N-Substituted α-trifluoromethyl β-nitro amines in the synthesis of fluorine-containing 1,2-diamines, amino alcohols, and β-amino acids

Article abstract of DOI:10.1007/s11172-009-0257-2

Reactions of 2-diazo-1,1,1-trifluoro-3-nitropropane or 1-trifluoromethyl-2- nitroethenes with amines and amino alcohols afforded N-mono- and N,N-disubstituted α-trifluoromethyl β-nitro amines, which were used to obtain a number of trifluoromethyl-containing 1,2-diamines, amino alcohols, and β-amino acids.

Full text of DOI:10.1007/s11172-009-0257-2

Russian Chemical Bulletin, International Edition, Vol. 58, No. 9, pp. 1886—1898, September, 2009
1886
NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines in the synthesis
of fluorineꢀcontaining 1,2ꢀdiamines, amino alcohols, and βꢀamino acids
V. Yu. Korotaev,a A. Yu. Barkov,b M. I. Kodess,b
I. B. Kutyashev,a P. A. Slepukhin,b and A. Ya. Zapevalovb
aA. M. Gorky Ural State University,
51 prosp. Lenina, 620083 Ekaterinburg, Russian Federation.
Fax: +7 (343) 261 5978. Eꢀmail: Vladislav.Korotaev@usu.ru
bI. Ya. Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences,
22/20 ul. S. Kovalevskoi, 620041 Ekaterinburg, Russian Federation.
Fax: +7 (343) 374 1189
Reactions of 2ꢀdiazoꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitropropane or 1ꢀtrifluoromethylꢀ2ꢀnitroethenes
with amines and amino alcohols afforded Nꢀmonoꢀ and N,Nꢀdisubstituted αꢀtrifluoromethyl
βꢀnitro amines, which were used to obtain a number of trifluoromethylꢀcontaining 1,2ꢀdiꢀ
amines, amino alcohols, and βꢀamino acids.
Key words: diazo compounds, nitroalkenes, organofluorine compounds, amines, amino
alcohols, βꢀamino acids, Xꢀray diffraction analysis.
It is known that βꢀnitro amines are widely used for
N,Nꢀdicarboxyethyl derivative of this diamine can serve
as a copperꢀselective complexone. In addition, it has
been demonstrated that 1ꢀtrifluoromethylꢀ1,2ꢀethyleneꢀ
diamines11,12 can successfully be employed for the synꢀ
thesis of potential biologically active fluoroquinolones12
and imidazolidines.13 In the present work, we studied the
methods of preparation and synthetic scope of Nꢀsubstiꢀ
tuted αꢀtrifluoromethyl βꢀnitro amines.
the synthesis of 1,2ꢀdiamines, amines, amino alcohols,
amino acids, and heterocyclic compounds with a number
of useful properties.1—4 However, their fluorineꢀcontainꢀ
ing analogs remain virtually uninvestigated.5 Earlier,6,7
Nꢀunsubstituted αꢀpolyfluoroalkyl βꢀnitro amines have
been obtained by condensation of fluorinated nitriles
with nitroalkanes followed by reduction of the reaction
products (βꢀnitro enamines) with the system NaBH4—
AcOH. However, this approach is unsuitable for the prepaꢀ
ration of βꢀnitro amines containing Nꢀalkyl and Nꢀaryl
substituents. For instance, reduction of Nꢀformylꢀ,
Nꢀacetylꢀ, and Nꢀphthalyl derivatives of 2ꢀaminoꢀ1,1,1ꢀ
trifluoroꢀ3ꢀnitropropane (prepared by treatment of the
latter with anhydrides or halides of the correspondꢀ
ing acids8) proceeded unambiguously to give complex
mixtures of unidentified products. Recently,9 a number of
αꢀtrifluoromethyl βꢀnitro amines have been obtained from
3,3,3ꢀtrifluoroꢀ1ꢀnitropropene; the reactivities of the
resulting amines have not been studied. With 1,1,1ꢀtrifluoroꢀ
3ꢀnitroꢀ2ꢀ(3ꢀtrifluoromethylphenyl)aminopropane as
an example, we have shown10 that fluorineꢀcontaining
βꢀnitro amines can be used for the synthesis of 1ꢀtriꢀ
fluoromethylꢀ1,2ꢀethylenediamines and their Nꢀmonoꢀ
or N,Nꢀdicarboxyethyl derivatives. We found that the
properties of the compounds obtained differ substantially
from those of nonfluorinated analogs. Since the stabilities
of their metal complexes, as well as the selectivities of
such ligands toward Cu2+ ions, become enhanced with
an increase in the number of Nꢀcarboxyethyl groups, a
Results and Discussion
For the synthesis of Nꢀsubstituted βꢀnitro amines, we
used 2ꢀdiazoꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitropropane (1) (prepared
by reduction of 2ꢀaminoꢀ3,3,3ꢀtrifluoroꢀ1ꢀnitropropene
with NaBH4 followed by diazotization of the resulting
saturated compound14) or fluorineꢀcontaining nitroꢀ
alkenes 2a,b prepared as individual stereoisomers in good
yields by dehydration of appropriate nitro alcohols in
the presence of P4O10 (see Refs 15, 16) (Scheme 1). The
transꢀconfiguration of compound 2a is evident from
3
1
the coupling constant JH,H = 13.5 Hz in its H NMR
spectrum. The H, 19F, and 13C NMR spectra of nitroꢀ
1
alkene 2b contain only one set of signals (see Experimenꢀ
1
tal). The signal for the Me group in the H NMR specꢀ
trum of compound 2b appears as a quartet of doublets
5
4
with JH,F = 2.0 Hz and JH,H = 1.2 Hz. The 19F NMR
spectrum shows a signal for the CF3 group at δF 102.92.
5
In the literature, δF 103.8 and 99.8 and JH,F = 2.1 and
2.0 Hz have been reported17 for the Zꢀ and Eꢀisomers of
2ꢀmethylꢀ3ꢀtrifluoromethylpentꢀ2ꢀenedinitrile, respecꢀ
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 1827—1838, September, 2009.
1066ꢀ5285/09/5809ꢀ1886 © 2009 Springer Science+Business Media, Inc.

NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1887
tively. However, all the above data are insufficient for
unambiguous conclusion about the configuration of comꢀ
pound 2b (Z or E).
distilled in vacuo, the R*,S*ꢀisomer was obtained, which
suggests its higher thermodynamic stability. Isolation of
all diastereomers 5 in the individual state was beyond the
scope of the present work.
Scheme 1
Scheme 3
Compound R1
R2
Compound
R1
R2
5
a
b
c
5
d
e
f
(CH2)5
(CH2)2O(CH2)2
Bn
H
H
H
Ph
3,4ꢀMe2C6H3
2ꢀMeOC6H4
H
Unlike documented18 fluorineꢀfree βꢀnitro amines,
compounds 4 and 5 form no stable hydrochlorides: when
treated with dry HCl, their solutions in benzene decompose
into the salt of the corresponding amine HNR1R2•HCl
(6) and nitroalkenes 2a,b. Partial deamination occurs
during distillation of nitro amines 4c—e and 5c—f in vacuo.
To determine the exact configuration of βꢀnitro amines
5a—f, we examined individual crystals of the most stable
isomer of nitro amine 5a by Xꢀray diffraction. This isomer
proved to have the R*,S*ꢀconfiguration. Structure 5a is in
the hindered conformation in which the H atoms at the
C(2) and C(3) atoms are antiperiplanar to each other
and the trifluoromethyl substituent is antiperiplanar with
respect to the nitro group (Fig. 1). The torsion angles
C(1)—C(2)—C(3)—C(4) and N(1)—C(2)—C(3)—N(2)
are 66.1° and 58.0°, respectively. The piperidine ring (in
the chair conformation) and the nitro group are in the
synclinal arrangement.
Reactions of diazo compound 1 (procedure A) or
nitroalkene 2a (procedure B) with amines in benzene gives
βꢀnitro amines 4 in moderate to high yields (Scheme 2).
Selected physicochemical characteristics of βꢀnitro amines
4 are given in Table 1. Nitroalkene 2a reacts with comꢀ
pounds 3a—j at ~20 °C, while diazoalkane 1 reacts with
less nucleophilic aromatic amines 3d—j at 60 °C.
Scheme 2
1
An analysis of the H NMR spectra of isomeric mixꢀ
tures of compounds 5a—f revealed differences between
the signals for each pair of diastereomers (see Table 2).
О(2)
Compounds R1
R2 Compounds R1
R2
3, 4
a
b
c
d
e
3, 4
О(1)
N(2)
C(3)
(CH2)5
(CH2)2O(CH2)2
f
g
h
i
H
H
H
H
H
3ꢀMeC6H4
3,4ꢀMe2C6H3
2,5ꢀMe2C6H3
2ꢀMeOC6H4
2ꢀClC6H4
H
Bn
Ph
Ph
C(5)
C(6)
H
C(4)
F(2)
Me
j
C(2)
Under the conditions of procedure B, reactions of
C(7)
N(1)
nitroalkene 2b with amines 3c,d,g,i proceed nonselectively
to give ~1 : 1 mixtures of the R*,S*ꢀ and R*,R*ꢀisomers of
compounds 5c—f. The major products from cyclic amines
3a,b are nitro amines 5a,b with the R*,S*ꢀconfiguration
(Scheme 3, Table 2). When a mixture of stereoisomers 5a
(30% R*,R*ꢀisomer) was kept at ~20 °C for 14 days or
C(9)
C(8)
C(1)
F(1)
F(3)
Fig. 1. General view of the structure of R*,S*ꢀisomer 5a.

1888
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Korotaev et al.
1
Table 1. H and 19F NMR and IR spectra of βꢀnitro amines 4a—j
Nitro
amine
NMR (СDCl3)
IR,
ν/cm–1
δH (J/Hz)
δF (J/Hz),
CF3 (d)
HX
HA
HB
R1
R2
[R1, R2]
4a
4b
4c
3.99 (dqd, 3JB,X
=
4.66 (dd,
4.50 (dd,
[1.46, 1.79 (both m, (CH2)3);
2.62, 2.90 (both m, CH2NCH2)]
94.46
1567, 1383
= 10.6, 3JH,F
=
2JA,B = 12.8, 2JA,B = 12.8,
(3JX,F = 8.3)
= 8.3, 3JA,X = 4.1)
4.01 (dqd, 3JB,X
3JA,X = 4.1)
3JB,X = 10.6)
4.55 (dd,
=
4.67 (dd,
[2.68, 2.97 (both m, CH2NCH2);
3.63 (m, CH2OCH2)]
94.32
(3JX,F = 8.1)
1565, 1382
= 10.7, 3JX,F
=
2JA,B = 13.0, 2JA,B = 13.0,
= 8.1, 3JA,X = 4.1)
3JA,X = 4.0)
3JB,X = 10.7)
4.46 (dd,
4.02 (m)
4.62 (dd,
1.76 (br.s, NH) 3.89, 4.05 (both d,
CH2Ph, 2J = 13.5);
88.55
(3JX,F = 7.0)
3424, 1603,
1564, 1523,
1500, 1453,
1379
2JA,B = 13.0, 2JA,B = 13.0,
3JA,X = 4.1)
3JB,X = 9.5)
7.37—7.26 (m, Ph)
4d
4.89 (m)
4.76 (dd,
4.58 (dd,
3.87 (br.s, NH) 6.76 (dd, Ho, 3J = 8.7,
1.1); 6.89 (tt, Hp, 3J =
86.96
(3JX,F = 6.6)
3395, 1622,
1605, 1566,
1519, 1499,
1430, 1381
1602, 1565,
1505, 1455,
1428, 1380
3392, 1611,
1562, 1493,
1329, 1381
2JA,B = 13.0, 2JA,B = 13.3,
3JA,X = 4.8)
3JB,X = 8.4)
= 7.4, 1.1); 7.24 (dd, Hm,
3J = 8.7, 7.4)
4e
4f
5.18 (dqd, 3JA,X
=
4.92 (dd,
4.72 (dd,
2.94 (q, NMe,
6.94−6.90 (m, Ho, Hp);
7.28 (dd, Hm, 3J = 8.9,
7.2)
91.94
(3JX,F = 7.6)
= 10.3, 3JX,F
=
2JA,B = 13.2, 2JA,B = 13.2, JH,F = 1.5)
5
= 7.6, 3JB,X = 4.1)
3JA,X = 10.3) 3JB,X = 4.1)
4.88 (ddqd,
4.75 (dd,
4.57 (dd,
3.82 (d, NH,
2.30 (s, Ме); 6.56 (dd,
86.92
(3JX,F = 6.5)
3JH ,NH = 10.6,
2JA,B = 13.3, 2JA,B = 13.3, 3JH ,NH = 10.6) H(6), J = 6.9, 2.3); 6.57
X
X
3JB,X = 8.2,
3JX,F = 6.5,
3JA,X = 4.9)
4.84 (ddqd,
3JA,X = 4.9)
3JB,X = 8.2)
(m, H(2)); 6.71 (dm, H(4),
3J = 7.5); 7.12 (dd, H(5),
3J = 7.5, 6.9)
4g*
4h
4i
4.74 (dd,
4.56 (dd,
3.71 (d, NH,
2.17 (s, Me); 2.21 (s, Ме);
86.99
3369, 1615,
3JH ,NH = 10.7,
2JA,B = 13.3, 2JA,B = 13.3, 3JH ,NH = 10.7) 6.52 (dd, H(6), 3J = 8.1,
(3JX,F = 6.5) 1557, 1507,
1450, 1423,
X
X
3JB,X = 8.2, 3JX,F
= 6.5, 3JA,X = 4.9)
4.92 (ddqd,
=
3JA,X = 4.9)
3JB,X = 8.2)
2.4); 6.56 (d, H(2), 3J = 2.4);
6.99 (d, H(5), 3J = 8.1)
1383
3420, 1620,
4.78 (dd,
4.62 (dd,
3.76 (d, NH,
2.15 (s, Me); 2.30 (s, Ме);
86.96
3JH ,NH = 10.6,
2JA,B = 13.3, 2JA,B = 13.3, 3JH ,NH = 10.6) 6.60 (s, H(6)); 6.63 (d,
(3JX,F = 6.5) 1588, 1564,
1534, 1460,
X
X
3JB,X = 8.0, 3JX,F
= 6.5, 3JA,X = 4.8)
4.90 (ddqd,
=
3JA,X = 4.8)
3JB,X = 8.0)
H(4), 3J = 7.5); 6.98 (d,
H(3), 3J = 7.5)
1431, 1380
3394, 1603,
4.77 (dd,
4.60 (dd,
4.57 (d, NH,
3.85 (s, OМе);
86.92
3JH ,NH = 10.6,
2JA,B = 13.4, 2JA,B = 13.4, 3JH ,NH = 10.8) 6.92—6.71 (m, Ar)
(3JX,F = 6.6) 1565, 1519,
1483, 1462,
X
X
3JB,X= 8.2, 3JX,F
=
3JA,X = 4.8)
3JB,X = 8.2)
= 6.6, 3JA,X = 4.9)
1435, 1380
3400, 1623,
4j
4.94 (ddqd,
4.82 (dd,
4.64 (dd,
4.62 (d, NH,
6.82 (ddd, H(4), 3J = 7.9,
86.75
3JH ,NH = 10.7,
2JA,B = 13.6, 2JA,B = 13.6, 3JH ,NH = 10.7) 7.5, 1.4); 6.89 (dd, H(6),
(3JX,F = 6.1) 1621, 1600,
1567, 1521,
X
X
3JB,X = 8.6,3JX,F
=
3JA,X = 4.4)
3JB,X = 8.6)
3J = 8.3, 1.4); 7.20 (ddd,
H(5), 3J = 8.3, 7.5, 1.4);
7.31 (dd, H(3), 3J = 7.9, 1.4)
= 6.4, 3JA,X = 4.4)
1487, 1468,
1430, 1380
*
13C NMR, δ : 18.58; 19.78; 55.30 (q, J = 30.7 Hz); 73.38; 111.71; 116.20; 124.29 (q, J = 284.0 Hz); 128.75; 130.49; 137.85; 142.34.
C
The spectra of the R*,S*ꢀisomers of compounds 5a—f
show a doublet quartets for the Me group. In the spectra
of the R*,R*ꢀisomers, the signal for this group appears as
a doublet (5a,b,f) or a doublet of quartets (5c—e) but with
amines 8—10 in 46—66% yields, depending on the synꢀ
thetic procedure (Scheme 4; Tables 3, 4). As in the aforeꢀ
said reactions with amines, compounds 7a,b react with
nitroalkene 2b to form stereoisomeric mixtures of prodꢀ
ucts. The optically active Sꢀ2ꢀaminopropanol (7c) reacts
nonselectively with compounds 1 and 2a even at –78 °C
in THF, giving products 10 with a diastereomer ratio
of 52 : 48.
the lower coupling constants 5JMe,CF
.
3
We also studied reactions of compounds 1 and 2a,b
with amino alcohols 7a—c. These reactions proceed
chemoselectively to give Nꢀ(2ꢀhydroxyalkyl) βꢀnitro

NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1889
1
Table 2. H and 19F NMR and IR spectra of βꢀnitro amines 5a—f
Nitro Content
NMR (СDCl3),
IR,
amine
of the
isomer
(%)a
ν/cm–1
δ
H (J/Hz)
δ
F (J/Hz),
CHCF3
CHNO2
Me
R1
R2
CF3
[R1, R2]
R*,S*ꢀ5a 70 3.56 (dq,
4.91 (dq,
1.62 (dq, 3J =
[1.36—1.52 (m, (CH2)3);
98.52 (dq, 3JH,F
=
3
3J = 10.8, 8.8) J = 10.8, 6.7) = 6.7, 5JH,F = 1.8) 2.55, 2.91 (both m, CH2NCH2)]
= 8.8, 5JH,F = 1.8) 1565, 1366
95.53 (d,
R*,R*ꢀ5a 30 3.67 (dq,
4.85 (dq,
1.66 (d, 3J = 6.8)
[1.36—1.52 (m, (CH2)3);
2.66, 2.79 (both m, CH2NCH2)]
[2.64, 2.98 (both m, CH2NCH2);
3J = 8.9, 7.9) 3J = 8.9, 6.8)
3JH,F = 7.9)
98.50 (dq, 3JH,F
=
c
R*,S*ꢀ5b 77b
—
4.90 (dq,
1.65 (dq, 3J =
3J = 10.8, 6.7) = 6.7, 5JH,F = 1.8) 3.52—3.71 (m, CH2OCH2)]
= 8.4, 5JH,F = 1.8) 1563, 1365
95.74 (d,
R*,R*ꢀ5b 23 3.77 (dq,
3J = 8.2, 7.8) 3J = 8.2, 6.8)
R*,S*ꢀ5c 47 3.61 (m) 4.73 (dq,
4.86 (dq,
1.85 (d, 3J = 6.8) [2.76, 2.89 (both m, CH2NCH2);
3.52—3.71 (m, CH2OCH2)]
3JH,F = 7.8)
1.63 (dq, 3J = 6.8, 1.84 (br.s,
5
91.63 (dq,
3J = 9.9, 7.4) JH,F = 1.3)
NH)
3.83, 4.08 (both d,
CH2Ph, 2J = 13.2);
7.22—7.35 (m, Ph)
3JH,F = 7.4,
5JH,F = 1.3)
3363, 1560,
1454, 1395
R*,R*ꢀ5c 53 4.12 (m)
R*,S*ꢀ5d 55 4.98 (m)
4.72 (dq,
1.58 (dq, 3J =
1.66 (br.s,
90.48 (dq, 3JH,F
=
3J = 7.4, 6.9) = 6.9, 5JH,F = 0.8) NH)
= 7.4, 5JH,F = 0.8)
4.92 (qd,
3J = 6.8, 5.6) = 6.8, 5JH,F = 1.1) 3J = 10.5)
4.86 (qd,
1.68 (dq, 3J =
3J = 6.9, 5.0) = 6.9, 5JH,F = 0.8) 3J = 10.8)
1.70 (dq, 3J =
4.27 (d, NH,
89.49 (dq, 3JH,F
=
3402, 1605,
6.73 (d, Ho, 3J = 8.6); = 6.9, 5JH,F = 1.1) 1560, 1514,
R*,R*ꢀ5d 45 4.45 (dqd,
3J = 10.8,
3.79 (d, NH, 6.86 (tm, Hp, 3J = 7.4); 88.39 (dq,
1500, 1444,
1395, 1362
7.22 (m, Hm)
3JH,F = 7.0,
7.0, 5.0)
5JH,F = 0.8)
R*,S*ꢀ5e 55 4.41 (br.m) 4.90 (qd,
3J = 7.0, 5.7) = 6.9, 5JH,F = 1.1)
1.69 (dq, 3J =
3.62 (br.s)
2.17 (s, Me); 2.20
(s, Mе); 6.49 (dd,
H(6), 3J = 8.1, 2.6);
6.56 (d, H(2), 3J = 2.6);
6.98 (d, H(5), 3J = 8.1)
2.15 (s, Ме); =
88.43 (dq, 3JH,F
89.54 (dq, 3JH,F
=
=7.0, 5JH,F = 1.1)
3400, 1619,
1590, 1559,
1511, 1452,
R*,R*ꢀ5e 45 4.09 (br.m) 4.84 (qd,
1.66 (dq, 3J =
3.20 (br.s)
3J = 6.9, 5.2) = 6.8, 5JH,F = 0.7)
2.19 (s, Me); 6.49 (dd, = 6.9, 5JH,F = 0.7) 1394, 1361
H(6), 3J = 8.1, 2.6);
6.54 (d, H(2), 3J = 2.6);
6.97 (d, H(5), 3J = 8.1)
3.85 (s, OMe); 3.86
(s, OМе); 6.74—6.91
(m, Ar)
c
R*,S*ꢀ5f 52 4.53 (m)
R*,R*ꢀ5f 48 4.96 (m)
4.90 (qd,
3J = 6.9, 5.7) = 6.8, 5JH,F = 1.2)
4.88 (qd,
3J = 6.9, 5.0)
1.70 (dq, 3J =
—
89.65 (dq, 3JH,F
= 7.0, 5JH,F = 1.2) 1590, 1559,
87.88 (dq, 3JH,F
1512, 1453,
= 7.0, 5JH,F = 0.6) 1394, 1362
=
3401, 1620,
1.68 (d, 3J = 6.8)
—
=
c
a Determined from the 19F NMR spectra of the reaction mixtures.
b 13C NMR, δ : 16.32 (q, J = 2.6 Hz); 49.44; 67.24; 68.07 (q, J = 26.0 Hz); 81.31; 125.39 (q, J = 291.9 Hz).
C
c The chemical shifts were not determined because of the overlap of the signals.
1
The high reactivity of compound 1 toward amines
The H NMR spectra of products 8 and 10 contain
two doublets of doublets for the protons of the nitromethyl
group. Because compound 10 (R2 = Me) has an asymꢀ
metric C atom, the signals for the CH2OH protons in its
spectrum appear as two doublets of doublets at δH 3.31
and 3.60 (major diastereoisomer) and 3.29 and 3.56
(minor diastereoisomer). The configurations of stereoisoꢀ
and amino alcohols and the lack of data on similar
noncatalytic reactions of aliphatic diazo compounds,
including trifluoromethylꢀcontaining analogs, motivated
us to study the mechanism of this process more thoroughly.
Note that the reactions of both nitroalkene 2a and diazo
compound 1 with amines and amino alcohols yield idenꢀ
tical products (see Schemes 2, 4). In addition, it is known
that diazoalkanes containing an acidic H atom in the
αꢀposition relative to the diazo group and an anionꢀstabiꢀ
lizing group tend to form alkenes in the presence of bases
1
meric products 10 were not determined. In the H and
19F NMR spectra of the R*,S*ꢀ and R*,R*ꢀisomers of
compounds 9a,b, the observed patterns are similar to those
noted above for βꢀnitro amines 5 (see Table 3).

1890
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Korotaev et al.
1
Table 3. H and 19F NMR and IR spectra of amino alcohols 8—10
Comꢀ
pound
Content of
the isomera
NMR (CDCl3)
H (J/Hz)
IR,
ν/cm–1
δ
δ
F (J/Hz),
CF3
(%)
CHCF3
4.04 (m)
R3CHNO2
R1
CHR2CH2OH
8a
8b
—
4.46, 4.66 (both dd,
1.95 (br.s,
OH + NH)
1.95 (br.s, OH + NH);
87.93 (d,
3344, 1566,
1385
CHAHBNO2, 2JA,B
= 13.1, 3JВ,X = 9.8,
3JА,X = 4.0)
=
2.87, 3.08 (both m, NCH2); JX,F = 7.0)
3
3.64 (m, OСН2)
—
4.13 (dqd,
4.59, 4.72 (both dd,
CHAHBNO2,
2.52 (q, NMe, 2.86, 2.97 (both dt, NCH2, 93.88 (dm,
5JH,F = 1.7)
3345, 3230,
1566, 1386
3JB,X = 10.5,
3JX,F = 6.7,
3JA,X = 3.7)
2J = 13.6, 3J = 5.1);
3.61 (t, OCH2, 3J = 5.1)
3JX,F = 8.0)
2JA,B = 13.1,
3JA,X = 10.5,
3JB,X = 3.7)
R*,S*ꢀ9a
R*,R*ꢀ9a
R*,S*ꢀ9b
49
51
77
3.63 (m)
1.68 (dq, Me, 3J =
= 6.8, 5JH,F = 1.4);
4.76 (qd, CHNO2,
3J = 6.8, 3.8)
1.60 (dq, Me, 3J =
= 6.8, 5JH,F = 0.8);
4.75 (dq, CHNO2,
3J = 8.3, 6.8)
2.50 (br.s,
OH + NH)
91.20 (dq,
3JH,F = 7.4,
5JH,F = 1.4)
2.50 (br.s, OH + NH);
2.82, 3.09 (both m, NCH2);
3.62 (m, OСН2)
3290, 1558,
1366
4.12 (m)
2.50 (br.s,
OH + NH)
89.93 (dq,
3JH,F = 7.5,
5JH,F = 0.8)
3.72 (dq, 3J = 1.66 (dq, Me, 3J =
= 10.6, 8.2)
2.47 (q, NMe,
5JH,F = 1.5)
98.73 (br.d,
3J = 8.2)
= 6.7, 5JH,F = 1.7);
4.95 (dq, CHNO2,
3J = 10.6, 6.7)
1.71 (d, Me, 3J =
= 6.8); 4.90 (m,
CHNO2)
2.12 (s, OH); 2.80, 2.93
(both m, NCH2); 3.56,
3306, 1563,
1396
R*,R*ꢀ9b
23
52
3.87 (m)
2.46 (s, NMe) 3.67 (both m, OСН2)
95.14 (d,
3JH,F = 7.3)
10b
3.08 (m)
4.43, 4.67 (both dd,
1.89 (br.d,
NH, J ≈ 10.0)
1.00 (d, 3 H, Me, J =
= 6.4); 2.35 (br.s, OH);
4.13 (m, CHMe); 3.31,
3.60 (both dd, OCHAHB,
2JA,B = 10.8, 3JA,X = 3.7,
3JB,X = 2.5)
87.73 (dd,
J = 7.0, 1.1)
CHAHBNO2, 2JA,B
= 12.8, 3JB,X = 9.6,
3JA,X = 3.9)
=
3552, 3350,
1565, 1384
10c
48
3.08 (m)
4.44, 4.67 (both dd,
1.44 (br.d,
NH, J ≈ 9.0)
1.09 (d, 3 H, Me, J =
= 6.5); 2.35 (br.s, OH);
4.13 (m, CHMe); 3.29,
3.56 (both dd, OCHAHB,
87.24 (dd,
J = 6.9, 1.0)
CHAHBNO2, 2JA,B
= 13.1, 3JA,X = 9.4,
3JB,X = 4.3)
=
2JA,B = 11.1, 3JA,X
= 3JB,X = 3.8)
=
a Determined from the 19F NMR spectra of the reaction mixtures.
b The major isomer.
c The minor isomer.
(B).19,20 One can assume that nitroalkene 2a is a plausible
intermediate in the reactions of diazo compound 1 with
amines or amino alcohols, which act as bases. An alternaꢀ
tive route may involve the formation of (nitromethyl)ꢀ
trifluoromethylcarbene followed by its insertion into the
N—H bond (Scheme 5).
and studied its reaction with diazo compound 1. It turned
out that the reaction mixture contains nondeuterated
compound 4b and only one isomer of deuterated product
4bꢀd1 in a ratio of 2 : 3. The ratio was determined using
1H and 19F NMR spectroscopy from the integral intensity
of the signal for the methine proton in compound 4b and
the integral intensities of the signals for the trifluoromethyl
group in compounds 4b and 4bꢀd1 (Scheme 6).
To verify these assumptions, we synthesized Nꢀdeuteroꢀ
morpholine (11; the deuteration degree is 60% (1H NMR))

NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1891
HA (4b)
Scheme 4
H
B (4b)
HB
(4bꢀd1)
HA
(4bꢀd1)
1
2
3
1
2
3
Comꢀ
pound
7a
7b
7c
R
R
R
Comꢀ
pound
8b
9a
9b
R
R
R
4.72
4.68
4.64
4.60
4.56
δ
H
Me
H
H
—
—
—
H
Me
H
Me
H
H
H
H
H
H
Me
H
Me
Me
H
1
Fig. 2. H NMR spectrum (400 MHz) of a mixture of products
4b and 4bꢀd1 in CDCl3 (the signals for the protons of the
nitromethyl group are shown).
8a
H
10
Me
αꢀposition with respect to the group CF3 and, accordꢀ
ingly, that the in situ generated carbene is inserted into
the N—H bond. Thus, the reaction does not involve the
formation of intermediate alkene 2a. The fact that this
reaction occurs under mild conditions and in the absence
of a catalyst is probably due to the presence of two elecꢀ
tronꢀwithdrawing substituents in compound 1.
Scheme 5
We studied transformations of the nitromethyl group
in βꢀnitro amines 4. Reduction of compounds 4a—h with
LiAlH4 in THF followed by treatment with dry HCl gave
1,2ꢀdiamines 12a—h as hydrochlorides in 50—81% yields
(Scheme 7). Under these conditions, the O—Me and
Ph—Cl bonds in nitro amines 4i,j undergo partial hydroꢀ
genolysis leading to a mixture of compounds 12j•HCl
(72%) and 12d•HCl (28%) (for 4j) or resulting in resiniꢀ
fication (for 4i). Individual hydrochlorides of diamines
Scheme 7
The 19F NMR spectrum of the reaction products shows
a doublet at δF 94.32 for nitro amine 4b and a singlet at δF
1
94.27. In the H NMR spectrum of compound 4b, the
signal for the HA proton of the nitromethyl group appears
as a lowꢀfield doublet of doublets (δH 4.67, 2JA,B = 13.0 Hz,
3JA,X = 10.7 Hz), while the signal for this proton in
the spectrum of deuterated product 4bꢀd1 appears as a
2
doublet of triplets at δH 4.66 with JA,B = 13.0 Hz and
3JH,D = 1.5 Hz (Fig. 2) because of the H—D spinꢀspin
coupling. This indicates that the D atom is only in the
Scheme 6
Compounds R1
R2 Compounds R1
R2
4, 12
4, 12
a
(CH2)5
(CH2)2O(CH2)2
f
g
h
i
H
H
H
H
H
3ꢀMeC6H4
3,4ꢀMe2C6H3
2,5ꢀMe2C6H3
2ꢀMeOC6H4
2ꢀClC6H4
b
c
d
e
H
Bn
Ph
Ph
H
Me
j

1892
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Korotaev et al.
Table 4. Physicochemical properties and elemental analysis data for nitro amines 4a—j and 5a—f and
amino alcohols 8—10
Comꢀ
pound
Yield
(%)
B.p./°C
(p/Torr)
M.p./°C
Found
Calculated
Molecular
formula
(%)
C
H
N
4a
4b
4c
4d
4e
4f
78a, 87b
90a, 85b
49a, 47b
70a, 78b
69a, 65b
77a, 75b
54a, 56b
86a, 87b
82a, 84b
90a, 91b
67b
75—76 (5)
83—84 (5)
110—112 (4)
126—128 (5)
105—108 (4)
—
—
—
42.24
42.48
36.82
36.85
48.27
48.39
46.15
46.16
48.41
48.39
48.48
48.39
50.13
50.38
50.40
50.38
45.49
45.46
40.26
40.24
44.86
45.00
39.60
39.67
50.61
50.38
48.51
48.39
52.11
52.17
47.61
47.49
29.67
29.71
33.32
33.34
33.30
33.34
36.44
36.53
33.15
33.34
5.76
5.79
4.89
4.82
4.40
4.47
3.86
3.87
4.49
4.47
4.47
4.47
5.01
5.00
4.85
5.00
4.18
4.20
2.98
3.00
6.41
6.29
5.55
5.41
5.23
5.00
4.44
4.47
5.49
5.47
4.70
4.71
4.54
4.49
5.15
5.13
5.10
5.13
5.51
5.69
5.26
5.13
12.35
12.38
12.30
12.28
11.14
11.29
12.02
11.96
11.35
11.29
11.58
11.29
10.64
10.68
10.60
10.68
10.54
10.60
10.42
10.43
11.81
11.66
11.31
11.57
10.78
10.68
11.20
11.29
10.05
10.14
10.10
10.07
13.76
13.86
13.01
12.96
13.05
12.96
12.18
12.17
13.14
12.96
C8H13F3N2О2
C7H11F3N2O3
C10H13F3N2O2
C9H9F3N2О2
—
—
—
C10H11F3N2O2
C10H11F3N2О2
C11H13F3N2O2
C11H13F3N2O2
C10H11F3N2О3
C9H8ClF3N2O2
C9H15F3N2O2
C8H13F3N2O3
C11H13F3N2O2
C10H11F3N2О2
C12H15F3N2О2
C11H13F3N2О3
C5H9F3N2O3
61—62
53—54
50—51
45—46
40—41
38—39c
—
4g
4h
4i
—
—
—
4j
—
5a
5b
5c
5d
5e
5f
61—62 (4)
83—86 (4)
103—104 (2)
108—110 (3)
126—128 (4)
107—110 (2)
110—111 (5)
95—98 (4)
94—96 (2)
87—88 (1)
88—89 (4)
68b
72b
—
68b
—
75b
—
58b
—
8a
8b
9a
9b
10
46a, 51b
59a, 60b
56b
—
—
C6H11F3N2O3
C6H11F3N2O3
C7H13F3N2O3
C6H11F3N2O3
—
66b
—
50a, 57b
—
a The compound was obtained according to method A.
b The compound was obtained according to method B.
c The melting point of the crystalline R*,S*ꢀisomer of compound 5a in the individual state.
12i,j were obtained when AlH3 was used as a reducing
agent (prepared in situ by addition of anhydrous H2SO4 to
a suspension of LiAlH4) (Scheme 7, see Experimental).
Reactions of compounds 4a—j with a molar excess
of indium in conc. HCl at ~20 °C (see Ref. 21) also yield
diamine hydrochlorides 12a—j•HCl; however, we believe
that this method is less preferred. Other known methods for
the synthesis of amines from nitroalkanes, viz., catalytic
hydrogenation22 or treatment with the system NaBH4—
NiCl2 (see Ref. 23), lead to complex mixtures of unidentiꢀ
fied products. Apparently, this is due to decomposition of
intermediates (unstable oximes and hydroxylamines)

NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1893
Scheme 9
during the reduction. Free diamines 12a—g,i,j were obꢀ
tained as colorless hygroscopic liquids or lowꢀmelting crysꢀ
tals in 100% yields by the action of aqueous KOH on the
corresponding hydrochlorides.
Reduction of Nꢀbenzylꢀβꢀnitro amine 4c with LiAlH4
is accompanied by the retroꢀHenry reaction. As a result,
treatment of the reaction mixture with dry HCl produces
a 6 : 1 mixture of hydrochlorides of the expected product
12c and Nꢀbenzylꢀ2,2,2ꢀtrifluoroethylamine24 (Scheme
1
8). The ratio of the products was determined by H and
19F NMR spectroscopy. For instance, the 19F NMR specꢀ
trum of the reaction mixture in DMSOꢀd6 shows a douꢀ
3
blet at δF 90.00 with the coupling constant JX,F = 7.6 Hz
(compound 12c) and a triplet at δF 90.3 for the group CF3
3
with the coupling constant JH,F = 9.4 Hz (Nꢀbenzylꢀ
1
2,2,2ꢀtrifluoroethylamine hydrochloride). The H NMR
spectrum contains, apart from the signals for product 12c,
a quartet at δΗ 3.13 (3JH,F = 9.4 Hz) for the protons of the
2,2,2ꢀtrifluoroethyl moiety and a singlet at δΗ 3.90 for
the methylene protons of the benzyl substituent. Indiꢀ
vidual hydrochloride 12c•HCl was isolated in 63% yield
by recrystallization of this mixture from ethyl acetate.
Scheme 10
Scheme 8
does not occur even when the carboxyethylating agent is
used in excess. Reactions of more nucleophilic diamine
12b with both one and two equivalents of acrylic acid
yield Nꢀsubstituted iminodipropionic acid 16 (Scheme 11).
Because compound 4k is unstable, hydrochloride
12k•HCl and free diamine 12k were obtained by a reacꢀ
tion of diazo compound 1 or nitroalkene 2a with pyrroꢀ
lidine in THF at –78 °C followed by in situ reduction of
intermediate 4k (Scheme 9).
Scheme 11
Reduction of nitro alcohols 8a,b with LiAlH4 followed
by treatment with aqueous KOH and dry HCl gives amino
alcohols 13a,b as hydrochlorides, although in lower yields
(23 and 22%, respectively). Apparently, this is due to the
formation of stable complexes of these products with Al3+
ions, which makes their isolation difficult. The formation
of monohydrochloride 13b•HCl can be attributed to the
steric effect of the Nꢀmethyl group (Scheme 10).
R = 3,4ꢀMe2C6H3
We failed to transform the nitromethyl group in comꢀ
pounds 4 into the aldehyde or carboxyl function (the Nef
reaction):1 strong resinification was observed in all cases,
regardless of the method used and the reaction conditions.
Carboxyethylation of compound 12g with acrylic acid
proceeds like that for 1,2ꢀdiamine10 to give an Nꢀmonoꢀ
(14) or N,Nꢀdicarboxyethyl derivative (15), depending
on the ratio of the reagents. Addition at the N(2) atom

1894
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Korotaev et al.
Thus, relatively easily accessible Nꢀmonoꢀ and N,Nꢀdiꢀ
substituted αꢀtrifluoromethyl βꢀnitro amines can be used
for the preparation of trifluoromethylꢀcontaining amines,
including optically active ones, which are promising buildꢀ
ing blocks for organic synthesis.
Experimental
1H and 13C NMR spectra were recorded on a Bruker
DRXꢀ400 spectrometer (400 and 100 MHz, respectively) in
DMSOꢀd6 and CDCl3. 19F NMR spectra were recorded on
Bruker DRXꢀ400 and Tesla BSꢀ587A spectrometers (376 and
Table 5. 1H and 19F NMR and IR spectra of diamine hydrochlorides 12a—j•HCl and hydroxy diamine hydrochlorides 13a,b•xHCl
Comꢀ
pound
NMR (DMSOꢀd6)
IR,
δ
H (J/Hz)
δ
F (J/Hz),
ν/cm–1
CF3
12a
12b
12c
1.53, 1.41 (both m, 3 H each, (CH2)3); 2.53, 2.86 (both m, 2 H each, NCH2); 2.93, 3.12
96.26
(d, 3JX,F = 8.8)
96.18
2942, 2859
+
(both m, 1 H each, CHAHBNH3+); 3.77 (m, 1 H, CHXCF3); 8.22 (br.s, 3 H, NH3
)
2.58, 2.90 (both m, 2 H each, NCH2); 2.96, 3.17 (both m, 1 H each, CHAHBNH3+);
2966, 2939,
2875
3319, 2926,
2873, 1587,
1477, 1455
3.61 (m, 4 H, OCH2); 3.89 (m, 1 H, CHCF3); 8.37 (br.s, 3 H, NH3
)
(d, 3JX,F = 8.6)
90.00
+
2.93, 3.09 (both m, 1 H each, CHAHBNH3+); 3.40 (br.s, 1 H, NH); 3.70 (m, 1 H,
CHXCF3); 3.86, 3.91 (both d, 1 H each, CH2Ph, 2J = 13.5); 7.25 (tt, 1 H, Hp,
(d, 3JX,F = 7.6)
J = 7.2, 1.2); 7.32 (tt, 2 H, Hm, J = 7.3, 1.1); 7.43 (d, 2 H, Ho, J = 7.2);
+
8.43 (br.s, 3 H, NH3
)
12d
12e
12f
3.06, 3.24 (both m, 1 H each, CHAHBNH3+); 4.72 (m, 1 H, CHXCF3); 6.31 (d, 1 H,
88.83
(d, 3JX,F = 7.1)
3389, 3017,
2920, 1603,
1519, 1499
3000, 2974,
2913, 2839
NH, JH ,NH = 9.7); 6.68 (tt, 1 H, Hp, J = 7.3, 1.0); 6.79 (dd, 2 H, Ho, J = 8.5,
X
+
1.0); 7.15 (dd, 2 H, Hm, J = 8.5, 7.3); 8.45 (br.s, 3 H, NH3
2.83 (q, 3 H, NMe, 5JMe,CF = 1.8); 3.20, 3.55 (both m, 1 H each, CHAHBNH3+);
)
93.48
3
5.16 (m, 1 H, CHXCF3); 6.83 (tt, 1 H, Hp, J = 7.2, 0.9); 7.11 (dd, 2 H, Ho,
(dq, 3J = 8.0,
J = 8.8, 0.9); 7.25 (dd, 2 H, Hm, J = 8.8, 7.3); 8.54 (br.s, 3 H, NH3
)
5JMe,CF = 1.8)
+
3
2.21 (s, 3 H, Ме); 3.04, 3.22 (both m, 1 H each, CHAHBNH3+); 4.68 (m, 1 H,
88.83
(d, 3JX,F = 7.1)
3405, 2977,
2926, 1611,
1595, 1527,
1492
3346, 3011,
2927, 2874,
1619, 1508,
1454
CHXCF3); 6.21 (d, 1 H, NH, JH ,NH = 9.7); 6.51 (d, 1 H, H(4), J = 7.4); 6.58
X
(dd, 1 H, H(6), J = 8.1, 2.3); 6.61 (m, 1 H, H(2)); 7.02 (t, 1 H, H(5), J = 7.7);
+
8.40 (br.s, 3 H, NH3
)
+
12g
12h
2.08 (s, 3 H, Ме); 2.13 (s, 3 H, Ме); 3.01, 3.21 (both dd, 1 H each, CHAHBNH3
,
88.27
(d, 3JX,F = 7.1)
2JA,B = 13.0, 3JA,X = 3.6, JB,X = 10.1); 4.61 (ddqd, 1 H, CHXCF3, 3JB,X = 10.1,
J
H ,NH = 9.9, 3JX,F = 7.1, 3JA,X = 3.6); 5.97 (d, 1 H, NH, JH ,NH = 9.9); 6.52 (dd,
1 H, H(6), J = 8.2, 2.3); 6.60 (d, 1 H, H(2), J = 2.3); 6.89 (dX, 1 H, H(5), J = 8.2);
X
+
8.33 (br.s, 3 H, NH3
)
2.14 (s, 3 H, Ме); 2.21 (s, 3 H, Ме); 3.22, 3.33 (both m, 1 H each, CHAHBNH3+);
88.87
(d, 3JX,F = 7.0)
3391, 2928,
2870, 1622,
1587, 1530,
1484, 1453
3341, 3010,
2928, 1589,
1525, 1465
3345, 3015,
2926, 1597,
1517, 1470
4.76 (m, 1 H, CHXCF3); 5.15 (d, 1 H, NH, JH ,NH = 9.9); 6.46 (d, 1 H, H(4),
J = 7.6); 6.63 (s, 1 H, H(6)); 6.90 (d, 1 H, H(3), J = 7.6); 8.30 (br.s, 3 H, NH3
X
+
)
12i
3.22, 3.32 (both m, 1 H each, CHAHBNH3+); 3.87 (s, 1 H, OMe); 4.75 (m, 1 H,
88.87
(d, 3JX,F = 7.0)
CHXCF3); 5.47 (d, 1 H, NH, JH ,NH = 10.5); 6.68—6.91 (m, 4 H, Ar); 8.21
X
+
(br.s, 3 H, NH3
)
12ja
3.23, 3.43 (both m, 1 H each, CHAHBNH3+); 5.04 (m, 1 H, CHXCF3); 5.75 (d, 1 H,
86.64
(d, 3JX,F = 7.0)
NH, JH ,NH = 10.3); 6.75 (ddd, 1 H, H(4), J = 7.9, 7.5, 1.4); 7.10 (dd, 1 H, H(6),
J = 8.2,X1.4); 7.20 (ddd, 1 H, H(5), J = 8.2, 7.5, 1.4); 7.32 (dd, 1 H, H(3), J = 7.9,
+
1.4); 8.26 (br.s, 3 H, NH3
)
13ab
13b
3.00, 3.15 (both m, 1 H each, CH2NH2+); 3.32 (m, 2 H, CHAHBNH3+); 3.67 (t, 2 H,
92.78
(br.s)
3307, 3021,
2958, 2870
CH2OH, 3J = 5.5); 4.44 (m, 1 H, CHXCF3); 7.97 (br.s, 2 H, NH2+); 8.78 (br.s,
+
3 H, NH3
)
2.44 (s, 1 H, Me); 2.59, 2.85 (both m, 1 H each, CH2NH3+); 3.00, 3.12 (both m,
95.39
(d, 3JX,F = 8.2)
3309, 2958,
2899
1 H each, CHAHBNH3+); 3.47 (m, 2 H, CH2OH); 3.85 (m, 1 H, CHXCF3);
+
5.07 (br.s, 1 H, OH); 8.28 (br.s, 3 H, NH3
)
a 13C NMR, δ : 36.65 (q, J = 2.2 Hz); 52.30 (q, J = 29.4 Hz); 113.69; 119.06; 119.15; 127.15 (q, J = 285.8 Hz); 129.40; 129.33; 142.33.
C
b 13C NMR, δ : 35.48; 48.50; 55.51 (q, J = 29.9 Hz); 57.53; 123.91 (q, J = 283.7 Hz).
C

NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1895
75 MHz, respectively) in DMSOꢀd6 and CDCl3. Tetramethylꢀ
Spectroscopic characteristics of βꢀnitro amines 4a—j and
5a—f are given in Tables 1 and 2; those of amino alcohols 8—10
are presented in Table 3. The yields, physicochemical constants,
and elemental analysis data for compounds 4a—j, 5a—f, and
8—10 are given in Table 4.
silane (1H, 13C) and C6F6 19F) were used as the internal
(
standards. IR spectra were recorded on a Perkin—Elmer Specꢀ
trumꢀBX II FTIR spectrometer in KBr pellets or thin films.
Diazo compound 1 was prepared as described earlier.14
The preparation of 3,3,3ꢀtrifluoroꢀ1ꢀnitropropene (2a) and
1,1,1ꢀtrifluoroꢀ3ꢀnitrobutꢀ2ꢀene (2b) was described in Refs 15
and 16. NꢀDeuteromorpholine (11) was synthesized according
to a known procedure.25
Reduction of βꢀnitro amines 4a—h and 8a,b (general proꢀ
cedure). A solution of an appropriate nitro compound 4 or 8
(14.5 mmol) in anhydrous THF (50 mL) was added dropwise
at 0 °C for 30 min to a stirred suspension of LiAlH4 (2.83 g,
74.5 mmol) in anhydrous THF (100 mL). The reaction mixture
was refluxed with stirring for 4 h and cooled to 0 °C. Water
(2.83 g), 10% KOH (3.92 g), and again water (8.49 g) were
successively added dropwise. The mixture was stirred for 15 min,
filtered, and concentrated in vacuo. The residue was dissolved in
anhydrous benzene (40 mL). Dry HCl was bubbled at 15 °C
through the resulting solution to saturation. The precipitate that
formed was filtered off, recrystallized from ethyl acetate or acetoꢀ
nitrile, and dried in vacuo to give 3,3,3ꢀtrifluoroꢀ2ꢀpiperidinoꢀ
propaneꢀ1ꢀamine hydrochloride (12a•HCl), 3,3,3ꢀtrifluoroꢀ
2ꢀmorpholinopropaneꢀ1ꢀamine hydrochloride (12b•HCl),
2ꢀ(Nꢀbenzylamino)ꢀ3,3,3ꢀtrifluoropropaneꢀ1ꢀamine hydrochloꢀ
ride (12c•HCl), 3,3,3ꢀtrifluoroꢀ2ꢀ(Nꢀphenylamino)propaneꢀ
1ꢀamine hydrochloride (12d•HCl), 3,3,3ꢀtrifluoroꢀ2ꢀ(Nꢀmethylꢀ
Nꢀphenylamino)propaneꢀ1ꢀamine hydrochloride (12e•HCl),
3,3,3ꢀtrifluoroꢀ2ꢀ[Nꢀ(3ꢀmethylphenyl)amino]propaneꢀ1ꢀamine
hydrochloride (12f•HCl), 2ꢀ[Nꢀ(3,4ꢀdimethylphenyl)amino]ꢀ
(E)ꢀ3,3,3ꢀTrifluoroꢀ1ꢀnitropropene (2a). 1H NMR (CDCl3),
3
3
δ: 7.11 (dq, 1 H, H(1), JH,H = 13.5 Hz, JH,F = 6.4 Hz); 7.47
(dq, 1 H, H(2), JH,H = 13.5 Hz, JH,F = 1.9 Hz). 19F NMR
(CDCl3), δ: 98.05 (dd, CF3, 3JH,F = 6.4 Hz, 4JH,F = 1.9 Hz).
1,1,1ꢀTrifluoroꢀ3ꢀnitrobutꢀ2ꢀene (2b). 1H NMR (CDCl3),
δ: 2.43 (qd, 3 H, Me, 5JH,F = 2.0 Hz, 4JH,H = 1.2 Hz); 7.06 (qq,
1 H, CH=, 3JH,F = 7.4 Hz, 4JH,H = 1.2 Hz). 19F NMR (CDCl3),
3
4
δ: 102.92 (dq, CF3, JH,F = 7.4 Hz, JH,F = 2.0 Hz). 13C NMR
3
5
4
(CDCl3), δ: 13.65 (q, C(4), JC,F = 1.6 Hz); 121.05 (q, C(2),
2JC,F = 37.3 Hz); 121.93 (q, C(1), JC,F = 271.1 Hz); 156.50
1
(q, C(3), 3JC,F = 5.8 Hz).
βꢀNitro amines 4a—j and Nꢀ(2ꢀhydroxyethyl) βꢀnitro amines
8a,b and 10 (general procedure A). A solution of appropriate
amine 3 or aminoethanol 7 (20.0 mmol) in benzene (25 mL) was
added dropwise for 20 min to a stirred solution of diazo comꢀ
pound 1 (3.38 g, 20.0 mmol) in benzene (25 mL). The resulting
solution was stirred at ~20 °C for 30 min (for 4a—c, 8a,b, and 10)
or at 60 °C for 2 h (for 4d—j). The reaction with Sꢀ2ꢀaminoꢀ
propanol (7c) was carried out in THF (25 mL) at –78 °C (for
10). Then the reaction temperature was brought to ~20 °C, the
solvent was removed under reduced pressure, and the residue
was recrystallized from hexane (for 4f—j) or distilled in vacuo
(for 4a—e, 8a,b, and 10).
βꢀNitro amines 4a—j, 5a—f, and Nꢀ(2ꢀhydroxyethyl) βꢀnitro
amines 8—10 (general procedure B). A mixture of nitroalkene 2a
or 2b (20.0 mmol) and an appropriate amine or aminoethanol
(20.0 mmol) in benzene (25 mL) was stirred at ~20 °C for
30 min (for 4a—c, 5a—c, 8a,b, and 9a,b) or 2 h (for 4d—j and
5d—f). The reaction with Sꢀ2ꢀaminopropanol (7c) was carried
out in THF (25 mL) at –78 °C (for 10). Then the reaction
mixture was treated as described under procedure A to give
1,1,1ꢀtrifluoroꢀ2ꢀ[(3ꢀmethylphenyl)amino]ꢀ3ꢀnitropropane (4f),
2ꢀ[(3,4ꢀdimethylphenyl)amino]ꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitropropane
(4g), 2ꢀ[(2,5ꢀdimethylphenyl)amino]ꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitroꢀ
propane (4h), 1,1,1ꢀtrifluoroꢀ2ꢀ[(2ꢀmethoxyphenyl)amino]ꢀ
3ꢀnitropropane (4i), and 2ꢀ[(2ꢀchlorophenyl)amino]ꢀ1,1,1ꢀ
trifluoroꢀ3ꢀnitropropane (4j) as white powders and 1,1,1ꢀtriꢀ
fluoroꢀ3ꢀnitroꢀ2ꢀpiperidinopropane (4a), 1,1,1ꢀtrifluoroꢀ2ꢀmorꢀ
pholinoꢀ3ꢀnitropropane (4b), 2ꢀbenzylaminoꢀ1,1,1ꢀtrifluoroꢀ
3ꢀnitropropane (4c), 2ꢀanilinoꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitropropane
(4d), 1,1,1ꢀtrifluoroꢀ2ꢀ(NꢀmethylꢀNꢀphenylamino)ꢀ3ꢀnitroꢀ
propane (4e), 1,1,1ꢀtrifluoroꢀ3ꢀnitroꢀ2ꢀpiperidinobutane (5a),
1,1,1ꢀtrifluoroꢀ2ꢀmorpholinoꢀ3ꢀnitrobutane (5b), 2ꢀbenzylꢀ
aminoꢀ1,1,1ꢀtrifluoroꢀ3ꢀnitrobutane (5c), 2ꢀanilinoꢀ1,1,1ꢀtriꢀ
fluoroꢀ3ꢀnitrobutane (5d), 2ꢀ[(3,4ꢀdimethylphenyl)amino]ꢀ1,1,1ꢀ
trifluoroꢀ3ꢀnitrobutane (5e), 1,1,1ꢀtrifluoroꢀ2ꢀ[(2ꢀmethoxyphenyl)ꢀ
amino]ꢀ3ꢀnitrobutane (5f), Nꢀ(3,3,3ꢀtrifluoroꢀ1ꢀnitropropꢀ
2ꢀyl)ꢀ2ꢀaminoethanol (8a), NꢀmethylꢀNꢀ(3,3,3ꢀtrifluoroꢀ1ꢀnitroꢀ
propꢀ2ꢀyl)ꢀ2ꢀaminoethanol (8b), Nꢀ(1,1,1ꢀtrifluoroꢀ3ꢀnitrobutꢀ
2ꢀyl)ꢀ2ꢀaminoethanol (9a), NꢀmethylꢀNꢀ(1,1,1ꢀtrifluoroꢀ
3ꢀnitrobutꢀ2ꢀyl)ꢀ2ꢀaminoethanol (9b), and Nꢀ(3,3,3ꢀtrifluoroꢀ
1ꢀnitropropꢀ2ꢀyl)ꢀ2ꢀaminopropanꢀ1ꢀol (10) as colorless liquids.
Table 6. Physicochemical properties and elemental analysis data
for diamine hydrochlorides 12a—j•HCl and hydroxy diamine
hydrochlorides 13a,b•xHCl
Comꢀ Yield M.p.
pound (%) /°C
Found
Calculated
Molecular
formula
(%)
N
C
H
12a
12b
12c
12d
12e
12f
55 204—205* 41.37 6.95 12.16 C8H16ClF3N2
41.30 6.93 12.04
65 228—229* 35.92 6.09 12.01 C7H14ClF3N2O
35.83 6.01 11.94
63
146—147 47.45 5.64 10.96 C10H14ClF3N2
47.16 5.54 11.00
60 199—200* 44.89 5.06 11.70 C9H12ClF3N2
44.92 5.03 11.64
58 191—192* 46.89 5.74 11.09 C10H14ClF3N2
47.16 5.54 11.00
76 209—210* 47.18 5.36 11.06 C10H14ClF3N2
47.16 5.54 11.00
12g
12h
12i
50 215—216* 49.18 6.03 10.62 C11H16ClF3N2
49.17 6.00 10.43
81 190—191* 49.13 6.09 10.51 C11H16ClF3N2
49.17 6.00 10.43
59 175—176* 44.25 5.18 10.24 C10H14ClF3N2O
44.37 5.21 10.35
12j
62 230—231* 39.03 4.12 10.08 C9H11Cl2F3N2
39.29 4.03 10.18
13a
13b
23
122—123 24.67 5.34 11.47 C5H13Cl2F3N2O
24.51 5.35 11.43
111—112 32.37 6.30 12.51 C6H14ClF3N2O
32.37 6.34 12.58
22
* Sublimation of the compound.

1896
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009
Korotaev et al.
1
Table 7. H and 19F NMR spectra of free diamines 12c—g,i,j
Diꢀ
amine
NMR (СDCl3)
R1
δ
H (J/Hz)
δ
F (J/Hz),
CF3
HX
HA
HB
NH2
R2
12c
3.03 (dqd,
3JB,X = 7.9,
3JX,F = 7.6,
3JA,X = 4.0)
2.97 (ddq,
2.76 (dd,
1.50 (br.s, NH, NH2)
3.86, 4.06 (both d,
CH2Ph, 2J = 13.2);
7.27 (m, Hp);
7.32—7.38 (m, Ph)
6.71 (dd, Ho, J =
= 8.6, 1.1); 6.78
(tt, Hp, J = 7.4,
1.1); 7.22 (dd, Hm,
J = 8.6, 7.4)
6.84 (tt, Hp, J =
= 7.3, 1.0); 6.92 (dd,
Ho, J = 8.7, 1.0); 7.27
(dd, Hm, J = 8.7, 7.3)
2.28 (s, Ме); 6.52 (m,
H(2), H(6)); 6.61 (d,
H(4), J = 7.7); 7.08
(t, H(5), J = 7.7)
2.16 (s, Ме); 2.20 (s,
Ме); 6.48 (dd, 1 H,
H(6), J = 8.1, 27);
6.54 (d, H(2), J = 2.7);
6.96 (d, H(5), J = 8.1)
3.87 (s, OMe); 6.70—6.76
(m, H(5), H(6)); 6.81
(dd, H(3), J = 7.9, 1.6);
6.87 (ddd, H(4), J = 7.9,
7.6, 1.6)
88.53
2JA,B = 13.1, 2JA,B = 13.1,
(d, 3JX,F = 7.6)
3JA,X = 4.0,
4JA,F = 0.7)
3.08 (ddq,
2
3JB,X = 7.9)
12d 3.87 (dqdd,
3.03 (dd,
1.24 (s)
4.38 (d, NH,
H ,NH = 9.2)
87.75
(d, 3JX,F = 7.4)
3JH ,NH = 9.2, JA,B = 13.5, 2JA,B = 13.5,
J
X
X
3JX,F = 7.4,
3JA,X = 5.4,
3JB,X = 4.8)
4.26 (dqd,
3JA,X = 9.9,
3JX,F = 8.0,
3JB,X = 4.4)
3.88 (m)
3JA,X = 5.4,
4JA,F = 0.8)
3JB,X = 4.8)
12e
12f
3.19 (dd,
3.10 (dd,
1.30 (br.s) 2.92 (q, Me,
5JMe,
= 1.3)
91.43
2JA,B = 13.4, 2JA,B = 13.4,
(dq, 3J = 8.0,
CF3
3JA,X = 9.9,
3JB,X = 4.4)
3.07 (dd,
3JA,X = 9.9,
3JB,X = 4.4)
3.03 (dd,
5JMe,CF = 1.3)
3
1.31 (br.s) 4.29 (d, NH,
87.71
(d, 3JX,F = 7.4)
2JA,B = 13.4, 2JA,B = 13.4,
J
H ,NH = 8.9)
X
3JA,X = 5.5)
3JB,X = 4.8)
12g 3.84 (dqt,
3.04 (d, 3JA,X = 3JB,X = 5.3)
1.26 (br.s) 4.13 (d, NH,
87.65
(d, 3JX,F = 7.4)
JH ,NH = 9.4,
JH ,NH = 9.4)
3JXX,F = 7.4,
3JA,X = 3JB,X
= 5.3)
X
=
12i
3.88 (m)
3.11 (ddq,
3.05 (dd,
1.53 (br.s) 4.76 (d, NH,
87.60
(d, 3JX,F = 7.0)
2JA,B = 13.5, 2JA,B = 13.5,
J
H ,NH = 8.9)
X
3JA,X = 4.6,
4JA,F = 0.6)
3JB,X = 6.4,)
12j* 3.94 (dqdd,
3.17 (ddq,
3.09 (dd,
1.38 (s)
5.07 (d, NH,
6.72 (ddd, H(4), J =
= 7.9, 7.4, 1.4); 6.79 (dd,
H(6), J = 8.2, 1.4);
7.15 (ddd, H(5), J =
= 8.2, 7.4, 1.4); 7.29
(dd, H(3), J = 7.9, 1.4)
87.67
(d, 3JX,F = 7.3)
2
3JH ,NH = 9.0, JA,B = 13.5, 2JA,B = 13.5,
J
H ,NH = 9.0)
X
X
3JX,F = 7.1,
3JA,X = 5.6,
3JB,X = 4.8)
JA,X = 5.6,
4JA,F = 0.8)
3JB,X = 4.8)
*
13C NMR, δ : 40.47 (q, J = 2.0 Hz); 56.59 (q, J = 28.4 Hz); 119.91; 118.80; 112.48 (q, J = 1.2 Hz); 125.85 (q, J = 284.5 Hz); 127.79;
C
129.43; 192.52.
3,3,3ꢀtrifluoropropaneꢀ1ꢀamine hydrochloride (12g•HCl),
2ꢀ[Nꢀ(2,5ꢀdimethylphenyl)amino]ꢀ3,3,3ꢀtrifluoropropaneꢀ
1ꢀamine hydrochloride (12h•HCl), Nꢀ(1ꢀaminoꢀ3,3,3ꢀtrifluoroꢀ
propꢀ2ꢀyl)ꢀ2ꢀaminoethanol dihydrochloride (13a•2HCl), and
Nꢀ(1ꢀaminoꢀ3,3,3ꢀtrifluoropropꢀ2ꢀyl)ꢀNꢀmethylꢀ2ꢀaminoethanol
hydrochloride (13b•HCl) as white powders.
Reduction of βꢀnitro amines 4i,j (general procedure). Anhyꢀ
drous H2SO4 (3.69 g, 18.8 mmol) was rapidly (~1 min) added
at –10 °C to a stirred suspension of LiAlH4 (2.83 g, 74.5 mmol)
in anhydrous THF (100 mL). Then a solution of an appropriate
βꢀnitro amine 4 (14.5 mmol) in anhydrous THF (50 mL) was
added for 30 min. The reaction mixture was treated as described
above for the reduction of βꢀnitro amines 4a—h. The following
hydrochlorides were obtained as white powders: 3,3,3ꢀtrifluoroꢀ
2ꢀ[Nꢀ(2ꢀmethoxyphenyl)amino]propaneꢀ1ꢀamine hydrochloride
(12i•HCl) and 2ꢀ[Nꢀ(2ꢀchlorophenyl)amino]ꢀ3,3,3ꢀtrifluoroꢀ
propaneꢀ1ꢀamine hydrochloride (12j•HCl). The spectroscopic
characteristics of hydrochlorides 12a—j•HCl and 13a,b•xHCl
(x = 1, 2) are given in Table 5. Their yields, melting points, and
elemental analysis data are presented in Table 6.
Free 1,2ꢀdiamines 12a—g,i,j were obtained in 100% yields
by treating the corresponding hydrochlorides with 20% aqueous
KOH. The products were extracted with CH2Cl2 and the
extracts were dried over CaCl2 and concentrated in vacuo.
The 1H and 19F NMR spectra of compounds 12a,b have been
described earlier.12 The spectra of free diamines 12c—g,i,j
are given in Table 7.
3,3,3ꢀTrifluoroꢀ2ꢀpyrrolidinopropaneꢀ1ꢀamine hydrochloride
(12k•HCl). A solution of pyrrolidine (0.71 g, 10.0 mmol)
in anhydrous THF (5 mL) was added dropwise at –78 °C

NꢀSubstituted αꢀtrifluoromethyl βꢀnitro amines
Russ.Chem.Bull., Int.Ed., Vol. 58, No. 9, September, 2009 1897
for 15 min to a stirred solution of diazo compound 1 (1.72 g,
10.0 mmol) or nitroalkene 2a (1.41 g, 10.0 mmol) in anhydrous
THF (15 mL). Then LiAlH4 (0.95 g, 25.0 mmol) was added
in portions of 0.19 g. The reaction mixture was stirred for 1.5 h
with gradual warming to ~20 °C and treated as described above
for the synthesis of compounds 12a—h•HCl. Yield 0.39 g (18%),
m.p. 191—192 °C (subl.). Found (%): C, 38.73; H, 6.32;
N, 13.02. C7H14F3N2•HCl. Calculated (%): C, 38.45; H, 6.45;
N, 12.81. 1H NMR (DMSOꢀd6), δ: 1.73 (m, 4 H, (CH2)2); 2.72,
2.92 (both m, 2 H each, CH2NCH2); 3.01, 3.13 (both m, 1 H
each, CHAHBNH3+); 3.92 (m, 1 H, CHXCF3); 7.96 (br.s, 3 H,
NH3+). 19F NMR (DMSOꢀd6), δ: 95.42 (d, CF3, 3J = 8.4 Hz).
3,3,3ꢀTrifluoroꢀ2ꢀpyrrolidinopropaneꢀ1ꢀamine (12k) was
obtained as described for diamines 12a—g,i,j; b.p. 61—64 °C
diffractometer (T = 100(2) K, MoꢀKα radiation, graphite monoꢀ
chromator, ω/2θ scan mode, 2θ < 52.7°). The unit cell paramꢀ
eters are a = 7.6975(8) Å, b = 15.4323(17) Å, c = 9.6510(16) Å,
3
α = β = γ = 90°, V = 1146.4(3) Å , space group Pna21, orthoꢀ
rhombic crystal system, Z = 4, dcalc = 1.392 g cm–3. C9H15F3N2O2.
The number of measured reflections was 3787. The number of
independent reflections was 1220 (Rint = 0.0202). Absorption
correction was not applied because of the low absorption value
(μ = 0.130 mm–1). The structure was solved by the direct
methods with the SHELXSꢀ97 program26 and refined by
the leastꢀsquares method in the anisotropic (isotropic for the
H atoms) approximation with the SHELXLꢀ97 program packꢀ
age.26 The H atoms were located geometrically using the riding
model. Final residuals are wR2 = 0.0857 and R1 = 0.0312 for 906
1
(8 Torr). H NMR (CDCl3), δ: 1.62 (br.s, 2 H, NH2); 1.78 (m,
reflections with I > 2σ (S = 1.002). The maximum and miniꢀ
–3
4 H, (CH2)2); 2.79 (m, 2 H, NCH2); 2.88—2.96 (m, 4 H, NCH2,
CHAHBN); 3.21 (m, 1 H, CHXCF3). 19F NMR (CDCl3), δ:
93.85 (d, CF3, 3J = 8.3 Hz).
mum residual electron densities are 0.123 and –0.136 e Å ,
respectively. Selected crystallographic parameters and the data
collection statistics have been deposited with the Cambridge
Crystallographic Data Center (CCDC No. 699 493).
Carboxyethylation of diamines 12b,g (general procedure).
A mixture of a diamine (10.0 mmol) and acrylic acid (0.72 g,
10.0 mmol or 1.44 g, 20.0 mmol) was refluxed in chloroform
(25 mL) for 6 h. On cooling to ~20 °C, the precipitate that
formed was filtered off and recrystallized from acetonitrile.
3ꢀ{[2ꢀ(3,4ꢀDimethylphenylamino)ꢀ3,3,3ꢀtrifluoropropyl]ꢀ
amino}propionic acid (14). Yield 56%, m.p. 188—189 °C.
Found (%): C, 55.12; H, 6.15; N, 9.35. C14H19F3N2O2. Calcuꢀ
lated (%): C, 55.26; H, 6.29; N, 9.21. IR, ν/cm–1: 3325, 1711,
1644, 1618, 1563, 1459, 1412. 1H NMR (DMSOꢀd6), δ: 2.06
(s, 3 H, Me); 2.11 (s, 3 H, Me); 2.31, 2.72 (both t, 2 H each,
CH2CH2CO22H, 3J = 6.7 Hz); 2.79, 2.86 (both dd, 1 H each,
References
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3
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13. V. Ya. Sosnovskikh, V. A. Kutsenko, A. Ya. Aizikovich,
V. Yu. Korotaev, Izv. Akad. Nauk, Ser. Khim., 1999, 2135
[Russ. Chem. Bull. (Engl. Transl.), 1999, 48, 2112].
14. A. Ya. Aizikovich, I. T. Bazyl´, Zh. Org. Khim., 1987, 23,
1330 [J. Org. Chem. USSR (Engl. Transl.), 1987, 23].
15. H. Shechter, D. E. Ley, E. B. Roberson, J. Am. Chem. Soc.,
1956, 78, 4984.
4.19 (ddqd, 1 H, CHXCF3, JH ,NH = 8.8 Hz, JB,X = 8.6 Hz,
3JX,F = 7.5 Hz, 3JA,X = 4.1 Hz);X5.59 (d, 1 H, NH—Ar, JH ,NH
=
X
= 8.8 Hz); 6.46 (dd, 1 H, H(6), J = 8.1 Hz, 3J = 2.3 Hz); 6.55
(d, 1 H, H(2), 3J = 2.3 Hz); 6.84 (d, 1 H, H(5), J = 8.1 Hz);
6.18—8.41 (br.s, 1 H, CO2H). 19F NMR (DMSOꢀd6), δ: 89.34
(d, CF3, 3JX,F = 7.5 Hz).
3
3,3´ꢀ{[2ꢀ(3,4ꢀDimethylphenylamino)ꢀ3,3,3ꢀtrifluoropropyl]ꢀ
imino}dipropionic acid (15). Yield 61%, m.p. 145—146 °C.
Found (%): C, 54.20; H, 6.10; N, 7.25. C17H23F3N2O4. Calcuꢀ
lated (%): C, 54.25; H, 6.16; N, 7.44. IR, ν/cm–1: 3303, 1713,
1
1618, 1565, 1459, 1412. H NMR (DMSOꢀd6), δ: 2.06 (s, 3 H,
Me); 2.11 (s, 3 H, Me); 2.03—2.39 (m, 4 H, CH2CH2CO2H);
2.59—2.90 (m, 6 H, CH2N, CH2CH2CO2H); 4.18 (m, 1 H,
CHXCF3); 5.44 (d, 1 H, NH—Ar, JH
= 8.2 Hz); 6.46
X,NH
(br.d, 1 H, H(6), J = 7.8 Hz); 6.54 (br.s, 1 H, H(2)); 6.83 (br.d,
1 H, H(5), J = 7.8 Hz); 11.98 (br.s, 2 H, CO2H). 19F NMR
(DMSOꢀd6), δ: 89.29 (d, CF3, 3J = 7.3 Hz).
3,3´ꢀ[(3,3,3ꢀTrifluoroꢀ2ꢀmorpholinopropyl)imino]dipropionic
acid (16). Yield 63%, m.p. 169—170 °C. Found (%): C, 45.81;
H, 6.22; N, 8.24. C13H21F3N2O5. Calculated (%): C, 45.61;
H, 6.18; N, 8.18. IR, ν/cm–1: 1690, 1457, 1404. 1H NMR
(DMSOꢀd6), δ: 2.30—2.43 (m,
4 H, CH2CH2CO2H);
2.49—2.85 (m, 10 H, N(CH2)2, CHAHBN, CH2CH2CO2H);
3.42—3.57 (m, 5 H, CHXCF3, O(CH2)2); 11.78—12.96 (br.s,
2
16. E. T. McBee, C. E. Hathaway, C. W. Roberts, J. Am. Chem.
Soc., 1956, 78, 4053.
H, CO2H). 13C NMR (DMSOꢀd6), δ: 32.07; 49.17;
17. Ya. Shen, G. Wang, J. Ni, J. Sun, Synthesis, 2003, 1574.
18. A. T. Blomquist, T. H. Shelley, J. Am. Chem. Soc., 1948,
70, 147.
49.45; 49.65; 49.92; 63.10 (q, J = 23.0 Hz); 67.26; 127.42 (q,
J = 291.3 Hz); 173.94. 19F NMR (DMSOꢀd6), δ: 95.46 (d, CF3,
3JX,F = 9.3 Hz).
19. N. Takamura, T. Mizoguchi, Tetrahedron Lett., 1973, 14,
4267.
Xꢀray diffraction analysis of the R*,S*ꢀisomer of compound
5a was performed on an Xcalibur 3 automatic singleꢀcrystal

1898
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Cho, Synthesis, 2001, 81.
26. G. M. Sheldrick, SHELXꢀ97, Programs for Crystal Structure
Determination and Refinement, University of Göttingen,
Göttingen (Germany), 1997.
22. V. V. Perekalin, Zh. Org. Khim., 1985, 21, 1111 [J. Org.
Chem. USSR (Engl. Transl.), 1985, 21].
23. J. O. Osby, B. Ganem, Tetrahedron Lett., 1985, 26, 6413.
24. G. M. Dubowchik, J. A. Michne, D. Zuev, Bioorg. Med.
Chem. Lett., 2004, 14, 3147.
25. A. Murray, D. L. Willams, in Organic Synthesis with Isotopes.
Part II. Compounds of Isotopic Hydrogen, Interscience Publ.,
New York, 1958.
Received December 5, 2008;
in revised form June 4, 2009