Monofluorinated aziridines in asymmetric synthesis of chiral fluorinated prop-2-yn-1-amines

Article abstract of DOI:10.1134/S1070428010070043

Nonracemic C-fluoroaziridines were synthesized for the first time by reaction of fluorocarbene with N-diphenylmethylidene-substituted natural amino acid esters. The products were shown to be used in asymmetric synthesis of chiral fluorinated prop-2-yn-1-amines via one-pot process involving isomerization of 2-fluoroaziridines into α-fluoro imines and subsequent reaction with alkynyldifluoroborane generated in situ.

Full text of DOI:10.1134/S1070428010070043

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 7, pp. 976–986. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © A.S. Konev, K. Abbaspour Tehrani, A.F. Khlebnikov, M.S. Novikov, J. Magull, 2010, published in Zhurnal Organicheskoi Khimii,
2010, Vol. 46, No. 7, pp. 980–990.
Monofluorinated Aziridines in Asymmetric Synthesis of Chiral
Fluorinated Prop-2-yn-1-amines
A. S. Koneva, K. Abbaspour Tehranib, A. F. Khlebnikova, M. S. Novikova, and J. Magullc
a St. Petersburg State University, Universitetskii pr. 26, St. Petersburg, 198504 Russia
e-mail: alexander.khlebnikov@pobox.spbu.ru
b Faculty of Sciences, Department of Applied Biological Sciences and Engineering,
Laboratory for Organic Chemistry, Vrije Universiteit, Brussel, Belgium
c Inorganic Chemistry Institute, Georg-August University, Göttingen, D-37077 Germany
Received May 20, 2009
Abstract—Nonracemic C-fluoroaziridines were synthesized for the first time by reaction of fluorocarbene with
N-diphenylmethylidene-substituted natural amino acid esters. The products were shown to be used in asym-
metric synthesis of chiral fluorinated prop-2-yn-1-amines via one-pot process involving isomerization of
2-fluoroaziridines into α-fluoro imines and subsequent reaction with alkynyldifluoroborane generated in situ.
DOI: 10.1134/S1070428010070043
Prop-2-yn-1-amines are widely used as medical
agents for the treatment of various diseases [1–10] and
as building blocks in the synthesis of polyfunctional
nitrogen-containing organic compounds [11–18]. De-
velopment of convenient synthetic approaches to chiral
prop-2-yn-1-amines [19–25] is an important problem,
taking into account that the use of nonracemic drugs
is one of the most important lines in modern medicine
[26–30].
eration of the process and reduction in the amount of
by-products in the case of substrates containing a me-
thoxycarbonylmethyl group (R = CH2CO2Me; A, R1 =
R2 = H) was rationalized assuming formation of inter-
mediate chelate A [31]. The formation of cyclic inter-
mediate implies that addition of arylethynyl nucleo-
phile at the C=N bond of substrates with a chiral
carbon atom (C* in A, R1 ≠ R2) could occur with high
diastereoselectivity due to rigidity of the transition
state and proximity of the chiral center to the reaction
center [32] (Scheme 1).
We recently showed that fluorinated prop-2-yn-1-
amines can readily be obtained by reaction of potas-
sium arylethynyltrifluoroborates with 3-fluoro-2,2-di-
phenylaziridine in the presence of boron trifluoride–
ether complex (Scheme 1) [31]. It was found that the
formation of fluorinated prop-2-yn-1-amines from
monofluoroaziridines involves Lewis acid-catalyzed
isomerization of 2-fluoroaziridines into α-fluoro imines
which then react with alkynyldifluoroborane. Accel-
Therefore, we presumed that the reaction sequence
including isomerization of chiral aziridine and subse-
quent reaction of the imine thus formed with potassium
alkynyltrifluoroborate should provide a simple and
convenient synthetic route to chiral functionalized
prop-2-yn-1-amines. The present article reports on our
first results of asymmetric synthesis of fluorinated
Scheme 1.
OMe
O
F
F
R1
R2
R
N
Ph
Ph
Ar
BF3K
F
F
B
BF3 ·Et2O
N
Ph
Ph
F
Ar
Ar
HN
H
R
Ph
Ph
A
976

MONOFLUORINATED AZIRIDINES IN ASYMMETRIC SYNTHESIS
977
Scheme 2.
R
NH
R
CH2Cl2, –20°C
Ph
Ph
COOMe
+
Cl–
N
Ph
Ph
H3N
COOMe
Va–Vc
IV
IIIa–IIIc
H
F
H
F
F
H
CHFBr2, active Pb, Bu4NBr (VI)
CH2Cl2, 20–40°C
Ph
Ph
N
R
N
R
Ph
N
R
+
IIIa–IIIc
Ph
Ph
COOMe
Ia–Ic
COOMe
IIa–IIc
Ph
COOMe
VII
R = Me (a), PhCH2 (b), (S)-MeEtCH (c).
prop-2-yn-1-amines from enantiomerically pure imines
through chiral fluoroaziridines.
leading to ylide VII which underwent cyclization to
1
19
aziridines I and II. In the H and F NMR spectra of
the reaction mixtures we observed signals from two
diastereoisomeric aziridines I and II. The formation of
only two diastereoisomeric products from Schiff base
IIIc possessing a non-racemizable (3S)-chiral center
and theoretically racemizable (2S)-chiral center indi-
cates the absence of racemization during the process.
Diastereoselectivity in the formation of fluoroaziri-
dines and their yields decrease in going from L-ala-
nine to L-isoleucine derivatives (Table 1), i.e., as the
size of the R substituent at the chiral center increases.
Diastereoisomeric aziridines are not converted into
each other during the reaction because of high barrier
to opening of the aziridine ring.
Monofluoroaziridines can be obtained in different
ways: by reaction of fluorocarbene with imines
[33, 34], by reduction of halofluoroaziridines with
Bu3SnH [35, 36], and by cyclization of β-fluoro-β-
bromo(chloro) amines in the presence of bases
[37, 38]. The two latter procedures imply basic con-
ditions, so that they are unsuitable for the synthesis of
nonracemic compounds derived from amino acids. The
procedure proposed by us recently for generation of
fluorocarbene via reduction of CHFBr2 with lead
[33, 34] makes it possible to synthesize monofluoro-
aziridines under neutral conditions, avoiding racemiza-
tion of imines derived from amino acid esters.
Chiral aziridines I and II were synthesized accord-
ing to Scheme 2. Enantiomerically pure Schiff bases
III were prepared as described in [39, 40] from benzo-
phenone imine (IV) and amino acid (L-alanine,
L-phenylalanine, and L-isoleucine) methyl ester hydro-
chlorides Va–Vc. The resulting Schiff bases were
brought into reaction with fluorocarbene which was
generated by reduction of CHFBr2 with active lead in
the presence of tetrabutylammonium bromide (VI)
under ultrasonic activation [33, 34]. The reaction in-
volved electrophilic attack by fluorocarbene on the
lone electron pair on the nitrogen atom in the imine,
In all cases, major isomer I was isolated as indivi-
dual substance, whereas minor isomer II was isolated
as a mixture with either the major isomer (Ia, Ib) or
the initial Schiff base (IIIc). The configuration of
aziridine Ia was determined by X-ray analysis (Fig. 1),
and the configuration of the other aziridines was deter-
mined by analysis of their 1H NMR spectra. The signal
from the aziridine proton in major isomers
(2S,2′R)-Ia–(2S,2′R)-Ic appeared in a stronger field
(δ 4.93–5.42 ppm) relative to the corresponding signal
of minor isomers (2S,2′S)-IIa–(2S,2′S)-IIc (δ 5.67–
5.73 ppm). As far as we know, fluoroaziridines I and
Table 1. Yields and ratios of diastereoisomeric fluoroaziridines I and II in the reaction mixtures obtained from Schiff bases
III and fluorocarbene
Schiff
base no.
Ratios of aziridines I and II in the
Preparative yields of aziridines, %
Aziridine no.
R
reaction mixture (1H NMR data)
(ratio I:II)
IIIa
IIIb
IIIc
Ia
Ib
Ic
IIa
IIb
IIc
Me
0.3:1
2.3:1
1.1:1
45% (Ia), 6% (Ia:IIa, 1:1.8)
22% (Ib), 13% (Ib:IIb, 1:1.5)
6% (Ic)
PhCH2
(S)-Et(Me)CH
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

KONEV et al.
ether complex to obtain a mixture of diastereoisomeric
978
prop-2-yn-1-amines Xa and XIa (26%) and indole XII
(17%) (Scheme 3).
As we showed previously [31], undesirable forma-
tion of indole derivative may be minimized by per-
forming isomerization of fluoroaziridines directly in
the presence of alkynyltrifluoroborates. In fact, follow-
ing the second approach, which implied mere treat-
ment of aziridine Ia with borate IXa in the presence of
1 equiv of BF3·Et2O in CH2Cl2 at room temperature,
we obtained a mixture of diastereoisomeric amines
Xa and XIa and indole XII at a ratio of 5.8 :1.2:1
(1H NMR data). When the reaction was carried out at
–20°C, the formation of indole XII was suppressed
completely, and the products were diastereoisomers Xa
and XIa at a ratio of 5:1 (1H NMR). Under analogous
conditions, the reaction of aziridine Ib with borate IXa
gave a mixture of diastereoisomeric amines Xb and
XIb at a ratio of 10:1 (1H NMR).
Fig. 1. Structure of the molecule of (2S,3′R)-2-(3-fluoro-2,2-
diphenylaziridin-1-yl)propanoate (Ia) according to the X-ray
diffraction data.
II represent first examples of chiral nonracemic
C-fluoro-substituted aziridines [41, 42]; analogous
chiral C-chloro- [43] and C-bromoaziridines [44] were
reported previously.
Insofar as the transformation of fluoroaziridines I
and II into fluorinated prop-2-yn-1-amines X and XI
involves intermediate formation of α-fluoro imine VIII
which lacks aziridine chiral center, diastereoisomeric
aziridines I and II could be brought into the reaction
without preliminary separation. In order to avoid iso-
merization of fluoroaziridine into α-fluoro imine VIII,
the possibility for imination of 2-fluoro-2,2-diphenyl-
acetaldehyde with α-amino acid ester could be con-
sidered. Unfortunately, known 2-fluoro-2,2-diphenyl-
acetaldehyde is fairly difficult to synthesize; in addi-
tion, this compound is unstable [46].
The transformation of aziridines I into target
fluorinated prop-2-yn-1-amines X and XI may be
accomplished in a stepwise mode or via a one-pot
procedure [31]. According to the first approach, aziri-
dine Ia was subjected to isomerization into α-fluori-
nated Schiff base VIIIa by the action of SbF3 as Lewis
acid [31, 34, 45]. Analogous isomerization of aziridine
Ib gave Schiff base VIIIb in 94% yield. Imine VIIIa
was treated (without isolation and purification) with
potassium 3-methoxyphenylethynyltrifluoroborate
(IXa) in methylene chloride at room temperature in the
presence of an equimolar amount of boron trifluoride–
The optimized conditions were applied to synthe-
size a series of fluorinated prop-2-yn-1-amines Xa–Xe
(Scheme 4, Table 2). These reactions led to the forma-
tion of mixtures of only two diastereoisomeric amines
Scheme 3.
Ph
N
R
SbF3, CH2Cl2, 40°C
Ph
Ia, Ib
F
COOMe
VIIIa, VIIIb
Me
COOMe
Ph
Ph
R'–BF3K (IXa), BF3 ·Et2O
CH2Cl2, 20–25°C
H
H
N
MeOOC
N
MeOOC
N
+
+
Ph
VIIIa
Ph
F
F
R
R'
R
R'
Ph
XII
Xa
XIa
R = Me (a), PhCH2 (b); R′ = 3-MeOC6H4C≡C.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

MONOFLUORINATED AZIRIDINES IN ASYMMETRIC SYNTHESIS
979
Scheme 4.
R1
COOMe
NH
R1
COOMe
NH
Ia or Ib, BF3 ·Et2O
CH2Cl2, –20°C
R2
R2
R2
+
BF3 K
Ph
Ph
Ph
Ph
F
F
IXa–IXc
Xa–Xe
XIa–XIe
X and XI. The major isomers were isolated as indivi-
dual substances and fully characterized. According to
the 1H, 13C, and 19F NMR spectra, minor isomers XIa–
XIe were always present in the reaction mixtures, but
we failed to isolate them pure.
contained a signal from the 1′-H proton at δ 4.44–
4.58 ppm (S); the corresponding proton in amines XI
with (R)-configuration of the C1′ atom resonated in
a weaker field (δ 4.70–4.79 ppm).
Scheme 5 rationalizes predominant formation of
(2S,1′S) isomers X. The reaction of fluoroaziridines I
with potassium alkynyltrifluoroborates involves inter-
mediate formation of α-fluoro imines and alkynyldi-
fluoroboranes which are likely to give rise to chelate
The (2S,1′S) configuration of amines Xa, Xd, and
Xe was proved by X-ray analysis (Fig. 2), and the
configuration of Xb and Xc was determined on the
1
basis of their H NMR spectra which characteristically
Xa
Xd
Xe
Fig. 2. Structure of the molecules of (2S,1′S)-2-{3-aryl-1-[fluoro(diphenyl)methyl]prop-2-yn-1-ylamino}propanoates Xa,
Xd, and Xe.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

KONEV et al.
980
Scheme 5.
BF3 ·Et2O
Ar
BF3 K
Ar
BF2
OMe
O
F
Ph
LA
N
O
R
H
F
F
B
LA
Ar
BF2
N
I
Ph
OMe
F
Ar
R
Ph
Ph
A
OMe
OMe
O
O
B
F
F
R
H
R
H
B
H2O
N
N
F
F
X
F
F
C
Ph
Ph
Ar
Ph
Ph
Ar
LA = BF3 ·OEt2 or ArC≡CBF2.
A. Rigid cyclic structure of intermediate A ensures
strong differentiation of sides of the C=N bond, so that
intramolecular alkynyl group transfer occurs through
attack at the less sterically hindered side of the C=N
bond in (S) isomer A and leads to (2S,1′S) isomer X. In
keeping with the proposed scheme, the stereoselec-
tivity should increase as the size of the substituent on
C2 increases. In fact, the ratio X:XI in the reaction
mixture changed from 5:1 to 10:1 in going from R1 =
H (Xa:XIa) to R1 = Ph (Xb:XIb).
EXPERIMENTAL
The attenuated total reflectance IR spectra were
recorded on an Avatar 370 FTIR spectrometer (Thermo
Nicolet), and the IR spectra were measured on a Carl
Zeiss UR-20 instrument from solutions in chloroform.
The optical rotations were determined on a Perkin–
1
Elmer 241 polarimeter. The H, 13C, and 19F NMR
spectra were recorded on a Bruker Avance DRX 250
spectrometer at 250, 63, and 235 MHz, respectively,
1
13
using CDCl3 as solvent. The H and C NMR spectra
were also obtained on a Bruker DPX-300 instrument at
300 and 75 MHz, respectively. The chemical shifts are
given relative to tetramethylsilane (1H, 13C) or CFCl3
(19F). The mass spectra (electrospray ionization) were
obtained on a VGQuattro II mass spectrometer. Silica
gel (grain size 0.040–0.063 mm, Merck) was used for
flash chromatography. Analytical thin-layer chroma-
To conclude, we were the first to synthesize chiral
C-fluoroaziridines by reaction of fluorocarbene with
benzophenone imines derived from chiral amino acid
esters. We also demonstrated that chiral C-fluoroaziri-
dines can be used in asymmetric synthesis of fluorinat-
ed prop-2-yn-1-amines via reaction with potassium
arylethynylborates in the presence of boron trifluoride–
ether complex.
Table 2. Asymmetric synthesis of prop-2-yn-1-amines from fluoroaziridines
Trifluoroborate
Yielda of X+XI, %
(ratio X:XI)b
Aziridine no.
Amine no.
R1
R2
Yield of X,a %
no.
Ia
Ib
Ia
Ia
Ib
IXa
IXa
IXb
IXc
IXc
Xa, XIa
Xb
H
3-MeO
3-MeO
H
43 (4.7:1)
35
18
35
–
Ph
H
Xc, XIc
Xd, XId
Xe
30 (4.2:1)
46 (3.4:1)
25
H
4-Et
28
25
Ph
4-Et
a
Preparative yield.
Ratio of isomers isolated by flash chromatography.
b
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

MONOFLUORINATED AZIRIDINES IN ASYMMETRIC SYNTHESIS
981
itate was washed thrice with a mixture of 10 ml of
methylene chloride and 20 ml of diethyl ether. The
organic phase was combined with the washings,
washed with water (3 ×40 ml), dried over sodium
sulfate, and filtered, and the solvent was removed
under reduced pressure. Recrystallization of the
residue from diethyl ether gave 503 mg (45%) of
methyl (2S,3′R)-2-(3-fluoro-2,2-diphenylaziridin-1-yl)-
propanoate (Ia) as colorless crystals with mp 166–
168°C, [α]D25 = +160° (c = 2.0, CH2Cl2). IR spectrum
(film), ν, cm–1: 3068, 2980, 2956, 1742 (C=O), 1603,
1496, 1447, 1397, 1300, 1208, 1190, 1175, 1056, 993,
tography was performed on glass plates (Merck)
coated with a 0.2-mm layer of silica gel containing
a 60F254 ultraviolet indicator. The melting points were
measured on a Buchi Melting Point B540 or Boetius
apparatus; uncorrected values are given. The elemental
compositions were determined on a Hewlett–Packard
HP-185B CHN analyzer. Methylene chloride was dis-
tilled over calcium hydride; boron trifluoride–ether
complex was distilled under reduced pressure prior to
use. Tetrabutylammonium bromide (VI) was dried in
a desiccator over P2O5. Dibromofluoromethane [47],
Schiff bases III [39, 40], potassium trifluoroborates IX
[48, 49], and active lead [50] were prepared according
to known procedures. Commercially available chem-
icals were used without preliminary purification, un-
less otherwise stated.
1
939, 911, 859, 776, 754, 701, 663. H NMR spectrum
(250 MHz), δ, ppm: 1.53 d (3H, CH3C, J = 7.0 Hz),
2.60 q.d (1H, CHCH3, JHH = 7.0, JHF = 3.9 Hz), 3.68 s
(3H, CH3O), 5.38 d (1H, CHF, J = 78.2 Hz), 7.15–
7.45 m (8H, Harom), 7.55–7.75 m (2H, Harom). 13C NMR
spectrum (63 MHz), δC, ppm: 17.3 (CH3C), 51.9
(CH3O), 56.5 d (CH3C, J = 3.6 Hz), 56.9 d (C3, J =
14.0 Hz), 84.8 d (CF, J = 244.7 Hz), 127.2, 128.0,
128.5, 128.7, 128.8, 129.9 d (J = 2.2 Hz), 134.9 d (J =
The X-ray diffraction data for compounds Ia, Xa,
Xd, and Xe were acquired on a STOE IPDS II diffrac-
tometer (monochromatized MoKα irradiation, λ =
0.71073 Å). The complete sets of crystallographic
data, as well as CIF files, were deposited to the Cam-
bridge Crystallographic Data Centre (entry nos. CCDC
704880–704882, 705390) and are available from
CCDC, 12 Union Road, Cambridge CB2 1EZ, UK
(e - m a i l : d e p o s i t @ c c d c . c a m . a c . u k , h t t p ://
www.ccdc.cam.ac.uk/deposit).
19
4.2 Hz), 138.3 d (J = 3.6 Hz), 173.0 (C=O). F NMR
spectrum: δF –176.1 ppm, d (J = 78.2 Hz). Found, %:
C 72.51; H 6.21; N 4.75. C18H18FNO2. Calculated, %:
C 72.22; H 6.06; N 4.68. X-Ray diffraction data:
C18H18FNO2, M 299.33; orthorhombic crystal system,
space group P212121; unit cell parameters: a =
8.7709(18), b = 12.205(2), c = 14.539(3) Å; V =
1556.4(5) Å3; Z = 4, T = 133(2) K; F(000) = 632;
dcalc = 1.277 mg/m3; Rall = 0.0336, wR2 = 0.0812; total
number of reflections 20106 (2692 independent reflec-
tions with Rint = 0.0502).
Methyl (2S,3S)-2-(diphenylmethylideneamino)-
3-methylpentanoate (IIIc). Yield 53%, colorless crys-
tals, mp 67–69°C, [α]D25 = –158.3° (c = 1.03, CHCl3).
1H NMR spectrum (300 MHz), δ, ppm: 0.75–0.95 m
(6H, CH3C), 1.15–1.35 m (1H, CH2), 1.50–1.70 m
(1H, CH2), 2.05–2.30 m (1H, CHC), 3.74 s (3H,
CH3O), 3.94 d (1H, CHN, J = 16.2 Hz), 7.05–7.15 m
(2H, Harom), 7.30–7.60 m (6H, Harom), 7.60–7.80 m
In addition, 67 mg (6%) of a mixture of (2S,3′S)-
and (2S,3′R)-2-(3-fluoro-2,2-diphenylaziridin-1-yl)-
propanoates Ia and IIa at a ratio of 1.8:1 was isolated
as colorless crystals with mp 105–145°C (decomp.).
13
(2H, Harom). C NMR spectrum (75 MHz, CDCl3), δC,
ppm: 11.5 (CH3), 15.8 (CH3), 25.2 (CH2), 39.1 (CHC),
51.8 (CH3O), 70.9 (CHN), 127.9, 128.0, 128.4, 128.5,
128.8, 130.2, 136.4, 139.7, 170.4 (C=N), 172.7 (C=O).
Found, %: C 77.80; H 7.68; N 4.65. C20H23NO2. Cal-
culated, %: C 77.64; H 7.49; N 4.53.
Methyl (2S,3′S)-2-(3-fluoro-2,2-diphenylaziridin-
1-yl)propanoate (IIa). 1H NMR spectrum (250 MHz),
δ, ppm: 1.35 d (3H, CH3C, J = 6.7 Hz), 2.70 q.d (1H,
CHMe, JHH = 6.7, JHF = 4.0 Hz), 3.77 s (3H, CH3O),
5.69 d (1H, CHF, J = 77.1 Hz), 7.10–7.40 m (10H,
Harom). 13C NMR spectrum (63 MHz), δC, ppm: 17.6
(CH3C), 52.3 (CH3O), 55.5 d (C3, J = 14.0 Hz), 55.7 d
(CHCH3, J = 3.4 Hz), 85.5 d (CHF, J = 244.4 Hz),
127.4, 127.99, 128.65, 128.67, 128.85, 130.3 d (J =
2.3 Hz), 134.2 d (J = 4.1 Hz), 138.1 d (J = 3.3 Hz),
172. 6 d (J = 0. 8 Hz). 19F NMR spectrum:
δF –176.5 ppm, d (J = 77.1 Hz).
Methyl 2-(3-fluoro-2,2-diphenylaziridin-1-yl)-
propanoates Ia and IIa. A mixture of 1.006 g
(3.8 mmol) of methyl (S)-2-(diphenylmethylidene-
amino)propanoate (IIIa), 3.62 g (18.8 mmol) of di-
bromofluoromethane, 3.12 g (15.1 mmol) of active
lead, and 4.87 g (15.1 mmol) of tetrabutylammonium
bromide (VI) in 15 ml of methylene chloride was
subjected to ultrasonic treatment for 59 h at 20–40°C.
The mixture was diluted with diethyl ether (30 ml), the
organic layer was separated, and the inorganic precip-
Methyl 2-(3-fluoro-2,2-diphenylaziridin-1-yl)-3-
phenylpropanoates Ib and IIb. A mixture of 2.375 g
(6.9 mmol) of methyl (S)-2-(diphenylmethylidene-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

KONEV et al.
982
were combined and evaporated under reduced pres-
sure, and the residual solvent was removed in a high
vacuum. According to the H NMR data, the residue
amino)-3-phenylpropanoate (IIIb), 6.37 g (33.2 mmol)
of dibromofluoromethane, 5.71 g (27.6 mmol) of
active lead, and 8.91 g (27.6 mmol) of quaternary
ammonium salt VI in 15 ml of methylene chloride was
subjected to ultrasonic treatment for 77 h at 20–40°C.
The mixture was then treated as described above. By
chromatographic purification of the crude product we
isolated 573 mg (22%) of methyl (2S,3′R)-2-(3-fluoro-
2,2-diphenylaziridin-1-yl)-3-phenylpropanoate (Ib) as
colorless crystals with mp 120–121°C, [α]D25 = +166.2°
(c = 2.0, CH2Cl2). IR spectrum (film), ν, cm–1: 3027,
2950, 2864, 1739, 1731 (C=O), 1603, 1493, 1447,
1435, 1401, 1309, 1204, 1175, 1150, 1076, 1037,
1
contained diastereoisomeric aziridines (2S,3S,3′R)-Ic
and (2S,3S,3′S)-IIc and initial Schiff base IIIc at
a ratio of 1.1:1.0:5.2. The ratio of compounds Ic and
IIc was 1.2:1 (19F NMR data). The main part of the
reaction mixture was treated as described above.
Recrystallization of the crude product from hexane–
diethyl ether gave 74 mg of aziridine Ic as colorless
crystals. The filtrate was subjected to chromatography
to isolate an additional portion, 23 mg, of Ic. Overall
yield 97 mg (6%).
1
1012, 950, 913, 851, 751, 697. H NMR spectrum
Methyl (2S,3S,3′R)-2-(3-fluoro-2,2-diphenylaziri-
din-1-yl)-3-methylpentanoate (Ic). mp 134–135°C,
[α]D25 = +174.8° (c = 1.10, CHCl3). IR spectrum
(CHCl3), ν, cm–1: 3045, 2970, 2880, 1750 (C=O),
1540, 1500, 1450, 1400, 1310, 1300–1120, 1080,
(250 MHz), δ, ppm: 2.79 m (1H, CHN), 3.22 m (2H,
CH2), 3.58 s (3H, CH3O), 4.93 d (1H, CHF, J =
76.8 Hz), 7.00–7.15 m (2H, Harom), 7.15–7.45 m (11H,
Harom), 7.45–7.7 m (2H, Harom). 13C NMR spectrum
(63 MHz), δC, ppm: 39.2 (CH2), 51.7 (CH3), 55.0 d
(C3, J = 13.8 Hz), 63.3 d (C2, J = 3.9 Hz), 84.8 d (CF,
J = 244.9 Hz), 126.9, 127.2, 127.9, 128.46, 128.49,
128.5, 128.9, 129.5, 129.9 d (J = 2.1 Hz), 134.7 d (J =
4.1 Hz), 136.69, 138.2 d (J = 3.3 Hz), 171.94 d (C=O,
J = 1.3 Hz). 19F NMR spectrum: δF –175.2 ppm, d
(J = 76.8 Hz). Found, %: C 76.35; H 5.85; N 3.66.
C24H22FNO2. Calculated, %: C 76.78; H 5.91; N 3.73.
1
1040, 1020. H NMR spectrum (300 MHz), δ, ppm:
0.92 t (3H, CH3CH2, J = 7.4 Hz), 1.13 d (3H, CH3CH,
J = 6.9 Hz), 1.41 m (1H, CH2), 1.56 m (1H, CH2),
1.97 m (1H, CHCH3), 2.55 pseudotriplet (1H, CHN,
J = 3.3 Hz), 3.57 s (3H, CH3O), 5.42 d (1H, CHF, J =
78 Hz), 7.10–7.25 m (2H, Harom), 7.25–7.45 m (6H,
H
arom), 7.60–7.70 m (2H, Harom). 13C NMR spectrum
(75 MHz), δC, ppm: 11.8 (CH3), 15.7 (CH3), 25.9
(CH2), 39.0 (CHCH3), 51.3 (CH3O), 54.8 d (C2, J =
14.0 Hz), 66.2 d (C2, J = 4.0 Hz), 85.9 d (CF, J =
244.1 Hz), 127.2, 127.9, 128.4, 129.1, 130.0 d (J =
2.2 Hz), 134.9 d (J = 4.2 Hz), 138.4 d (J = 3.2 Hz),
171.7 (C=O). 19F NMR spectrum: δF –172.80 ppm, d
(J = 78 Hz). Found, %: C 73.94; H 7.07; N 4.22.
C21H24FNO2. Calculated, %: C 73.88; H 7.09; N 4.10.
In addition, 328 mg (13%) of a mixture of aziri-
dines Ib and IIb at a ratio of 1:1.5 was isolated.
Methyl (2S,3′S)-2-(3-fluoro-2,2-diphenylaziridin-
1
1-yl)-3-phenylpropanoate (IIb). H NMR spectrum
(250 MHz), δ, ppm: 2.92 m (2H, CHN, CH2), 3.21 m
(1H, CH2), 3.62 s (3H, CH3O), 5.73 d (1H, CHF, J =
77.4 Hz), 6.7–6.9 m (2H, Harom), 7.00–7.50 m (13H,
Harom). 13C NMR spectrum (63 MHz), δC, ppm: 38.3
(CH2), 52.1 (CH3), 56.1 d (C3, J = 14.0 Hz), 62.6 d
(C2, J = 3.1 Hz), 84.9 d (CF, J = 245.1 Hz), 126.5,
127.5, 127.9, 128.2, 128.75, 128.79, 128.95, 129.2,
130.6 d (J = 2.1 Hz), 134.0 d (J = 4.1 Hz), 136.72,
137.8 d (J = 3.3 Hz), 171.3 d (C=O, J = 1.2 Hz).
19F NMR spectrum: δF –176.9 ppm, d (J = 77.4 Hz).
The NMR spectral data for methyl (2S,3S,3′S)-2-(3-
fluoro-2,2-diphenylaziridin-1-yl)-3-methylpentanoate
(IIc) were obtained by analysis of the spectra of a mix-
ture of IIc and IIIc. 1H NMR spectrum, (250 MHz), δ,
ppm: 0.67 t (3H, CH3CH2, J = 7.3 Hz), 1.11 d (3H,
CH3CH, J = 7.3 Hz), 1.77 m (1H, CHCH3),
2.85 pseudotriplet (1H, CHN, J = 4.4 Hz), 3.57 (3H,
CH3O), 5.67 d (1H, CHF, J = 79 Hz), signals from the
CH2 group and aromatic protons were overlapped by
those of the initial Schiff base. 19F NMR spectrum:
δF –172.75 ppm, d (J = 79 Hz).
Methyl 2-(3-fluoro-2,2-diphenylaziridin-1-yl)-3-
methylpentanoates Ic and IIc. A mixture of 1.403 g
(4.5 mmol) of compound IIIc, 4.36 g (22.7 mmol) of
dibromofluoromethane, 3.759 g (18.2 mmol) of active
lead, and 5.865 g (18.2 mmol) of tetrabutylammonium
bromide (VI) in 20 ml of methylene chloride was
subjected to ultrasonic treatment for 108 h at 20–40°C.
A 0.2-ml sample of the reaction mixture was extracted
with three portions of a mixture of 0.5 ml of diethyl
ether and 0.2 ml of methylene chloride, the extracts
Methyl (S)-2-[(2-fluoro-2,2-diphenylethylidene)-
amino]propanoate (VIIIa). A mixture of 10 mg
(0.03 mmol) of aziridine Ia and 2 mg (0.01 mmol) of
antimony(III) fluoride in methylene chloride was
heated for 3 h under reflux. The mixture was cooled
and filtered from SbF3, and the filtrate was concen-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

MONOFLUORINATED AZIRIDINES IN ASYMMETRIC SYNTHESIS
983
trated under reduced pressure. The residue was Schiff
base VIIIa as an orange oily substance with a purity of
~93% (1H NMR); it was used in further synthesis
amine Xa as colorless crystals with mp 57–58°C,
[α]D25 = +12.8° (c = 1.0, CH2Cl2). IR spectrum (film), ν,
cm–1: 3340, 3328 (NH), 3058, 2967, 2938, 2835, 1721
(C=O), 1604, 1573, 1483, 1451, 1433, 1372, 1309,
1289, 1198, 1159, 1131, 1050, 970, 877, 852, 781, 757,
1
without additional purification. H NMR spectrum
(250 MHz), δ, ppm: 1.48 d (3H, CH3C, J = 6.8 Hz),
3.73 s (3H, CH3O), 4.14 q (1H, CHCH3, J = 6.8 Hz),
7.0–7.6 m (10H, Harom), 8.15 d (1H, CH=N, J =
10.6 Hz). 13C NMR spectrum (63 MHz), δC, ppm: 18.6
(CH3C), 52.1 (CH3O), 67.0 (CH), 97.9 d (CF, J =
175.9 Hz), 127.1 d (J = 6.9 Hz), 127.2 d (J = 6.7 Hz),
128.19, 128.24, 128.5 d (J = 2.0 Hz), 139.3 d (J =
22.5 Hz), 139.4 d (J = 22.6 Hz), 168.6 d (C=N,
J = 32.1 Hz), 172.1 (C=O). 19F NMR spectrum:
δF –142.0 ppm, d (J = 10.6 Hz).
1
742, 703, 689. H NMR spectrum (250 MHz), δ, ppm:
1.21 d (3H, CH3C, J = 6.9 Hz), 2.1 br.s (NH), 3.53 q
(1H, CH3CH, J = 6.9 Hz), 3.58 s (3H, CH3OC6H4),
3.68 s (3H, CH3OCO), 4.50 d (1H, CFCH, J =
17.9 Hz), 6.50–6.90 m (3H, Harom), 7.0–7.15 m (1H,
H
H
arom), 7.15–7.35 m (6H, Harom), 7.35–7.50 m (2H,
arom), 7.50–7.70 m (2H, Harom). 13C NMR spectrum
(63 MHz), δC, ppm: 18.5 (CH3CH), 51.9 (CH3CH),
55.2 (CH3O), 55.3 (CH3O), 57.0 d (CFCH, J =
26.2 Hz), 86.2 d (C6H4C≡C, J = 5.9 Hz), 87.0 d
(C6H4C≡C, J = 0.9 Hz), 99.7 d (CF, J = 183.6 Hz),
114.7, 116.5, 123.69, 123.99, 126.3 d (J = 8.8 Hz),
126.6 d (J = 7.8 Hz), 127.9 m (6C), 129.2, 140.8 d (J =
23.0 Hz), 141.0 d (J = 22.9 Hz), 159.1, 175.4 (C=O).
19F NMR spectrum: δF –151.8 ppm, d (J = 17.9 Hz).
Found, %: C 75.27; H 6.17; N 3.28. C27H26FNO3. Cal-
culated, %: C 75.15; H 6.07; N 3.25. X-Ray diffraction
data: C27H26FNO3, M 431.49; triclinic crystal system,
space group P1; unit cell parameters: a = 6.2062(3),
b = 8.8691(4), c = 21.3492(11) Å; α = 92.524(4)°, β =
97.993(4)°, γ = 91.494(4)°; V = 1161.97(10) Å3; Z = 2;
T = 133(2) K; F(000) = 456; dcalc = 1.233 mg/mm3;
Rall = 0.0710, wR2 = 0.2005; total number of reflections
9920 (7046 independent reflections with Rint = 0.0568).
Methyl (S)-2-[(2-fluoro-2,2-diphenylethylidene)-
amino]-3-phenylpropanoate (VIIIb). A mixture of
12 mg (0.03 mmol) of aziridine Ib and 2 mg
(0.01 mmol) of SbF3 in methylene chloride was heated
for 3 h under reflux. The mixture was cooled and
filtered from SbF3, and the filtrate was concentrated
under reduced pressure. The orange oily residue was
Schiff base VIIIb which was sufficiently pure (~94%)
1
for use in further synthesis. H NMR spectrum
(250 MHz), δ, ppm: 3.05 d.d (1H, CH2, J = 13.7,
10.0 Hz), 3.28 d.d (1H, CH2, J = 13.7, 4.0 Hz), 3.67 s
(3H, CH3O), 4.09 d.d (1H, CH, J = 10.0, 4.0 Hz),
6.70–7.60 m (15H, Harom), 7.72 d (1H, CH=N, J =
19
10.7 Hz). F NMR spectrum: δF –142.4 ppm, d (J =
10.7 Hz).
Amines Xa–Xe and XIa–XIe (general procedure).
A mixture of 0.4 mmol of aziridine Ia or Ib and
0.4 mmol of potassium alkynyltrifluoroborate IXa–
IXc in 8 ml of methylene chloride was cooled to
–20°C, a solution of 0.4 mol of BF3·Et2O in 4 ml of
methylene chloride was added dropwise under stirring
in a nitrogen atmosphere, and the mixture was stirred
for 5 h at –20°C and hydrolyzed with 10 ml of water.
The organic phase was separated, the aqueous phase
was extracted with methylene chloride (3×10 ml), the
extracts were combined with the organic phase, dried
over Na2SO4, and filtered, and the solvent was
removed under reduced pressure. The residue was
purified by column chromatography on silica gel using
hexane–diethyl ether as eluent.
The data for compound XIa were derived from
the spectra of its mixture with diastereoisomer Xa.
1H NMR spectrum (250 MHz), δ, ppm: 1.24 d (3H,
CH3C, J = 7.3 Hz), 2.1 br.s (NH, Xa + XIa), 3.64 s
(3H, CH3OC6H4), 3.67* s (CH3OCO), 3.83 q (1H,
CH3CH, J = 7.3 Hz), 4.71 d (1H, CFCH, J = 19.5 Hz).
13C NMR spectrum (63 MHz), δC, ppm: 19.3 (CH3CH),
51.8 (CH3CH), 55.2* (CH3O), 55.3* (CH3O), 56.6 d
(CFCH, J = 24.8 Hz), 85.6 d (C6H4C≡C, J = 5.0 Hz),
87.2 d (C6H4C≡C, J = 0.7 Hz), 99.7* d (CF, J =
183.6 Hz), 114.7*, 116.4* (Carom), 123.68, 124.02,
126.3* d (J = 8.8 Hz), 126.5 d (J = 8.3 Hz), 127.87 d
(J = 1.1 Hz), 128.06 d (J = 1.7 Hz), 128.1 d (J =
0.7 Hz), 129.2*, 140.4 d (J = 22.9 Hz), 141.1 d (J =
23.2 Hz), 159.1*, 175.5 (C=O). 19F NMR spectrum:
δF –154.7 ppm, br.s.
Methyl (2S,1′S)- and (2S,1′R)-2-[1-fluoro(di-
phenyl)methyl-3-(3-methoxyphenyl)prop-2-yn-1-yl-
amino]propanoates Xa and XIa. A mixture of amines
Xa and XIa at a ratio of 4.7 :1 was obtained from
120 mg (0.4 mmol) of aziridine Ia and 96 mg
(0.4 mmol) of compound IXa. Yield 75 mg (43%).
Recrystallization of that mixture gave 31 mg (18%) of
Methyl (2S,1′S)-2-[1-fluoro(diphenyl)methyl)-3-
(3-methoxyphenyl)prop-2-yn-1-ylamino]-3-phenyl-
propanoate (Xb) was synthesized from 112 mg
* Hereinafter, signals from protons or carbon atoms overlapped by
those of the other stereoisomer are marked with an asterisk.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

KONEV et al.
984
19
(0.3 mmol) of aziridine Ib and 71 mg (0.3 mmol) of
compound IXa. Yield 53 mg (35%), mp 93–94°C;
[α]D25 = +79.1° (c = 1.0, CH2Cl2). IR spectrum (film), ν,
cm–1: 3342 (NH), 3060, 3023, 2941, 1725 (C=O),
1603, 1573, 1479, 1451, 1434, 1288, 1199, 1162,
nals of amine Xc. F NMR spectrum: δF –154.6 ppm,
d (J = 19.4 Hz).
Methyl (2S,1′S)- and (2S,1′R)-2-{3-(4-ethyl-
phenyl)-1-[fluoro(diphenyl)methyl]prop-2-yn-1-yl-
amino}propanoates Xd and XId (mixture of dia-
stereoisomers at a ratio of 3.4:1) were synthesized
from 120 mg (0.4 mmol) of aziridine Ia and 95 mg
(0.4 mmol) of compound IXc. Yield 80 mg (46%).
Recrystallization of the mixture gave 48 mg (28%) of
isomer Xd as colorless crystals with mp 103–104°C;
[α]D25 = +12.4° (c = 0.9, CH2Cl2). IR spectrum (film), ν,
cm–1: 3332 (NH), 3059, 3027, 2967, 2928, 2864, 1719
(C=O), 1599, 1510, 1495, 1451, 1433, 1372, 1314,
1283, 1206, 1160, 1121, 1058, 970, 908, 832, 796,
1
1040, 998, 966, 873, 779, 754, 737, 701. H NMR
spectrum (250 MHz), δ, ppm: 2.2 br.s (1H, NH),
2.78 d.d (1H, CH2, J = 13.6, 8.0 Hz), 2.90 d.d (1H,
CH2, J = 13.6, 5.5 Hz), 3.57 s (3H, CH3O), 3.69 d.d
(1H, 2-H, J = 5.5, 8.0 Hz), 3.75 s (3H, CH3O), 4.44 d
(1H, CFCH, J = 18.5 Hz), 6.6–6.9 m (3H, Harom), 7.0–
13
7.5 m (16H, Harom). C NMR spectrum (63 MHz), δC,
ppm: 39.9 (CH2), 51.8 (C2), 55.2 (CH3O), 57.8 d
(CFCH, J = 25.4 Hz), 62.2 (CH3O), 86.3 d (C6H4C≡C,
J = 4.9 Hz), 86.9 d (C6H4C≡C, J = 0.8 Hz), 99.7 d (CF,
J = 183.8 Hz), 114.7, 116.4, 123.7, 124.0, 126.1 d (J =
8.7 Hz), 126.4, 126.5 d (J = 8.1 Hz), 127.8 d (2C, J =
1.6 Hz), 127.87 d (4C, J = 0.8 Hz), 128.2, 129.1,
129.4, 137.6, 140.6 d (J = 23.1 Hz), 141.1 d (J =
22.8 Hz), 159.1, 174.8 (C=O). 19F NMR spectrum:
δF –153.1 ppm, br.s. Found, %: C 78.17; H 6.00;
N 2.67. C33H30FNO3. Calculated, %: C 78.08; H 5.96;
N 2.76.
1
741. H NMR spectrum (250 MHz), δ, ppm: 1.19 t
(3H, CH3CH2, J = 7.6 Hz), 1.28 d (3H, CH3CH, J =
6.9 Hz), 2.17 br.s (NH), 2.60 q (2H, CH3CH2, J =
7.6 Hz), 3.61 q (1H, CH3CH, J = 6.9 Hz), 3.64 s (3H,
CH3O), 4.56 d (1H, CFCH, J = 17.5 Hz), 7.06 pseudo-
doublet (2H, Harom, J = 8.3 Hz), 7.15 pseudodoublet
(2H, Harom, J = 8.3 Hz), 7.20–7.40 m (6H, Harom), 7.40–
7.55 m (2H, Harom), 7.55–7.65 m (2H, Harom). 13C NMR
spectrum (63 MHz), δC, ppm: 15.32 (CH3CH2), 18.5
(CH3CH), 28.7 (CH3CH2), 51.9 (CH3CH), 55.2
(CH3O), 57.0 d (CFCH, J = 26.2 Hz), 85.5 d
(C6H4C≡C, J = 6.0 Hz), 87.2 d (C6H4C≡C, J =
0.9 Hz), 99.7 d (CF, J = 183.6 Hz), 119.9, 126.3 d (J =
8.7 Hz), 126.6 d (J = 7.8 Hz), 127.7, 127.87–127.94 m
(6C), 131.47, 140.89 d (J = 23.0 Hz), 140.93 d (J =
23.0 Hz), 144.58, 175.4 (C=O). 19F NMR spectrum:
δF –151.3 ppm, d (J = 17.5 Hz). Found, %: C 78.56;
H 6.62; N 3.22. C28H28FNO2. Calculated, %: C 78.30;
H 6.57; N 3.26. X-Ray diffraction data: C28H28FNO2,
M 429.51; monoclinic crystal system, space group
P21; unit cell parameters: a = 8.9901(7), b = 6.1408(6),
c = 21.413(2) Ǻ; β = 93.696(7)°; V = 1179.65(18) Å3;
Z = 2; T = 133(2) K; F(000) = 456; dcalc = 1.209 mg×
mm–3; Rall = 0.1817, wR2 = 0.1784; total number of
reflections 14133 (4562 independent reflections with
Rint = 0.1661).
Methyl (2S,1′S)- and (2S,1′R)-2-[1-fluoro(di-
phenyl)methyl-3-phenylprop-2-yn-1-ylamino]pro-
panoates Xc and XIc (mixture of diastereoisomers at
a ratio of 4.2:1) were synthesized from 120 mg
(0.4 mmol) of aziridine Ia and 83 mg (0.4 mmol) of
compound IXb. Yield 49 mg (30%), mp 87–88°C. IR
spectrum (film), ν, cm–1: 3332 (NH), 3059, 2967,
1741, 1720 (C=O), 1598, 1491, 1451, 1313, 1205,
1158, 1121, 1058, 970, 910.
1
Compound Xc. H NMR spectrum (250 MHz), δ,
ppm: 1.29 d (3H, CH3CH, J = 6.9 Hz), 1.70 br.s (NH),
3.61 q (1H, CH3CH, J = 6.9 Hz), 3.65 s (3H, CH3O),
4.58 d (1H, CFCH, J = 17.8 Hz), 7.10–7.70 m (15H,
Harom). 13C NMR spectrum (63 MHz), δC, ppm: 19.3
(CH3CH), 51.9 (CH3CH), 55.2 (CH3O), 57.0 d
(CFCH, J = 26.2 Hz), 86.3 d (PhC≡C, J = 5.8 Hz),
87.1 d (PhC≡C, J = 0.9 Hz), 99.7 d (CF, J = 183.7 Hz),
122.7, 126.2 d (J = 8.8 Hz), 126.5 d (J = 7.8 Hz),
127.84–127.95 m (6C), 128.09, 128.15, 131.5, 140.8 d
(J = 23.0 Hz), 140.9 d (J = 22.7 Hz), 175.3 (C=O).
19F NMR spectrum: δF –151.7 ppm, d (J = 17.8 Hz).
Found, %: C 77.85; H 6.21; N 3.36. C26H24FNO2. Cal-
culated, %: C 77.78; H 6.03; N 3.49.
The data for amine XId were derived from the
spectra of its mixture with Xd. H NMR spectrum
1
(250 MHz), δ, ppm: 1.30 t (3H, CH3CH2, J = 7.3 Hz),
the CH3CH signal was overlapped by the CH3CH2
signal of Xd, 1.55 br.s (NH, Xd + XId, H2O], 2.60* q
(2H, CH3CH2, J = 7.3 Hz), 3.72 s (3H, CH3O), 3.91 q
(1H, CH3CH, J = 7.0 Hz), 4.77* d (1H, CFCH, J =
19.3 Hz), 13C NMR spectrum (63 MHz), δC, ppm:
15.33 (CH3CH2), 19.3 (CH3CH), 28.8* (CH3CH2),
51.8 (CH3CH), 54.0 (CH3O), 56.7 d (CFCH, J =
24.9 Hz), 84.9 d (C6H4C≡C, J = 5.2 Hz), 87.4 d
1
Compound XIc. H NMR spectrum (250 MHz), δ,
ppm: 1.32 d (3H, CH3CH, J = 7.0 Hz), 3.72 s (3H,
CH3O), 3.91 q (1H, CH3CH, J = 7.0 Hz), 4.79 d (1H,
CFCH, J = 19.4 Hz); signals from the NH and aromat-
ic protons were overlapped by the corresponding sig-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 7 2010

MONOFLUORINATED AZIRIDINES IN ASYMMETRIC SYNTHESIS
985
(C6H4C≡C, J = 0.7 Hz), 99.7 d (CF, J = 184.8 Hz),
119.9,* 126.3* (J = 8.6 Hz), 126.5 d (J = 8.2 Hz),
127.7,* 127.83 (3C), 128.01 d (J = 1.8 Hz), 128.06
(2C), 131.49, 140.5 d (J = 22.9 Hz), 141.1 d (J =
23.1 Hz), 144.61, 175.6 (C=O). 19F NMR spectrum:
δF –154.3 ppm, d (J = 19.3 Hz).
room temperature and hydrolyzed with 15 ml of water.
The organic phase was separated, the aqueous phase
was extracted with methylene chloride (3×6 ml), the
extracts were combined with the organic phase, dried
over Na2SO4, and filtered, the solvent was removed
under reduced pressure, and the residue was subjected
to flash chromatography on silica gel using hexane–
diethyl ether as eluent to isolate 37 mg (17%) of
a 6.2:1.0 mixture of diastereoisomeric compounds Xa
and XIa and 37 mg (26%) of indole XII.
Methyl (2S,1′S)-2-{3-(4-ethylphenyl)-1-[fluoro-
(diphenyl)methyl]prop-2-yn-1-ylamino}-3-phenyl-
propanoate (Xe) was synthesized from 112 mg
(0.3 mmol) of aziridine Ib and 71 mg (0.3 mmol) of
compound IXc. Yield 37 mg (25%), mp 133–135°C,
[α]D25 = +80.3° (c = 1.0, CH2Cl2). IR spectrum (film), ν,
cm–1: 3350 (NH), 3059, 3024, 2971, 2931, 2863, 1725
(C=O), 1601, 1494, 1451, 1279, 1198, 1176, 1060,
Methyl (S)-2-(3-phenyl-1H-indol-1-yl)propano-
ate (XII). Yellow oily substance. IR spectrum (film), ν,
cm–1: 3028, 2950, 1739 (C=O), 1601, 1549, 1461,
1397, 1372, 1305, 1197, 1173, 1099, 1049, 961,
1
1
998, 958, 906, 832, 796, 740, 699. H NMR spectrum
910, 851, 767, 740, 698, 694. H NMR spectrum
(250 MHz), δ, ppm: 1.19 t (3H, CH3CH2, J = 7.6 Hz),
2.17 br.s (NH), 2.60 q (2H, CH3CH2, J = 7.6 Hz),
2.78 d.d (1H, CH2, J = 13.6, 7.9 Hz), 2.89 d.d (1H,
CH2, J = 13.6, 5.6 Hz), 3.57 s (3H, CH3O), 3.70 m
(1H, CHCO2Me), 4.44 d (1H, CFCH, J = 17.9 Hz),
6.90–7.60 m (19H, Harom). 13C NMR spectrum
(63 MHz), δC, ppm: 15.3 (CH3CH2), 28.7 (CH3CH2),
39.9 (CH2Ph), 51.8 (CHCO2Me), 57.9 d (CFCH, J =
25.5 Hz), 62.3 (CH3O), 85.7 d (C6H4C≡C, J = 5.1 Hz),
87.1 d (C6H4C≡C, J = 0.8 Hz), 99.7 d (CF, J =
183.8 Hz), 119.9, 126.1 d (J = 8.7 Hz), 126.4, 126.5 d
(J = 8.0 Hz), 127.6, 127.8 d (2C, J = 1.6 Hz), 127.9
(4C), 128.2, 129.4, 131.5, 137.7, 140.7 d (J =
23.1 Hz), 141.1 d (J = 22.8 Hz), 144.5, 174.8 (C=O).
19F NMR spectrum: δF –152.8 ppm, d (J = 17.9 Hz).
Found, %: C 80.59; H 6.46; N 2.60. C34H32FNO2. Cal-
culated, %: C 80.76; H 6.38; N 2.77. X-Ray diffraction
data: C34H32FNO2, M 505.61; monoclinic crystals,
space group P21; unit cell parameters: a = 9.3098(7),
b = 5.9421(5), c = 25.298(2) Å; β = 94.239(6)°; V =
1395.7(2) Å3; Z = 2; T = 133(2) K; F(000) = 536;
dcalc = 1.203 mg/mm3; Rall = 0.1049, wR2 = 0.1786;
total number of reflections 11713 (5294 independent
reflections with Rint = 0.1075).
(250 MHz), δ, ppm: 1.86 d (3H, CH3C, J = 7.3 Hz),
3.72 s (CH3O), 5.20 q (1H, CH3CH, J = 7.3 Hz), 7.10–
7.50 m (7H, Harom), 7.60–7.75 m (2H, Harom), 7.90–
13
8.00 m (1H, Harom). C NMR spectrum (63 MHz), δC,
ppm: 17.6 (CH3C), 52.6 (CH3O), 53.5 (CHN), 109.4,
118.1, 120.1, 120.4, 122.3, 122.8, 125.9, 126.4, 127.5,
128.7, 135.3, 136.9, 171.6 (C=O). Mass spectrum, m/z
(Irel, %): 281 (16) [M + 2]+, 280 (100) [M + 1]+.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 08-03-00 112) and by the Government of Flanders
(Program for Bilateral Collaboration, grant no. 05-03-
34811). A.S. Konev is grateful to the St. Petersburg
Authorities for financial support.
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