X-ray structure analyses of syn/anti-conformers of N-furfuroyl-, N-benzoyl-, and N-picolinoyl-substituted (2R)-bornane-10,2-sultam derivatives

Article abstract of DOI:10.1002/hlca.200890153

The synthesis and the X-ray structure of the three new N-(arylcarbonyl)- substituted derivatives 2a-2c of (2R)-bornane-10,2-sultam are presented and discussed. Direct comparison of the solid-state analyses shows that the dipole-directed SO₂/C=O

Full text of DOI:10.1002/hlca.200890153

Helvetica Chimica Acta – Vol. 91 (2008)
1409
X-Ray Structure Analyses of syn/anti-Conformers of N-Furfuroyl-, N-
Benzoyl-, and N-Picolinoyl-Substituted (2R)-Bornane-10,2-sultam
Derivatives
by Karolina Koszewskaa), Anna Pia˛teka), Christian Chapuis*b)1), and Janusz Jurczak*a)b)
a) Department of Chemistry, University of Warsaw, Pasteura 1, PL-02-093Warsaw
b) Institute of Organic Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, PL-01-224 Warsaw
(phone: þ 41227803610; fax: þ 41227803334; e-mail: christian.chapuis@firmenich.com;
phone: þ 48226320578; fax þ 48226326681; e-mail: jurczak@icho.edu.pl)
The synthesis and the X-ray structure of the three new N-(arylcarbonyl)-substituted derivatives 2a –
2c of (2R)-bornane-10,2-sultam are presented and discussed. Direct comparison of the solid-state
analyses shows that the dipole-directed SO2/C¼O anti-/syn-conformations may be very sensitive to weak
electronic/electrostatic repulsions of the heteroatom lone pairs. The optimum interactions are reached
when the lone pair of the b-positioned heteroatom is oriented in the O(3)¼C(11)ꢀN(1) plane. Such rare
syn-conformations may be observed with at least up to 1.8 kcal/mol higher energy as compared to their
ground states. Additionally, these anti/syn-conformations are also very sensitive to external influences
such as, for example, the crystal-packing forces.
Introduction. – Due to dipole-moment interactions [1a], N-acyl-substituted (2R)-
bornane-10,2-sultam derivatives are known, in the solid state, to be mostly in the
thermodynamically more stable SO2/C¼O anti-periplanar conformation. This fact,
supported by more than twohundred X-ray-structure analyses has strongly influenced,
under nonchelating conditions, the rationalizations on the origin of the diastereose-
lectivity for this widely used chiral auxiliary [1b]. More than a decade ago, we suggested
that the syn-periplanar conformation could lead to a more reactive species and thus
could eventually participate during the course of the reaction by displacing the anti/syn
equilibrium [2][3]. We were first to report on an X-ray-structure analysis of a
nonchelated SO2/C¼O syn-periplanar conformer for the N-pyruvoyl-substituted (2R)-
bornane-10,2-sultam [2b]2). Since this chiral sultam was earlier recognized as a
disguised pseudo-C2-symmetric promoter (reminiscent of a 2,5-disubstituted pyrroli-
dine [4]), it is particularly difficult to define which of the anti- or syn-conformers is
responsible for the observed induction. Indeed, it is only recently, by studying the
asymmetric 1,3-dipolar cycloadditions of chiral 2-oxoethanenitrile oxides to symmetric
alkenes, that we have been able to demonstrate the higher reactivity of the nonchelated
SO2/C¼O syn-conformers, and also to present two more examples of these rare syn-X-
1
)
)
Present address: Firmenich SA, Corporate R&D Division, P.O. Box 239, CH-1211 Geneva 8.
The DH for syn-s-trans, anti-s-trans, syn-s-cis, anti-s-cis conformers are 1.5, 0.0, 15.3, and 6.2 kcal/
mol, resp. For the first example of a TiCl4 chelate, see [1a].
2
ꢀ 2008 Verlag Helvetica Chimica Acta AG, Zürich

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Helvetica Chimica Acta – Vol. 91 (2008)
ray-structure analyses [5][6]3). This higher reactivity is believed to result from a better
electronic delocalization on the sultam moiety through a more planar N-atom, as shown
by comparison of its pyramidal height (DhN)4) between SO2/C¼O anti/syn N-acyl
conformers. This latter DhN parameter was earlier shown to be directly correlated with
the SꢀNꢀC¼O dihedral angle, and to reach local and global minima near ca. 1708 and
ꢀ 108, respectively [2a]. Most of these exceptional syn-examples concern substrates
which possess a heteroatom in the b-position, often connected to a sp2 C(a)-atom. To
study the interactions of the b-heteroatom lone pair(s) (lp) with both the SO2 and C¼O
moieties, as well as its influence on the anti/syn-conformations, we decided to prepare
some simple conformationally rigid new derivatives possessing these features, as shown
in the Scheme.
Scheme
a) NaH, toluene, 2-furoyl chloride; 64%. b) NaH, toluene, benzoyl chloride; 96%. c) NaH, toluene,
picolinoyl chloride; 51%.
Results. – We were aware that substituted derivatives, such as (2R)-N-(phenyl-
glyoxyloyl)bornane-10,2-sultam [2b]5), adopt a SO2/C¼O anti-conformation due to
supplementary steric reasons. Consequently, we decided to acylate sultam 1 with 2-furoyl
chloride (¼ furan-2-carbonyl chloride) in toluene, after deprotonation with NaH, to
afford the unreported heterocyclic derivative 2a in 64% yield. We were disappointed to
notice that its X-ray-structure analysis exhibits an unanticipated SO2/C¼O anti,
O¼CꢀCꢀO s-cis disposition (Fig. 1). Calculations at the B3LYP/6-31G** level [10]
confirmed that this conformer is indeed the most stable as compared to both the anti-s-
trans and syn-s-trans conformations, although only by a small difference of ca. 1.1–
1.6 kcal/mol (Table 1). This conformation may result from the fact that the furan O lp
are out of the NꢀC¼O plane and thus do not efficiently interfere with the syn-carbonyl
lp. On the other hand, this out-of-plane disposition also disfavors an anti-s-trans
disposition, due to electronic/electrostatic interactions with both S¼O substituents6).
3
)
A search in the past decade of the CCDC database (2007), allowed us to uncover two recent
supplementary SO2/C¼O syn-structures, neither recognized nor discussed as such by their authors
[7].
Defined as the orthogonal distance between the N-atom and the plane including the three N
substituents. For alternative approaches to estimate the pyramidality of the N-atom, see [8].
More recently, this X-ray structure was rediscovered by Chinese authors [9].
Predictive calculations suggest that (2R)-N-(oxazole-2-carbonyl)bornane-10,2-sultam might possi-
bly adopt a syn-s-cis conformation (1.3kcal/mol, as compared to syn-s-trans 3.3 kcal/mol, anti-s-cis
0.0 kcal/mol, and anti-s-trans 1.5 kcal/mol) in the crystalline state.
4
)
5
6
)
)

Helvetica Chimica Acta – Vol. 91 (2008)
1411
Fig. 1. ORTEP View of (2R)-N-furoylbornane-10,2-sultam (2a) (arbitrary atom numbering). Ellipsoids
are represented at the 50% probability level.
Table 1. Calculated Dihedral Angles and Energy Differences for Conformers of 2a, 2b, and 2c
Conformation
SꢀNꢀC¼O [8]
O¼CꢀCꢀO/C/N [8]
DH [kcal/mol]
2a
anti-s-cis
anti-s-trans
syn-s-cis
syn-s-trans
anti
127.3
124.8
ꢀ 20.4
ꢀ 22.9
141.1
ꢀ 20.1
151.5
ꢀ 18.1
166.6
ꢀ 31.1
ꢀ 47.8
ꢀ 39.3
0.0
0.0
1.1
5.1
1.6
0.0
6.5
1.0
2b
2c
syn
ꢀ 16.7
anti-s-cis
anti-s-trans
syn-s-cis
syn-s-trans
148.8
a
141.3141.7
ꢀ 12.0
ꢀ 16.9
)
ꢀ 79.8
8.7
1.8
140.7
a) Corresponds to conformer 2cA. Conformer 2cB is 0.1 kcal/mol higher in energy.
The N-benzoyl derivative 2b7) was similarly prepared (NaH, toluene, PhCOCl;
96%) to measure its X-ray-structure analysis, which shows a largely favored SO2/C¼O
anti disposition, as expected and confirmed by calculations (Fig. 2 and Table 1).
We indeed synthesized derivative 2b for conformational comparison with the also
unreported N-picolinoyl analogue 2c (NaH, toluene, picolinoyl chloride (¼ pyridine-2-
carbonyl chloride) [13]; 51%). The X-ray-structure analysis of this heterocyclic
analogue 2c exhibits three conformers in the crystalline cell (Figs. 3– 5 ). Two of them,
(A in Fig. 3 and B in Fig. 4) are very similar and express the more stable anti-s-trans
conformer, as confirmed by calculations. The main difference arises from the N(2) lp,
which points either above O(1) in structure 2cA8) or in-between O(1) and O(2) in
7
)
Although erroneously mentioned in reference [11], 2b was neither prepared nor described in [12],
nor elsewhere.
Conformer 2cA is reminiscent of the conformation exhibited by 2b, as shown by comparison of their
O(3)ꢀC(11)ꢀC(12)ꢀC(13) dihedral angles, measured as ꢀ 32.4(3) and ꢀ 33.08(18)8, resp.
8
)

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Helvetica Chimica Acta – Vol. 91 (2008)
Fig. 2. ORTEP View of (2R)-N-benzoylbornane-10,2-sultam (2b) (arbitrary atom numbering). Ellip-
soids are represented at the 50% probability level.
Fig. 3. ORTEP View of (2R)-N-picolinoylbornane-10,2-sultam (2c) (conformer A; arbitrary atom
numbering). Ellipsoids are represented at the 50% probability level.
structure 2cB, while the third one, 2cC (Fig. 5), shows the expected syn-s-trans
conformation, ca. 1.8 kcal/mol higher in energy (Table 1).
The anti-s-trans 2a and anti-s-cis 2c conformers were not detected in the solid state,
although they are energetically similarly close to their ground states (ca. 1.0 – 1.1 kcal/
mol higher in energy, in vacuum, Table 1). This shows the importance of supplementary
external influences, such as the packing forces in the crystalline state9) or the solvent
polarity in solution [15] for the control of the syn/anti and s-cis/trans ratios with respect
to steric, electrostatic, electronic, and dipolar primary parameters.
9
)
This specific influence is also expressed by structural comparison of direct crystalline analogues,
such as the main (4S,5S)-stereoisomers obtained after [3 þ 2] cycloadditions of the N-(2-
oxoethanenitrile oxide) of (2R)-bornane-10,2-sultam to either trans-stilbene or trans-4,4’-
dimethylstilbene, which surprisingly exhibit syn-s-trans (ca. 1.8 kcal/mol) [6] and anti-s-trans
conformations (0.0 kcal/mol) [14], resp.

Helvetica Chimica Acta – Vol. 91 (2008)
1413
Fig. 4. ORTEP View of (2R)-N-picolinoylbornane-10,2-sultam (2c) (conformer B; arbitrary atom
numbering). Ellipsoids are represented at the 50% probability level.
Fig. 5. ORTEP View of (2R)-N-picolinoylbornane-10,2-sultam (2c) (conformer C; arbitrary atom
numbering). Ellipsoids are represented at the 50% probability level.
Discussion. – Examination of the CCDC data base of the past decade confirms that
the pyramidalization in N-acylbornane-10,2-sultam derivatives is generally dependent
on the SꢀNꢀC¼O torsional angle10) (Fig. 6). This dihedral angle, statistically
determined to be ca. 1538, ranges from ca. 121 to 1728 with a DhN height decreasing
from ca. 0.39 to 0.11 Š, respectively11)12). A pure anti-periplanar conformation is
nevertheless difficult to reach due to the strong steric repulsion of the pseudo-
equatorial C(3)-atom, and the DhN height seems to reach a minimum of ca. 0.11 Š for
angles between ca. 160 – 1758 [2a].
10
)
)
For the previous decade, see [2a].
An exception concerns a specific anti-clinal case, where a sp2 C(a)-atom is included in a b-
substituted cyclobutene ring, with DhN ¼ 0.412 Š and SꢀNꢀC¼O ¼ 144.18 [16] (see Fig. 6).
Supplementary information (DhN, torsional angles, and references) of the CCDC examples used for
Figs. 6 and 7 can be obtained from the main authors.
11
12
)

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Helvetica Chimica Acta – Vol. 91 (2008)
Fig. 6. Graph of the dihedral angle SꢀNꢀC¼O [8] vs. the pyramidal height DhN [Š] for anti-conformers
On the other hand, syn-periplanarity, where the C¼O is bisecting the O¼S¼O
angle, varies from ca. ꢀ 19 to ꢀ 98 and the DhN height decreases from 0.133 to 0.066 Š,
respectively12)13) (Fig. 7).
Fig. 7. Graph of dihedral angle SꢀNꢀC¼O [8] vs. the pyramidal height DhN [Š] for syn-conformers
The syn-conformer 2cC exhibits a very similar O(3)¼C(11)ꢀC(12)ꢀN(2) dihedral
angle (128.1(2)8, Table 2) when compared to the O(3)¼C(13)ꢀC(14)¼O(4) torsion
angle of the (2R)-N-pyruvoylbornane-10,2-sultam (121.2(5)8 [2b]). Due to the
bisecting disposition of the N(2B)-atom with respect to the O¼S¼O moiety, 2cB
possesses practically symmetrical C(2)ꢀNꢀS¼O(1)/O(2) torsional angles (Table 2).
13
)
A structure where the C(a)-atom is included in a b-substituted cyclopropyl ring, and which does not
include a heteroatom in the b-position, exhibits an exceptional DhN of 0.124 Š for SꢀNꢀC¼O ¼
ꢀ8.88 [7a] (see Fig. 7). Alternatively, the slope could have a positive trend for SꢀNꢀC¼O dihedral
angles between ca. either ꢀ 11 and ꢀ 58, or 171 and 1768, due to strong repulsive constraints which
result in a greater pyramidalization [2a].

Helvetica Chimica Acta – Vol. 91 (2008)
1415
Table 2. Selected Bond Lengths [Š] and Angles [8] for 2a, 2b, and 2c
2a
2b
2cA
2cB
2cC
S¼O(1)
1.4314(10)
1.4346(9)
1.4219(9)
1.4320(10)
1.7114(10)
1.7873(13)
1.4851(15)
1.4023(16)
1.2166(15)
1.4970(17)
117.29(6)
110.33(8)
115.67(9)
119.79(8)
1.4279(13)
1.4380(13)
1.7166(15)
1.7907(18)
1.483(2)
1.389(2)
1.220(2)
1.492(3)
118.35(8)
112.11(11)
115.38(14)
123.41(12)
1.4223(14)
1.4386(13)
1.7159(15)
1.7953(18)
1.487(2)
1.401(2)
1.216(2)
1.492(3)
118.51(8)
111.70(11)
114.82(15)
124.30(13)
1.4286(13)
1.4358(14)
1.7058(15)
1.788(2)
1.483(2)
1.380(2)
1.220(2)
1.504(3)
118.44(8)
113.25(12)
128.49(15)
117.69(13)
S¼O(2)
SꢀN
1.7116(10)
1.7875(13)
1.4872(14)
1.3990(17)
1.2148(16)
1.4737(17)
117.27(6)
111.51(8)
116.20(10)
122.00(8)
ꢀ 119.86(8)
110.39(8)
140.13(9)
139.00(11)
SꢀC(10)
NꢀC(2)
NꢀC(11)
C(11)ꢀO(3)
C(11)ꢀC(12)
O(1)¼S¼O(2)
C(2)ꢀNꢀS
C(2)ꢀNꢀC(11)
C(11)ꢀNꢀS
C(2)ꢀNꢀS¼O(1)
C(2)ꢀNꢀS¼O(2)
C(3)ꢀC(2)ꢀNꢀS
SꢀNꢀC(11)¼O(3)
ꢀ 131.15(9)
ꢀ 111.76(13) ꢀ 114.99(12) ꢀ 125.12(13)
99.20(9)
116.69(12)
132.38(14)
152.43(15)
145.24(18)
149.77(17)
0.266
112.30(12)
137.39(14)
144.57(15)
164.92(18)
174.26(17)
0.269
102.97(13)
140.22(13)
ꢀ 11.5(3)
128.1(2)
129.49(19)
0.066
144.86(9)
136.61(11)
139.16(13)
151.97(12)
0.335
O(3)¼C(11)ꢀC(12)ꢀO/C/N ꢀ 17.98(19)
NꢀC(11)ꢀC(12)ꢀC(13)
DhN [Š]
ꢀ 21.4(2)
0.284
Puckering parameter q2
0.385
0.377
0.255
0.337
0.366
SꢀNꢀC(2)ꢀC(1)ꢀC(10) F2 102.70
77.43117.27
107.85
92.00
The five-membered heterocyclic sultam envelope may be characterized by the Cremer
and Pople puckering parameters q2 and F2 [17] (Table 2)14), which support the fact
that 2b and 2cA possess the most pseudo-equatorial and pseudo-axial S¼O(1)
substituent, respectively.
Conclusions. – We synthesized and presented the solid-structure analyses of three
new N-(arylcarbonyl) derivatives of (2R)-bornane-10,2-sultam. Direct comparison of
the X-ray-structure analysis of 2b and 2c shows that the SO2/C¼O syn/anti-
conformation may be very sensitive to weak electronic/electrostatic repulsions of the
heteroatom lone pairs. The optimum interactions are reached when the lp of the b-
positioned heteroatom is in the O(3)¼C(11)ꢀN(1) plane. Such rare syn-conformations
may still be observed in the solid state, when being as high in energy as 1.8 kcal/mol as
compared to their ground-states2)6)9)14). Additionally, these anti/syn-conformations
are also very sensitive to external influences, such as the crystalline packing forces9) or
the solvent polarity [15].
Financial support from the Ministry of Science and Higher Education (Grant PBZ-KBN-126/T09/06)
is gratefully acknowledged. The X-ray measurements were recorded in the Crystallographic Unit of the
Physical Chemistry Laboratory at the Chemistry Department of the University of Warsaw.
14
)
We have also calculated these two parameters for both the CCDC syn examples [18]. The b-
substituted cyclopropyl derivative shows a q2 ¼ 0.341 and F2 ¼ 98.40 [7a], while the isoxazolidine
derivative has q2 ¼ 0.318 and F2 ¼ 96.57 (DhN ¼ 0.133 Š, SꢀNꢀC¼O ¼ ꢀ18.68) [7b]. Their
corresponding anti-s-trans conformers are ca. 17.1 and 5.8 kcal/mol, resp., higher in energy.

1416
Helvetica Chimica Acta – Vol. 91 (2008)
Experimental Part
X-Ray-Structure Analyses (Table 3). All crystal measurements were performed on a KM4CCD k-
axis diffractometer with graphite-monochromated MoKa radiation. The crystal was positioned at 62 mm
from the CCD camera. Then 1050 frames were measured at 18 intervals with a counting time of 4 s for 2a,
2111 frames were measured at 0.58 intervals with a counting time of 7 s for 2b, and 1100 frames were
measured at 1.08 intervals with a counting time of 22 s for 2c. The data were corrected for Lorentz and
polarization effects. Empirical correction for absorption was applied [19]. Data reduction and analysis
were carried out with the Oxford Diffraction Ltd. programs [20]. The structure was solved by direct
methods [21] and refined by using SHELXL [22]. The refinement was based on F2 for all reflections,
except those with very negative F2. Weighted R factors wR and all goodness-of-fit S values are based on
F2. Conventional R factors are based on F with F set to zero for negative F2. The Fo2 > 2s(F2o ) criterion
was used only for calculating R factors and is not relevant to the choice of reflections for the refinement.
The R factors based on F2 are about twice as large as those based on F. All H-atoms were located
geometrically, and their positions and temperature factors were not refined. Scattering factors were taken
from Tables 6.1.1.4 and 4.2.4.2 of [23]. The known configurations of the asymmetric centers were
confirmed by the Flack-parameter refinement [24]. Crystallographic data (excluding structural factors)
Table 3. Crystal Data and Structure Refinement of Compounds 2a, 2b, and 2c
2a
2b
2c
Empirical formula
Mr [g/mol]
Temp. [K]
Wavelength [Š]
Crystal system
Space group
Unit-cell dimensions
a [Š]
C15H19NO4S
309.37
100(2)
00.7.7110077330.71073
orthorhombic
P212121
C17H21NO3S
319.41
110(2)
C16H20N2O3S
320.40
120(2)
monoclinic
P21
monoclinic
P21
7.9860(6)
8.0079(7)
22.6661(17)
90
1449.5(2)
4
7.9471(3)
10.1004(4)
10.1256(4)
107.826(3)
773.75(5)
2
13.9959(8)
10.2183(7)
16.0408(11)
92.025(5)
2291.1(3)
6
b [Š]
c [Š]
b [8]
V [Š3]
Z
Dx [Mg/m3]
1.418
0.239
1.371
0.222
1.393
0.227
m [mmꢀ1
]
F(000) electrons
Crystal size [mm]
q Range [8]
656
340
1020
0.55 ꢁ 0.35 ꢁ 0.20
2.70 – 28.64
ꢀ 10 ꢂ h ꢂ 10
ꢀ 10 ꢂ k ꢂ 10
ꢀ 29 ꢂ l ꢂ 30
0.45 ꢁ 0.20 ꢁ 0.15 0.35 ꢁ 0.20 ꢁ 0.15
2.69 – 28.61
2.74 – 27.50
Index ranges
ꢀ 10 ꢂ h ꢂ 10
ꢀ 13 ꢂ k ꢂ 13
ꢀ 13 ꢂ l ꢂ 13
12691, 3730
0.01530.0274
ꢀ 18 ꢂ h ꢂ 18
ꢀ 13 ꢂ k ꢂ 13
ꢀ 20 ꢂ l ꢂ 20
39259, 10489
Reflections collected, unique 24118, 3585
R(int)
0.0219
Refinement method
Data, restraints, parameters
Goodness-of-fit on F2
R(F) (I > 2s(I))
Full-matrix least-squares on F2
3585, 0, 261
1.026
0.0239
3730, 1, 201
1.060
0.0237
10489, 1, 601
0.929
0.0307
wR(F2) (all)
0.0614
0.0650
0.0657
Abs. struct. parameter
Extinction coefficient
Largest peak and holes [Š
ꢀ 0.01(5)
0.0264(17)
0.263, ꢀ 0.289
ꢀ 0.01(4)
0.01(3)
ꢀ3
]
0.258, ꢀ 0.195
0.750, ꢀ 0.309

Helvetica Chimica Acta – Vol. 91 (2008)
1417
for 2a, 2b, and 2c were deposited as supplementary material with the Cambridge Crystallographic Data
Centre and allocated the deposition numbers CCDC 667772, 667770, and 667771, resp. These data can be
obtained free of charge via www.ccdc.ac.uk/data_request/cif.
(2-Furyl)[(3aS,6R,7aR)-hexahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano[2,1]benzisothiazol-
1-yl]methanone (2a). To an ice-cold suspension of 60% NaH in mineral oil (70 mg, 1.75 mmol) in dry
toluene (3ml) under Ar, a soln. of (2 R)-bornane-10,2-sultam (250 mg, 1.16 mmol) in toluene (3ml) was
slowly added. After 1 h, a soln. of 2-furoyl chloride (0.23ml, 2.33mmol) in toluene (3ml) was added
dropwise over 30 min. The resulting mixture was stirred overnight at r.t. H2O was then added to the
mixture, and the aq. phase was extracted with AcOEt. The org. phase was dried (MgSO4) and
concentrated and the crude material purified by column chromatography (CC) (hexane/AcOEt 9 :1): 2a
(64%). M.p. 211 – 2138. [a]2D0 ¼ ꢀ89.5 (c ¼ 1.0, CHCl3). IR: 3147, 3014, 2999, 2966, 2934, 1659, 1469, 1340,
1311, 1303, 1190, 1116, 1115, 776, 757, 558, 486. 1H-NMR (500 MHz, CDCl3): 1.02 (s, 3 H); 1.27 (s, 3 H);
1.36 – 1.49 (m, 2 H); 1.87 – 1.94 (m, 2 H); 1.95 – 2.05 (m, 2 H); 2.08 – 2.13( m, 1 H); 3 .49 (d(AB), J ¼ 13.5,
1 H); 3.58 (d(AB), J ¼ 13.5, 1 H); 4.25 (dd, J ¼ 4.5, 7.75, 1 H); 6.53– 6.54 ( m, 1 H); 7.54 (dd, J ¼ 0.5, 3.5,
1 H); 7.64 – 7.66 (m, 1 H). 13C-NMR (125 MHz, CDCl3): 20.0 (q); 21.3( q); 26.4 (t); 33.3 (t); 38.4 (t); 45.2
(d); 47.8 (s); 48.2 (s); 53.8 (t); 66.1 (d); 112.0 (d); 120.4 (d); 146.0 (s); 147.1 (d); 157.5 (s). ESI-MS: 332.1
([M þ Na]þ), 641.1 ([2M þ Na]þ). HR-ESI-MS: 332.0935 (C15H19NNaO4Sþ; calc. 332.0932).
[(3aS,6R,7aR)-Hexahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano[2,1]benzisothiazol-1-yl]phe-
nylmethanone (2b). As described for 2a, with 60% NaH in mineral oil (70 mg, 1.75 mmol), (2R)-
bornane-10,2-sultam (250 mg, 1.16 mmol), and benzoyl chloride (0.27 ml, 2.33 mmol): 2b (96%). M.p.
148 – 1498. [a]2D0 ¼ ꢀ170.4 (c ¼ 1.0, CHCl3). IR: 3437, 2970, 2939, 2910, 2881, 1673, 1343, 1291, 1167, 1151,
1
1103, 1055, 728, 695, 556, 524. H-NMR (500 MHz, CDCl3): 1.02 (s, 3 H); 1.34 (s, 3H); 1.37 – 1.49 ( m,
2 H); 1.88 – 2.00 (m, 3H); 2.05 – 2.15 ( m, 2 H); 3.42 (d(AB), J ¼ 13.5, 1 H); 3.52 (d(AB), J ¼ 14, 1 H);
4.19 (dd, J ¼ 4.5, 7.25, 1 H); 7.42 – 7.45 (m, 2 H); 7.53– 7.57 ( m, 1 H); 7.76 (m, 2 H). 13C-NMR (125 MHz,
CDCl3): 19.9 (q); 21.3( q); 26.5 (t); 33.2 (t); 38.4 (t); 45.1 (d); 47.8 (s); 48.1 (s); 53.6 (t); 66.0 (d); 128.0
(2d); 129.5 (2d); 132.7 (d); 133.8 (s); 170.1 (s). ESI-MS: 342.2 ([M þ Na]þ), 661.3([2 M þ Na]þ). HR-
ESI-MS: 342.1147 (C17H21NNaO3Sþ; calc. 342.1140).
[(3aS,6R,7aR)-Hexahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano[2,1]benzisothiazol-1-yl](pyr-
idin-2-yl)methanone (2c). To picolinic acid (290 mg, 2.36 mmol), thionyl chloride (7 ml) was slowly
added, and the mixture was refluxed for 2 h. After cooling, toluene (15 ml) was added, and the soln. was
evaporated. The procedure was repeated two more times, to remove all the excess SOCl2. The obtained
picolinoyl chloride was used in the next step without further purification.
As described for 2a, with 60% NaH in mineral oil (70 mg, 1.75 mmol), (2R)-bornane-10,2-sultam
(250 mg, 1.16 mmol), and picolinoyl chloride [13]: 2c (51% yield. M.p. ¼ 87 – 908. [a]2D0 ¼ ꢀ184.3(c ¼ 1.0,
1
CHCl3). IR: 2960, 2883, 1675, 1330, 1305, 1170, 1116, 1139, 751, 557, 490. H-NMR (500 MHz, CDCl3):
1.02 (s, 3 H); 1.32 (s, 3H); 1.37 – 1.49 ( m, 2 H); 1.87 – 2.03( m, 5 H); 3 .43 d((AB), J ¼ 13.5, 1 H); 3.56
(d(AB), J ¼ 13.5, 1 H); 4.39 (t, J ¼ 7, 1 H); 7.45 – 7.48 (m, 1 H); 7.82 – 7.87 (m, 2 H); 8.72 – 8.73( m, 1 H).
13C-NMR (125 MHz, CDCl3): 20.0 (q); 21.9 (q); 26.3( t); 33.6 (t); 39.2 (t); 45.5 (d); 47.7 (s); 48.6 (s); 53.4
(t); 66.7 (d); 124.6 (d); 126.4 (d); 136.8 (d); 148.8 (d); 151.1 (s); 167.0 (s). ESI-MS: 343.1 ([M þ Na]þ),
663.2 ([2M þ Na]þ). HR-ESI-MS: 343.1079 (C16H20N2NaO3Sþ; calc. 343.1092).
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Received March 13, 2008