High pressure intramolecular Diels-Alder reactions of vinylsulfonates and vinylsulfonamides

Article abstract of DOI:10.1016/S0040-4020(99)01073-X

Acceleration of the intramolecular Diels-Alder reaction of vinylsulfonic esters and amides bearing acyclic and carbocyclic 1,3-diene moieties by application of high pressure leads to excellent yields of sultones and sultams, respectively, at ambient temperature. The influence of pressure on the stereoselectivity of these processes has been investigated. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(99)01073-X

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 873–879
High Pressure Intramolecular Diels–Alder Reactions of
Vinylsulfonates and Vinylsulfonamides
a
a
b
a,
*
¨
Bernd Plietker, Dieter Seng, Roland Frohlich and Peter Metz
a
¨
¨
Institut fur Organische Chemie, Technische Universitat Dresden, Mommsenstr. 13, D-01062 Dresden, Germany
b
¨
¨
¨
Organisch-Chemisches Institut, Universitat Munster, Corrensstraße 40, D-48149 Munster, Germany
Dedicated to Doz. Dr Wolf D. Habicher on the occasion of his 60th birthday
Received 5 November 1999; accepted 7 December 1999
Abstract—Acceleration of the intramolecular Diels–Alder reaction of vinylsulfonic esters and amides bearing acyclic and carbocyclic 1,3-
diene moieties by application of high pressure leads to excellent yields of sultones and sultams, respectively, at ambient temperature. The
influence of pressure on the stereoselectivity of these processes has been investigated. ᭧ 2000 Elsevier Science Ltd. All rights reserved.
Since both the intermolecular as well as the intramolecular
Diels–Alder reaction feature negative volume of
activation, application of high pressure causes a marked
increase in rate for both versions.1–7 We report our investi-
gations on the influence of high pressure on yield and
stereochemical outcome of the intramolecular [4ϩ2]
cycloaddition of vinylsulfonic esters and amides derived
from hydroxyalkyl or aminoalkyl substituted 1,3-dienes,
respectively.8
a
During our studies on the intramolecular Diels–Alder reac-
tion of vinylsulfonates 1 (XˆO), we found that reflux in
Scheme 1.
Table 1. Intramolecular Diels–Alder reactions of vinylsulfonic acid derivatives 1
1–3
X
R1
R2
R3
13 kbar, CH2Cl2, room temp.
Toluene, BHT, reflux
2:3a
Yield (%)b
2:3a
Yield (%)b
a
b
c
d
e
O
O
O
NBn
NBn
H
H
H
Me
H
H
H
Me
H
H
Me
1.0:2.3
1.0:2.0
3.6:1.0
1.0:1.6
1.0:1.9
88
78
79
79
81
1.0:1.0
1.4:1.0
4.7:1.0
1.0:1.0
1.6:1.0
76c
64c
76c
76
Me
t-Bu
H
Me
61
a Determined by capillary GC on the crude products.
b Isolated yield.
c Ref. 9.
Keywords: Diels–Alder reactions; pressure; reactions under; sultones; sultams.
* Corresponding author. E-mail: metz@coch01.chm.tu-dresden.de
0040–4020/00/$ - see front matter ᭧ 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(99)01073-X

874
B. Plietker et al. / Tetrahedron 56 (2000) 873–879
1a–c as well as vinylsulfonamides12,13 1d,e smoothly
cyclized at room temperature when a pressure of 13 kbar
was applied. The presence of BHT is not necessary under
these conditions, and the yields are significantly higher
compared to those obtained in refluxing toluene at ambient
pressure (Scheme 1, Table 1).
Analysis of the crude products by capillary GC confirmed
that only diastereomers 2 and 3 were formed under both
conditions. The relative configuration of the cycloadducts
1
was determined by diagnostic H NMR coupling constants
and NOEs. By invoking transition states with equatorial
orientation of the substituent R1 on a chair-like folded tether
(Fig. 1), the observed diastereoselectivities can be readily
rationalized. For vinylsulfonates 1a,b and vinylsulfon-
amides 1d,e with R2ˆH, the more compact endo transition
state leading to cis fused products 3 is favored at high
pressure, whereas there is either no (1a,d) exo/endo dis-
crimination or a small exo preference (1b,e) at normal
pressure. Interestingly, for substrate 1c with R2ˆMe, the
unfavorable steric interaction between R2 and the hydrogen
atom on the carbinol center in the endo transition state still
predominantly influences the stereochemical outcome at
13 kbar. As a consequence, diastereoselectivity decreases
with increasing pressure in this case.
Figure 1. Transition states (TS) for the intramolecular Diels–Alder
reaction of vinylsulfonic acid derivatives 1.
The degree of endo preference for the cycloaddition of
vinylsulfonate 1a was studied at different temperatures
(Ϫ20, 0, 20ЊC: CH2Cl2; 40ЊC: toluene) and pressures (Fig.
2). For this substrate with R2ˆH, simple diastereoselectivity
increases with increasing pressure and decreasing tempera-
ture. Obviously, at a temperature of Ϫ20ЊC, a maximum de
is already reached at 10 kbar.
Figure 2. Dependence of diastereomeric excess on temperature and
pressure for the cycloaddition of vinylsulfonate 1a to endo sultone 3a.
toluene was required for efficient cycloaddition at ordinary
pressure.9,10 In order to suppress side reactions at this
elevated temperature, addition of a small amount of the
radical scavenger BHT proved beneficial. While attempts
to trigger cyclization of these substrates at lower tempera-
ture using different Lewis acids failed, application of high
pressure11 turned out to be effective. Thus, vinylsulfonates
In contrast to the situation with acyclic 1,3-dienes 1, only
endo adducts are formed from substrates 4a9,14 and 4b
incorporating a cyclic 1,3-diene unit at normal pressure
already (Scheme 2, Table 2). This is probably due to non-
bonding interactions involving a hydrogen atom on the
saturated C2-bridge syn to the six-membered heterocycle
in the alternative exo transition states. At 13 kbar, the
Scheme 2.
preference for adducts 5 with equatorial methyl group is
significantly enhanced. Stereochemical assignment for 5b
and 6b rests on diagnostic H NMR coupling constants
Table 2. Intramolecular Diels–Alder reactions of vinylsulfonic acid
derivatives 4
1
4–6
X
13 kbar, CH2Cl2, room temp.
Toluene, BHT, reflux
and NOEs and was unambiguously established for 5b by
X-ray diffraction analysis (Fig. 3).15
5:6a
Yield (%)b
5:6a
Yield (%)b
a
b
O
54.6:1
92
93
10.2:1
9.3:1
58c
77
The vinylsulfonates 1a–c and 4a used for this study were
available from alcohols 7 and 9 as described,9 while the
vinylsulfonamides 1d,e and 4b were prepared by treatment
of the N-benzylamines 8 and 10 derived from 7 and 9,
respectively, with vinylsulfonyl chloride (Scheme 3).12
NBn 30.3:1
a Determined by capillary GC on the crude products.
b Isolated yield.
c Ref. 9.

B. Plietker et al. / Tetrahedron 56 (2000) 873–879
875
with a Hewlett Packard 5972 detectorϩa Hewlett Packard
5890 GC (GC/MS) and a Finnigan MAT 95. Microanalyses
were performed by the analytical laboratory of the Institut
¨
fu¨r Organische Chemie, Technische Universitat Dresden.
High pressure reactions were run in a Hofer apparatus.
(3E)-3,5-Hexadien-1-yl methanesulfonate. To a solution
of 7a17 (980 mg, 10 mmol) in dry THF (60 mL) cooled to
0ЊC is added dropwise triethylamine (1.11 g, 11 mmol) and
freshly distilled mesyl chloride (1.25 g, 11 mmol) under
argon. The mixture is stirred for 8 h at 0ЊC and treated
with saturated aqueous NH4Cl (8 mL). After extraction of
the aqueous layer with diethyl ether ꢀ3 × 80 mL†; washing
of the combined organic layers with 2N HCl (80 mL),
saturated aqueous NaHCO3 (80 mL), and water (80 mL),
drying over MgSO4, and evaporation of the solvent in
vacuo, the mesylate of 7a (1.74 g, 99%) is obtained. Rf
Figure 3. Crystal structure of sultam 5b.15,16
Scheme 3. (a) MsCl, Et3N, THF, 0ЊC, 99% from 7a or MsCl, 2,6-lutidine, CHCl3, 0ЊC, 92% from 7b or MsCl, pyridine, CHCl3, 0ЊC, 87% from 9. (b) BnNH2,
80ЊC, 62% 8a, 66% 8b, 75% 10. (c) CH2yCHSO2Cl, 2,6-lutidine, CH2Cl2, 0ЊC, 87% 1d or CH2yCHSO2Cl, Et3N, CH2Cl2, 0ЊC, 85% 1e, 95% 4b.
Experimental
0.27 (pentane/diethyl ether, 3:2); IR (neat): 3019 (w),
2868 (w), 1654 (w), 1603 (w), 1355 (s, SO2OR), 1176 (s,
SO2OR), 1008 (m), 974 (s), 959 (s), 834 (m), 794 (m), 529
(m) cmϪ1; 1H NMR (CDCl3): d 2.47 (q, Jˆ6.7 Hz, 2H), 2.93
(s, 3H), 4.19 (t, Jˆ6.7 Hz, 2H), 4.99 (d, Jˆ10.2 Hz, 1H),
5.10 (d, Jˆ16.7 Hz, 1H), 5.58 (dt, Jdˆ14.7 Hz, Jtˆ7.0 Hz,
1H), 6.12 (m, 1H), 6.26 (m, 1H); 13C NMR (CDCl3): d 32.2
(t), 37.3 (q) 68.9 (t), 116.8 (t), 127.7 (d), 134.3 (d), 136.3 (d).
General experimental information
All reactions requiring exclusion of moisture were run under
argon using flame-dried glassware. Solvents were dried by
distillation from potassium (THF) or else CaH2. Flash
chromatography was performed on Merck silica gel 60
(40–63 mm). Capillary GC analyses were performed with
a Shimadzu GC-14A or GC-14B, a Shimadzu C-R6A
integrator, a HP 5 column, 25 m length, 0.25 mm i.d.,
0.25 mm film. HPLC separations were performed with a
Waters 616 pump, a Waters 2410 detector and a Nucleosil
100-5 (5 mm, 250 mm length, 4 mm i.d.) column (analytical
scale), a Waters 600 pump, a Knauer K-2400 detector, and a
Nucleosil 100-5 (5 mm, 250 mm length, 10 or 20 mm i.d.) or
a Porasil 100-10 (10 mm, 250 mm length, 30 mm i.d.)
column (semi-preparative scale), and a Waters Delta Prep
3000, a Knauer K-2400 detector, and a Porasil 125 (15–
20 mm, 300 mm length, 50 mm i.d.) column (preparative
scale). Melting points were determined on a Kofler micro-
N-Benzyl-N-[(3E)-3,5-hexadien-1-yl]amine (8a). A solu-
tion of the mesylate of 7a (1.5 g, 8.5 mmol) in benzylamine
(80 mL) freshly distilled from CaCl2 is stirred for 6 h at
80ЊC. After cooling, the mixture is treated with 2N NaOH
(20 mL) and extracted with pentane ꢀ5×50 mL†: The
combined extracts are dried over MgSO4, the solvent is
removed in vacuo, and the residue is purified by flash chro-
matography (pentane/diethyl ether, 1:1,ϩ1% triethylamine)
to give 8a (980 mg, 62%) as a colorless liquid. Rf 0.38 (pen-
tane/diethyl ether, 1:1,ϩ1% triethylamine); IR (neat): 3402
(br, w, N–H), 3027 (m), 3010 (m), 2927 (s), 2871 (s), 2836
(s), 2817 (s), 1650 (w), 1605 (w), 1495 (s), 1120 (m), 1028
1
(s), 901 (m), 734 (s), 698 (s) cmϪ1; H NMR (CDCl3): d
scope desk. H NMR and 13C NMR spectra were obtained
1
on a Bruker ASP-300 (1H: 300 MHz, 13C: 75.47 MHz) or a
Bruker DRX-500 (1H: 500 MHz, 13C: 125.8 MHz);
mcˆmultiplet centered at, brˆbroad. 13C multiplicities
were determined using DEPT pulse sequences. FT-IR spec-
tra were obtained on a Nicolet 205; wˆweak, sˆstrong,
mˆmedium, brˆbroad. Mass spectra (70 eV) were recorded
1.42 (br s, 1H), 2.32 (m, 2H), 2.72 (t, Jˆ6.9 Hz, 2H), 3.80 (s,
2H), 5.00 (d, Jˆ10.1 Hz, 1H), 5.12 (d, Jˆ16.7 Hz, 1H), 5.69
(dt, Jdˆ14.6 Hz, Jtˆ7.1 Hz, 1H), 6.12 (dd, Jˆ14.7 Hz,
Jˆ10.2 Hz, 1H), 6.33 (ddd, Jˆ16.7 Hz, Jˆ10.2 Hz,
Jˆ10.2 Hz, 1H), 7.26 (mc, 1H) 7.28–7.36 (m, 4H); 13C
NMR (CDCl3): d 33.0 (t), 48.4 (t), 53.8 (t), 115.4 (t),

876
B. Plietker et al. / Tetrahedron 56 (2000) 873–879
126.8 (d), 128.0 (d), 128.3 (d), 132.3 (d), 132.7 (d), 136.9
(d), 140.3 (s). MS (GC/MS) m/z (relative intensity): 120 (35)
[MϩϪC5H7], 91 (100) [C7Hϩ7 ], 65 (16), 51 (5), 41 (12), 39
(12); HRMS Calcd for (C13H19NϩHϩ) [MϩHϩ]: 188.149.
Found: 189.151.
2961 (m), 2872 (w), 1703 (m), 1644 (s), 1495 (m), 1452 (s),
1377 (m), 990 (s), 752 (s), 695 (s) cmϪ1; 1H NMR (CDCl3):
d 1.08 (d, Jˆ6.2 Hz, 3H), 1.71 (d, Jˆ6.2 Hz, 3H), 2.08–
2.27 (m, 2H), 2.72 (mc, 1H), 3.72 (d, Jˆ13.1 Hz, 1H), 3.82
(d, Jˆ13.1 Hz, 1H), 5.41–5.65 (m, 2H), 5.99–6.05 (m, 2H)
7.15–7.42 (m, 5H); 13C NMR (CDCl3): d 17.9 (q), 20.3 (q),
40.1 (t), 51.3 (d), 52.2 (t), 125.8 (d), 126.8 (d), 128.3 (d),
128.9 (d), 131.1 (d), 132.5 (d), 134.0 (d), 139.5 (s). MS
(GC/MS) m/z (relative intensity): 215 (1) [Mϩ], 200 (1)
[MϩϪCH3], 134 (100) [MϩϪC6H9], 91 (100) [C7Hϩ7 ], 81
(5) [C6Hϩ9 ], 65 (17); HRMS Calcd for (C15H21NϩHϩ)
[MϩHϩ]: 216.175. Found: 216.174.
N-Benzyl-N-(3E)-3,5-hexadien-1-yl vinylsulfonamide (1d).
To a solution of amine 8a (500 mg, 2.67 mmol) in CH2Cl2
(10 mL) cooled to 0ЊC are added dropwise under argon 2,6-
lutidine (0.6 mL, 5.35 mmol) and vinylsulfonyl chloride18
(0.5 mL, 5.35 mmol). After stirring for 12 h at 0ЊC, the
mixture is diluted with diethyl ether (4 mL) and subjected
to flash chromatography (pentane/diethyl ether, 1:1) to give
1d (644 mg, 87%) as a slightly yellow liquid. Rf 0.8
(pentane/diethyl ether, 1:1); IR (neat): 3063 (m), 3033
(m), 3012 (m), 2929 (m), 1600 (w), 1496 (m), 1455 (m),
1339 (s, SO2N), 1257 (m), 1149 (s, SO2N), 1045 (m), 1007
(m), 969 (m), 939 (m), 905 (m), 791 (m), 764 (m), 744 (m),
N-Benzyl-N-[(4E,6E)-4,6-octadien-2-yl] vinylsulfonamide
(1e). To a solution of amine 8b (200 mg, 0.927 mmol) in
CH2Cl2 (8 mL) cooled to 0ЊC are added dropwise under
argon triethylamine (0.13 mL, 0.93 mmol) and vinyl-
sulfonyl chloride18 (0.09 mL, 0.93 mmol). The mixture is
stirred for 1 h at 0ЊC, filtered through a pad of silica gel,
and diluted with diethyl ether (10 mL). After washing with
ice-cold 2N HCl (10 mL), saturated aqueous NaHCO3
(20 mL), and brine (10 mL), the organic layer is dried
over MgSO4. Evaporation of the solvent in vacuo at 0ЊC
yields 1e (242 mg, 85%) as a slightly yellow oil. Rf 0.64
(pentane/diethyl ether, 2:1); IR (neat): 3020 (w), 2977 (m),
2935 (m), 2916 (m), 1454 (m), 1338 (s, SO2N), 1175 (s),
1145 (s, SO2N), 991 (s), 921 (s), 734 (s), 656 (m) cmϪ1; 1H
NMR (CDCl3): d 1.11 (d, Jˆ6.9 Hz, 3H), 1.40 (d,
Jˆ6.3 Hz, 3H), 2.29 (m, 1H), 2.42 (m, 1H), 3.85 (m, 1H),
4.30 (s, 2H), 5.41–5.71 (m, 2H), 5.85 (d, Jˆ9.7 Hz, 1H),
5.99–6.05 (m, 2H), 6.18 (d, Jˆ16.5 Hz, 1H), 6.40 (dd,
Jˆ16.5 Hz, Jˆ9.7 Hz, 1H), 7.21–7.40 (m, 5H).
700 (m), 655 (m), 560 (m), 542 (m) cmϪ1 1H NMR
;
(CDCl3): d 2.18 (mc, 2H), 3.10 (t, Jˆ7.4 Hz, 2H), 4.26 (s,
2H), 4.92 (d, Jˆ10.1 Hz, 1H), 5.02 (d, Jˆ16.7 Hz, 1H), 5.69
(dt, Jdˆ14.7 Hz, Jtˆ7.1 Hz, 1H), 5.84 (d, Jˆ9.8 Hz, 1H),
5.88 (dd, Jˆ14.7 Hz, Jˆ10.4 Hz, 1H), 6.15 (d, Jˆ16.5 Hz,
1H), 6.16 (ddd, Jˆ16.7 Hz, Jˆ10.3 Hz, Jˆ10.3 Hz, 1H),
6.36 (dd, Jˆ16.5 Hz, Jˆ9.8 Hz, 1H), 7.29 (mc, 5H); 13C
NMR (CDCl3): d 31.6 (t), 46.7 (t), 51.2 (t), 116.1 (t),
126.4 (t), 127.9 (d), 128.3 (d), 128.6 (d), 130.2 (d), 133.3
(d), 135.3 (d), 136.0 (s), 136.6 (d).
(4E,6E)-4,6-Octadien-2-yl methanesulfonate. To a solu-
tion of 7b19 (2.85 g, 22.3 mmol) in dry CHCl3 (40 mL)
cooled to 0ЊC is added dropwise 2,6-lutidine (3.58 g,
33.5 mmol) and freshly distilled mesyl chloride (3.05 g,
26.8 mmol) under argon. The mixture is stirred overnight
at 0ЊC and diluted with diethyl ether (25 mL). After washing
with 2N HCl (20 mL), saturated aqueous NaHCO3 (20 mL),
and brine (20 mL), drying over MgSO4, and evaporation of
the solvent in vacuo at 0ЊC, the mesylate of 7b (4.22 g, 92%)
is obtained as a colorless oil. Rf 0.32 (cyclohexane/ethyl
acetate, 3:1); IR (neat): 3654 (w), 2987 (s), 2929 (s),
2262 (m), 1598 (s), 1445 (s), 1354 (s, SO2OR), 1176
(s, SO2OR), 1096 (s), 1006 (s), 917 (s), 818 (s), 755 (s),
1-(1,3-Cyclohexadienyl)-propan-2-yl methanesulfonate.
To a solution of 99 (1.70 g, 12.3 mmol) in dry CHCl3
(55 mL) cooled to 0ЊC is added dropwise pyridine (1.94 g,
24.6 mmol) and freshly distilled mesyl chloride (2.80 g,
24.6 mmol) under argon. The mixture is stirred for 2 days
at 0ЊC and diluted with diethyl ether (55 mL). After washing
with 2N HCl (20 mL), saturated aqueous NaHCO3 (20 mL),
and water (20 mL), drying over MgSO4, and evaporation of
the solvent in vacuo, flash chromatography (cyclohexane/
ethyl acetate, 2:1) gives the mesylate of 9 (2.32 g, 87%) as a
colorless liquid. Rf 0.30 (cyclohexane/ethyl acetate, 2:1); IR
(neat): 3038 (s), 2983 (w), 2938 (m), 2873 (w), 2827 (m),
1649 (w), 1591 (w), 1497 (w), 1455 (m), 1437 (m), 1426
(m), 1382 (m), 1352 (s, SO2OR), 1338 (s, SO2OR), 1241
(m), 1220 (w), 1172 (s, SO2OR), 1126 (m), 1039 (m), 1009
(m), 972 (s), 925 (s), 899 (s), 796 (m), 751 (m), 695 (s), 528
1
663 (s) cmϪ1; H NMR (CDCl3): d 1.39 (d, Jˆ6.2 Hz,
3H), 1.71 (d, Jˆ6.9 Hz, 3H), 2.36–2.46 (m, 2H), 2.94 (s,
3H), 4.77 (mc, 1H), 5.39–5.51 (m, 1H), 5.57–5.69 (m, 1H),
5.96–6.13 (m, 2H); 13C NMR (CDCl3): d 18.0 (q), 20.8 (q),
38.6 (q), 39.7 (t), 79.5 (d), 124.3 (d), 129.0 (d), 130.9 (d),
134.5 (d). MS (GC/MS) m/z (relative intensity): 204 (1)
[Mϩ], 134 (24) [MϩϪC6H9], 108 (80) [MϪCH3SO3H], 93
(100), 81 (71) [C6Hϩ9 ], 79 (77), 77 (19), 67 (20), 53 (19), 43
(20).
1
(s) cmϪ1; H NMR (CDCl3): d 1.41 (d, Jˆ6.2 Hz, 3H),
2.05–2.22 (m, 6H), 2.30 (dd, Jˆ6.1 Hz, Jˆ14.0 Hz, 1H),
2.50 (dd, Jˆ7.2 Hz, Jˆ14.0 Hz, 1H), 2.90 (s, 3H), 4.88 (mc,
1H), 5.71 (m, 2H), 5.85 (mc, 1H, 3-H); 13C NMR (CDCl3): d
21.2 (q), 22.7 (t), 22.8 (t), 38.6 (q), 44.6 (t), 78.4 (d), 122.7
(d), 124.3 (d), 125.0 (d), 133.4 (s). MS (GC/MS) m/z (rela-
tive intensity): 216 (3) [Mϩ], 121 (9), 120 (27)
[MϩϪCH3SO3H], 105 (34), 91 (100), 79 (46), 78 (55), 77
(32), 65 (12), 63 (5), 51 (8), 43 (6), 41 (8), 39 (13).
N-Benzyl-N-[(4E,6E)-4,6-octadien-2-yl]amine (8b).
A
solution of the mesylate of 7b (4.22 g, 20.5 mmol) in
benzylamine (200 mL) freshly distilled from CaCl2 is stirred
for 12 h at 40ЊC and 2 h at 80ЊC. After cooling, the mixture
is treated with 2N NaOH (40 mL) and extracted with pen-
tane ꢀ5×100 mL†: The combined extracts are dried over
MgSO4, the solvent is removed in vacuo, and the residue
is purified by flash chromatography (cyclohexane/ethyl
acetate, 3:1,ϩ1% triethylamine) to give 8b (2.94 g, 66%).
Rf 0.39 (cyclohexane/ethyl acetate, 3:1,ϩ1% triethyl-
amine); IR (neat): 3398 (br, w, N–H), 3062 und 3026 (m),
N-Benzyl-N-[1-(1,3-cyclohexadienyl)-propan-2-yl]amine
(10). A solution of the mesylate of 9 (1.8 g, 8.3 mmol) in
benzylamine (15 mL) freshly distilled from CaCl2 is stirred
for 12 h at 80ЊC. After cooling, the mixture is treated with

B. Plietker et al. / Tetrahedron 56 (2000) 873–879
877
2N NaOH (15 mL) and extracted with pentane ꢀ5×10 mL†:
The combined extracts are dried over MgSO4, the solvent is
removed in vacuo, and the residue is purified by flash chro-
matography (pentane/ethyl acetate, 1:1,ϩ1% triethylamine)
to give 10 (1.41 g, 75%) as a slightly yellow liquid. Rf 0.19
(pentane/diethyl ether, 1:1,ϩ1% triethylamine); IR (neat):
3320 (w, N–H), 3031 (m), 2962 (m), 2926 (s), 2870 (s),
2824 (s), 1650 (w), 1600 (w), 1494 (m), 1465 (s), 1453
(s), 1372 (m), 1345 (m), 1195 (m), 1140 (m), 1117 (m),
the crude products. Flash chromatography using the solvent
systems listed in the individual entries with the Rf values
yields the pure cycloadducts.
For thermal reactions of vinylsulfonates 1a–c, 4a and data
of the sultones 2/3a–c, 5a, see Ref. 9. The reaction times for
the high pressure reactions were as follows: 2a/3a from 1a
(24 h), 2b/3b from 1b (12 h), 2c/3c from 1c (12 h), 5a/6a
from 4a (12 h).
1
1028 (m), 733 (s), 697 (s) cmϪ1; H NMR (CDCl3): d
1.09 (d, Jˆ6.2 Hz, 3H), 1.77 (br s., 1H), 1.97 (mc, 2H),
2.10 (mc, 3H), 2.23 (dd, Jˆ13.7 Hz, Jˆ7.9 Hz, 1H), 2.81
(mc, 1H), 3.72 (d, Jˆ13.2 Hz, 1H), 3.87 (d, Jˆ13.2 Hz, 1H),
5.68 (mc, 2H), 5.86 (mc, 1H), 7.28 (mc, 5H); 13C NMR
(CDCl3): d 20.5 (q), 22.9 (t), 26.3 (t), 45.6 (t), 49.9 (d),
51.3 (t), 121.4 (d), 124.1 (d), 124.6 (d), 126.8 (d), 128.1
(d), 128.4 (d), 136.8 (s), 140.6 (s). MS (GC/MS) m/z (rela-
tive intensity): 226 (0.2) [MϩϪH], 135 (5), 134 (50)
[MϩϪC7H9], 92 (9), 91 (100) [C7Hϩ7 ], 77 (9), 65 (13), 39
(6). Anal. Calcd for C16H21N: C, 84.53; H, 9.31; N, 6.17.
Found C, 84.36; H, 9.23; N, 6.55.
Sultams 2d/3d from 1d
Thermal reaction: 12 h; high pressure reaction: 24 h.
Preparative separation of the diastereomers could not be
achieved by chromatography or crystallization. The mixture
generated under high pressure was used for assignment of
the NMR signals. Diastereomeric mixture. Rf 0.55 (pentane/
diethyl ether, 1:2); IR (KBr): 3024 (w), 2971 (w), 2944 (m),
2929 (w), 2879 (w), 1651 (w), 1494 (m), 1455 (m), 1331 (s,
SO2N), 1318 (s, SO2N), 1262 (w), 1148 (s, SO2N),1138 (s,
SO2N), 922 (w), 863 (m), 728 (m), 709 (m), 698 (m), 608
(w) cmϪ1. Anal. Calcd for C15H19NO2S: C, 64.95; H, 6.90;
N, 5.05. Found C, 64.67; H, 6.97; N, 5.45.
N-Benzyl-N-[1-(1,3-cyclohexadienyl)-propan-2-yl] vinyl-
sulfonamide (4b). To a solution of amine 10 (100 mg,
0.44 mmol) in CH2Cl2 (3 mL) cooled to 0ЊC are added
dropwise under argon triethylamine (0.07 mL, 0.44 mmol)
and vinylsulfonyl chloride18 (0.05 mL, 0.44 mmol). After
stirring for 1 h at 0ЊC, the mixture is diluted with diethyl
ether (3 mL) and subjected to flash chromatography
(cyclohexane/diethyl ether, 1:1) to give 4b (133 mg,
95%) as a colorless oil. Rf 0.22 (cyclohexane/diethyl
ether, 1:1); IR (neat): 3031 (m), 2935 (m), 2870 (w), 1650
(w), 1430 (m), 1510 (m), 1358 (s, SO2N), 1305 (m), 1172
(s, SO2N), 977 (m), 920 (s), 899 (s), 784 (m), 748 (m), 550
(m) cmϪ1; 1H NMR (CDCl3): d 1.05 (d, Jˆ6.8 Hz, 3H), 1.91
(mc, 2H), 2.04 (mc, 3H), 2.27 (dd, Jˆ13.5 Hz, Jˆ5.4 Hz,
1H), 2.81 (mc, 1H), 4.21 (d, Jˆ16.0 Hz, 1H), 4.28
(d, Jˆ16.0 Hz, 1H), 5.48 (mc, 1H), 5.58 (mc, 1H), 5.73
(mc, 1H), 5.79 (d, Jˆ9.8 Hz, 1H), 6.12 (d, Jˆ16.5 Hz,
1H), 6.35 (dd, Jˆ16.5 Hz, Jˆ9.8 Hz, 1H), 7.18 (mc, 3H),
7.30 (mc, 2H).
(1Rء,2Rء)-N-Benzyl-2-ethyl-3-cyclohexene-1,20-sultam (2d).
1H NMR (CDCl3): d 1.52 (mc, 2H), 1.84 (mc, 1H), 2.12–
2.24 (m, 2H), 2.38 (mc, 1H), 2.79 (mc, 1H), 2.85 (mc, 1H),
3.02 (ddd, Jˆ13.8 Hz, Jˆ4.2 Hz, Jˆ2.5 Hz, 1H), 3.40 (ddd,
Jˆ13.7 Hz, Jˆ13.4 Hz, Jˆ2.7 Hz, 1H), 4.21 (d, Jˆ14.3 Hz,
1H), 4.42 (d, Jˆ14.3 Hz, 1H), 5.42 (mc, 2H), 7.29 (mc, 5H);
13C NMR (CDCl3): d 19.7 (t), 23.9 (t), 29.3 (t), 38.6 (d),
47.2 (t), 50.2 (t), 60.5 (d), 127.2 (d), 127.8 (d), 128.3 (d),
128.4 (d), 128.6 (d), 136.1 (s). MS (GC/MS) m/z (relative
intensity): 278 (0.1) [MϩϩH], 277 (0.6) [Mϩ], 213 (7)
[MϩϪSO2], 212 (5), 121 (7), 120 (73), 118 (7), 92 (10),
91 (100) [C7Hϩ7 ], 79 (19), 77 (14), 67 (11), 65 (13), 41
(6), 39 (7).
(1Rء,2Sء)-N-Benzyl-2-ethyl-3-cyclohexene-1,20-sultam (3d).
1H NMR (CDCl3): d 1.60 (mc, 2H), 1.94 (mc, 1H), 2.12–
2.24 (m, 2H), 2.28 (mc, 1H), 2.97 (mc, 2H), 3.22 (ddd,
Jˆ5.1 Hz, Jˆ5.1 Hz, Jˆ2.9 Hz, 1H), 3.28–3.38 (m, 1H),
4.11 (d, Jˆ14.4 Hz, 1H), 4.48 (d, Jˆ14.4 Hz, 1H), 5.70
(mc, 2H), 7.29 (mc, 5H); 13C NMR (CDCl3): d 18.7 (t),
24.6 (t), 25.8 (t), 35.0 (d), 46.8 (t), 49.8 (t), 58.0 (d),
127.0 (d), 127.7 (d), 127.9 (d), 128.3 (d), 128.9 (d), 136.4
(s). MS (GC/MS) m/z (relative intensity): 277 (2.4) [Mϩ],
213 (4) [MϩϪSO2], 212 (8), 186 (5), 132 (5), 122 (6), 120
(6), 118 (9), 107 (5), 106 (6), 105 (13), 92 (12), 91 (100)
[C7Hϩ7 ], 79 (22), 78 (6), 77 (15), 67 (5), 65 (13), 51 (5), 41
(6), 39 (7).
General procedure for intramolecular Diels–Alder
reactions
Thermal: A solution of the vinylsulfonate or the vinyl-
sulfonamide (0.4 mmol) in toluene (15 mL) is added rapidly
via canula to a refluxing solution of BHT (5 mg) in toluene
(15 mL) under argon. The resultant solution is vigorously
stirred for the time indicated.
High pressure: A solution of the vinylsulfonate or the vinyl-
sulfonamide (0.4 mmol) in CH2Cl2 (10 mL) is added to a
Teflon᭨ vial. The vial is closed, inserted into the high
pressure apparatus, and subjected to a pressure of 13 kbar
at room temperature for the time indicated.
Sultams 2e/3e from 1e
Thermal reaction: 12 h; high pressure reaction: 12 h.
Preparative separation of the diastereomers could not be
achieved by chromatography. However, fractional crystal-
lization yielded a sample highly enriched in 2e that allowed
assignment of the NMR signals. Diastereomeric mixture. Rf
0.37 (pentane/diethyl ether, 2:1); IR (KBr): 3023 (w), 2959
(m), 2873 (w), 1496 (m), 1456 (m), 1331 (s, SO2N), 1313
Workup: The reaction mixture is filtered through a pad of
silica gel and concentrated in vacuo at a temperature not
exceeding 40ЊC. Diastereomeric ratios were determined by
capillary gas chromatography (FID detection, 300ЊC detec-
tor temperature, 200ЊC injector temperature, temperature
program 10ЊC minϪ1 from 80 to 300ЊC) on a sample of
(s, SO2N), 1146 (s, SO2N), 922 (w), 843 (w), 735 (m) cmϪ1
.

878
B. Plietker et al. / Tetrahedron 56 (2000) 873–879
1
(1Rء,2Rء,5Rء,20Rء)-N-Benzyl-5-methyl-2-propyl-cyclohex-
3-ene-1,20-sultam (2e). 1H NMR (CDCl3): d 1.07 (d,
Jˆ7.2 Hz, 3H), 1.08 (d, Jˆ7.0 Hz, 3H), 1.40 (mc, 1H),
1.64 (ddd, Jˆ13.7 Hz, Jˆ2.5 Hz, Jˆ2.5 Hz, 1H), 1.99
(mc, 1H), 2.09 (mc, 1H), 2.53 (mc, 1H), 2.70 (mc, 1H),
2.75 (mc, 1H), 4.07 (ddq, Jdˆ12.3 Hz, Jqˆ7.0 Hz,
Jdˆ2.5 Hz, 1H), 4.24 (d, Jˆ16.4 Hz, 1H), 4.51 (d,
Jˆ16.4 Hz, 1H), 5.38 (mc, 1H), 5.63 (mc, 1H), 7.23–7.40
(m, 5H); 13C NMR (CDCl3): d 20.1 (q), 21.4 (q), 26.5 (t),
29.2 (d), 36.5 (t), 38.1 (d), 46.9 (t), 55.3 (d), 55.4 (d), 127.0
(d), 127.2 (d), 127.3 (d), 128.2 (d), 133.1 (d), 139.4 (s).
(s), 799 (s), 590 (s), 568 (m), 542 (m), 448 (m) cmϪ1; H
NMR (CDCl3): d 1.24 (mc, 1H), 1.35 (mc, 1H), 1.42 (mc,
2H), 1.49 (d, Jˆ7.5 Hz, 3H), 1.78 (mc, 2H), 1.79 (ddd,
Jˆ13.1 Hz, Jˆ5.8 Hz, Jˆ2.7 Hz, 1H), 2.05 (ddd,
Jˆ13.1 Hz, Jˆ10.0 Hz, Jˆ3.1 Hz, 1H), 2.72 (mc, 1H),
3.14 (dd, Jˆ10.0 Hz, Jˆ5.8 Hz, 1H), 3.51 (ddq,
Jdˆ8.4 Hz, Jqˆ7.5 Hz, Jdˆ2.7 Hz, 1H), 4.13 (d,
Jˆ14.8 Hz, 1H), 4.66 (d, Jˆ14.8 Hz, 1H), 6.22 (d,
Jˆ8.4 Hz, 1H), 6.35 (dd, Jˆ8.3 Hz, Jˆ8.3 Hz, 1H), 7.23–
7.39 (m, 5H).
(1Rء,2Sء,5Sء,20Rء)-N-Benzyl-5-methyl-2-propyl-cyclohex-
3-ene-1,20-sultam (3e). 1H NMR (CDCl3): d 1.08 (d,
Jˆ6.7 Hz, 3H), 1.34 (d, Jˆ7.1 Hz, 3H), 1.40 (mc, 1H),
1.48 (ddd, Jˆ15.8 Hz, Jˆ3.1 Hz, Jˆ3.1 Hz, 1H), 1.72
(ddd, Jˆ15.8 Hz, Jˆ6.9 Hz, Jˆ6.9 Hz, 1H), 2.30 (mc,
2H), 3.19 (mc, 1H), 3.22 (ddd, Jˆ6.3 Hz, Jˆ2.7 Hz,
Jˆ2.7 Hz, 1H), 3.38 (ddq, Jqˆ7.1 Hz, Jdˆ6.9 Hz,
Jdˆ3.1 Hz, 1H), 4.14 (d, Jˆ14.9 Hz, 1H), 4.51 (d,
Jˆ14.9 Hz, 1H), 5.56 (mc, 1H), 5.60 (dd, Jˆ10.2 Hz,
Jˆ5.0 Hz, 1H), 7.23–7.40 (m, 5H); 13C NMR (CDCl3): d
16.4 (q), 21.3 (q), 26.4 (t), 30.3 (d), 31.1 (d), 31.5 (t), 48.8
(t), 52.8 (d), 57.8 (d), 127.1 (d), 127.2 (d), 127.6 (d), 128.0
(d), 133.8 (d), 137.0 (s).
Acknowledgements
Financial support of this work by the Deutsche Forschungs-
gemeinschaft and the Fonds der Chemischen Industrie is
gratefully acknowledged. We thank Prof. G. Erker, Univer-
sitat Mu¨nster, and Prof. L. F. Tietze, Universitat Gottingen,
for their help with some high pressure Diels–Alder
reactions.
¨
¨
¨
References
1. Ciobanu, M.; Matsumoto, K. Liebigs Ann.-Recl. 1997, 623–
635.
¨
Sultams 5b/6b from 4b
2. Klarner, F.-G.; Diedrich, M. K.; Wigger, A. E. Chemistry under
Extreme or Non-Classical Conditions; van Eldik, R., Hubbard,
C. D., Eds.; Wiley: New York, 1997, pp 103–161.
3. Jurczak, J.; Gryko, D. T. Chemistry under Extreme or Non-
Classical Conditions; van Eldik, R., Hubbard, C. D., Eds.;
Wiley: New York, 1997, pp 163–188.
Thermal reaction: 3 h; high pressure reaction: 12 h. By
HPLC (analytical scale) a sample highly enriched in 6b
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reaction.
4. Ibata, T. Organic Synthesis at High Pressures; Matsumoto, K.,
Archeson, R. M. Eds.; Wiley: New York, 1991, pp 213–285.
5. Matsumoto, K.; Toda, M.; Uchida, T. Organic Synthesis at
High Pressures; Matsumoto, K., Archeson, R. M., Eds.; Wiley:
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6. Uyehara, T.; Yamamoto, Y. Organic Synthesis at High
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(1Rء,2Sء,4Sء,20Sء)-N-Benzyl-1-propylbicyclo[2.2.2]oct-5-
ene-2,20-sultam (5b). Mp 124ЊC; Rf 0.23 (pentane/diethyl
ether, 1:1); IR (neat): 3052 (m), 2983 (m), 2947 (s), 2935
(s); 2914 (m), 2870 (m), 1650 (w), 1450 (m), 1440 (w), 1382
(m), 1354 (s, SO2N), 1338 (s), 1326 (s), 1296 (m), 1197 (m),
1172 (s, SO2N), 1139 (m), 1099 (m), 1051 (m), 943 (m), 915
(m), 899 (s), 891 (s), 871 (s), 801 (s), 736 (m), 711 (m), 593
1
(s), 573 (m), 549 (m), 466 (m) cmϪ1; H NMR (CDCl3): d
7. For a recent reference, see: Diedrich, M. K.; Klarner, F.-G.;
¨
1.10 (d, Jˆ6.9 Hz, 3H), 1.25 (mc, 1H), 1.35 (mc, 1H), 1.42
(mc, 1H), 1.48–1.65 (m, 3H), 1.79 (ddd, Jˆ10.3 Hz,
Jˆ5.8 Hz, Jˆ2.9 Hz, 1H), 2.05 (ddd, Jˆ10.3 Hz,
Jˆ9.8 Hz, Jˆ2.9 Hz, 1H), 2.72 (mc, 1H), 2.97 (dd,
Jˆ9.7 Hz, Jˆ5.9 Hz, 1H), 4.17 (d, Jˆ16.4 Hz, 1H), 4.26
(ddq, Jdˆ11.7 Hz, Jqˆ6.9 Hz, Jdˆ2.5 Hz, 1H), 4.53 (d,
Jˆ16.3 Hz, 1H), 6.07 (d, Jˆ8.0 Hz, 1H), 6.40 (dd,
Jˆ8.0 Hz, Jˆ8.0 Hz, 1H), 7.23–7.39 (m, 5H); 13C NMR
(CDCl3): d 20.2 (q), 24.3 (t), 27.9 (d), 29.4 (d), 34.6 (t),
38.5 (s) 38.6 (t), 46.4 (t), 52.4 (d), 57.8 (d), 127.0 (d), 127.2
(d), 128.4 (d), 132.9 (d), 134.0 (d), 139.5 (s). MS (GC/MS)
m/z (relative intensity): 317 (0.2) [Mϩ], 132 (5), 105 (5), 104
(3), 103 (4), 93 (12), 92 (88), 91 (100) [C7Hϩ7 ], 79 (6), 78
(6), 77 (13), 65 (15), 51 (4). Anal. Calcd for C18H23NO2S: C,
68.10; H, 7.30; N, 4.41. Found C, 67.99; H, 7.63; N, 4.37.
J. Am. Chem. Soc. 1998, 120, 6212–6218.
8. Metz, P. J. Prakt. Chem. 1998, 340, 1–10.
¨
9. Metz, P.; Fleischer, M.; Frohlich, R. Tetrahedron 1995, 51,
711–732.
10. Metz, P.; Fleischer, M. Synlett 1993, 399–400.
¨
11. Galley, G.; Patzel, M. J. Chem. Soc., Perkin Trans. 1 1996,
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¨
12. Metz, P.; Seng, D.; Frohlich, R.; Wibbeling, B. Synlett 1996,
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¨
14. Metz, P.; Fleischer, M.; Frohlich, R. Synlett 1992, 985–987.
15. Crystal data for 5b: C18H23NO2S, Mˆ317.43, orthorhombic,
space group Pbca (No. 61), aˆ11:364ꢀ1†; bˆ12:412ꢀ1†;
cˆ45:777ꢀ2† A; Vˆ6456:8ꢀ8† A ; Zˆ16; Dcˆ1:306 g cmϪ3
;
ꢀ
ꢀ 3
mˆ2:08 cmϪ1; empirical absorption correction with SORTAV
(1Sء,2Rء,4Rء,20Sء)-N-Benzyl-1-propylbicyclo[2.2.2]oct-5-
ene-2,20-sultam (6b). Rf 0.21 (pentane/diethyl ether, 1:1);
IR (neat): 3048 (m), 2981 (m), 2945 (s), 2927 (s), 2919 (m),
2878 (m), 1651 (w), 1378 (m), 1350 (s, SO2N), 1341 (s),
1331 (s), 1292 (m), 1194 (m), 1168 (s, SO2N), 1142 (m),
1102 (m), 1048 (m), 941 (m), 912 (m), 902 (s), 890 (s), 868
ꢀ0:9596ϽCϽ0:9596†; Fꢀ000†ˆ2720; colorless crystal with
3
ꢀ
dimensions 0:2×0:2×0:2 mm ; lˆ0:71073 A; Tˆ198ꢀ2† K; Q
range 3.01–30.05Њ, index ranges Ϫ11ՅhՅ15; Ϫ17ՅkՅ16;
Ϫ58ՅlՅ64; 29196 reflections collected, 9028 independent
‰Rintˆ0:045Š; full-matrix least-squares refinement on F2, 339
parameters, GOF on F2 1.030, final
R
indices ‰IϾ2sꢀI†Š

B. Plietker et al. / Tetrahedron 56 (2000) 873–879
879
Rˆ0:048 and wR2ˆ0:104; largest difference peak and hole 0.30
Universitat Gottingen, 1997). Crystallographic data of 5b were
deposited with the Cambridge Crystallographic Data Centre.
16. Keller, E., schakal 97, A Computer Program for the Graphic
Representation of Molecular and Crystallographic Models;
¨
¨
and Ϫ0.39 e AϪ3. The data set was collected with a Nonius
˚
KappaCCD diffractometer using a rotating anode generator
FR591. Programs used: data collection Collect (Nonius, B. V.,
1994), data reduction Denzo-SMN (Otwinowski, Z., Minor, W.
Methods in Enzymology 1997, 276, 307–326), absorption correc-
tion SORTAV (Blessing, R. H. Acta Cryst. 1995, A51, 33–37;
Blessing, R. H. J. Appl. Cryst. 1997, 30, 421–426), structure
solution shelxs-97 (Sheldrick, G. M. Acta Cryst. 1990, A46,
467–473), structure refinement shelxl-97 (Sheldrick, G. M.,
¨
Universitat Freiburg, 1997.
17. Martin, S. F.; Tu, C.; Chou, T. J. Am. Chem. Soc. 1980, 102,
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