Influence of norbornanone substituents on both the Wagner-Meerwein skeletal rearrangements under sulfonation conditions and the diastereoselectivity of the corresponding N,N′-bis-fumaroyl sultams in uncatalyzed Diels-Alder cycloadditions to cyclopenta-1,3-diene

Article abstract of DOI:10.1016/j.tetlet.2013.05.147

The Wagner-Meerwein domino rearrangement of norbornanone skeletons, under sulfonation conditions, is strongly influenced by the absence of a gem-dimethyl moiety at C(7). As a result, sulfonation at C(10) is less efficient due to a divergent pathway in the intermediate double bond formation and/or isomerization. Furthermore, the absence of such a gem-dimethyl moiety in the corresponding norbornane[10,2]sultam derivatives, sterically influences the orientation of the SO(1) and SO(2) substituents, hence on the π-facial steric shielding of the thermodynamically more stable anti-s-cis N-alkenoyl dienophiles. As a consequence, their diastereoselective [4+2] cycloadditions to cyclopenta-1,3-diene, under nonchelating conditions, are not as efficient due to a less pseudo axial SO(1) and the consequent loss of pseudo C ₂-symmetry.

Full text of DOI:10.1016/j.tetlet.2013.05.147

Tetrahedron Letters 54 (2013) 4247–4249
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Tetrahedron Letters
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Influence of norbornanone substituents on both the Wagner–
Meerwein skeletal rearrangements under sulfonation conditions
0
and the diastereoselectivity of the corresponding N,N -bis-fumaroyl
sultams in uncatalyzed Diels–Alder cycloadditions to
cyclopenta-1,3-diene
Anna Pi a˛ tek , Christian Chapuis b,
a,
⇑
⇑
,
a
Department of Chemistry, University of Warsaw, Pasteura 1, Warsaw 02-093, Poland
Institute of Organic Chemistry, Polish Academy of Science, Kasprzaka 44/52, Warsaw 01-224, Poland
b
a r t i c l e i n f o
a b s t r a c t
Article history:
The Wagner–Meerwein domino rearrangement of norbornanone skeletons, under sulfonation conditions,
is strongly influenced by the absence of a gem-dimethyl moiety at C(7). As a result, sulfonation at C(10) is
less efficient due to a divergent pathway in the intermediate double bond formation and/or isomeriza-
tion. Furthermore, the absence of such a gem-dimethyl moiety in the corresponding norbornane[10,2]sul-
tam derivatives, sterically influences the orientation of the S@O(1) and S@O(2) substituents, hence on the
Received 14 February 2013
Revised 22 May 2013
Accepted 30 May 2013
Available online 7 June 2013
p
-facial steric shielding of the thermodynamically more stable anti-s-cis N-alkenoyl dienophiles. As a
Keywords:
consequence, their diastereoselective [4+2] cycloadditions to cyclopenta-1,3-diene, under nonchelating
conditions, are not as efficient due to a less pseudo axial S@O(1) and the consequent loss of pseudo
C -symmetry.
2
Wagner–Meerwein rearrangements
Diels–Alder cycloadditions
Norbornane[10,2]sultam derivatives
0
Ó 2013 Elsevier Ltd. All rights reserved.
N,N -Bis-fumaroyl sultams
(
+)-(1R,4R)-Camphor 1a, due to its availability in both enantio-
We earlier synthesized and studied the influence of the S@O(1)
1
2
meric forms, the crystalline properties imparted to its derivatives,
as well as its widely studied chemistry, is an excellent starting
material for the synthesis of chiral auxiliaries and catalysts. Its
devoid sulfinamide analogue, the six-membered ring camphor
1
3,14d
15
sultam analogue,
as well as auxiliary 6b, similarly obtained
1
2
from (ꢀ)-(1R,4R)-fenchone (1b). Based on X-ray analyses of their
3
4
5
corresponding 10-sulfonic acid 2a, via intermediates 3a, 4a,
N-alkenoyl derivatives, as well as those of saccharin derived sul-
6
16
and 5a, led to the discovery of the well-known (2R)-bornane-
0,2-sultam 6a.7 (Scheme 1) This imparts a very high reactivity
and diastereoselectivity to variety of dienophiles and its
efficiency was extended to a wide range of diverse reactions. Its
Me(9) substituent was initially thought to have a steric influence
on the approach of the reactant,9 but very quickly, in view of
non-inversion of the chiral induction under either chelated and
tams, we concluded that Me(9) has a decisive steric impact on
1
the pseudo equatorial orientation of S@O(2), and hence on the
a
pseudo C
less, the presence of a gem-dimethyl moiety in position C(3) influ-
enced strongly the anti/syn SO /C@O conformation, which is
particularly important in the absence of either a chelating Lewis
2
-symmetry, which is thus lost in its absence. Neverthe-
8
2
1
7
2
acid, or pseudo C -symmetry. We thus became interested in pre-
1
0
non-chelated conditions, this hypothesis had to be abandoned.
A disguised pseudo C -symmetry, resulting from the pseudo axial
paring analogues devoid of gem-dimethyl substitution at both C(3)
and C(7).
2
orientation of the S@O(1), and pseudo equatorial orientation of
C(2)–C(3), as sterically important substituents, in either the
We initially started from the reported (ꢀ)-(1S,4S)-iso-fenchone
1c,1 but unfortunately, this substitution influenced strongly the
kinetics of the Wagner–Meerwein rearrangements during its sulfo-
nation, and precluded the expected skeletal transformation accord-
8
SO
2
/C@O anti or syn conformations, thus mimicking a (2R,5R)-
1
1
dimethylpyrrolidine model, was subsequently recognized.
1
9
ing to the well established mechanism. As a consequence, the
2
0
secondary sulfonated intermediate F was recovered and did not
furnish the desired primary sulfonic acid 2c under various
⇑
Corresponding authors. Tel.: +48 228220211; fax: +48 228225996 (A.P.); tel.:
41 227803610; fax: +41 227803334 (C.C.).
+
21
conditions. We next turned our attention toward the reported
E-mail addresses: apiatek@chem.uw.edu.pl (A. Pi a˛ tek), Christian.chapuis@firme
nich.com (C. Chapuis).
Present address: Firmenich SA, Corporate R&D Division, PO Box 239, CH-1211
Geneva 8.
2
2,23
(
ꢀ)-(1R,4S)-1-methyl-2-norbornanone 1d,
and fortunately, in
this case, the Wagner–Meerwein cascade rearrangements allowed
isolation of the new sulfonic acid 2d (H SO , Ac O, 26% yield)
2 4 2
2
4
20
0
040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.05.147

4
248
A. Pi a˛ tek, C. Chapuis / Tetrahedron Letters 54 (2013) 4247–4249
(
Scheme 1). By analogy, this latter compound was subjected to a
desmethyl sultam 6d20 was isolated in 33% yield, after NaBH
4
O1 (Scheme 1). This was acylated with
5
series of reported conditions, used earlier for the synthesis of
6
3
reduction in MeOH/H
2
2
5,26
15
a
and 6b, so that via the corresponding sulfonyl chloride
fumaroyl chloride (NaH, toluene, 75% yield), and its [4+2] cycload-
dition to cyclopenta-1,3-diene, in the absence of a chelating Lewis
d (SOCl , 60% yield), sulfonamide 4d (NH OH, 1,4-dioxane, 55%
2
4
yield), and sulfonimide 5d (concd HCl, 88% yield), the desired
2 2
acid, in CH Cl is reported in Table 1.
R3
R2
R3
R2
R3
R2
H SO , Ac O
R3
2
2
4
2
HCl
R3
R2
R
1
R3
R2
1
R
R
1
R1
1
R1
R
R
O
O
N
R1 R2 R3
a Me H
b H Me H
S
O(1)
SO X
2
1
1
1
1
H
5a-d
O(2)
2
a-d X = OH
a-d X = Cl
SOCl2
c H
d H
H
H
Me
3
H
4a-d X = NH
NH OH
NaBH4
2
4
R3
R2
O
6a-d
R3
2
NaH, toluene
R
O
CPD R3
R2
fumaroyl chloride
3
1
R1
O
3
R1
R2
R
R
7
6
a-d
R1
9
CH Cl
2
2
N
2
6
a-d
NR
SO2
1
0
SO2
O
8
a-d
7a-d
6a-d R = H
Scheme 1.
Table 1
Entry
Dienophile
Time (h)
Temperature (°C)
Conversion (%)
Yield (%)
de (%)
C(2)–N–S@O(1) (°)
S–N–C@O (°)
DhN (Å)
1
2
3
4
5
6
7a
7a
7b
7b
7d
7d
4
1
4
4
24
24
ꢀ78
20
>99
>99
92
>99
21
95
>98
83
89
84
82
85
61
10
103.5a
150.7a
0.230a
0.155a
0.156c
ꢀ78
124.0a
115.9c
153.4a
159.0c
20
95
b
ꢀ78
20
90
80
a
From X-ray structure analyses of the corresponding anti-s-cis N-crotonoyl derivatives.15
b
c
Not determined
⁄⁄
Calculated at the B3LYP-6.31G level on the corresponding anti-s-cis N-crotonoyl derivative. The syn-s-cis conformer (S–N–C@O = ꢀ13.7°; C(2)–N–S@O(1) = 120°,
D
hN = 0.066 Å) being 5.24 and 1.46 kcal/mol higher in energy in either the gas phase, or in CH
2
Cl
2
, respectively.
R1
R1
R1
R3
R1
R2
H
R1
H+
R3
R2
R3
R2
R3
R2
+
1
R
R2
O
R2
O+
HO
R3
R3
1a-d
H
H
A
1
=
R
HO3S+
R2
R2
HO3S+
R1 = H
R2
HO3S
+
R1
R2
R2
R2
R1
HO
.
.
.
.
H
O
R3
HO
R3
R3
R3
R3
R3
R3 = H
E
D
B
R1
R1
R1
R1
SO3H
R2
R2
R2
SO3H
+
R1
R3
R2
R2
R1
- H+
2
R2
O
R
..
R2
O
R3
O
+
H
O
H
..
SO3H
F
2a,b,d SO3H
C
Scheme 2.

A. Pi a˛ tek, C. Chapuis / Tetrahedron Letters 54 (2013) 4247–4249
4249
1
Sulfonation of 1 is particularly efficient when R = Me (1a). In
3. Crist, B. V.; Rodgers, S. L.; Lightner, D. A. J. Am. Chem. Soc. 1982, 104, 6040–6045.
4. Kempe, T.; Norin, T. Acta Chem. Scand. 1973, 27. 1452-1452.
1
cases where R = H, the yields of the corresponding sulfonic acid
are much lower. Indeed, in these cases, the intermediate exocy-
5.
Davis, F. A.; Jenkins, R. H.; Awad, S. B.; Stringer, O. D.; Watson, W. H.; Galloy, J. J.
Am. Chem. Soc. 1982, 104, 5412–5418.
2
clic allylic alcohol B has both the possibility and the time to isom-
erize into the thermodynamically more stable endocyclic isomer D,
which under sulfonation conditions concurrently affords the sec-
6. Patterson, T. S.; Loudon, J. D. J. Chem. Soc. 1932, 1725–1744.
7
.
Oppolzer, W.; Chapuis, C.; Bernardinelli, G. Helv. Chim. Acta 1984, 67, 1397–
401.
Oppolzer, W. Pure Appl. Chem. 1988, 60, 39–49.
1
8.
2
ondary sulfonic acids F (Scheme 2). When R is not Me, this path-
9. Chapuis, C. Ph. D. Thesis No. 2144, University of Geneva, 1984, p 54.
10. See footnote 7 and page 161 in: Chapuis, C.; de Saint Laumer, J.-Y.; Marty, M.
Helv. Chim. Acta 1997, 80, 146–172.
3
way becomes the major one, especially for R = Me (1c). We earlier
27
studied and rationalized in detail, for both mono, and bis fuma-
11. Kim, B. H.; Curran, D. P. Tetrahedron 1993, 49, 293–318.
royl sultams, the influence of either the solvent,14 the temperature,
12. Chapuis, C.; Kawecki, R.; Urbanczyk-Lipkowska, Z. Helv. Chim. Acta 2001, 84,
579–588.
13. Piatek, A.; Chapuis, C.; Jurczak, J. Helv. Chim. Acta 2002, 85, 1973–1988.
28
or the chelating rigidifying effect of the Lewis acids on the [4+2]
2
5,26
15,28
cycloadditions of 7a,
and 7b,
for which the obtained abso-
14. (a) Chapuis, C.; Kucharska, A.; Rzepecki, P.; Jurczak, J. Helv. Chim. Acta 1998, 81,
lute configuration was ascertained by both X-ray structure analyses
2314–2325; (b) Chapuis, C.; Kucharska, A.; Jurczak, J. Tetrahedron: Asymmetry
1
4d,27
2000, 11, 4581–4591; (c) Kucharska, A.; Gorczynska, R.; Chapuis, C.; Jurczak, J.
of the cycloadducts,
diol, after reduction with LiAlH
the conversion and the diastereoselectivity were measured by
and the optical properties of the known
29
Chirality 2001, 13, 631–633; (d) Piatek, A.; Chapuis, C.; Jurczak, J. J. Phys. Org.
Chem. 2003, 16, 700–708.
4
.
In the specific case of 7d, both
1
H
15. Piatek, A.; Chojnacka, A.; Chapuis, C.; Jurczak, J. Helv. Chim. Acta 2005, 88,
NMR analyses of the crude cycloadduct, by integration of the ole-
finic protons at 7.46 ppm for 7d, 5.91 ppm for the major diastereo-
isomer (2S,3S)-8d, and 5.45 ppm for the minor example. Dienophile
2441–2453.
1
1
6. Bernardinelli, G.; Chapuis, C.; Kingma, A. J.; Wills, M. Helv. Chim. Acta 1997, 80,
607–1612.
7. Koszewska, K.; Piatek, A.; Chapuis, C.; Jurczak, J. Helv. Chim. Acta 2008, 91,
1
7
d, of opposite topicity, is less reactive than its analogues 7a, and
1409–1418.
1
18. (a) Pfunder, B.; Tamm, C. Helv. Chim. Acta 1969, 52, 1630–1643; (b) Komppa, G.;
Nyman, G. A. Just. Liebigs Ann. Chem. 1936, 523, 87–100; (c) Wallach, O.; Vivck,
P. Just. Liebigs Ann. Chem. 1908, 362, 174–200; (d) Hartshorn, M. P.; Wallis, A. F.
A. J. Chem. Soc. 1964, 5254–5260.
7b. Furthermore, when R = H (7b, 7d), due to the absence of steric
pressure on S@O(2), the S@O(1) substituent tends to adopt a pseu-
do equatorial orientation. As a consequence, in the dipole-stabilized
and thermodynamically more stable anti-s-cis disposition of the
1
9. Bruckner, R. Advanced Organic Chemistry: Reaction Mechanisms; Academic Press,
2001. p. 192, 238, 441..
dienophile, the bottom C
a-si face is less efficiently protected by
0. Selected data: F R = H, R3 = Me: 1H NMR (200 MHz): 9.52 (br s, 1OH); 3.88 (d,
J = 3.2, 1H); 2.60–2.35 (m, 2H); 2.14–1.88 (m, 2H); 1.80–1.74 (m, 1H); 1.19 (s,
2
2
the S@O(1) substituent, and thus at ꢀ78 °C, the diastereoselectivity
3
3
H); 1.00 (s, 6H). 13C NMR (50 MHz): 211.3; 64.6; 56.2; 44.8; 42.6; 38.3; 37.4;
2.1; 23.2; 20.6. HRMS(ESI) calculated for C10H O NaS [M+Na]: 255.0667,
16 4
diminishes as observed for 7b (entry 3), and more evidently for 7d
(
entry 5), as compared to 7a (entry 1). At room temperature, the
efficiency of 7d, due to the lost pseudo C -symmetry, is practically
zero (entry 6), as a result of the lack of conformational SO /C@O
anti/syn-s-cis rigidity, in contrast to 7b (entry 4), and to the pseudo
-symmetrical 7a (entry 2). The lack of reactivity for 7d may even-
tually be rationalized by a poorer electronic delocalization of the
1
found: 255.0669. 2d: H NMR (500 MHz): 5.67 (br s, 1OH), 3.38 (d, J = 14.5,
1H); 3.11 (d, J = 14.5, 1H), 2.85–2.82 (m, 2H), 1.96–1.89 (m, 2H), 1.82 (m, 1H),
2
1
4
.50–1.46 (m, 4H). 13C NMR (125 MHz): 218.1 (C2, s), 56.1 (C1, s), 51.2 (C8, t),
2.5 (C3, t), 39.3 (C4, d), 33.2 (C6, t), 28.6 (C7, t), 28.6 (C5, t). HRMS(ESI)
2
1
calculated for C
8
H
11
O
4
S [MꢀH]: 203.0378, found: 203.0384. 6d: H NMR
C
2
(200 MHz): 4.37 (br s, 1NH); 3.36 (d, J = 13.4, 1H); 3.29–3.27 (m, 1H); 3.24 (d,
J = 13.4, 1H); 2.32 (br s, 1H); 1.79–1.68 (m, 4H); 1.55–1.20 (m, 4H). 13C NMR
p-
(
50 MHz): 61.6; 53.8; 53.5; 40.7; 38.9; 37.2; 30.7; 28.8. HRMS(ESI) calculated
dienophilic system into the sultam moiety, as a result of an ineffi-
cient anomeric stabilization of the nitrogen lone pair into the less
for C 12NO
8
H
2
S [MꢀH]: 186.0589, found: 186.0594.
2
1. (a) Bartlett, P. D.; Knox, L. H. Org. Synth. 1965, 45, 12–14; (b) Treibs, W.; Lorenz,
⁄
10
anti-periplanar S@O(1)
In conclusion, we have confirmed that 7d, with a less pseudo ax-
ial S@O(1), hence lacking pseudo C -symmetry, resulting from the
absence of a gem-dimethyl moiety at C(7), is less efficient in terms
of reactivity and diastereoselectivity. In order to confirm our
hypothesis, we are preparing the nor-(2R)-bornane-10,2-sultams,
lacking a single Me substituent at either position 8,30 or 9.
r bond.
T. Chem. Ber. 1949, 82, 400–405.
2. Ramachandran, P. V.; Chen, G. M.; Brown, H. C. J. Org. Chem. 1996, 61, 88–94.
3. Wendeborn, S.; Nussbaumer, H.; Schaetzer, J.; Winkler, T. Synlett 2010, 1966–
2
2
2
1
968.
24. Structure 2d is erroneously described in: Hari, A.; Miller, B. L. Org. Lett. 1999, 1,
109–2111.
5. Chapuis, C.; Rzepecki, P.; Bauer, T.; Jurczak, J. Helv. Chim. Acta 1994, 78, 145–
50.
26. Bauer, T.; Chapuis, C.; Kucharska, A.; Rzepecki, P.; Jurczak, J. Helv. Chim. Acta
998, 81, 324–329.
7. Achmatowicz, M.; Chapuis, C.; Rzepecki, P.; Jurczak, J. Helv. Chim. Acta 1999, 82,
82–190.
8. Chojnacka, A.; Piatek, A.; Chapuis, C.; Jurczak, J. Tetrahedron: Asymmetry 2006,
7, 822–828.
2
2
1
31
1
2
2
2
Acknowledgments
1
1
This work was supported by the Faculty of Chemistry of War-
saw (501-64BST-163220). We are grateful to Prof. Janusz Jurczak
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Horton, D.; Machinami, T.; Takagi, Y. Carbohydr. Res. 1983, 121, 135–161; (c)
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Hama, H.; Matsuura, Y.; Okada, K.; Moriwake, T. Synlett 1991, 819–820.
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C. T.; Teo, K. C. Can. J. Chem. 1973, 51, 2893–2901.
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(
University of Warsaw and Polish Academy of Sciences) for his help
and encouragement.
3
3
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