Enaminosulfones from 3-trifloxypropene iminium salts: A 1,5(O→C) trifluoromethylsulfonyl shift

Article abstract of DOI:10.1515/znb-2002-0408

Treatment of semicyclic 3-trifloxypropene iminium triflates 4a-c,e,f, in which the iminium function is part of a six-membered ring, with a polymer-supported tertiary amine leads to 3-[(trifluoromethyl)sulfonyl]-1,4,5,6-tetrahydropyridines 7. Related five-

Full text of DOI:10.1515/znb-2002-0408

Enaminosulfones from 3-Trifloxypropene Iminium Salts: A 1,5(O5C)
Trifluoromethylsulfonyl Shift*
Ralf Neumann, Hans-Georg Herz, and Gerhard Maas
Division of Organic Chemistry I, University of Ulm, Albert-Einstein-Allee 11, D-89081 Ulm
Reprint requests to Prof.Dr.G.Maas.E-mail: gerhardm. aas@chemieu. ni-ulmd. e
Dedicated to Prof. Dr. Bärbel Schulze on the occasion of her 60th birthday
Z.Naturforsch. 57b, 427Ð434 (2002); received February 4, 2002
Enamines, Iminium Salts, Rearrangement
Treatment of semicyclic 3-trifloxypropene iminium triflates 4aÐc,e,f, in which the iminium
function is part of a six-membered ring, with a polymer-supported tertiary amine leads to 3-
[(trifluoromethyl)sulfonyl]-1,4,5,6-tetrahydropyridines 7.Related five- and seven-membered
cyclic iminium salts do not react to give the corresponding enaminosulfones.
Introduction
study has already been reported by us [9].The new
salts 4aÐc were obtained in the same manner, i.e.
by O-sulfonylation of enaminoketones 3aÐc with
triflic anhydride.The enaminoketones were ob-
tained in two steps, by analogy with published pro-
cedures [9, 10] from N-substituted lactams 1a,b via
the corresponding lactam acetals 2a,b (Scheme 1).
The NMR spectra of 4aÐc indicated the presence
of only one isomer to which the Z, s-trans configu-
ration of the propene iminium unit was assigned
by analogy with related salts [3, 9].
Triflic anhydride (Tf2O) is the reagent of choice
for the introduction of the trifluoromethylsulfonyl
(CF3SO2) group into a variety of organic sub-
strates, and the resulting compounds often have a
unique chemical reactivity [1].A case in point is
given by 3-trifloxypropene iminium triflates which
are obtained by O-sulfonylation of enaminones
with Tf2O [2, 3] and which are suited for trans-
formations that are not known for related [4] 3-
chloropropene iminium salts.3-Trifloxypropene
iminium triflates are susceptible to nucleophilic
substitution [2, 5], can be involved in intra- [6] und
intermolecular [7] aromatic substitution reactions,
and can be transformed into a wide range of pro-
pyne iminium triflates by ꢀ-elimination of triflic
acid [6, 8, 9].The latter transformation is either
achieved with the help of a tertiary amine base or
under purely thermal conditions.
In this communication, we report that certain
semicyclic 3-trifloxypropene iminium triflates
upon treatment with an amine base do not yield
propyne iminium triflates but are converted into
enaminosulfones.
Results and Discussion
The preparation of the semicyclic 3-trifloxypro-
pene iminium triflates 4dÐg investigated in this
* Presented in part at the 5th Conference on Iminium
Salts (ImSaT-5), Stimpfach-Rechenberg (Germany), Scheme 1.Conditions: a) (MeO) 2SO2, 80 ∞C, then
September 11Ð13, 2001.
NaOEt (2 equiv.); b) H3CCOAr, 80 ∞C. Tf = CF3SO2.
0932Ð0776/2002/0400Ð0427 $06.00 ” 2002 Verlag der Zeitschrift für Naturforschung, Tübingen · www.znaturforsch.com
D
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428
R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
When iminium salts 4b,c were kept in acetoni- removed conveniently by filtration from the pro-
trile solution at 20 ∞C, elimination of triflic acid duct mixture.Treatment of 4aÐc with this base led
(HOTf) from the cation took place, and a mixture to the formation of the cyclic enaminosulfones
of propyne iminium triflates 5 and tricyclic azepi- 7aÐc in good yields (Scheme 3).In the same man-
nium salts 6 was obtained (Scheme 2).This trans-
ner, the N-allyl or N-homoallyl-substituted imi-
formation was complete within one day, and it was nium salts 4e,f were converted into 7e,f (Scheme
found that the ratio 5b:6b remained unchanged af- 4).The identity of these compounds was estab-
ter 77 days in solution.The analogous conversion
lished by an X-ray crystal structure analysis of 7f
of 4a into a mixture of 5a and 6a required a higher (Fig.1).The 1H and 13C signals of the enaminosul-
activation energy; it was achieved by heating at fones could be fully assigned with the help of
160 ∞C in acetonitrile solution in a closed pressure 1H,13C correlation spectra (gs-HMBC); the 13C
vessel.Only in this case, a separation of the two
iminium salts 5 and 6 was undertaken.
chemical shifts are given in Table 1.An interesting
1
detail in the H NMR spectra (500 MHz) of 7aÐc
is the temperature-dependency of the signal for
the exocyclic CH2CO protons, which is very broad
at 305 K but appears as a sharp singlet at 343 K.
This dynamic behavior is probably associated with
the heavy 1,2,3-trisubstitution of the tetrahy-
dropyridine ring which slows down the free rota-
tion around the CringÐCmethylene bond (C2ÐC3 in
Fig.1).
The formation of enaminosulfones 7 is likely to
begin with deprotonation at the ring position C-3
Scheme 2.See Table 1 for conditions and yields.
The smooth elimination of triflic acid from (3-
thienyl)-substituted 3-trifloxypropene iminium
salts 4b,c with formation of a propyne iminium salt
was not unexpected, since we have observed be-
fore that this transformation is facilitated when the
trifloxy-substituted carbon atom of 4 bears an
electron-donating (het)aryl substituent [3, 9].On
the other hand, the formation of azepinium salts
6aÐc is a novel feature of the reactivity of 3-
trifloxypropene iminium salts [10].The scope of
this 1,7-cyclization reaction, which can be consid-
ered as an intramolecular aromatic substitution re-
action, will be described elsewhere.
We were surprised to find that the ꢀ-elimination
of HOTf from propene iminium salts 4aÐc could
not be achieved, as in other cases, with the help of
an amine base.A polymer-supported base, di-
methylaminomethyl-polystyrene, was used for this
purpose, since the resulting ammonium salt can be
Scheme 3.See Scheme 1 for R and Ar.
Table 1.Thermal elimination of triflic acid from 4aÐc
(solvent: acetonitrile); conditions and products (see
Scheme 2).
Com-
pound
Conditions
Products
4a
4b
4c
160 ∞C/4 h
20 ∞C/29 h
20 ∞C/11 h
5a (71%), 6a (18%)a
5b (44.5%), 6b (55.5%)b
4c (7%), 5c (55%), 6c (38%)b
a
Yields of isolated products;
products not separated; relative yields are given.
b
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R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
429
Scheme 4.Conditions: a) Dimethylaminomethyl-poly-
styrene, CH3CN, 1 h, rt.
however, the yield was considerably lower than in
the thermally induced [9] elimination reaction (45
vs. 81%).The six-membered cyclic iminium salts
4e,f afforded enaminosulfones 7e,f in good yields.
From the seven-membered system 4 g, an unde-
fined product mixture was obtained in which nei-
ther a propyne iminium salt nor an enaminosul-
fone could be detected by NMR spectroscopy; the
broad NMR signals rather indicated the formation
of oligomeric product.On the other hand, the exo-
cyclic N-substituent appears to be important, too:
Treatment of the iminium salt analogous to 4e, but
with N-Me instead of N-allyl, with the polymer-
supported amine base gave again an unspecified
Fig.1. Stereographic plot (ORTEP) of the structure of
7f in the crystal.Hydrogen atoms are not shown.The N-
homoallyl group occupies two positions, corresponding
to a pseudoequatorial and pseudoaxial orientation with
respect to the tetrahydropyridine ring which assumes a
half-chair conformation.Dashed bonds mark the disor-
˚
der of the homoallyl group.Selected bond lengths [A ]:
S-O2 1.431(2), S-O3 1.431(3), S-C4 1.689(3), C4-C5
1.372(4), C5-N 1.330(4). Bond lengths [∞]: S-C4-C5
123.4(2), C4-C5-C6 123.7(2), N-C5-C6 115.3(2), C5-N-
C15a 125.9(3), C5-N-C15b 118.2(4). Torsion angles [∞]:
C3-C4-C5-N 8.2(4), C4-C5-N-C15a 151.9(4), C4-C5-N- product mixture rather than an enaminosulfone.
C15b-159.6(4), N-C5-C6-C7 83.6(3).
These results show that the base treatment of
semicyclic iminium salts 4 depends in a delicate
manner on ring size and substituents at the pro-
pene iminium unit.Further experiments will show
of iminium salts 4 (Scheme 4).The facile deproto-
whether some of the present limitations of our en-
nation of iminium salts at this position is known aminosulfone synthesis can be overcome by the
[11, 12].In the resulting enamine (shown as the
use of a different base.
dipolar resonance structure), 1,5(O5C) migra-
The transformation 457 represents a novel ap-
tion of the CF3SO2 group could occur, and a sub- proach to ꢀ-(trifluoromethylsulfonyl) enamines.
sequent tautomerization would provide the final Compounds of this type [13Ð17] as well as other
product.
enaminosulfones [18, 19] have been prepared by
The relevance of the six-membered cyclic imi- several different methods none of which would al-
nium salt structure for this transformation was il- low the synthesis of the cyclic enamines 7.Cyclic
lustrated by some experiments with five- to seven- ꢀ-tosyl enamines have recently been used as pre-
membered iminium salts 4dÐg which were all cursors to indolizidine alkaloids [20].Due to their
treated with dimethylaminomethyl-polystyrene combination of different functional groups, tetra-
(Scheme 4).From the five-membered ring system
hydropyridines 7 should also be useful for further
4d, only propyne iminium salt 5d was obtained; synthetic transformations.
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430
R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
Table 2. 13C NMR data of enaminosulfones 7aÐc,e,f (in CD3CN, δ/ppm).
Com- NCH2,ring NCH2CH2 N(CH2)2CH2 NC=C NC=C NCH2R CF3
CH2CO C=O Other signals
pound
(1JC,F [Hz])
7a
50.6
50.7
50.5
21.9
21.9
21.9
25.1
25.2
25.4
89.3
89.7
89.5
158.5 52.2
158.8 56.2
158.3 52.2
122.3
(328.5)
41.0
42.0
41.9
194.3 123.5 (C-2Thie), 127.7 (C-4Thie),
128.1 (C-5Thie), 129.9 (CAr), 130.8
(CAr), 135.7 (C-Cl), 138.2
(C-3Thie), 140.3 (C-1Ar
)
7b
7c
122.4
(328.1)
189.4 127.6 (C-4Thie), 127.7 (o-CPh),
128.1 (C-5Thie), 128.7 (p-CPh),
129.9 (m-CPh), 134.3 (C-2Thie),
137.2 (C-1Ph), 141.9 (C-3Thie
)
122.3
(328.2)
189.4 CH2-Thienyl: 123.4 (C-2), 127.6
(C-4), 128.1 (C-5), 138.2 (C-3);
CO-Thienyl: 127.6 (C-4), 128.1
(C-5), 134.3 (C-2), 141.9 (C-3)
194.3 117.5 (=CH2), 129.9 (o-CAr),
130.8 (m-CAr), 133.6 (CH=CH2),
135.7 (C-1Ar), 140.3 (C-Cl)
7e
7f
50.6
50.5
22.0
21.9
25.1
25.2
88.8
88.4
158.7 55.3
158.4 52.6
122.4
(328.3)
40.8
40.8
122.4
(328.3)
194.2 33.2 (CH2CH=CH2), 118.2
(=CH2), 130.0 (o-CAr), 130.8
(m-CAr), 135.5 (CH=CH2), 135.7
(C-1Ar), 140.3 (C-Cl)
Experimental Section
toluene (20 ml) during 90 min, the mixture was
heated at reflux for 2 h.The precipitate of NaBr
was separated by centrifugation, the solvent was
evaporated, and the residue was distilled at 125Ð
132 ∞C/0.01 mbar to give 9.79 g (54%) of 1a as a
colorless liquid. Ð IR: ν = 1640, 1492, 1465, 1447,
1415, 1352, 1331, 1269 (all vs), 1230, 1176, 992, 959
General remarks
Reactions were carried out in dry solvents and
under an argon atmosphere.Dimethylamino-
methyl-polystyrene was heated at 90 ∞C for 5 days
to remove water.Triflic anhydride was distilled
from phosphorus pentoxide prior to use.
1
(all s) cmÐ1. Ð H NMR (CDCl3, 200.13 MHz):
NMR spectra were taken on Bruker AMX 500
and AC 200 instruments.As the internal reference,
Me4Si was used for the proton spectra and the
solvent signal for the 13C NMR spectra
[δ(CDCl3 = 77.0 ppm, δ(CD3CN) = 1.3 ppm].
Throughout the experimental section, signal as-
signments 2Ј-HÐ6Ј-H and C-2ЈÐC-6Ј are for the
tetrahydropyridine ring.IR spectra were recorded
on a Perkin Elmer IR 883 spectrometer.Micro-
analyses were carried out with an analyzer system
Elementar Vario El at the Division of Analytical
Chemistry of the University of Ulm.Column chro-
matography was performed under hydrostatic con-
ditions (silica gel 60, Macherey-Nagel, 70Ð230
mesh).
δ = 1.73Ð1.80 (m, 4H, 4-H, 5-H), 2.42 (m, 2 H, 3-
H), 3.22 (m, 2 H, 6-H), 4.56 (s, 2 H, NCH2Thie),
7.01 (dd, 1 H, 2-HThie), 7.12 (dd, 1 H, 4-HThie), 7.27
(dd, 1 H, 5-HThie). Ð 13C NMR (CDCl3, 50.3
MHz): δ = 21.5, 23.3, 32.5 (C-3), 45.5 (NCH2Thie),
47.3 (C-6), 122.8, 126.1, 127.8, 138.2, 169.7 (C=
O). Ð C10H13NOS (195.28).
1-(4-Chlorophenyl)-2-{1-[(thien-3-yl)methyl]-
hexahydropyridin-2-ylidene}-1-ethanone (3a)
A two-phase mixture of 1a (15.62 g, 0.08 mol)
and of dimethyl sulfate (10.09 g, 0.08 mol) was
heated at 80 ∞C for 12 h.After cooling, the homo-
geneous oil was washed with ether (50 ml), and
residual solvent was removed in vacuo.The resi-
due was slowly added to a solution of NaOEt
1-(3-Thienylmethyl)piperidin-2-one (1a)
A suspension of sodium (2.30 g, 0.10 g-atom) in [from sodium (3.68 g, 0.16 g-atom) in ethanol
toluene (200 ml) was heated at reflux and a solu- (80 ml)].After 2 h, the precipitate was filtered off
tion of piperidin-2-one (9.90 g, 0.10 mol) in tolu- with suction under argon, the solvent was evapo-
ene (40 ml) was added during 2 hours.The mixture
rated, and the residue was distilled at 130 ∞C/0.008
was kept at reflux temperature for additional 4 h, mbar to give 17.78 g of 2,2-diethoxy-1-[(thien-3-yl)-
during which time a white jelly-like solid formed, methyl]piperidine (2a) which was used immedi-
then cooled to rt.After addition of a solution of
ately. A mixture of this acetal (17.78 g, 0.066 mol)
3-(bromomethyl)thiophene (17.7 g, 0.10 mol) in and of 4-chloroacetophenone (10.20 g, 0.066 mol)
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R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
431
was heated at 80 ∞C for 10 h.The alcohol formed
was evaporated at 14 mbar, and the liquid residue
was removed in vacuo, and the remaining oil was was converted into a solid by addition of ether and
converted into a solid by addition of ether and vigorous stirring.Recrystallization from EtOH-
vigorous stirring.Recrystallization from EtOH Ð ether provided 3c (23.83 g, 79%) as a finely crys-
ether gave 3a (15.29 g, 70%) as colorless flakes; talline solid, m.p. 105 ∞C. Ð IR (KBr): ν = 1589
m.p. 127Ð128 ∞C. Ð IR (KBr): ν = 1608 (s), 1586 (s), 1529 (vs), 1483 (vs), 1354 (m), 1324 (m), 1299
(m), 1566 (m), 1535 (vs), 1518 (vs), 1473 (s) cmÐ1. Ð (m), 1272 (m), 1260 (m), 1227 (m), 1175 (s), 1074
1
1H NMR (CDCl3, 500.14 MHz): δ = 1.70Ð1.75 (m, (m) cmÐ1. Ð H NMR (CDCl3, 500.14 MHz): δ =
2 H, 4Ј-CH2), 1.79Ð1.84 (m, 2 H, 5Ј-CH2), 3.38 1.72 (quin, 2 H, 4Ј-CH2), 1.81 (quin, 2 H, 5Ј-CH2),
(2 t, 4 H, 3Ј-CH2, 6Ј-CH2), 4.50 (s, 2 H, 3.36Ð3.39 (m, 4 H, 3Ј-CH2, 6Ј-CH2), 4.50 (s, 2 H,
NCH2Thie), 5.78 (s, 1 H, 2-H), 6.99 (dd, 1 H, J = NCH2Thie), 5.76 (s, 1 H, 2-H), 7.01 (dd, J = 5.0,
5.0, 1.4 Hz, 4-HThie), 7.10 (dd, 1 H, J = 3.0, 1.3 Hz, 1.3 Hz, 1 H), 7.12 (dd, J = 3.0, = 1.3 Hz, 1 H), 7.17
2-HThie), 7.33 (dd, 1 H, J = 5.0, 3.0 Hz, 5-HThie), (dd, J = 5.0, 3.0 Hz, 1 H), 7.34 (dd, J = 5.0, = 3.0
7.26/7.62 (AAЈBBЈ, 4 HAr). Ð 13C NMR (CDCl3, Hz, 1 H), 7.35 (dd, J = 5.0, 1.3 Hz, 1 H), 7.63 (dd,
125.8 MHz): δ = 19.1 (C-4Ј), 22.8 (C-5Ј), 28.3 J = 3.0, 1.3 Hz, 1 H). Ð 13C NMR (CDCl3, 125.8
(C-3Ј), 50.2 (C-6Ј), 51.8 (NCH2Thie), 90.8 MHz): δ = 19.2 (C-4Ј), 23.9 (C-5Ј), 28.1 (C-3Ј), 50.1
(NC=C), 121.6 (C-2Thie), 126.3 (C-4Thie), 126.7 (C-6Ј), 51.7 (NCH2Thie), 91.7 (NÐC=C), 121.5,
(5-CThie), 127.9, 128.4, 135.8 (CÐCl), 136.2 (C- 124.8, 126.3, 126.5, 126.8, 127.0, 136.5, 146.9, 164.0
3Thie), 141.2, 164.7 (NC=C), 185.9 (C=O). Ð (C-2Ј), 181.7 (C=O) Ð C16H17NOS2 (303.45):
C18H18ClNOS (331.86): calcd. C 65.15, H 5.47, calcd. C 63.33, H 5.65, N 4.62; found C 62.94, H
N 4.22; found C 64.93, H 5.59, N 4.19.
5.70, N 4.57.
6-{(Z)-2-(4-Chlorophenyl)-2-[(trifluoromethyl)-
sulfonyloxy]ethenyl}-1-(3-thienylmethyl)-2,3,4,5-
tetrahydropyridinium trifluoromethanesulfonate
(4a)
2-(1-Benzylhexahydropyridin-2-ylidene)-1-
(3-thienyl)-1-ethanone (3b)
By analogy with the preceding procedure, 1-
benzylpiperidin-2-one (1b) was converted into 1-
benzyl-2,2-diethoxypiperidine (2b, b.p. 121 ∞C/
0.009 mbar). Reaction of freshly distilled 2b
(97.5 g, 0.37 mol) with 3-acetylthiophene (46.7 g,
0.37 mol) and work-up as described above pro-
vided 3b (89.1 g, 81%) as a yellow solid, m.p. 113Ð
114 ∞C. Ð IR (KBr): ν = 1601 (m), 1529 (vs), 1480
(s), 1449 (m), 1353 (m), 1329 (m), 1228 (m), 1170
A
solution of enaminoketone 3a (3.32 g,
10.0 mmol)) in CH2Cl2 (15 ml) was added drop-
wise to a cooled (Ð18 ∞C) solution of triflic anhy-
dride (1.85 ml, 11.0 mmol) in CH2Cl2 (10 ml).Af-
ter stirring for 30 min at Ð18 ∞C and for 30 min at
20 ∞C, most of the solvent was evaporated at 0.01
mbar.Ether was added until the solution re-
mained turbid.Upon cooling at 0 ∞C, solid 4a sep-
arated which was recrystallized from CH2Cl2-ether
to give a colorless solid, m.p. 107Ð108 ∞C; yield:
4.50 g (74%). Ð IR (KBr): ν = 1667 (m), 1593 (w),
1534 (w), 1491 (w), 1415 (s), 1267 (vs), 1223 (sh),
1158 (s), 1135 (s), 1091 (m), 1031 (vs), 1015 (m)
cmÐ1. Ð 1H NMR (CD3CN, 500.14 MHz): δ = 1.86
(quin, 2 H, 4Ј-CH2), 1.93 (mc, 2 H, 3Ј-CH2), 3.17
(t, 2 H, 5Ј-CH2), 3.79 (t, 2 H, 2Ј-CH2), 5.23 (s, 1
H, NCH2Thie), 7.21 (dd, J = 5.1, 1.4 Hz, 1 H, 4-
1
(s), 1074 (m) cmÐ1. Ð H NMR (CDCl3, 500.14
MHz): δ = 1.67 (quin, 2 H, 4Ј-CH2), 1.75 (quin, 2
H, 5Ј-CH2), 3.23Ð3.39 (m, 4 H, 3Ј-CH2, 6Ј-CH2),
4.44 (s, 2 H, NCH2Ph), 5.58 (s, 1 H, 2-H), 7.04 (dd,
J = 5.0, 3.0 Hz, 1 H, 5-HThie), 7.13 (d, 2 H, o-HPh),
7.19 (dd, 1 H, 4-HThie), 7.20 (t, 1 H, p-HPh), 7.28
(t, 2 H, m-HPh), 7.46 (m, J = 3.0, 1.6 Hz, 1 H, 2-
H
Thie). Ð 13C NMR (CDCl3, 125.8 MHz): δ = 19.3
(C-4Ј), 23.0 (C-5Ј), 28.1 (C-3Ј), 50.6 (C-6Ј), 55.9
(NCH2Ph), 92.0 (NÐC=C), 124.8 (C-5Thie), 126.2
(o-CPh), 126.7 (C-2Thie), 127.0 (C-4Thie), 127.3 (p-
CPh), 128.8 (m-CPh), 135.6 (C-1Ph), 147.0 (C-3Thie),
164.3 (C-2Ј), 181.9 (C=O). Ð C18H19NOS (297.41):
calcd. C 72.69, H 6.44, N 4.71; found C 71.49, H
6.46, N 4.79.
H
Thie), 7.22 (t, J = 1. 7 Hz, 1 H, Holefin), 7.52 (dd,
J = 5.0, 3.0 Hz, 1 H, 5-HThie), 7.57/7.77 (AAЈBB’,
4
4 HAr), 7.65 (dd, J = 3.0, 1.3 Hz, 1 H, 2-HThie). Ð
13C{1H} NMR (CD3CN, 125.8 MHz): δ = 17.4 (C-
4Ј), 21.2 (C-3Ј), 33.9 (C-5Ј), 54.1 (C-2Ј), 58.1 (N-
1
CH2Thie), 114.9 (N=C-C), 119.1 (q, JC,F = 320.1
Hz, OTfcov), 122.1 (q, JC,F = 320.4 Hz, TfOÐ),
1
1-(3-Thienyl)-2-[1-(3-thienylmethyl)hexa-
hydropyridin-2-ylidene]-1-ethanone (3c)
128.8 (CThie), 128.9 (CThie), 129.9 (m-CAr), 130.0
(C-1Ar), 130.5 (o-CAr), 131.6 (C-3Thie), 139.5 (C-
A mixture of acetal 2a (see above, 26.94 g, 0.10 Cl),
152.0
(C-OTf),
181.8
(C-6Ј).
Ð
mol) and of 3-acetylthiophene (12.62 g, 0.10 mol) C22H18ClF6NO6S3 (613.99): calcd. C 39.12, H 2.95,
was heated at 80 ∞C for 12 h.The alcohol formed
N 2.28; found C 39.10, H 2.92, N 2.31.
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432
R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
1-Benzyl-6-{(Z)-2-(3-thienyl)-2-[(trifluoromethyl)-
sulfonyloxy]ethenyl}-2,3,4,5-tetrahydopyridinium
trifluoromethanesulfonate (4b)
C18H17F6NO6S4 (585.56): calcd. C 36.92, H 2.93, N
2.39; found C 36.60, H 3.21, N 2.31.
6-[2-(4-Chlorophenyl)ethynyl]-1-[(thien-3-yl)-
methyl]-2,3,4,5-tetrahydropyridinium trifluoro-
methanesulfonate (5a) and 11-(4-chlorophenyl)-
4,5,8,9-tetrahydro-6H-pyrido[1,2-a]thieno[2,3-e]-
azepinium trifluoromethanesulfonate (6a)
Prepared as described for 4a from enaminoke-
tone 3b (2.23 g, 7.5 mmol) in CH2Cl2 (25 ml) and
Tf2O (1.39 ml, 8.3 mmol) in CH2Cl2 (25 ml) at
Ð18 ∞C.Colorless solid, mp..72
∞C; yield: 3.30 g
(76%). Ð IR (KBr): ν = 1661 (s), 1423 (s), 1282
(vs), 1264 (vs), 1232 (s), 1220 (s), 1202 (s), 1167
A solution of 4a (4.91 g, 8.0 mmol) in CH3CN
(10 ml) was heated at 160 ∞C for 4 h in a closed
thick-walled Schlenk tube.After cooling, the solu-
tion was concentrated to half the volume and
ether was added until an oil separated.The super-
natant solution was removed with a pipette, the oil
was dissolved in CH3CN (10 ml), and ether was
added until the cloudiness of the solution no
longer disappeared immediately after addition.
Upon cooling at Ð78 ∞C, a brownish solid sepa-
rated which was isolated by filtration (the mother
liquor was kept, vide infra) and recrystallized from
CH3CN-ether to yield 6a as a yellow solid.To the
mother liquor was added ether until the solution
remained turbid.Vigorous stirring at 0 ∞C caused
the separation of a brownish solid which was
recrystallized from CH2Cl2-ether at Ð30 ∞C to fur-
nish 5a as a dark-yellow solid.
(s), 1155 (s), 1142 (s), 1029 (s) cmÐ1. Ð H NMR
1
(CD3CN, 500.14 MHz, 263 K): δ = 1.81Ð1.85 (m,
2 H, 4Ј-H), 1.88Ð1.92 (m, (2 H, 3Ј-H), 3.18 (s, br,
2 H, 5Ј-H), 3.73 (t, 2 H, 2Ј-H), 5.23 (s, 2 H,
NCH2Ph), 7.28 (s, 1 H, Holefin), 7.44Ð7.50 (m, 5 H,
HPh), 7.56 (dd, J = 5.1, 1.4 Hz, 1 H, 4-HThie), 7.63
(dd, J = 5.3, 3.1 Hz, 1 H, 5-HThie), 8.05 (dd, J = 2. 8
Hz, 1.6 Hz, 1 H, 2-HThie). Ð 13C{1H} NMR
(CD3CN, 50.32 MHz, 263 K): δ = 17.3 (C-4Ј), 20.9
(C-3Ј), 33.6 (C-5Ј), 53.8 (C-2Ј), 62.6 (NCH2Ph),
1
112.3 (N=C-CH), 118.9 (q, JC,F = 319.8 Hz,
1
OTfcov), 121.7 (q, JC,F = 320.3 Hz, TfOÐ), 126.4
(C-4Thie), 130.0 (C-5Thie), 130.1 (CPh), 130.3 (CPh),
130.9, 131.0, 131.7 (C-1Ph), 132.9 (C-3Thie), 148.7
(C-OTf), 181.6 (s, C-6Ј).
(579.56): calcd. C 41.45, H 3.30, N 2.42; found
C 41.25, H 3.22, N 2.46.
Ð C20H19F6NO6S3
5a: Yield: 2.63 g (71%); m.p. 127Ð128 ∞C. Ð IR
(KBr): ν = 2208 (vs, CϵC), 1640 (s), 1278, 1261,
1156, 1029 (all vs) cmÐ1. Ð 1H NMR (CD3CN,
500.14 MHz): δ = 1.80Ð1.87 (m, 2 H, 4Ј-CH2),
1.90Ð1.96 (m, 2 H, 3Ј-H), 3.11 (t, 2 H, 5Ј-H), 3.77
(m, 2 H, 2Ј-H), 5.32 (s, 2 H, NCH2Thie), 7.21 (dd,
J = 5.0, 1.4 Hz, 1 H, 4-HThie), 7.52 (dd, J = 5.0, 3.0
1-(3-Thienylmethyl)-6-{(Z)-2-(3-thienyl)-2-[(tri-
fluoromethyl)sulfonyloxy]ethenyl}-2,3,4,5-tetra-
hydropyridinium trifluoromethanesulfonate (4c)
Prepared as described for 4a from enaminoke- Hz, 1 H, 5-HThie), 7.63 (dd, J = 2.9, 1.4 Hz, 1 H, 2-
tone 3c (1.52 g, 5.0 mmol) in CH2Cl2 (15 ml) and
H
Thie), 7.55/7.74 (AAЈBB’, 4 H, HAr). Ð 13C{1H}
Tf2O (0.92 ml, 5.5 mmol) in CH2Cl2 (10 ml) at Ð NMR (CD3CN, 125.8 MHz): δ = 17.4 (C-4Ј), 21.2
16 ∞C.Bright-yellow solid, mp. .105 Ð106 ∞C; yield: (C-3Ј), 35.1 (C-5Ј), 53.8 (C-2Ј), 59.0 (NCH2Thie),
2.40 g (82%). Ð IR (KBr): ν = 1662 (s), 1422 (vs), 83.6 (CϵCAr), 114.0 (CϵCAr), 117.8 (C-1Ar),
1
1264 (vs), 1248 (s), 1231 (s), 1222 (s), 1205 (s), 122.1 (q, JC,F = 320.8 Hz, TfOÐ), 128.0, 128.5,
1161 (s), 1141 (s), 1031 (s) cmÐ1. Ð 1H NMR 128.8 (3 CThie), 130.5 (CAr), 132.6 (C-3Thie), 136.1
(CD3CN, 500.14 MHz, 273 K): δ = 1.81 (mc, 2 H, (o-CAr), 140.0 (C-Cl), 167.7 (C-6Ј).
4Ј-H), 1.89 (mc, 2 H, 3Ј-H), 3.12 (t, 2 H, 5Ј-H), 3.73 C19H17ClF3NO3S2 (463.92): calcd. C 49.19, H 3.69,
(t, 2 H, 2Ј-H), 5.19 (s, 2 H, NCH2Thie), 7.14 (t, 1 N 3.02; found C 48.62, H 3.91, N 2.87.
Ð
H, Holefin); CH2-thienyl: 7.18 (dd, J = 5.0, 1.3 Hz,
6a: Yield: 0.66 g (18%); m.p. 194 ∞C. Ð IR (KBr):
1 H, 4-H), 7.51 (dd, J = 5.0, 3.0 Hz, 1 H, 5-H), 7.63 ν = 1640 (m), 1554 (s), 1514 (m), 1491 (m), 1441 (s),
(dd, J = 3.0, 1.3 Hz, 1 H, 2-HThie); C(OTf)-thienyl: 1385 (m), 1263 (vs), 1225 (s), 1152 (s), 1031 (vs)
7.52 (dd, J = 5.1, 1.4 Hz, 1 H, 4-H), 7.61 (dd, J = cmÐ1. Ð 1H NMR (CD3CN, 500.14 MHz): δ = 1.77Ð
5.3, 2.9 Hz, 1 H, 5-H), 8.01 (dd, J = 3.0, 1.4 Hz, 1 1.86 (m, 4 H, 7-H, 8-H), 2.96 (t, 2 H, 9-H), 3.96 (t,
H, 2-H). Ð 13C{1H} NMR (CD3CN, 125.8 MHz, 2 H, 6-H), 4.73 (s, 2 H, 4-H), 6.75 (s, 1 H, 10-H), 7.34
273 K): δ = 17.3 (C-4Ј), 21.0 (C-3Ј), 33.6 (C-5Ј), (d, J = 5.1 Hz, 1 H, 3-H), 7.54/7.62 (AAЈBB’, 4 HAr),
53.7 (C-2Ј), 57.6 (NCH2Thie), 112.2 (N=C-CH), 7.97 (d, J = 5.1 Hz, 1 H, 2-H). Ð 13C{1H} NMR
118.9 (q, 1JC,F = 319.5 Hz, OTfcov), 121.5 (q, 1JC,F
=
(CD3CN, 125.8 MHz): δ = 17.8 (C-8), 21.7 (C-7),
320.0 Hz, TfOÐ), 126.5, 128.7 (3 CThie), 130.0, 32.3 (C-9), 55.6 (C-4), 55.6 (C-6), 121.5 (C-10),
130.9, 131.6, 132.9, 148.7 (C-OTf), 181.3 (C-6Ј). Ð 128.7 (C-3), 129.9 (CAr), 132.6 (CAr), 136.1
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R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
433
(C-2), 136.6 (C-3a), 137.8 (C-Cl), 138.8 (C-11a), 1-(Thien-3-yl)-2-{1-[(thien-3-yl)methyl]-3-
141.2 (C-1Ar), 150.9 (C-11), 175.2 (C-9a). Ð [(trifluoromethyl)sulfonyl]-1,4,5,6-
C19H17ClF3NO3S2 (463.92): calcd. C 49.19, H 3.69, tetrahydropyridin-2-yl}ethan-1-one (7c)
N 3.02; found C 48.60, H 3.76, N 2.93.
Yield: 79%; m.p. 124Ð125 ∞C. Ð IR (KBr): ν =
1671 (s), 1552 (vs), 1510 (m), 1413 (m), 1359 (m),
1332 (m), 1318 (m), 1235 (m), 1212 (s), 1188 (vs),
1172 (vs), 1131 (vs), 1091 (vs), 1029 (m), 1011 (m)
cmÐ1. Ð 1H NMR (CD3CN, 500.14 MHz): δ = 1.88
(quin, 2 H, 5Ј-H), 2.52 (t, 2 H, 4Ј-H), 3.37 (t, 2 H,
6Ј-H), 4.44 (s, 2 H, NCH2Thie), 4.58 (s, br, 2 H,
CH2CO); CH2-Thienyl: 6.99 (dd, J = 5.0, 1.3 Hz, 1
H, 4-H), 7.19 (dd, J = 2.9, 1.3 Hz, 1 H, 2-H), 7.41
(dd, J = 5.0, 2.9 Hz, 1 H, 5-H); CO-Thienyl: 7.44
(dd, J = 5.1, 2.8 Hz, 1 H, 5-H), 7.50 (dd, J = 5.1,
1.3 Hz, 1 H, 4-H), 8.21 (dd, J = 2.9, 1.3 Hz, 1 H,
2-H). Ð C17H16F3NO3S2 (435.49): calcd. C 46.89,
H 3.70, N 3.22; found C 46.73, H 3.79, N 3.17.
Preparation of enaminosulfones 7aÐc,e,f
General procedure
Dimethylaminomethyl-polystyrene
(257 mg,
1.06 mmol) was added at 20 ∞C in several portions
to a solution of iminium triflate 4 (1.0 mmol) in
CH3CN (10 ml).A color change from yellow to
red was observed after a few minutes.After 1 h,
the polymer was removed by filtration and washed
twice with CH3CN (2 ¥ 10 ml).The combined or-
ganic phases were concentrated to leave a dark-
red oil.In the case of 4aÐc, trituration with ether
gave enaminosulfones 7aÐc as solids which were
recrystallized from CH2Cl2-ether.In the case of
4e,f, the oily residue was subjected to column chro-
matography (silica gel, CH3CN as eluent) to give
enaminosulfones 7e,f which were recrystallized
from CH3CN-ether.
2-{1-Allyl-3-[(trifluoromethyl)sulfonyl]-1,4,5,6-
tetrahydropyridin-2-yl}-1-(4-chlorophenyl)ethan-1-
one (7e)
Synthesis starting from salt 4e [9]; yield: 79%;
m.p. 103 ∞C. Ð IR (KBr): ν = 1694 (s), 1591 (m),
1369 (m), 1331 (vs), 1211 (s), 1187 (vs), 1150 (m),
1022 (m) cmÐ1. Ð 1H NMR (CD3CN, 500.14
MHz): δ = 1.85Ð1.96 (m, 2 H, 5Ј-H), 2.52 (t, 2 H,
4Ј-H), 3.38 (t, 2 H, 6Ј-H), 3.85 (d, 2 H, NCH2,allyl),
4.54 (br s, 2 H, CH2CO), 5.14 (d, J = 17.3 Hz, 1
H, =CH2), 5.21 (d, J = 10.9 Hz, 1 H, =CH2), 5.78
(mc, 1H, CH=CH2), 7.52/7.93 (AAЈBB’, 4 HAr). Ð
C17H17ClF3NO3S (407.84): calcd. C 50.07, H 4.20,
N 3.43; found C 49.79, H 4.23, N 3.28.
1-(4-Chlorophenyl)-2-{1-[(thien-3-yl)methyl]-3-
[(trifluoromethyl)sulfonyl]}-1,4,5,6-tetrahydro-
pyridin-2-yl]ethan-1-one (7a)
Yield: 73%; m.p. 134 ∞C. Ð IR (KBr): ν = 1690
(s), 1589 (m), 1552 (vs), 1330 (vs), 1212 (s), 1199
(s), 1176 (vs), 1128 (s), 1092 (s), 1031 (m) cmÐ1. Ð
1H NMR (CD3CN, 500.14 MHz): δ = 1.88 (quin, 2
H, 5Ј-H), 2.52 (t, 2 H, 4Ј-H), 3.34 (t, 2 H, 6Ј-H),
4.45 (s, 2 H, NCH2Thie), 4.58 (s, br, 2 H, CH2CO),
6.99 (dd, J = 5.1, 1.2 Hz, 1 H, 4-HThie), 7.20 (dd,
J = 2.8, 1.2 Hz, 1 H, 2-HThie), 7.41 (dd, J = 5.0, 2.9
Hz, 1 H, 5-HThie), 7.49/7.91 (AAЈBB’, 4 HAr). Ð
C19H17ClF3NO3S2 (463.92): calcd. C 49.19, H 3.69,
N 3.02; found C 48.67, H 3.80, N 2.93.
2-{1-(But-3-en-1-yl)-3-[(trifluoromethyl)sulfonyl]-
1,4,5,6-tetrahydropyridin-2-yl}-1-(4-chloro-
phenyl)ethan-1-one (7f)
Synthesis starting from salt 4f [9]; yield: 77%;
m.p. 93 ∞C. Ð IR (KBr): ν = 1693 (s), 1589 (m),
1546 (s), 1333 (s), 1210 (m), 1191 (vs), 1167 (s),
1091 (m) cmÐ1. Ð 1H NMR (CD3CN, 500.14
MHz): δ = 1.94 (mc, 2 H, 5Ј-CH2), 2.32 (q, 2 H,
CH2CH=CH2), 2.50 (t, 2 H, 4Ј-CH2), 3.26 (t, 2 H,
NCH2CH2CH=), 3.42 (t, 2 H, 6Ј-CH2), 4.58 (br s,
2 H, CH2CO), 5.03 (dd, J = 10.2, 1.9 Hz, 1 H,
=CH2), 5.08 (dd, J = 17.1, 1.8 Hz, 1 H, =CH2), 5.76
(mc, 1H, CH=CH2), 7.53/7.95 (AAЈBB’, 4 HAr). Ð
C17H17ClF3NO3S (407.84): calcd. C 50.07, H 4.20,
N 3.43; found C 49.79, H 4.23, N 3.28.
2-{1-Benzyl-3-[(trifluoromethyl)sulfonyl]-1,4,5,6-
tetrahydropyridin-2-yl}-1-[(thien-3-yl)methyl]-
ethan-1-one (7b)
Yield: 74%; m.p. 145Ð147 ∞C. Ð IR (KBr): ν =
1676 (s), 1547 (vs), 1358 (m), 1332 (s), 1262 (m),
1204 (s), 1186 (s), 1171 (s), 1131 (s), 1092 (s), 1030
1
(s) cmÐ1. Ð H NMR (CD3CN, 500.14 MHz): δ =
1.90 (quin, 2 H, 5Ј-H), 2.55 (t, 2 H, 4Ј-H), 3.34 (t,
2 H, 6Ј-H), 4.48 (s, 2 H, NCH2Ph), 4.40Ð4.70 (s,
br, 2 H, CH2CO), 7.19 (2 HAr), 7.30 (1 HAr), 7.37
(2 HAr), 7.43 (dd, J = 5.2, 2.8 Hz, 1 H, 5-HThie),
7.49 (dd, J = 5.1, 1.4 Hz, 1 H, 4-HThie), 8.18 (dd,
J = 2.8, 1.3 Hz, 1 H, 2-HThie). Ð C19H18F3NO3S2
X-ray crystal structure determination of 7f
Crystal data: C18H19ClF3NO3S, triclinic space
¯
(429.47): calcd. C 53.14, H 4.22, N 3.26; found C group P1; a = 5.602(1), b = 8.859(1), c = 19.788(2)
˚
53.16, H 4.41, N 3.14.
A, α = 84.11(1), ꢀ = 87.26(1), γ = 82.59(1)∞; Dcalc =
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434
R.Neumann et al. · Enaminosulfones from 3-Trifloxypropene Iminium Salts
1.447 g·cmÐ3; Z = 2.Data collection: crystal size
Crystallographic data (excluding structure
1.10 ¥ 0.64 ¥ 0.38 mm; Stoe IPDS instrument, factors) for the structure reported in this paper
monochromatized MoKα radiation; T = 295(2) K, have been deposited with the Cambridge Crystal-
13606 reflections collected, 3472 unique reflections lographic Data Centre as supplementary publica-
(Rint = 0.0258). Structure solution and refinement tion no.CCDC-178456.Copies of the data can be
was achieved with the program system SHELX-97 obtained free of charge on application to CCDC,
[21].Full-matrix least-squares refinement of 264
12 Union Road, Cambridge CB2 1EZ, UK
parameters (18 restraints) against F2 values gave [Fax: Int.Code +(1223)336-033;
the following R values: R = 0.0651 and Rw = 0.1495 E-mail: deposit@ccdc.cam.ac.uk].
for all data, and R = 0.0522, Rw = 0.1413 for 2690
observed reflections [I > 2σ(I)].The residual elec-
Acknowledgements
Ð3
˚
tron density was between 0.40 and Ð0.33 e·A
.
Two orientations of the N-homoallyl moiety were
found in the solid sate which affected the methy- Forschungsgemeinschaft and the Fonds der Chemi-
lene groups C15 and C16 (Fig.1) and consequently schen Industrie is gratefully acknowledged.H-.G.
also the hydrogen atom positions at the olefinic Herz thanks the State of Baden-Württemberg for
Support of this work by the Deutsche
bond.This disorder was treated appropriately, and
the occupancy factors for the two positions were
refined to give values of 0.58 and 0.42.
a postgraduate fellowship.
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