)-1b 12.6–12.8 min, s(S)-1b 13.4–13.6 min;
s(R)-1d 6.5–6.7 min, s(S)-1d 7.2–7.4 min; s(R)-1e 6.0–6.2 min, s(S)-1e
8.1–8.3 min); 1.0 mL/min flow rate, n-hexane–iPrOH–MeOH
3. Conclusion
Herein, we have studied the acylative kinetic resolution of
racemic heterocyclic amines with the acyl chloride of enantiopure
(R)-2-phenoxypropionic acid. It has been found that acylation of
3,4-dihydro-3-methyl-2H-[1,4]benzothiazine proceeds with the
best stereoselectively when compared with other racemic amines.
An efficient method for the preparation of the (S)-enantiomer of
3,4-dihydro-3-methyl-2H-[1,4]benzothiazine via a kinetic resolu-
tion protocol using (R)-2-phenoxypropionyl chloride has been
developed. We have also demonstrated the possibility of recycling
(R)-2-phenoxypropionic acid, the product of the acidic hydrolysis
of the diastereoisomerically pure amide.
100:1:0.5 for amine 1c
(s(R)-1c 16.3–16.8 min, s(S)–1c 17.1–
17.5 min). Analytical chiral HPLC of amine 1f was performed
after pre-column derivatization with benzoyl chloride;4g
n-hexane–iPrOH 20:1
(
s(S)-Bz-1f 12.5 min, s(R)-Bz-1f 19.5 min).
Analytical chiral HPLC of acid (R)-5 was performed on a Knauer
Smartline-1100 instrument using Chiralpak AD column
(250 ꢁ 4.6 mm), detection at 220 nm, 1 mL/min flow rate;
n-hexane–iPrOH–TFA
20:1:0.02 s(S)-5 7.1–7.3 min, s(R)-5
a
4. Experimental
4.1. General
(
9.1–9.5 min). Analytical reversed-phase HPLC of amide 6f was
performed on an Agilent 1100 instrument using a Phenomenex
Racemic 7,8-difluoro-3,4-dihydro-3-methyl-2H-[1,4]-benzox-
azine 1a and 3,4-dihydro-3-methyl-2H-[1,4]-benzoxazine 1b,9
3,4-dihydro-3-methyl-2H-[1,4]-benzothiazine 1c,4g 2-methyl-
1,2,3,4-tetrahydroquinoline 1d,10 and 6-fluoro-2-methyl-1,2,3,4-
tetrahydroquinoline 1e,3e were obtained according to the
literature procedures. Other reagents are commercially available.
The solvents were dried according to standard methods11 and used
freshly prepared. Flash column chromatography was performed
using Silica gel 60 (230–400 mesh) (Alfa Aesar, UK). Melting points
were obtained on a SMP3 apparatus (Barloworld Scientific, UK) and
are uncorrected. Optical rotations were measured on a Perkin
Elmer M341 polarimeter. The 1H, 13C and 19F NMR spectra were
recorded on a Bruker Avance 500 spectrometer with tetramethyl-
silane and hexafluorobenzene as the internal standards. The NMR
spectra of amides 6a–f were recorded in DMSO-d6 at 100 °C; the
Luna
C
18(2) column (250 ꢁ 4.6 mm), detection at 220 nm,
0.8 mL/min flow rate; MeCN–H2O 7:3 (s(S,R)-6f 8.05–8.07 min,
s(R,R)-6f 8.85–8.86 min).
Crystallographic data for compounds (S,R)-6c and (S,R)-6e have
been deposited with the Cambridge Crystallographic Data Centre
(CCDC Nos. 1484576 and 1485429). Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK [fax: +44(0) 1223 336033 or e-mail:
deposit@ccdc.cam.ac.uk].
4.2. Ethyl (R)-2-phenoxypropionate (R)-4
A solution of diisopropyl azodicarboxylate (5.25 g, 24.5 mmol)
in toluene (50 mL) was added dropwise to a solution of ethyl L-lac-
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S. A. Vakarov et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
tate (2.89 g, 24.5 mmol), phenol (2.31 g, 24.5 mmol) and triph-
enylphosphine (6.43 g, 24.5 mmol) in toluene (100 mL) under stir-
ring at ꢀ20 °C. The reaction mixture was stirred at ꢀ20 °C for 2 h,
then at room temperature for 48 h, and then evaporated to dryness
under reduced pressure. The residue was treated with hexane
(50 mL), the precipitate was filtered off and then washed with hex-
ane (50 mL). The mother liquor and washings were evaporated to
dryness under reduced pressure. The residue was purified by flash
column chromatography on silica gel (eluent hexane–ethyl acet-
ate) to afford 3.05 g (64%) of compound (R)-4 as colorless oil.
solution of acyl chloride 2a (1.84 g, 10 mmol) [obtained from sca-
lemic acid (R)-3, 96.5% ee] in toluene (30 mL). The reaction mixture
was kept at room temperature for 24 h and then evaporated to dry-
ness under reduced pressure. Acetonitrile (20 mL) and saturated
aqueous Na2CO3 (20 mL) were added to the residue and the reac-
tion mixture was stirred vigorously for 1 h, after which acetonitrile
was removed under reduced pressure, and the aqueous solution
was washed with chloroform (4 ꢁ 15 mL), acidified with 4 M HCl
to pH 1–2 and extracted with chloroform (4 ꢁ 10 mL). The organic
layers were washed with saturated aqueous NaCl (4 ꢁ 20 mL),
dried over MgSO4 and evaporated to dryness under reduced pres-
sure to afford 1.26 g (76%) of acid (R)-5 as a colorless solid, mp
[a] [a]
20 = +46.6 (c 1.0, MeOH) {lit.12 20 = +47.2 (c 0.5, MeOH); 99%
D D
ee}. 1H NMR (500 MHz, CDCl3): d 1.24 (3H, t, J = 7.1 Hz, COOCH2-
CH3); 1.62 (3H, d, J = 6.8 Hz, 2-Me); 4.22 (2H, q, J = 7.1 Hz, OCH2);
4.74 (1H, q, J = 6.8 Hz, CH); 6.88 (2H, dd, J = 8.7, 1.0 Hz, Ho); 6.97
(1H, tt, J = 7.4, 1.0 Hz, Hp); 7.27 (2H, dd, J = 8.7, 7.4 Hz, Hm). 13C
NMR (126 MHz, CDCl3): d 14.10; 18.55; 61.23; 72.60; 115.10;
121.53; 129.50; 157.59; 172.25. Anal. Calcd. for C11H14O3: C,
68.02; H, 7.26. Found: C, 68.01; H, 7.07.
88–90 °C;
[a]
20 = +21.1 (c 1.0, CHCl3). HPLC (Chiralpak AD,
D
n-hexane–iPrOH–TFA 20:1:0.02): 99.6% ee. Anal. Calcd for
C9H10O3: C, 65.05; H, 6.06. Found: C, 65.18; H, 6.25.
4.6. Kinetic resolution of racemic amines 1a–f. General
procedure
4.3. (R)-2-Phenoxypropionic acid (R)-5
A solution of acyl chloride (R)-2a (92 mg, 0.5 mmol) in toluene
(5 mL) was added to a solution of amine 1a (1b–f) (1.0 mmol) in
toluene (5 mL) under stirring at +20 °C. The reaction mixture was
kept in a thermostat at +20 °C for 6 h and then successively washed
with 4 M HCl (2 ꢁ 4 mL), saturated aqueous NaCl (4 ꢁ 5 mL), 5%
NaHCO3 (2 ꢁ 5 mL), and water (2 ꢁ 5 mL). The mixture was then
dried over MgSO4 and evaporated to dryness under reduced pres-
sure. The residue was analyzed by GC or RP-HPLC, then recrystal-
lized to yield the major (S,R)-diastereoisomers of amides 6a–6f.
Acidic aqueous solutions (after washing with 4 M HCl) were col-
lected, alkalized with Na2CO3 to pH ꢂ9 and extracted with chloro-
form (2 ꢁ 5 mL); the organic layers were washed with water
(2 ꢁ 5 mL), dried over MgSO4 and evaporated to dryness under
reduced pressure. The residue was analyzed by chiral HPLC (in
the case of amine 1e, the residue was treated with benzoyl chloride
prior to RP-HPLC as described in Ref. 4g). Each experiment was
performed in duplicate.
At first, 2 M NaOH (5.2 mL, 10.4 mmol) was added dropwise to a
solution of compound (R)-4 (1.01 g, 5.2 mmol) in ethanol (20 mL)
with stirring at 4 °C. The reaction mixture was stirred at room tem-
perature for 24 h, and then evaporated to dryness under reduced
pressure. The residue was dissolved in water (40 mL), washed with
ethyl ether (2 ꢁ 10 mL), acidified with 4 M HCl to pH 1–2 and
extracted with ethyl ether (4 ꢁ 20 mL). The organic layers were
washed with saturated aqueous NaCl (2 ꢁ 40 mL), dried over
MgSO4, and evaporated to dryness under reduced pressure. The
residue was recrystallized from hexane to yield 0.77 g (89%) of
compound (R)-5 as a colorless solid, mp 86–88 °C (hexane) (lit.
85–87 °C,12 83 °C13); [ 20 = +16.2 (c 0.6, CHCl3) {lit.13 20 = +19
a] [a]
D D
(c 1.0, CHCl3)}. HPLC (Chiralpak AD, n-hexane–iPrOH–TFA
20:1:0.02): 95.6% ee. Anal. Calcd for C9H10O3: C, 65.05; H, 6.06.
Found: C, 64.95; H, 6.24. 1H and 13C NMR spectra were identical
to those published for (S)-5.14
4.6.1. (S,R)-7,8-Difluoro-3,4-dihydro-3-methyl-N-(20-
phenoxypropionyl)-2H-[1,4]benzoxazine (S,R)-6a
4.4. (R)-2-Phenoxypropionyl chloride (R)-2a
Yield 107 mg (64%) as colorless crystals, mp 97–98 °C (n-hex-
Oxalyl chloride (1.09 mL, 12.5 mmol) was added to a solution of
ane–ethyl acetate); [a]
20 = +63.5 (c 1.0, CHCl3). Anal. Calcd for
D
acid (R)-5 (0.83 g, 5 mmol) and DMF (5
l
L) in CH2Cl2 (20 mL). The
C18H17F2NO3: C, 64.86; H, 5.14; N, 4.20; F, 11.40. Found: C, 64.89;
reaction mixture was stirred at room temperature for 6 h, and then
evaporated to dryness under reduced pressure. The residue was
dried over P2O5 in vacuo to afford 0.92 g (99%) of compound (R)-
2a as a yellowish oil, which had an unpleasant odor. Anal. Calcd
for C9H9ClO2: C, 58.55; H, 4.91. Found: C, 58.78; H, 5.07. 1H NMR
spectrum was identical to that published for racemic chloride 2a.5
H, 5.20; N, 4.11; F, 11.19. GC >99.8% de. Retention times (GC), 1H,
13C and 19F NMR were identical to those published for amide
(R⁄,S⁄)-6a.5
4.6.2. (S,R)-3,4-Dihydro-3-methyl-N-(20-phenoxypropionyl)-2H-
[1,4]benzoxazine (S,R)-6b
Yield 88 mg (59%) as colorless crystals, mp 121–122 °C (n-hex-
4.5. Enantiomeric enrichment of scalemic acid (R)-5 (95.6% ee)
ane–ethyl acetate); [a]
20 = +117 (c 1.1, CHCl3). Anal. Calcd for
D
C
18H19NO3: C, 72.71; H, 6.44; N, 4.71. Found: C, 72.70; H, 6.61;
Method A: At first, NaOH (0.25 g, 6.25 mmol) was added to a
solution of acid (R)-5 (2.00 g, 12.0 mmol) in acetone (26 mL). The
reaction mixture was stirred at room temperature until complete
dissolution of NaOH and then evaporated. The residue was washed
with chloroform (2 ꢁ 15 mL), recrystallized from acetone, and then
dissolved in water (10 mL). The aqueous solution was acidified
with 4 M HCl to pH 1–2 at cooling (+4 °C), and then extracted with
chloroform (4 ꢁ 10 mL). The organic layers were washed with sat-
urated aqueous NaCl (4 ꢁ 20 mL), dried over MgSO4 and evapo-
rated to dryness under reduced pressure to afford 0.34 g (17%) of
N, 4.52. GC >99.8% de. Retention times (GC), 1H, 13C and 19F NMR
were identical to those published for amide (R⁄,S⁄)-6b.5
4.6.3. (S,R)-3,4-Dihydro-3-methyl-N-(20-phenoxypropionyl)-2H-
[1,4]benzothiazine (S,R)-6c
Yield 124 mg (79%) as colorless crystals, mp 126–127 °C (n-hex-
ane–ethyl acetate);
[a] (s(S,R)-6c
20 = +198 (c 1.3, CHCl3). GC
D
28.13 min): de >99.8%. 1H NMR (500 MHz, DMSO-d6, 100 °C): d
1.03 (3H, d, J = 6.7 Hz, C3-CH3); 1.56 (3H, d, J = 6.3 Hz, H-30); 2.79
(1H, dd, J = 12.3, 4.3 Hz, H-2A); 3.22 (1H, dd, J = 12.3, 5.8 Hz, H-
2B); 5.02 (1H, q, J = 6.3 Hz, H-20); 5.14 (1H, qdd, J = 6.3, 5.8,
4.4 Hz, H-3); 6.55 (2H, dd, J = 8.7, 1.0 Hz, Ho); 6.85 (1H, tt, J = 7.4,
1.0 Hz, Hp); 7.10–7.17 (4H, m, Hm, H6 and H7); 7.24–7.31 (2H,
m, H-5 and H8). 13C NMR (126 MHz, DMSO-d6, 100 °C): d 16.62;
17.58; 33.54; 45.12; 70.11; 114.57; 120.57; 124.64; 126.15;
(R)-5 as a colorless powder, mp 86–88 °C; [a]
20 = +20.4 (c 1.0,
D
CHCl3). HPLC (Chiralpak AD, n-hexane–iPrOH–TFA 20:1:0.02):
99.4% ee.
Method B: A solution of amine (RS)-1b (0.28 g, 0.15 mmol) and
PhNEt2 (0.22 g, 1.5 mmol) in toluene (20 mL) was added to a
Please cite this article in press as: Vakarov, S. A.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.004

6
S. A. Vakarov et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
126.78; 127.24; 128.61; 130.10; 133.52; 156.51; 169.06. Anal.
Calcd for C18H19NO2S: C, 68.98; H, 6.11; N, 4.47; S, 10.23. Found:
C, 69.09; H, 6.30; N, 4.42; S, 10.38.
J = 15.8, 8.6 Hz, H-3B); 4.72 (1H, dqd, J = 8.5, 6.4, 1.3 Hz, H-2);
5.24 (1H, q, J = 6.4 Hz, H-20); 6.92–6.96 (3H, m, Ho and Hp); 7.03
(1H, td, J = 7.5, 1.0 Hz, H-5); 7.16 (1H, t, J = 7.8 Hz, H-6); 7.24–
7.29 (3H, m, Hm and H-4); 7.89 (1H, br d, J = 7.8 Hz, H-7). 13C
NMR (126 MHz, DMSO-d6, 100 °C): d 17.26; 20.84; 35.55; 54.46;
71.76; 115.46 (2C); 116.64; 120.79; 123.35; 124.65; 126.39;
128.88; 130.71; 140.58; 156.70; 167.91. HRMS (ESI) calcd for
4.6.4. (S,R)-2-Methyl-N-(20-phenoxypropionyl)-1,2,3,4-
tetrahydroquinoline (S,R)-6d
Yield 27 mg (18%) as a yellow oil after flash column chromatog-
raphy (n-hexane–ethyl acetate, fast eluting diastereomer); [
a]
=
C
18H20NO2 [M+H]+ 282.1489. Found: 282.1489.
20
D
+192 (c 0.4, CHCl3). GC (s(S,R)-6d 26.52 min, s(R,R)-6d 26.95 min):
96.0% de. 1H NMR (500 MHz, DMSO-d6, 100 °C): d 1.02 (3H, d,
J = 6.6 Hz, C2-CH3); 1.32 (1H, dddd, J = 13.1, 9.4, 6.5, 5.7 Hz, H-
3A); 1.55 (3H, d, J = 6.3 Hz, H-30); 2.18 (1H, ddt, J = 13.1, 7.3,
5.8 Hz, H-3B); 2.33 (1H, ddd, J = 15.3, 9.4, 5.8 Hz, H-4A); 2.61
(1H, dt, J = 15.3, 5.8 Hz, H-4B); 4.65 (1H, m, H-2); 5.17 (1H, q,
J = 6.3 Hz, H-20); 6.52 (2H, dd, J = 8.7, 1.0 Hz, Ho); 6.85 (1H, tt,
J = 7.4, 1.0 Hz, Hp); 7.09–7.14 (3H, m, Hm and Hquin); 7.17–7.24
(3H, m, Hquin). 13C NMR (126 MHz, DMSO-d6, 100 °C): d 17.39;
19.01; 24.19; 30.74; 47.37; 70.27; 114.85; 120.63; 124.83;
125.19; 125.68; 127.17; 128.59; 134.14; 135.81; 156.61; 168.80.
4.7. (S)-3,4-Dihydro-3-methyl-2H-[1,4]benzothiazine (S)-1c
A solution of acyl chloride (R)-2a (0.92 g, 5 mmol) in toluene
(50 mL) was added to a solution of amine 1c (1.65 g, 10 mmol) in
toluene (50 mL) under stirring at ꢀ20 °C. The reaction mixture
was stirred at ꢀ20 °C for 24 h, then successively washed with
4 M HCl (2 ꢁ 50 mL), saturated aqueous NaCl (3 ꢁ 100 mL), 5%
NaHCO3 (2 ꢁ 50 mL) and H2O (2 ꢁ 100 mL), dried over MgSO4,
and evaporated to dryness under reduced pressure. The residue
was recrystallized from n-hexane–ethyl acetate to afford 1.25 g
(80%) of amide (S,R)-6c (de >99.9% according to GC) as colorless
crystals.
HRMS (ESI) calcd for
296.1649.
C
19H22NO2 [M+H]+ 296.1645. Found:
Amide (S,R)-6c (1.25 g, 4 mmol) was dissolved in glacial acetic
acid (9 mL), after which concentrated HCl (9 mL) was added to
the resulting solution. The reaction mixture was heated at 90–
95 °C for 20 h, then cooled to room temperature, evaporated to half
the volume, poured into 4 M HCl (50 mL) and extracted with ethyl
acetate (3 ꢁ 10 mL). The organic layers were washed with satu-
rated aqueous NaCl (3 ꢁ 20 mL), dried over MgSO4, and evaporated
to dryness. The residue was purified by flash column chromatogra-
phy on silica gel (n-hexane–ethyl acetate) to yield 0.62 g (94%) of
4.6.5. (S,R)-6-Fluoro-2-methyl-N-(20-phenoxypropionyl)-1,2,3,4-
tetrahydroquinoline (S,R)-6e
Yield 52 mg (33%) as colorless crystals, mp 118–120 °C (n-hex-
ane–ethyl acetate);
[a] (s(S,R)-6e
20 = +214 (c 1.0, CHCl3). GC
D
26.55 min, s(R,R)-6e 26.75 min): 98.6% de. 1H NMR (500 MHz,
DMSO-d6, 100 °C): d 1.02 (3H, d, J = 6.6 Hz, C2-CH3); 1.32 (1H,
ddt, J = 13.2, 9.2, 6.0 Hz, H-3A); 1.53 (3H, d, J = 6.3 Hz, H-30); 2.18
(1H, ddt, J = 13.2, 7.2, 6.0 Hz, H-3B); 2.33 (1H, ddd, J = 15.4, 9.2,
6.0 Hz, H-4A); 2.63 (1H, dt, J = 15.4, 5.7 Hz, H-4B); 4.66 (1H, m,
H-2); 5.19 (1H, q, J = 6.3 Hz, H-20), 6.58 (2H, d, J = 8.6 Hz, Ho);
6.87 (1H, tt, J = 7.4, 1.0 Hz, Hp); 6.94 (1H, td, J = 8.7, 3.0 Hz, H-7);
7.00 (1H, dd, J = 9.0, 3.0 Hz, H-5); 7.14 (2H, dd, J = 8.6, 7.4 Hz,
Hm); 7.29 (1H, dd, J = 8.7, 5.2 Hz, H-8). 19F NMR (470 MHz,
DMSO-d6, 100 °C): d 45.89 (unres. m, F-6). 13C NMR (126 MHz,
DMSO-d6, 100 °C): d 17.11; 18.87; 24.21; 30.29; 47.34; 70.43;
112.21 (d, J = 23.1 Hz); 113.64 (d, J = 22.4 Hz); 114.81; 120.64;
126.52 (d, J = 8.4 Hz); 128.60; 132.07 (d, J = 2.7 Hz); 136.49 (br
m); 156.57; 159.20 (d, J = 243.1 Hz); 168.74. Anal. Calcd for
acid (R)-5 as colorless crystals, mp 84–86 °C, [a]
20 = +21.1 (c 1.0,
D
CHCl3). HPLC (Chiralpak AD, n-hexane–iPrOH–TFA 20:1:0.02):
99.4% ee. Anal. Calcd for C9H10O3: C, 65.05; H, 6.06. Found: C,
65.03; H, 6.21. 1H and 13C NMR spectra were identical to those
published for (S)-5.14
The acidic aqueous layer was alkalized with Na2CO3 and
extracted with benzene (3 ꢁ 10 mL). The organic layers were
washed with water (3 ꢁ 20 mL), dried over Na2SO4, and evaporated
to dryness under reduced pressure. The residue was purified by
flash column chromatography on silica gel (from n-hexane–
benzene to benzene) to afford 0.61 g (92%) of amine (S)-1c as a
C19H20FNO2: C, 72.82; H, 6.43; N, 4.47; F, 6.06. Found: C, 72.93;
H, 6.38; N, 4.47; F, 5.99.
colorless oil. [
a
]
20 = ꢀ77.8 (c 1.0, CHCl3) {lit.15
[
a
]
20 = ꢀ79.0 (c 1.2,
D
D
CHCl3)}.
HPLC
(Chiralcel
OD-H,
n-hexane–iPrOH–MeOH
4.6.6. (R,R)-2-Methyl-N-(20phenoxypropionyl)-indoline (R,R)-6f
Yield 25 mg (18%) as a colored oil after flash column chro-
matography on silica gel (n-hexane–ethyl acetate, fast eluting
100:1:0.5): >99.9% ee. 1H and 13C NMR spectra were identical to
those published for (S)-1c.15 HRMS (ESI) calcd for C9H12NS
[M+H]+ 166.0685. Found: 166.0687.
diastereomer); [a]
20 = +1.3 (c 0.8, CHCl3). HPLC (Phenomenex Luna
D
C 18 (2), MeCN–H2O 7:3): 99.6% de. 1H NMR (500 MHz, DMSO-d6,
100 °C): d 1.22 (3H, d, J = 6.4 Hz, C2-CH3); 1.52 (3H, d, J = 6.4 Hz,
H-30); 2.64 (1H, br d, J = 15.9 Hz, H-3A); 3.32 (1H, dd, J = 15.9,
8.7 Hz, H-3B); 4.78 (1H, dqd, J = 8.6, 6.4, 1.5 Hz, H-2); 5.25 (1H, q,
J = 6.4 Hz, H-20); 6.94–6.98 (3H, m, Hp and Ho); 7.03 (1H, td,
J = 7.5, 1.0 Hz, H-5); 7.16 (1H, t, J = 7.8 Hz, H-6); 7.24–7.30 (3H,
m, H-4 and Hm); 7.89 (1H, d, J = 7.8 Hz, H-7). 13C NMR (126 MHz,
DMSO-d6, 100 °C): d 16.76; 21.00; 35.55; 54.60; 71.96; 115.46;
116.62; 120.97; 123.39; 124.67; 126.39; 128.99; 130.72; 140.58;
Acknowledgments
The authors thank Dr. Pavel A. Slepukhin for performing X-ray
diffraction and Dr. Ilya N. Ganebnykh for recording HRMS spectra.
The work was financially supported by the Russian Science Foun-
dation (grant 14-13-01077).
A. Supplementary data
156.61; 167.65. HRMS (ESI) calcd for
282.1489. Found: 282.1489.
C
18H20NO2 [M+H]+
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetasy.2016.10.
004.
4.6.7. (S,R)-2-Methyl-N-(20-phenoxypropionyl)-indoline (S,R)-6f
Yield 38 mg (27%) as a colorless amorphous solid after flash col-
umn chromatography on silica gel (n-hexane–ethyl acetate, slow
References
eluting diastereomer); [a]
20 = +43.7 (c 0.6, CHCl3). HPLC (Phenom-
D
1. Kagan, H. B.; Fiaud, J. C. Top. Stereochem. 1988, 18, 249–330.
2. (a) Breuer, M.; Ditrich, K.; Habicher, T.; Hauer, B.; Kebeler, M.; Stürmer, R.;
Zelinski, T. Angew. Chem., Int. Ed. 2004, 43, 788–824; (b) Müller, C. E.; Schreiner,
P. E. Angew. Chem., Int. Ed. 2011, 50, 6012–6042; (c) Krasnov, V. P.; Gruzdev, D.
A.; Levit, G. L. Eur. J. Org. Chem. 2012, 1471–1493.
enex Luna C 18 (2), MeCN–H2O 7:3): 98.8% de. 1H NMR (500 MHz,
DMSO-d6, 100 °C): d 1.21 (3H, d, J = 6.4 Hz, C2-CH3); 1.55 (3H, d,
J = 6.4 Hz, H-30); 2.64 (1H, br d, J = 15.8 Hz, H-3A); 3.35 (1H, dd,
Please cite this article in press as: Vakarov, S. A.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.004

S. A. Vakarov et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
7
3. (a) Charushin, V. N.; Krasnov, V. P.; Levit, G. L.; Korolyova, M. A.; Kodess, M. I.;
Chupakhin, O. N.; Kim, M. H.; Lee, H. S.; Park, Y. G.; Kim, K.-C. Tetrahedron:
Asymmetry 1999, 10, 2691–2702; (b) Krasnov, V. P.; Levit, G. L.; Andreyeva, I.
N.; Grishakov, A. N.; Charushin, V. N.; Chupakhin, O. N. Mendeleev Commun.
2002, 12, 27–28; (c) Chulakov, E. N.; Gruzdev, D. A.; Levit, G. L.; Sadretdinova, L.
Sh.; Krasnov, V. P.; Charushin, V. N. Russ. Chem. Bull. 2011, 60, 948–955; (d)
Chulakov, E. N.; Levit, G. L.; Tumashov, A. A.; Sadretdinova, L. Sh.; Krasnov, V. P.
Chem. Heterocycl. Compd. 2012, 48, 724–732; (e) Gruzdev, D. A.; Chulakov, E. N.;
Levit, G. L.; Ezhikova, M. A.; Kodess, M. I.; Krasnov, V. P. Tetrahedron: Asymmetry
2013, 24, 1240–1246.
4. (a) Krasnov, V. P.; Levit, G. L.; Bukrina, I. M.; Andreeva, I. N.; Sadretdinova, L.
Sh.; Korolyova, M. A.; Kodess, M. I.; Charushin, V. N.; Chupakhin, O. N.
Tetrahedron: Asymmetry 2003, 14, 1985–1988; (b) Krasnov, V. P.; Levit, G. L.;
Kodess, M. I.; Charushin, V. N.; Chupakhin, O. N. Tetrahedron: Asymmetry 2004,
15, 859–862; (c) Gruzdev, D. A.; Levit, G. L.; Krasnov, V. P.; Chulakov, E. N.;
Sadretdinova, L. Sh.; Grishakov, A. N.; Ezhikova, M. A.; Kodess, M. I.; Charushin,
V. N. Tetrahedron: Asymmetry 2010, 21, 936–942; (d) Levit, G. L.; Gruzdev, D. A.;
Krasnov, V. P.; Chulakov, E. N.; Sadretdinova, L. Sh.; Ezhikova, M. A.; Kodess, M.
I.; Charushin, V. N. Tetrahedron: Asymmetry 2011, 22, 185–189; (e) Gruzdev, D.
A.; Levit, G. L.; Kodess, M. I.; Krasnov, V. P. Chem. Heterocycl. Compd. 2012, 48,
748–757; (f) Gruzdev, D. A.; Levit, G. L.; Krasnov, V. P. Tetrahedron: Asymmetry
2012, 23, 1640–1646; (g) Gruzdev, D. A.; Vakarov, S. A.; Levit, G. L.; Krasnov, V.
P. Chem. Heterocycl. Compd. 2014, 49, 1795–1807; (h) Vakarov, S. A.; Gruzdev,
D. A.; Chulakov, E. N.; Sadretdinova, L. Sh.; Ezhikova, M. A.; Kodess, M. I.; Levit,
G. L.; Krasnov, V. P. Chem. Heterocycl. Compd. 2014, 50, 838–855.
6. (a) Takamura, M.; Yanagisawa, H.; Kanai, M.; Shibasaki, M. Chem. Pharm. Bull.
2002, 50, 1118–1121; (b) Shi, Y.-J.; Hughes, D. L.; McNamara, J. M. Tetrahedron
Lett. 2003, 44, 3609–3611; (c) Crassous, P.-A.; Cardinaletti, C.; Carrieri, A.;
Bruni, B.; Di Vaira, M.; Gentili, F.; Ghelfi, F.; Giannella, M.; Paris, H.; Piergentili,
A.; Quaglia, W.; Schaak, S.; Vesprini, C.; Pigini, M. J. Med. Chem. 2007, 50, 3964–
3968; (d) Fujita, M.; Okuno, S.; Lee, H. J.; Sugimura, T.; Okuyama, T. Tetrahedron
Lett. 2007, 48, 8691–8694; (e) Vartak, A. P.; Crooks, P. A. Org. Process Res. Dev.
2009, 13, 415–419; (f) Fujita, M.; Wakita, M.; Sugimura, T. Chem. Commun.
2011, 3983–3985.
7. Manimaran, T.; Stahly, G. P. Tetrahedron: Asymmetry 1993, 4, 1949–1954.
8. Satyanarayana, T.; Kagan, H. B. Tetrahedron 2007, 63, 6415–6422.
9. Hayakawa, I.; Hiramitsu, T.; Tanaka, Y. EP Patent 47,005, 1982; Chem. Abstr.
1982, 97, 55821b.
10. Oldham, W.; Johns, I. B. J. Am. Chem. Soc. 1939, 61, 3289–3291.
11. Armarego, W. L. F.; Chai, C. L. L. Purification of Laboratory Chemicals, 6th ed.;
Butterworth Heinemann: USA, 2009.
12. Chen, C.; Zhu, S.-F.; Liu, B.; Wang, L.-X.; Zhou, Q.-L. J. Am. Chem. Soc. 2007, 129,
12616–12617.
13. Tottie, L.; Baeckström, P.; Moberg, C.; Tegenfeldt, J.; Heumann, A. J. Org. Chem.
1992, 57, 6579–6587.
14. Boyd, E.; Chavda, S.; Eames, J.; Yohannes, Y. Tetrahedron: Asymmetry 2007, 18,
476–482.
15. Gruzdev, D. A.; Chulakov, E. N.; Sadretdinova, L. Sh.; Kodess, M. I.; Levit, G. L.;
Krasnov, V. P. Tetrahedron: Asymmetry 2015, 26, 186–194.
5. Vakarov, S. A.; Gruzdev, D. A.; Sadretdinova, L. Sh.; Chulakov, E. N.; Pervova, M.
G.; Ezhikova, M. A.; Kodess, M. I.; Levit, G. L.; Krasnov, V. P. Tetrahedron:
Asymmetry 2015, 26, 312–319.
Please cite this article in press as: Vakarov, S. A.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.10.004