Diastereoselectivity in the hetero [4+2] cycloaddition of cyclopentadiene to N-benzyliminoacetyl derivatives of (2R)-bornane-10,2-sultam and other chiral secondary alcohols

Article abstract of DOI:10.1016/S0957-4166(01)00356-1

Various protonated chiral glyoxyloyl-α-imino-N-benzyl hetero-dienophiles have been examined in the diastereoselective exo-cycloaddition to cyclopentadiene at -78°C promoted by CF₃CO₂^-BF₃, a dissociated non-nucleophilic counter ion. The best π-facial selectivities were observed with (2R)-bornane-10,2-sultam (76% d.e.) and (2R)-10-dicyclohexylsulfonamoyl-isoborneol (80% d.e.) as chiral auxiliaries. These conditions were found to be superior in terms of yields and selectivities as compared to analogous aza-dienophiles treated with simple Lewis acids or under thermal conditions. Absolute configurations were assigned on the basis of an X-ray analysis of the major cycloadduct (3′S)-3a as well as by chiroptical comparison with the corresponding new amino alcohol (-)-(3S)-4a. Plausible transition states are briefly discussed on the basis of PM3 conformational calculations.

Full text of DOI:10.1016/S0957-4166(01)00356-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 1939–1945
Diastereoselectivity in the hetero [4+2] cycloaddition of
cyclopentadiene to N-benzyliminoacetyl derivatives of
(2R)-bornane-10,2-sultam and other chiral secondary alcohols
Sławomir Szyman´ski,a Christian Chapuisb,*,† and Janusz Jurczaka,b,
*
aDepartment of Chemistry, Warsaw University, Pasteura 1, PL-02-093 Warsaw, Poland
bInstitute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44, PL 01-224 Warsaw, Poland
Received 13 July 2001; accepted 8 August 2001
Abstract—Various protonated chiral glyoxyloyl-a-imino-N-benzyl hetero-dienophiles have been examined in the diastereoselective
exo-cycloaddition to cyclopentadiene at −78°C promoted by CF3CO2−BF3, a dissociated non-nucleophilic counter ion. The best
p-facial selectivities were observed with (2R)-bornane-10,2-sultam (76% d.e.) and (2R)-10-dicyclohexylsulfonamoyl-isoborneol
(80% d.e.) as chiral auxiliaries. These conditions were found to be superior in terms of yields and selectivities as compared to
analogous aza-dienophiles treated with simple Lewis acids or under thermal conditions. Absolute configurations were assigned on
the basis of an X-ray analysis of the major cycloadduct (3%S)-3a as well as by chiroptical comparison with the corresponding new
amino alcohol (−)-(3S)-4a. Plausible transition states are briefly discussed on the basis of PM3 conformational calculations.
© 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
hydrogenation with sacrifice of the inducing stereogenic
center and concomitant reduction of unprotected unsat-
urated linkages. For this reason, we recently opted for
the alternative acyl substitution.11e Thus, when the N-
glyoxyloyl-(2R)-bornane-10,2-sultam 1a19 was treated
with tosyl isocyanate, followed by cyclopentadiene in
toluene, a selectivity of 60% d.e. was observed when the
cycloaddition was catalyzed by TiCl4 at −78°C. The
diastereoselectivity decreased to 28% d.e. of the oppo-
site (3%S) diastereoisomer when the reaction was con-
ducted at 20°C in the absence of Lewis acid. More
recently, reduction with LiAlH4 to the optically pure
new amino alcohol (−)-(3S)-4b,20 regenerated the (2R)-
bornane-10,2-sultam in 95% yield.
The hetero-Diels–Alder reaction of electron deficient
reactive imines with 1,3-dienes is a potent tool for the
synthesis of six-membered ring alkaloids,1 carbocyclic
stable ribofuranosylamines analogues2 or prostaglandin
H1 and thromboxane A2 antagonists.3 This methodol-
ogy, using specifically glyoxyloyl derived imines, has
been further extended to the asymmetric version4 by
means of chiral catalysts,5 chiral dienes6 or cyclic7/
acyclic chiral heterodienophiles.8 In this latter case, the
chiral auxiliary is usually connected either directly to
the nitrogen atom, using either a chiral amino acid9 or
amine,10 or by connection to the acyl moiety.11 Finally,
double diastereoselection combining both options was
also exploited.12 The resulting cycloadducts have utility
in the preparation of unnatural amino acids13 or chiral
ligands for asymmetric reduction,14 the transfer hydro-
genation of ketones,15 in the Kharasch–Sosnovsky reac-
tion,16 the addition of dialkylzinc to aldehydes and
imines17 and the rearrangement of meso-epoxides.18
We now wish to report the analogous reaction per-
formed with an N-benzyl substituent under Stella’s 1:1
mixed Brønsted/Lewis acids conditions,10a with com-
parison of several chiral auxiliaries.
2. Results
When the chiral auxiliary is connected directly to the
nitrogen atom, its removal is often performed by
The N-glyoxyloyl-(2R)-bornane-10,2-sultam 1a (readily
obtained by ozonolysis of the corresponding N,N%-bis-
fumaroyl21 or N-crotonoyl22 derivatives), was treated
* Corresponding authors. E-mail: christian.chapuis@firmenich.com;
jurczak@icho.edu.pl
,
with benzylamine in the presence of 3 A molecular
† Present address: Firmenich SA, Corporate R & D Division, PO Box
239, CH-1211 Geneva 8, Switzerland. Tel.: 022 780 36 10; fax: 022
780 33 34.
sieves in CH2Cl2 at 20°C for 30 min, prior to addition
of trifluoroacetic acid (1.0 mol. equiv.) and boron tri-
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00356-1

1940
S. Szyman´ski et al. / Tetrahedron: Asymmetry 12 (2001) 1939–1945
OH
R
O
LiAlH4
R*
O
O
N
N
CF3
R*
F3B
CH2Ph
H2NCH2Ph
CF3CO2H
R*
O
(-)-(3S)-4a R = CH2Ph
(-)-(3S)-4b R = SO2Tol
(3'S)-3a-3f
CH2Ph
O
PhH2C
N
.
BF3 OEt2
1a-1f
O
H
N
R*
2a-2f
O
(3'R)-3a-3f
Ph
O
O
a) R* =
b) R* =
e) R* =
c) R* =
N
SO2
Ph
d) R* =
f) R* =
O
O
O
SO2N(cHex)2
SO2N(CH2Ph)2
fluoride etherate (1.0 mol. equiv.) at −78°C. Subsequent
addition of cyclopentadiene (1.0 mol. equiv.) to the
crude heterodienophile 2a, afforded after 5 h at −78°C a
12:88 diastereoisomeric mixture of (3%R)/(3%S)-exo-3a
(76% d.e.), easily separated and isolated in 80% yield by
chromatography (Table 1, entry 1).
by means of the known glyoxylate 1c,25 resulted in a
slight increase in the diastereoselectivity to 53% d.e.
(entry 3), while 70% d.e. was obtained when the known
and more efficient (1R)-8-phenylmenthyl glyoxylate 1d26
generated the aza-dienophile 2d (entry 4). This last
result is to be compared with the 76% d.e. observed
under analogous Stella’s conditions by Garcia-Mera et
al.,11f as well as the 20% d.e. reported under uncatalyzed
addition for the (−)-8-phenylmenthyl N-tosyl
analogue.11b
The main cycloadduct (3%S)-exo-3a (Fig. 1), was recrys-
tallized from hexane/ethyl acetate and submitted to X-
ray analysis for determination of the absolute and
relative (3%S)-exo configuration, prior to further LiAlH4
reduction to the new optically pure amino alcohol (−)-
(3S)-4a.23 It is noteworthy that, under these conditions,
the diastereoselectivity, which is not modified in toluene,
is higher but opposite to that observed with TiCl4.11e
The best p-facial selectivity, reaching 80% d.e., was
obtained with the known glyoxylate 1e,27 prepared from
the commercially available isoborneol-derived dicyclo-
hexyl sulfonamide28 (entry 5). Comparatively, the steri-
cally and conformationally less constrained dibenzyl
analogue, developed by Yamamoto,29 was slightly less
efficient and afforded (3%S)-3f in 85% isolated yield with
72% d.e. (entry 6).
When the known (1R)-menthyl glyoxylate 1b24 was
treated under identical conditions, the p-facial selectiv-
ity only reached 42% d.e. in favor of the (3%S) cycload-
duct 3b as shown, after reduction, by chiroptical
comparison of the corresponding alcohol (3S)-4a (entry
2). This was nevertheless encouraging with respect to
the 12% d.e. reported under uncatalyzed conditions
with the (−)-menthyl N-tosyl analogue.11b Replacement
of the shielding iso-propyl moiety by a sterically more
demanding phenyl substituent on the prosthetic group,
3. Discussion
The very high exo-selectivity resulting from this type of
aza-Diels–Alder reaction was earlier explained on the
basis of minimized hydrophobic interactions in aqueous
or wet solvents9,30 or greater second order orbital elec-
tronic requirements of the N-withdrawing group.2b
With respect to the hetero-dienophile 2a, all attempts to
calculate the different concerted transition states at the
PM3 level were unsuccessful.31 This suggests either a
highly asynchronous mechanism32 or a different mecha-
nistic pathway, such as, for example, a stepwise Man-
nich type reaction.33 Thus, these reversible steps could
partially account for a thermodynamic control of the
more stable exo-stereoisomers. In view of this ambigu-
ity, we restrained our calculations to the conforma-
tional stability and reactivity of (2R)-2a (Table 2).
Table 1.
Entry
Dienophile
Isolated yield
(%)
(3%R)-3a–3f/(3%S)-3a
–3f
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
80
75
78
80
82
85
12:88
29:71
23:77
15:85
10:90
14:86

S. Szyman´ski et al. / Tetrahedron: Asymmetry 12 (2001) 1939–1945
1941
Figure 1. ORTEP diagram of (3%S)-exo-3a with arbitrary atom numbering. Ellipsoids are represented at the 40% probability level.
Table 2.
(2R)-2a
DHform (kcal
LUMO (eV)
SꢀNꢀCꢁO (°)
Ca-re at coef
Nb-re at coef
Ca-si at coef
Nb-si at coef
mol−1
)
syn-s-trans
syn-s-cis
anti-s-cis
105.73
94.95
90.12
88.60
−5.89
−5.94
−5.80
−5.51
−48.0
−11.5
163.0
0.35
−0.31
0.35
−0.36
0.36
−0.40
0.35
−0.33
0.33
−0.34
0.34
0.38
−0.35
0.39
anti-s-trans
140.5
−0.33
−0.32
The anti-s-trans conformer 2a is thermodynamically the
most stable conformer as consequence of an
ize the main (3%S)-3a formation, either by a steric
approach on the Ca-si face of the anti-s-cis conformer35
and/or by a cumulative steric and electronic approach
on the Ca-si face of the syn-s-cis conformer.34 Indeed,
as expressed by the sum of the square of the specific
Ca–Nb atomic p-facial coefficients, the preferred elec-
tronic approach is opposite to the steric one in the case
of the anti-s-cis conformer, as already earlier observed
for analogous homo-34 and hetero-dienophiles.36
a
intramolecular H-bond between the HꢀN+ atom and
the pseudo equatorial SꢁO group. It follows that the
p-system of the reactive OꢁCꢀCꢁN moiety is not fully
aligned with the SO2ꢀN lone pair as shown by the
strong deviation of the SꢀNꢀCꢁO dihedral angle
(140.5°).34 This results in a lower reactivity as shown by
both the highest LUMO level (−5.51 eV) and the
smallest global sum of the square of the Ca–Nb atomic
coefficients,34 as compared to the three other considered
coplanar conformations. In contrast, the syn-s-trans
conformer is (by far) too high in energy to statistically
enter into consideration. As a consequence, the most
reactive coplanar species are the syn-s-cis conformer 2a,
as expressed by its low LUMO level, as well as the
thermodynamically more stable anti-s-cis conformer,
which possesses the greatest global sum of the square of
the Ca–Nb atomic coefficients. Independently from a
concerted/non-concerted mechanism, we thus rational-
In the case of the secondary alcohols 2b–2f as cycload-
dition control elements, Oppolzer earlier proposed,37
supported by a recent X-ray analysis,11f that the most
favorable conformation is reached when the alkoxy
CꢀH bond is syn-periplanar with the CꢁO moiety of the
ester. As a consequence, all these prosthetic groups
possess an identical sterically induced Ca-si topicity,
when the (E) CꢁN+ bond is s-cis with that of the CꢁO.
PM3 calculations confirmed the thermodynamic stabil-
ity and higher reactivity of the s-cis over the s-trans
Cα-re steric approach opposed
to the pseudo axial S=O moiety
Cα-si steric approach opposed
to the pseudo axial S=O moiety
N
S O
N
H
Ph
+
O
O
O
N
H
O
+
N
O
N
Ph
S
Cα-si electronic and steric
approach opposed
to the C(2)-C(3) substituent
S
O
+
N
O
O
Ti
Cl4
SO2Tol
anti-s-trans
anti-s-cis
syn-s-cis

1942
S. Szyman´ski et al. / Tetrahedron: Asymmetry 12 (2001) 1939–1945
conformers (Table 3). Despite the fact that the N+ꢀH
and CꢁO bonds are parallel, an intramolecular weak
hydrogen bond character with the carbonyl moiety is
not excluded and could partially account for this con-
formational stability/reactivity.
5.3. General procedure for the cycloaddition reactions
Benzylamine (321 mg, 0.33 mL, 3.0 mmol) was added
at 0°C to a suspension of glyoxyloyl derivative 1 (3.0
,
mmol) and molecular sieves (3 A, 0.6 g) in CH2Cl2 (6
mL). After 30 min the flask was cooled to −78°C and
CF3CO2H (342 mg, 0.23 mL, 3.0 mmol) and BF3·OEt2
(426 mg, 0.38 mL, 3.0 mmol) were added dropwise,
followed by a solution of cyclopentadiene in CH2Cl2 (1
M, 3.0 mL, 3.0 mmol). After 5 h at −78°C, the reaction
was quenched by addition of satd aqueous NaHCO3.
The mixture was extracted with CH2Cl2, washed to
4. Conclusion
The [4+2]-cycloadditions of chiral glyoxyloyl derived
a-imino-dienophiles to cyclopentadiene promoted by
Stella’s 1:1 CF3CO2H/BF3·Et2O conditions are superior
in terms of diastereoselectivity and chemical yield when
compared to the corresponding Lewis acids or thermal
conditions reported for analogous aza-Diels–Alder
reactions. The resulting cycloadducts are of consider-
able interest in medicinal chemistry as valuable starting
materials for the straightforward synthesis of aris-
teromycin,11b amidomycin,38 carbovir NCS61484639
and are prone to further specific chemical/skeletal
transformations.40 Acyclic dienes may also open access
to MQPA thrombin inhibitor,41 streptolutin42 or
carpamic acid.43 Finally, both antipodes of the most
efficient cyclic or acyclic camphor derived sulfonamide
auxiliaries are commercially available and readily
recovered.
Table 4. Crystal data and structure refinement for (3%S)-3a
Identification code
Empirical formula
Formula weight
Temperature (K)
(3%S)-3a
24H30N2O3S
426.56
C
293(2)
,
Wavelength (A)
1.54178
Monoclinic, C2
Crystal system, space group
Unit cell dimensions
,
a (A)
22.882(5)
8.237 (2), 125.80(3) (°)
14.002(3)
2140.5(8)
4, 1.324
,
b (A)
,
c (A)
3
,
Volume (A )
Z, Calculated density (Mg/m3)
Absorption coefficient (mm−1
F(000)
)
1.571
912
Crystal size (mm)
q-Range for data collection (°)
Index ranges
0.14×0.21×0.54
3.89–78.94
−235h528, 05k510,
−175l50
5. Experimental
5.1. General
Reflections collected/unique
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
Final R indices [I\2|(I)]
R indices (all data)
1595/1530 [Rint=0.0394]
Full-matrix least-squares on F2
1530/1/272
See Ref. 44
1.051
5.2. X-Ray structure determination of (3%S)-3a
R1=0.0576, wR2=0.1352
R1=0.0666, wR2=0.1436
0.00(5)
0.0033(5)
0.337 and −0.212
Absolute structure parameter
Extinction coefficient
Suitable crystals were grown from a hexane/AcOEt
soln. The measurements were run on a Nonius
MACH3 diffractometer using Express softpress soft-
ware, without absorption corrections. Table 4 shows
details of the data collection and refinement and Table
5 shows selected bond lengths and angles. In the final
steps of the least-squares procedure, all but Me group
H-atoms were kept fixed at their calculated positions.
The structures were solved by the SHELXS-8645 and
refined with the SHELXL-9346 programs. The known
configuration of the asymmetric centers of the sultam
unit has been confirmed by the Flack parameter refine-
ment.47 Lists of the fractional atomic coordinates,
isotropic thermal parameters and bond lengths and
angles have been deposited at the Cambridge Crystallo-
graphic Data Centre as supplementary material (3%S)-3a
reg. no CCDC 164399.
Largest diff. peak and hole
−3
,
(e A
)
,
Table 5. Selected bond lengths (A) and angles (°)
S(11)ꢀO(1)
S(11)ꢀO(2)
S(11)ꢀN(12)
O(2)ꢀS(11)ꢀO(1)
C(2)ꢀN(12)ꢀS(11)
C(2)ꢀN(12)ꢀC(13)
C(13)ꢀN(12)ꢀS(11)
S(11)ꢀN(12)ꢀC(13)ꢀO(14)
DhN(12)
1.424(7)
1.381(7)
1.665(6)
117.3(5)
111.1(5)
117.9(6)
124.3(5)
151.9(6)
0.225(5)
Table 3.
OꢁCꢀCꢁN+
2b
85.06
−6.16
83.78
2c
2d
2e
2f
s-trans DH (kcal mol−1
s-trans LUMO (ev)
)
133.51
−6.10
132.10
−6.12
116.21
−5.96
115.87
−6.01
6.74
101.87
−5.26
99.30
−5.31
6.70
−5.37
s-cis DH (kcal mol−1
s-cis LUMO (eV)
)
−6.17
−5.26

S. Szyman´ski et al. / Tetrahedron: Asymmetry 12 (2001) 1939–1945
1943
neutrality with brine, dried, evaporated and the residue
purified by chromatography (see Table 1 for yields). The
main cycloadducts were further purified by
crystallization.
129.2; 129.3; 133.7; 133.9; 136.6; 151.8; 172.9; 177.4.
LSIMS HR calculated for C30H38NO2H+: 444.2903,
obtained 444.2867.
5.8. Cycloadduct (3%S)-3e
5.4. Cycloadduct (3%S)-3a
IR: 3443; 3062; 2936; 2857; 1731; 1494; 1453; 1393; 1324;
1235; 1167; 1144; 1109; 1050; 982; 894; 845; 774; 745. 1H
NMR: 0.79–0.82 (m 2H); 0.90 (s 3H); 1.05 (s 3H);
1.05–1.35 (m 8H); 1.53–2.06 (m 20H); 2.35 (s 0.10H); 2.38
(s 0.90H); 2.56–2.62 (d 0.10H); 2.65–2.71 (d 0.90H);
3.14–3.33 (m 4H); 3.69–3.76 (m 2H); 4.82–4.88 (dd 0.1H);
4.93–4.98 (dd 0.90H); 6.17–6.25 (m 1H); 6.45–6.49 (m
1H); 7.16–7.43 (m 5H). 13C NMR: 20.5; 20.7; 25.4; 26.7;
27.2; 30.8; 32.8; 33.2; 40.0; 44.7; 46.9; 48.3; 49.4; 49.7;
54.1; 57.7; 58.7; 63.0; 66.3; 79.0; 127.1; 128.4; 129.2;
133.5; 136.7; 139.4; 170.7. LSIMS HR calculated for
C36H52N2O4S+: 608.3647, obtained 608.3666. Elem. anal.
calculated: C, 71.05%; H, 8.55%; N, 4.61%; S, 5.26%;
obtained C, 71.02%; H, 8.48%; N, 4.57%; S, 4.67%.
Mp 151–152°C; [h]D −155.5 (c=0.31, CHCl3); IR: 3447;
3096; 2992; 2964; 2917; 2864; 1698; 1483; 1442; 1406;
1328; 1274; 1248; 1213; 1127; 1103; 1057; 902; 892; 776;
1
754; 738. H NMR: 0.96 (s 3H); 1.17 (s 1H); 1.26–1.39
(m 3H); 1.68 (s 1H); 1.85–2.07 (m 7H); 3.01 (s 1H); 3.12
(s 1H); 3.43 (d 2H); 3.50 (d 2H); 3.80–3.88 (m 2H);
6.27–6.31 (m 1H); 6.52–6.57 (m 1H); 7.21–7.39 (m 5H).
13C NMR: 20.1; 20.4; 21.0; 26.6; 32.9; 38.6; 44.7; 45.5;
47.7; 50.9; 53.2; 58.6; 64.4; 65.4; 66.7; 74.2; 127.1; 128.3;
129.4; 134.4; 136.9; 163.2. LSIMS HR calculated for
C24H30N2O3S+: 426.1977, obtained 426.1977. Elem. anal.
calculated: C, 67.61%; H, 7.04%; N, 6.57% obtained C,
67.01%; H, 7.25%; N, 6.42%.
5.5. Cycloadduct (3%S)-3b
5.9. Cycloadduct (3%S)-3f
IR: 3401; 3085; 3028; 2978; 2922; 2876; 1744; 1506; 1457;
1388; 1376; 1309; 1246; 1168; 1138; 1106; 1091; 1022; 984;
921; 875; 772; 752; 701. H NMR: 0.62–0.94 (m 12H);
IR: 3442; 3062; 2953; 2881; 1721; 1604; 1495; 1455; 1335;
1247; 1148; 1052; 1028; 941; 894; 847; 790; 750; 700. H
1
1
NMR: 0.77–0.93 (m 2H); 0.80 (s 3H); 1.01 (s 3H);
1.04–1.31 (m 4H); 1.60–1.75 (m 5H); 1.90–2.05 (m 2H);
2.29 (s 1H); 2.51–2.57 (d 1H); 3.12 (s 0.28H); 3.19 (s
1.72H); 3.41–3.63 (qAB 2H); 3.42 (s 0.14); 3.43 (s 0.86H);
5.00–5.05 (dd 1H); 6.07–6.11 (dd 1H); 6.36–6.41 (m 1H);
2.19–2.34 (m 15H). 13C NMR: 20.5; 27.3; 30.4; 39.7; 44.6;
46.8; 48.2; 49.4; 49.9; 51.2; 58.9; 63.0; 66.3; 78.7; 127.2;
128.1; 128.4; 128.8; 129.0; 129.4; 133.3; 133.6; 136.2;
136.8; 169.7. LSIMS HR calculated for C38H44N2O4S+:
624.3021, obtained 624.3011. Elem. anal. calculated C,
73.08%; H, 7.05%; N, 4.49%, obtained C, 72.67%; H,
7.28%; N, 4.10%.
0.96–2.05 (m 7H); 2.28 (s 0.29H); 2.29 (s 0.71H); 3.04 (s
1H); 3.49 (qAB 0.29H); 3.52 (qAB 0.71H); 3.86 (d
0.29H); 3.90 (d 0.71H); 4.55–4.70 (m 1H); 4.83–4.96 (m
2H); 6.22–6.25 (m 1H); 6.45–6.49 (m 1H); 7.20–7.37 (m
5H). 13C NMR: 16.2; 16.5;21.0; 22.2; 22.1; 23.3; 26.4;
34.3; 34.4; 40.8; 40.8; 41.0; 46.7; 47.1; 47.2; 48.9; 59.2;
64.6; 65.1; 74.3; 76.1; 127.1; 128.3; 128.3; 128.8; 129.1;
129.2; 133.8; 136.6; 154.8; 159.3. LSIMS HR calculated
+
for C24H33NO2 : 367.2511, found 367.2518.
5.6. Cycloadduct (3%S)-3c
IR: 3449; 3063; 2986; 2937; 2857; 1739; 1708; 1601; 1493;
1447; 1380; 1324; 1235; 1191; 1170; 1112; 1025; 909; 856;
761; 740. 1H NMR: 1.04–1.08 (d 1H); 1.11–1.63 (m 6H);
1.71–1.92 (m 4H); 2.01 (s 0.77H); 2.04 (s 0.23H); 2.20 (s
1H); 2.58 (dt 1H); 3.10–3.39 (qAB 0.23H); 3.21–3.53
(qAB 0.77H); 3.67 (d 0.23H); 3.73 (d 0.77H); 4.90–5.04
(dt 1H); 6.05–6.13 (m 1H); 6.23–6.33 (m 1H); 7.09–7.31
(m 10H). 13C NMR: 24.9; 26.0; 32.2; 32.3; 34.2; 34.6;
46.3; 48.5; 48.9; 49.9; 50.2; 58.7; 58.8; 64.0; 64.3; 64.8;
65.6; 75.6; 76.1; 126.5; 127.0; 127.6; 127.7; 128.2; 128.2;
128.3; 129.1; 129.2; 133.2; 133.6; 136.6; 136.7; 139.3;
5.10. (1S)-2-Benzyl-2-aza-bicyclo[2.2.1]hept-5-en-(3S)-
yl-methanol (3S)-4a
A solution of cycloadduct (3%S)-3a (213 mg, 0.5 mmol)
in dry THF (2.5 mL) was added dropwise to a suspension
of LiAlH4 (17 mg, 0.5 mmol) in dry THF (2.5 mL). After
30 min at 20°C, the reaction was quenched with H2O, the
mixture was extracted with THF, dried and evaporated
to afford after chromatographic purification both (3S)-
4a and the (2R)-bornane-10,2-sultam in 95% respective
yields. [h]2D0 −6.8 (c 1.02; CHCl3). IR: 3369; 3061; 2985;
2871; 1673; 1604; 1565; 1495; 1454; 1368; 1324; 1264;
1189; 1078; 1029; 911; 834; 768; 747. 1H NMR: 1.25–1.29
(d 1H); 1.67–1.72 (d 1H); 1.83 (t 1H); 2.18 (s 1H); 2.69
(d 1H); 3.31–3.45 (m 5H); 3.69 (d 1H); 6.10–6.14 (m 1H);
6.41–6.45 (m 1H); 2.16–2.28 (m 5H). 13C NMR: 34.4; 46;
47.1; 59.1; 64.2; 64.6; 65.4; 73.2; 127.3; 128.6; 129.2;
132.6; 138.0; 140.0. LSIMS HR calculated for
C14H18NO+: 216.1383, obtained 216.1363.
+
143.3; 173.1. LSIMS HR calculated for C26H29NO2 :
387.2193, obtained 387.2185.
5.7. Cycloadduct (3%S)-3d
IR: 3444; 3059; 2956; 2924; 2801; 1735; 1599; 1495; 1454;
1365; 1325; 1234; 1187; 1161; 1094; 999; 905; 863; 766;
736. 1H NMR: 0.76–0.99 (m 6H); 1.08 (s 3H); 1.10 (s 3H);
1.17–1.62 (m 7H); 1.78–2.05 (m 3H); 2.79 (s 0.85H); 2.88
(s 0.15H); 3.28–3.63 (m 2H); 3.71 (d 0.15H); 3.87 (d
0.85H); 4.68–4.83 (m 1H); 6.14–6.23 (m 1H); 6.34–6.38
(m 1H); 7.13–7.42 (m 10H). 13C NMR: 22.0; 26.3; 28.0;
31.4; 34.8; 39.9; 41.6; 46.4; 47.2; 49.0; 50.5; 59.2; 63.6;
64.7; 65.3; 74.5; 74.8; 125.2; 125.6; 127.2; 128.1; 128.4;
5.11. (1S)-2-(Toluene-4-sulfonyl)-2-aza-bicyclo[2.2.1]-
hept-5-en-(3S)-yl-methanol (3S)-4b
Obtained similarly to (3S)-4a from the corresponding
cycloadduct11e in 95% yield. [h]D20 −4.8 (c 1.02; CHCl3).

1944
S. Szyman´ski et al. / Tetrahedron: Asymmetry 12 (2001) 1939–1945
IR: 3448; 3410; 3061; 2957; 2891; 1595; 1494; 1402;
1343; 1322; 1251; 1158; 1092; 1040; 1014; 892; 815; 755;
723. H NMR: 1.40–1.45 (d 1H); 1.81–1.85 (d 1H); 2.42
Vol. E21c, p. 2905; (c) Jørgensen, K. A. Angew. Chem.,
Int. Ed. 2000, 39, 3558.
1
5. (a) Bromidge, S.; Wilson, P. C.; Whiting, A. Tetrahedron
Lett. 1998, 39, 8905; (b) Yao, S.; Johannsen, M.; Hazell,
R. G.; Jørgensen, K. A. Angew. Chem., Int. Ed. 1998, 37,
3121; (c) Yao, S.; Saaby, S.; Hazell, R. G.; Jørgensen, K.
A. Chem. Eur. J. 2000, 6, 2435; (d) Morgan, P. E.;
McCargue, R.; Whiting, A. J. Chem. Soc., Perkin Trans.
1 2000, 515. For examples using simple imines, see Ref. 4.
6. (a) Hamada, T.; Zenkoh, T.; Sato, H.; Yonemitsu, O.
Tetrahedron Lett. 1991, 32, 1649; (b) Danheiser, R. L. J.
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imines, see Ref. 4.
(s 3H); 2.79 (t 1H); 2.99 (s 1H); 3.23–3.29 (dd 1H);
3.67–3.80 (m 1H); 3.92–4.032 (m 1H); 4.63 (d 1H);
5.73–5.77 (dd 1H); 6.01–6.06 (m 1H); 7.24–7.66 (dd
4H). 13C NMR: 21.7; 46.4; 47.1; 60.2; 61.0; 65.6; 66.8;
71.2; 128.3; 129.7; 133.9; 135.3; 137.2; 143.9. LSIMS
HR calculated for C14H17NO3SNa+: 302.0835, obtained
302.0821. Elem. anal. calculated C, 60.21%; H, 6.09%;
N, 5.02%; S, 11.47%; obtained C, 60.04%; H, 6.33%; N,
4.82%; S, 11.21%.
7. Ager, D.; Cooper, N.; Cox, G. G.; Garro-He´lion, F.;
Harwood, L. M. Tetrahedron: Asymmetry 1996, 7, 2563.
8. McFarlane, A. K.; Thomas, G.; Whiting, A. Tetrahedron
Lett. 1993, 34, 2379.
Acknowledgements
9. Waldmann, H.; Braun, M. Liebigs Ann. Chem. 1991,
1045.
We are indebted to Dr. Z. Urbanczyk-Lipkowska for
X-ray analysis of (3%S)-3a. This work was supported by
the State Committee for Scientific Research: Grants
PBZ 6.05/T09/1999 and 3 T09 108 16.
10. (a) Stella, L.; Abraham, H.; Feneau-Dupont, J.; Tinant,
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Beiley, P. D.; Brown, G. R.; Korber, F.; Reed, A.;
Wilson, R. D. Tetrahedron: Asymmetry. 1991, 2, 1263; (c)
Bailey, P. D.; Wilson, R. D.; Brown, G. R. J. Chem. Soc.,
Perkin Trans. 1 1991, 1337; (d) Abraham, H.; Stella, L.
Tetrahedron 1992, 48, 9707; (e) Trova, M. P.; McGee, K.
F. Tetrahedron 1995, 51, 5951. The rationalization pro-
posed in Ref. 10c is based on a conformation possessing
1,3-allylic strain factors. PM3 calculations suggest that
the orthogonal Ph substituent prefers to be syn-peripla-
nar with the NꢁC bond. A stabilization by an intramolec-
ular p···H interaction is not fully excluded. The diene
would thus attack on the sterically less hindered p-face of
the double bond.
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