Mendeleev Commun., 2006, 16(1), 15–16
Stereoselective formation of a 3,5-trans-disubstituted 1,4-tetramethylene-
(
4
tetrahydro-2,2-furylidene)ammonium salt in bromination of 2-phenylthiopent-
-enoic acid dialkylamide
Antonina V. Lozanova, Tanzila M. Ugurchieva, Mikhail V. Zlokazov, Andrei V. Stepanov and
Vladimir V. Veselovsky*
N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 119991 Moscow, Russian Federation.
DOI: 10.1070/MC2006v016n01ABEH002235
The reaction of N-(2-phenylthiopent-4-enoyl)pyrrolidine with bromine results in the stereoselective formation of 1,4-tetra-
methylene(5S*-bromomethyl-3R*-phenylthiotetrahydro-2,2-furylidene)ammonium bromide.
Previously,1,2 we reported a new type of ring–chain tautomerism
that involved a reversible transformation of γ-halobutyric dialkyl-
amides 1 into dialkyl(tetrahydro-2,2-furylidene)ammonium halides
i, SOCl , room temperature
ii, pyrrolidine
OH
2
N
2
. For instance, for X = Br and R = Me, the ratio of tautomers 1
PhS
PhS
PhS
and 2 in a solution in CDCl at 30 °C amounts to 58:42; it
O
O
3
1
changes to 80:20 at 45 °C ( H NMR data). The purpose of this
3
study is to determine whether similar immonium salts can result
from halogen addition to the dialkylamides of γ-unsaturated
carboxylic acids and whether they can undergo ring–chain con-
version.
N
i, NaH, DMF, room temperature
ii, AllBr
O
NR2
R
X
R
N
O
4
N
O
PhS
Br
Br2
CHCl3, 0 °C
X
O
1
2
X = Cl, Br, I
Br
5
†
Enamide 4, which can be easily obtained by the allylation
†
of corresponding acetic acid derivative 3 (96% yield), was the
test compound.
We found that the reaction of dialkylamide 4 with bromine
1.06 equiv.) in CHCl at 0 °C smoothly and stereospecifically
The structure of hitherto unknown salt 5 was confirmed by a
combination of elemental and spectroscopic analyses. In parti-
cular, the relative configuration of substituents in compound 5
1
(
was established using H NMR spectroscopic data. The B3LYP
3
gives 1,4-tetramethylene(5S*-bromomethyl-3S*-phenylthiotetra-
hydro-2,2-furylidene)ammonium bromide 5 (94% yield).
calculations in the 6-31G basis showed that the preferable con-
formations of both possible stereoisomers were characterised
by a considerable deviation of the C-4 atom from the plane
of the tetrahydrofuran ring (Figure 1). The coupling constants
†
†
N-(Phenylthioacetyl)pyrrolidine 3: prepared by routine procedures
5
from known phenylthioacetic acid as colourless crystals, mp 78–79 °C
3
t
1
calculated from these data using the known procedure for the
(
from a hexane–Bu OMe mixture). H NMR (200.13 MHz, CDCl ) d:
3
HC-3, H C-4 and HC-5 protons in trans-isomer 5 are in good
1
.90 (m, 4H, 2CH ), 3.45 (m, 4H, 2CH N), 3.64 (s, 2H, CH S), 7.25
2
2
2
2
–
1
agreement with experimental data (Table 1). For cis-5, the
deviation of the calculated constants from the observed values
is more considerable, up to the full discrepancy for Jα-HC-4–HC-5
2.72 Hz (Jexp 6.4 Hz). The final conclusion on the relative
trans-configuration of substituents in salt 5 was made based on
measurements of Overhauser’s nuclear effects, which showed a
spatial proximity of the α-HC-4 and HC-5 protons with the
phenyl group’s ortho protons, as well as an NOE for the HC-3
and 7.45 (2m, 5H, H-aryl). IR (KBr, n/cm ): 684, 728, 812, 912, 1028,
1
1
068, 1164, 1192, 1228, 1252, 1344, 1416, 1436, 1484, 1572, 1588,
620, 1636, 2872, 2948, 2968, 3060. Found (%): C, 65.31; H, 6.80;
N, 6.24; S, 14.22. Calc. for C H NOS (%): C, 65.12; H, 6.83; N, 6.33;
12
15
S, 14.49.
(
±)-N-(Phenylthiopent-4-enoyl)pyrrolidine 4: colourless crystals,
t
1
mp 46–47 °C (from a hexane–Bu OMe mixture). H NMR (200.13 MHz,
CDCl ) d: 1.80 (m, 4H, 2CH ), 2.45 and 2.76 (2m, 2H, HC-3), 3.40 (m,
3
2
4
5
6
1
H, 2CH N), 3.70 (dd, 1H, CHS, J 11 and 6 Hz), 5.10 (m, 2H, H C=),
2
2
and β-HC-4 protons with one of the CH Br protons.
–
1
2
.80 (m, 1H, HC=), 7.30 and 7.50 (2m, 5H, H-aryl). IR (KBr, n/cm ):
92, 752, 808, 928, 1012, 1064, 1112, 1192, 1256, 1328, 1440, 1472,
572, 1628, 1640, 2876, 2908, 2932, 2968, 3064. Found (%): C, 69.07;
A thorough NMR study of the solutions of analytically pure
salt 5 in CDCl did not show any additional signals that could
3
suggest its reversible transformation into the corresponding
chain form (cf. refs. 1 and 2).
H, 7.17; N, 5.47; S, 12.01. Calc. for C H NOS (%): C, 68.92; H, 7.33;
1
5
19
N, 5.36; S, 12.27.
1
,4-Tetramethylene(5S*-bromomethyl-3R*-phenylthiotetrahydro-2,2-
Note that immonium salts like compound 5 are postulated to
be likely intermediates in the halolactonisation of γ-unsaturated
furyliden)ammonium bromide 5: colourless crystals (from MeCN),
mp 131–136 °C. H NMR (200.13 MHz, CDCl ) d: 1.90–2.35 (m, 4H,
CH ), 2.58 (ddd, 1H, HC-4e, J 1.0, 6.4, 13.9 Hz), 3.44 (ddd, 1H, H-4a,
J 8.5, 9.8, 13.9 Hz), 3.50–3.70 (m, 2H, CH N), 3.69 (dd, 1H, CH–Br,
1
3
Table 1 Calculated coupling constants (Jcalc) and H–C–C–H torsion angles
2
2
(
jcalc) for proton pairs in stereoisomers 5.
2
J 6.3 Hz, J 10.8 Hz), 3.86 (dd, 1H, CH–Br, J 7.1, 10.8 Hz), 3.90–4.00
trans-5
cis-5
(
6
m, 1H, CHN), 4.19–4.32 (m, 1H, CHN), 4.68 (dddd, 1H, HC-5, J 6.3,
.4, 7.1, 9.8 Hz), 5.11 (dd, 1H, HC-3, J 8.5, 1.0 Hz), 7.37–7.54 (m, 5H,
Jexp
jcalc/°
Jcalc/Hz
jcalc/°
Jcalc/Hz
–1
H-aryl). IR (KBr, n/cm ): 508, 656, 708, 780, 800, 852, 976, 1060,
1
2
128, 1152, 1208, 1248, 1300, 1344, 1404, 1420, 1452, 1692, 2840,
876, 2948, 3012. Found (%): C, 43.16; H, 4.60; Br, 37.48; N, 3.40;
HC-3 – β-HC-4
HC-3 – α-HC-4
23.3
87.8
7.69
0.98
9.34
5.42
23.5
95.9
14.4
8.91
1.17
8.39
2.72
8.5
1.0
9.8
6.4
β-HC-4 – HC-5 158.5
α-HC-4 – HC-5 38.0
S, 7.48. Calc. for C H Br NOS (%): C, 42.77; H, 4.55; Br, 37.94;
1
5
19
2
105.2
N, 3.33; S, 7.61.
Mendeleev Commun. 2006 15
Lozanova, Antonina V.
