Diastereoselective alkyl Grignard 1,4-additions to para-substituted (2R)-N-cinnamoylbornane-10,2-sultam derivatives: Influence of N-atom pyramidalization

Article abstract of DOI:10.1002/hlca.201100197

Several typical ¹³C-NMR displacements (of C=O, C(α), C(β), and C_ipso), as well as conformational or energy properties (S-N-C=O dihedral angle, ΔE syn/anti; HOMO/LUMO) could be correlated with the electronic parameters of p-substitute

Full text of DOI:10.1002/hlca.201100197

Helvetica Chimica Acta – Vol. 94 (2011)
2141
Diastereoselective Alkyl Grignard 1,4-Additions to para-Substituted (2R)-N-
Cinnamoylbornane-10,2-sultam Derivatives: Influence of N-Atom
Pyramidalization
by Anna M. Pia˛teka), Agnieszka Sadowskaa)1), Christian Chapuis*b)2), and Janusz Jurczak*a)b)
a) Department of Chemistry, University of Warsaw, Pasteura 1, PL-02-093 Warsaw
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)
Dedicated to Dr. Charles Fehr, on the occasion of his 65th birthday
Several typical 13C-NMR displacements (of C¼O, C(a), C(b), and Cipso), as well as conformational
or energy properties (SꢀNꢀC¼O dihedral angle, DE syn/anti; HOMO/LUMO) could be correlated with
the electronic parameters of p-substituted N-cinnamoylbornane-10,2-sultams 2. Even under nonchelat-
ing conditions, the pyramidalization of the sultam N-atom decreases for electron-attracting p-
substituents, inducing a modification of the sultam-ring puckering. Detailed comparison of the X-ray
structure analyses of 2b, 2d, and 2m showed that the orientation of the sterically directing pseudo-axial
S¼O(2) and HꢀC(2) is modified and precludes any conclusion about the p-facial stereoelectronic
influence of the N lone pair on the alkyl Grignard 1,4-addition. We also showed that the aggregating alkyl
Grignard reagent may be used in equimolar fashion, demonstrating that the sultam moiety is chelated
with a Lewis acid such as MgBr2. The Schlenk equilibrium may also be used to generate the appropriate
conditions of effective 1,4-diastereoselectivity. Although the anti-s-cis/syn-s-cis difference of conforma-
tional energies for N-cinnamoyl derivatives 2 is higher than for the simple N-crotonoyl analogue, an X-
ray structure analysis of the SO2/C¼O syn derivative 10 confirms the predictive validity of our
conformational calculations for DE ꢁ 1.8 kcal/mol.
Introduction. – The (2R)-bornane-10,2-sultam auxiliary 1 [1] generally exerts a
decisive steric influence on the C(a) atom of its N-alkenoyl derivatives, and has been
judiciously recognized as a disguised pseudo-C2-symmetric promoter [2]. In contrast,
its steric influence on the remote C(b) atom is almost inexistent3). Since we have tried,
for years, to show the stereoelectronic influence of the N lone pair (lp) on the N-
alkenoyl moiety [5], we became particularly interested in chemical reactions
exclusively restrained to the C(b) atom. Although they are quite rare, several 1,4-
1
)
)
)
Master Thesis No. 236362 University of Warsaw (30th June 2010), presented at the ꢂMultiple Faces
of Chemistry: from Marie Curie to Nowadaysꢃ in Paris, France (31st Jan.–1st Feb. 2011).
Present address (and correspondence to): Firmenich SA, Corporate R&D Division, P.O. Box 239,
CH-1211 Geneva 8.
Thus, for example, the conjugate addition of an organozirconocene proceeds with only 9% d.e. on
the N-crotonoylbornane-10,2-sultam [3a], while, in absence of electronic conjugation with the
carbonyl group, syn-dihydroxylation involving the C(b) atom proceeds with only 0 – 20% d.e., even
in the cooperative presence of two conformationally rigidifying and directing prosthetic groups [4].
In this latter case, it is noteworthy that the weak purely steric influence of the sultam moiety on
C(b) directs the approach on the same face as for a C(a) steric attack.
2
3
ꢀ 2011 Verlag Helvetica Chimica Acta AG, Zꢁrich

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Helvetica Chimica Acta – Vol. 94 (2011)
additions to N-alkenoylbornane-10,2-sultams have been reported4). In 2004, we
suggested that this hypothetic stereoelectronic effect5) could be potentially demon-
strated by simple Grignard addition to appropriately para (¼ p)-substituted cinnamoyl
derivatives. In the meantime, a Chinese group reported this transformation [20], but
unfortunately their experimental protocol is unsuitable for our mechanistic postulate.
Indeed, primarily interested in complete chemical conversions, Liu and co-workers
initiated the conjugated addition at ꢀ 788, and then increased the temperature to
ꢀ 408, until completion of the reaction. They rationalized their results on the basis of
Oppolzerꢃs initial model [9a] but did not discuss the poorer diastereoselectivities
observed for sterically more demanding, hence less reactive, Grignard reagents, and,
moreover, did not find any electronic correlation. Since we recently demonstrated that
the unchelated minor SO2/C¼O syn-conformer may, in some instances, be more
reactive than its thermodynamically more stable anti-conformer [21]6), the conforma-
tional rigidity of the N-alkenoyl side chain is primordial to the N-lp stereoelectronic
control, in opposition to the C2-symmetrical steric influence, exerted by either the
S¼O(2) or C(3) substituents, on the C(a) atom [2], hence, apparently to a much lesser
extent, on the C(b) atom. We thus decided to reinvestigate, in more detail, the 1,4-
addition of the simple ethyl Grignard reagent to p-substituted cinnamoyl derivatives of
type 27), at a conformationally rigidifying and constant low temperature, since such a
4
)
Indeed, whereas chemical reactions involving either the C(a) or both C(a) and C(b) atoms are
legion (>300 reports), specific reactions at the C(b) atom are limited, e.g., to either MeNO2/DBU/
THF/DMPU [6] (DBU ¼ 1,8-diazabicyclo[5.4.0]undec-7-ene, DMPU ¼ tetrahydro-1,3-dimethylpyr-
imidin-2(1H)-one), or electrochemical CO2 [7], or RSꢀ [8] Michael additions, as well as the 1,4-
additions of simple Grignard reagents [9], Mg-cuprates [10], Li-cuprates [11], tBuHgCl- or InꢀCuI-
generated alkyl radical [12], RhI or CuI/zirconocenes [3], EtAlCl2 or CuI/zincates [13], TiCl4/
allylSiMe3 [14], TiCl4/Cl3CLi [15], or Li-enolates [16]. Method [6] apparently does not involve any
chelate and gave ca. 50% d.e. in favor of the same face as for a C(a) steric attack, anti to the N lp, in
case of the more reactive SO2ꢀC¼O syn s-cis conformer. The same p-facial selectivity was also
obtained in almost all the other examples of chelation [3b][8 – 16] (see the discussion for
exceptions). The absolute configuration of the 1,4-adducts was not determined in [3a][7][11f][12]
[13b][14]. We are indebted to Prof. M. J. Wu for providing confirmation. In accord with the senior
author, whom we thank for his answer (25th Oct. 2010), we must establish that the absolute
configurations as depicted for compounds 18 and 19 in [13a] do not correspond to those expected
from Oppolzerꢃs original reports (Table 1, Entry 11 in [11a]) [11e]. The case of [9e] is noteworthy,
since the C(b) atom is under the direct C(a)-re steric influence of the second bornane-10,2-sultam
chirophor. The case of [7] is also noteworthy (50% (R) configuration at the newly created
stereogenic b-center, as suggested by the respective 1H-NMR analyses [11e][15] and this work)
since it is not a nucleophilic addition to 2d, but rather a radical anion coupling to CO2 as
electrophilic agent. In our case, radical addition of iPrI or cHexI (In, InCl3, H2O) to 2d according to
[12] afforded 7d (87% yield, 25% d.e.) and 8d (75% yield, 13% d.e.) as minor diastereoisomers. The
fact that for nonchelated N-alkenoylsultams, the sense of induction is both reversed and contra-
steric, is consistent with a stereoelectronic control [11a][17]. Similarly, the stereoelectronic
influence may also be invoked for the contra-steric trapping of the corresponding enolates [9a]. No
information concerning the ambiguous absolute configuration of the starting material used in [11g]
was forthcoming (28th Oct. 2010).
5
6
7
)
)
)
See the conclusions in [18] and [19a].
Thus following the AcreeꢀCurtinꢀHammett principle [22].
Harder nucleophiles such as MeMgCl or PhMgCl are known to react principally in a 1,2-fashion
[9][20].

Helvetica Chimica Acta – Vol. 94 (2011)
2143
substitution should electronically influence the C(b) reactive center, without any
substantial drastic direct perturbations.
Results. – First of all, we synthesized an electronically and statistically relevant
series of adequately p-substituted (2R)-N-cinnamoylbornane-10,2-sultams (Scheme),
comprising the reported fully characterized derivatives 2b [20b][19][23][24], 2d8)
[6][8][11a][14][19][20][23][25] – [27], 2k9) [25d][26], 2l10) [28], 2m [19b][19d][28],
and their un- or very partially characterized analogues 2a [23], 2c [20a][19a][17c][26]
[27], 2e [28], 2f [20][29], 2g [20][19a][19d][26][28], 2h [26][27a], and 2i [29], as well
as the unreported substrate 2j. The conjugate addition of 2.2 mol-equiv. of EtMgBr
(THF, ꢀ 788, 4 h; see General Procedure B as well as Footnote 37 in the Exper. Part) to
Scheme
ESI-MS: 368.3 ([M þ Na]þ). HR-ESI-MS: 368.1296 (C19H23NNaO5Sþ; calc. 368.1327).
IR (KBr): 2995, 2943, 2881, 2231, 1675, 1631, 1344, 1319, 1289, 1237, 1221, 1164, 1133, 1117, 1067,
1039, 989, 883, 827, 760, 535, 494, 424 cmꢀ1. ESI-MS: 393.1 ([M þ Na]þ). HR-ESI-MS: 393.1249
(C20H22N2NaO3Sþ, calc. 393.1210).
8
)
)
9
)
ESI-MS: 446.1 ([M þ Na]þ). HR-ESI-MS: 446.1072 (C20H25NNaO5Sþ, calc. 446.1065).
10

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Helvetica Chimica Acta – Vol. 94 (2011)
2a afforded 3a with 80% d.e. after complete conversion (Table 1). This ratio (ꢂ2%)
1
was obtained by direct integration of the Me(8) signal in the H-NMR spectrum, as
earlier reported in a similar case [11e][15]. Indeed, the Me(8) signal of the
corresponding minor diastereoisomer systematically resonated at higher field by ca.
0.26 – 0.28 ppm for all the analogues 3a – 3m. This ratio was also confirmed by
comparison of the C(2) signal in the 13C-NMR spectrum, since a similar shift of ca.
0.15 – 0.17 ppm to higher field was observed for the minor stereoisomers of 3a – 3m11).
For the corresponding p-MeO and p-MeS derivatives 2b and 2e, the diastereoselectiv-
ities reached 76 and 77% d.e., respectively (Table 1). The entropically less chaotic p-
Me derivative 2c gave a p-facial selectivity of 79% d.e., similar to 2a, while the
unsubstituted N-cinnamoyl substrate 2d [20] exhibited 73% d.e. In the halogen series,
the diastereoselectivity decreased from 78 to 67 and 64% d.e. for the p-Fadduct 3f [20],
p-Cl adduct 3g [20], and p-Br adducts 3h, respectively. The p-CF3O derivative 2i is
sterically comparable to 2b but was slightly less selective, with 73% d.e. This trend was
even more pronounced for the p-CF3 analogue 2j (62% d.e.), as compared to 2c12).
The absolute configuration of this series was based on the X-ray structure analysis of
3f13) [32], associated with its correlation with the major stereoisomers in both the 1H-
and 13C-NMR analyses of 3a – 3m. The loss of selectivity was even more pronounced
for the adducts with electron-demanding substituents such as p-cyano adduct 3k (49%
Table 1. Diastereoselectivities and Hammett, IR, and NMR Parameters for 2a – 2m
d.e. log(d.r.) Conv. spara
[%]
sInductive sResonance ˜n(C¼O) ˜n(C(a)¼C(b)) ˜n(C¼Carom) d(HꢀC(a)) d(HꢀC(b))
[%]a)
[cmꢀ1
]
[cmꢀ1
]
[cmꢀ1
]
[ppm]
[ppm]
2a 80 0.954
2b 76 0.865
2c 79 0.931
2d 73 0.807
2e 77 0.886
2f 78 0.908
2g 67 0.704
2h 64 0.659
2i 73 0.807
2j 62 0.630
2k 49 0.466
2l 45 0.421
2m 46 0.432
100
100
100
100
100
100
100
100
100
100
100
74
ꢀ 0.41
ꢀ 0.27
0.29 ꢀ 0.46 1669
0.27 ꢀ 0.45 1671
1614
1616
1623
1624
1614
1626
1628
1628
1634
1632
1631
1629
1628
1596
1599
1606
1600
1589
1598
1587
1593
1604
1617
1607
1600
1599
7.04
7.07
7.12
7.17
7.11
7.07
7.14
7.15
7.14
7.23
7.24
7.28
7.29
7.75
7.79
7.77
7.79
7.74
7.75
7.73
7.71
7.75
7.78
7.75
7.81
7.79
ꢀ 0.14 ꢀ 0.04 ꢀ 0.11 1676
0.00
0.06
0.15
0.24
0.26
0.35
0.53
0.70
0.73
0.78
0.00
0.00 1678
0.23 ꢀ 0.20 1671
0.50 ꢀ 0.34 1678
0.46 ꢀ 0.23 1676
0.44 ꢀ 0.19 1676
0.55 ꢀ 0.19 1682
0.45
0.56
0.59
0.65
0.08 1683
0.13 1675
0.12 1676
0.15 1672
15
a) For chemical yields, see the Exper. Part.
11
)
)
)
Alternatively, the same kind of shifts were observed for either the C(3) (ca. 0.15 – 0.22 ppm), or the
C(9) signals (ca. 0.33 – 0.51 ppm). In the 1H-NMR analyses, the Me(8) and Me(9) signals resonated
in the region d(H) 0.90 – 1.03 and 1.09 – 1.31 ppm, respectively (see also Table 6 for 13C-NMR
attributions).
12
13
Thus contrasting with the almost isosteric couple 2d/2f since the electronically more demanding F-
atom is sterically considered as slightly larger than a H-atom [30a]. The steric demand of a CF3
i
group is thus in between that of a Me and a Pr substituent [30b]. 19F-NMR Analysis was also used
earlier for the determination of the d.e. [21][31] in specific cases such as 3f, 3i, and 3j.
Dihedral angle SꢀNꢀC¼O ¼ 153.28 and DhN ¼ 0.226 ꢄ.

Helvetica Chimica Acta – Vol. 94 (2011)
2145
d.e.), p-methylsulfonyl derivative 3l (45% d.e.), and p-nitro analogue 3m (46%
d.e.)14). In both the latter cases, the conversion was incomplete, thus demonstrating the
negative influence of the strongly electron-withdrawing groups on both the kinetics and
diastereoselectivities, as presented in both Table 1 and Fig. 1. The general trend
thus expressed may be resumed by Eqn. 1. The electronic parameter spara may also
be decomposed into its sInductive and sResonnance component15), as earlier determined
and systematically indexed [33]. In this manner, a better bi-linear regression was
found:
log(d.r.) ¼ ꢀ0.459spara þ 0.834
(n ¼ 13, R2 ¼ 0.83, standard deviation (s.d.) ¼ 0.834)
(1)
log(d.r.) ¼ ꢀ0.433sInductive ꢀ 0.603sResonance þ 0.815 (n ¼ 13, R2 ¼ 0.87, s.d. ¼ 0.075) (2)
Fig. 1. Diastereoselectivity (log(d.r.)) of the 1,4-addition of EtMgBr to 2a – 2m at ꢀ 788 in THF as a
function of the Hammett constant spara
In contrast to previous studies correlating the barrier of rotation around the N-atom
in the IR analyses of simple p-substituted cinnamamides [34], we were unable to find any
significant correlations between either the ˜n(C¼O) (1676 ꢂ 7 cmꢀ1), the ˜n(C(a)¼C(b))
(1624 ꢂ 10 cmꢀ1), or the ˜n(C¼Carom), (1602 ꢂ 15 cmꢀ1) and the electronic parameters
(R2 ꢁ 0.75). Similarly, the 1H-NMR data showed that the d(H) of HꢀC(b) of 2a – 2m is
strongly influenced by the direct steric and anisotropic effect of the proximate aromatic
ring, and no valid correlation was found, in contrast to the d(H) of HꢀC(a) which may
well be expressed by Eqn. 3. A similar observation was earlier already reported for
14
)
)
This trend is opposite to the increased diastereoselectivities partially observed in the case of the
sterically demanding silyl monocuprate 1,4-addition to p-substituted N-cinnamoyl derivatives of
type 2 [11e].
We found that spara ¼ 0.981sInductive þ 1.205sResonance þ 0.012 (n ¼ 13, R2 ¼ 0.98, s.d. ¼ 0.063).
15

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Helvetica Chimica Acta – Vol. 94 (2011)
simple cinnamic acid esters, cinnamamides, and similar compounds [35]. The
predictabilities were even more impressive in the 13C-NMR spectra of 2a – 2m (see
Table 6, Exper. Part), where the d(C) of all the main C-atoms of the N-cinnamoyl side
chains were particularly well correlated with the electronic parameters, as expressed by
Eqns. 4 – 7.
d(HꢀC(a)) ¼ 0.089sInductive þ 0.334sResonance þ 7.167 (n ¼ 13, R2 ¼ 0.96, s.d. ¼ 0.018) (3)
d(C¼O) ¼ ꢀ1.092sInductive ꢀ 1.436sResonance þ 164.383 (n ¼ 13, R2 ¼ 0.97, s.d. ¼ 0.078) (4)
d(C(a)) ¼ 4.553sInductive þ 8.204sResonance þ 117.502 (n ¼ 13, R2 ¼ 0.99, s.d. ¼ 0.287) (5)
d(C(b)) ¼ ꢀ3.996sInductive – 2.435sResonance þ 145.536 (n ¼ 13, R2 ¼ 0.99, s.d. ¼ 0.128) (6)
d(Cipso) ¼ 5.534sInductive þ 17.785sResonance þ 133.951 (n ¼ 13, R2 ¼ 0.99, s.d. ¼ 0.434) (7)
At this point, to demonstrate the crucial role of the temperature on the conforma-
tional equilibrium, hence the diastereoselectivities of such reactions, we briefly deter-
mined the Eyring plot of 2d, by performing the quantitative conjugate addition of EtMgBr
in THF at ꢀ 638 (72% d.e.), ꢀ 428 (68% d.e.), ꢀ 188 (66% d.e.), and 08 (60% d.e.).
These results are shown in Fig. 2, which allowed us to determine the corresponding
enthalpic (DDH= ¼ 0.59 kcal/mol), and entropic (DDS= ¼ 0.73 cal/(K mol)) factors,
obtained from both the slope, and the intercept, respectively. These values are close to
those already reported for the transition states of DielsꢀAlder reactions, for similar
dienophiles [36].
Fig. 2. Eyring plot for the temperature dependence of the EtMgBr 1,4-addition to 2d in THF
Finally, we also studied the steric contribution of the nucleophile by adding, at
ꢀ 788 in THF, 2.2 mol-equiv. of the more reactive alkyl MgCl reagents of increasing
bulkiness to 2d. Thus, after 4 h and full conversion, the already reported adducts 4d – 8d

Helvetica Chimica Acta – Vol. 94 (2011)
2147
could be isolated [20]16). Their diastereoisomer ratios were also determined and
1
13
confirmed by H-17) and C-NMR18) analyses, respectively, and their absolute
configurations were analogously determined, as in the case of 2d, with the help of the
reported X-ray structure analyses of 5g (R1 ¼ Cl, R2 ¼ Bu) [37], 6g (R1 ¼ Cl, R2 ¼ Bn)
[38], and 7f [39] (R1 ¼ F, R2 ¼ iPr)19). The corresponding observed diastereoselectiv-
ities, as well as the steric parameters of the nucleophile alkyl MgCl, are reported in
Table 2 as well as in Fig 3. The Taft steric parameter ꢀ Es was earlier obtained from
kinetic data, by acid- and base-catalyzed hydrolysis of esters in aqueous acetone [40],
and approximately follows the size of the group. It is independent from polar effects
[41] but may be sensitive to solvation, field, or resonance effects [42], and its
correlation with the observed diastereoselectivity for adducts 3d – 8d is not perfect, as
shown by Eqn. 8.
Chartonꢃs n values, which are independent of kinetic data and are derived from the
van der Waals radii [43], gave a more interesting correlation (Eqn. 9).
The best linear regression was obtained from Meyerꢃs steric parameter Va
(Eqn. 10), obtained by MM2 calculations, and which corresponds to the volume of
the portion of the substituent that is within 3 ꢄ of the reaction center [44]20). In all
three cases (Eqn. 8 – 10), the diastereoselectivity diminished with respect to the
increasing size of the nucleophile, meaning that the transition-state energy differences
decrease for the transfer of bulky substituents. A similar trend was earlier observed for
Table 2. Diastereoselectivities for the Adducts 3d – 8d, Steric Factors, and HOMO and LUMO Levels of
the Nucleophiles Alkyl MgR
d.e. [%] log(d.r.) Yielda) Taft ꢀ Es Charton u Meyer
HOMO LUMO
Va · 102 [eV]
[eV]
[%]
EtMgCl
PrMgCl
BuMgCl
BnMgCl
iPrMgCl
78 (3d)
76 (4d)
72 (5d)
58 (6d)
46 (7d)
0.908
0.865
0.788
0.575
0.432
0.213
96
95
95
0.07
0.36
0.39
0.38
0.47
0.79
0.56
0.68
0.68
0.70
0.76
0.87
4.31
4.78
4.79
5.09
5.74
6.25
ꢀ 0.246
ꢀ 0.247
ꢀ 0.245
ꢀ 0.242
ꢀ 0.234
ꢀ 0.228
ꢀ 0.044
ꢀ 0.044
ꢀ 0.044
ꢀ 0.042
ꢀ 0.045
ꢀ 0.045
79b)
94
cHexMgCl 24 (8d)
91
a) Isolated by CC (SiO2). b) Besides the 1,2-adduct (8%).
IR (KBr; in cmꢀ1): 4d: 2957, 2931, 2882, 1693, 1453, 1418, 1383, 1322, 1272, 1237, 1214, 1205, 1164,
1131, 1114, 1065, 1032, 989, 772, 699, 611; 5d: 2956, 2928, 1693, 1454, 1412, 1375, 1327, 1274, 1235,
1211, 1164, 1132, 1111, 1065, 1039, 987, 761. 700, 610; 6d: 3027, 2959, 1693, 1495, 1453, 1412, 1375,
1326, 1273, 1235, 1213, 1164, 1132, 1114, 1067, 1039, 987, 759, 697, 613; 7d: 2959, 1696, 1494, 1454,
1413, 1385, 1327, 1269, 1212, 1164, 1133, 1111, 1065, 1039, 987, 757, 700, 612; 8d: 2923, 2852, 1695,
1450, 1413, 1375, 1327, 1269, 1235, 1213, 1164, 1132, 1112, 1066, 1039, 987, 782, 757, 699, 610.
Me(8) of minor diastereoisomer, at higher field by ca. 0.16 – 0.29 ppm.
C(2), and C(9) of minor diastereoisomer, at higher field by ca. 0.16 – 0.19 and ca. 0.23 – 0.36 ppm,
resp.
16
)
17
18
)
)
19
20
)
)
Dihedral angle SꢀNꢀC¼O and DhN; for 5g, 160.38 and 0.200 ꢄ; for 6g, 150.28 and 0.217 ꢄ; for 7f,
158.18 and 0.175 ꢄ.
As shown earlier, the Es, n, and Va values, as well as the van der Waals radii are linearly inter-
correlated [45].

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Helvetica Chimica Acta – Vol. 94 (2011)
Fig. 3. Diastereoselectivity vs. Meyerꢀs steric values for Grignard-nucleophile 1,4-addition to 2d
the N-crotonoyl- [9a][46] and N-cinnamoylbornane-10,2-sultams [20], although with
apparently higher diastereoselectivities, on addition of bromo Grignard reagents21)!
The fact that a linear correlation was obtained for all three steric parameters suggests
that the influence of the nucleophile is essentially steric in nature.
log(d.r.) ¼ ꢀ1.040(ꢀ Es) þ 1.057 (n ¼ 6, R2 ¼ 0.77, s.d. ¼ 0.145)
log(d.r.) ¼ ꢀ2.469n þ 2.379 (n ¼ 6, R2 ¼ 0.86, s.d. ¼ 0.116)
log(d.r.) ¼ ꢀ37.485 Va þ 2.564 (n ¼ 6, R2 ¼ 0.95, s.d. ¼ 0.066)
(8)
(9)
(10)
Discussion. – The stereoelectronic influence of a N lp was initially suggested by
Eschenmoser and co-workers [47], and both Oppolzer et al. [9a][48] and Curran et al.
[49] invoked this possibility, before discarding it22) in favor of a purely steric
rationalization [2]. We earlier suggested that both steric and stereoelectronic influences
may match or mismatch, depending on the SO2/C¼O syn or anti conformation,
respectively [50]. Furthermore, we also suggested that the minor syn-s-cis conformer is
more reactive than its more stable concurrent anti-s-cis partner, and may thus
eventually participate to the global stereochemical course of the reaction [5] (Fig. 4).
21
)
)
In that latter case, the d.e. determinations by HPLC analyses were not performed directly with the
crude 1,4-adducts but after derivatization.
22
In view of the poor correlation of the diastereoselectivity and the electronic nature of the attacking
reagent, as well as the fact that the reactive sites are not directly connected to the N-atom. See page
311 and ref. 48a in [2]. This may be due to the fact that essentially C(a) or C(a) and C(b) attacks
were considered, and that the steric influence on C(a) is apparently much stronger than the
stereoelectronic effect.

Helvetica Chimica Acta – Vol. 94 (2011)
2149
Fig. 4. Hypothetical stereoelectronic influence of the N lone pair
To illustrate the stereoelectronic role of the N lp, we shall pedagogically use the
ꢂbananaꢃ-bond description of an unsaturation, as proposed in the 1930ꢃs by Pauling [51],
in contrast to the Hꢁckel representation, resulting from a combination of both a s- and
p-bond [52]. Despite the fact that some theoretical chemists consider both models to be
practically equivalent [53], the latter one is much better known, better accepted, and,
therefore, found in most modern textbooks. In the first representation, the N lp tends to
distinguish between both equivalent adjacent bonds, by delocalization to the carbonyl
O-atom of the anti-periplanar bent bond, rendering this one more labile. Consequently,
a nucleophilic attack on the SO2/C¼O syn-s-cis C(b) atom should stereoelectronically
preferentially occur from the ꢂbottomꢃ C(a)-re face23), since the anti-periplanar broken
C(a)ꢀC(b) ꢂbananaꢃ bond would preferentially delocalize on the carbonyl by assisting
the opening of the weakest anti-periplanar C¼O bent bond. If this memory-aid rule of
thumb is correct, we should retrieve a similar trend in the Hꢁckel description, and,
therefore, we calculated the corresponding HOMO, LUMO, and conformational
energies of substrates 2a – 2m, as expressed in Table 3, at the B3LYP/6-31G** level
[54]. These calculations, performed on both anti-s-cis and syn-s-cis conformers 2a – 2m
show several general trends. First of all, for both of them, the pyramidality of the N-
atom globally decreases for electron-withdrawing substituents and is crudely correlated
with the electronic parameters according to Eqn. 11. Systematically, the N-atom is more
planar in the syn-s-cis, as compared to the anti-s-cis conformation (ca. 0.16 – 0.17 ꢄ vs.
0.24 – 0.25 ꢄ). As earlier remarked by comparison of X-ray analyses, this pyramidality
23
)
Although the reacting center is the C(b) C-atom, we prefer throughout this report to distinguish
both p-faces with respect to the C(a) atom. This has the advantage of being directly comparable
with the plethora of previous discussions/rationalizations concerning chemical reactions involving
either the C(a) or both C(a) and C(b) atoms, as well as to avoid any inversion of priority on the
C(b) atom when the Michael acceptor is branched to other than aryl substituents. Oppolzer and co-
workers reported that the reverse contra-steric si-face 1,4-addition is observed in the case of the
unchelated SO2/C¼O anti-s-cis conformation [11a].

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Helvetica Chimica Acta – Vol. 94 (2011)
2151
is related to the SꢀNꢀC¼O dihedral angle [5][55], itself correlated with the electronic
parameters according to Eqn. 12.
DhNsyn ¼ ꢀ0.012sInductive ꢀ 0.014sResonance þ 0.172 (n ¼ 13, R2 ¼ 0.75, s.d. ¼ 0.003)
SꢀNꢀC¼Oanti ¼ 1.306sInductive þ 2.623sResonance þ 150.644
(11)
(n ¼ 13, R2 ¼ 0.92, s.d. ¼ 0.229) (12)
Prediction of the MO energies is also possible, in view of the relationships shown in
Eqns. 13 – 16. Both the HOMO and the LUMO of the anti-s-cis conformers are slightly
higher in energy as compared to those of their corresponding syn-s-cis conformers.
Nevertheless, the reactivity of the Michael acceptor is mostly dependent on the LUMO
C(b) coefficients, as their square values are relevant, according to the Schrçdinger
reactivity equation [5], hence from the donating properties of the aromatic moiety, in
either a pushꢀpull or pullꢀpull combination with the sultam moiety. Depending on the
considered p-face, the C(b) LUMO coefficients are slightly different, due to the N lp
desymmetrization, but not as systematically as would be expected from the ꢂbananaꢃ
bond theory. Indeed, in both reactive conformations, the preferred stereoelectronic
attack is favored on the expected p-face in eight cases out of thirteen (bold numbers),
and is systematically ꢂoppositeꢃ for electron-attracting substituents. Finally, to reach an
SO2/C¼O syn conformation, the calculated conformational energy increases for
electron withdrawing groups, according to Eqn. 17. This also contributes to a lower
reactivity of the electronically poor Michael acceptors, since they are statistically more
inclined to adopt the anti-s-cis mismatching conformation.
HOMOanti ¼ ꢀ0.030sInductive ꢀ 0.051sResonance ꢀ 0.227
(n ¼ 13, R2 ¼ 0.88, s.d. ¼ 0.006) (13)
HOMOsyn ¼ ꢀ0.030sInductive ꢀ 0.051sResonance ꢀ 0.233
(n ¼ 13, R2 ¼ 0.87, s.d. ¼ 0.006) (14)
LUMOanti ¼ ꢀ0.031sInductive ꢀ 0.042sResonance ꢀ 0.066
(n ¼ 13, R2 ¼ 0.90, s.d. ¼ 0.005) (15)
LUMOsyn ¼ ꢀ0.031sInductive ꢀ 0.044sResonance ꢀ 0.072
(n ¼ 13, R2 ¼ 0.90, s.d. ¼ 0.005) (16)
DE ¼ 0.671sInductive þ 0.546sResonance þ 6.199 (n ¼ 13, R2 ¼ 0.94, s.d. ¼ 0.057) (17)
Oppolzer et al. [9a] and Liu and co-workers [20] underlined the necessity to use an
excess of at least 2.0 mol.-equiv. of Grignard reagent for a complete conversion. This
observation suggests, as proposed by Oppolzer, a chelated intermediate aggregated
with a second equivalent of metallic nucleophile24). This chelation usually involves the
24
)
Such an aggregate was also invoked to explain the absence of 1,6-addition in case of a N-(2,4-
dienoyl) substrate [9a]; furthermore, > 3.0 mol-equiv. were necessary for bis-chelated N-fumaroyl
derivatives [9e].

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pseudo-equatorial S¼O(1) substituent [56]. In a later work, the enolate generated after
1,4 -addition was trapped in situ by an electrophile, and the observed final
diastereoselectivity could only be explained by chelation with the pseudo-axial
S¼O(2) group25). Unsatisfied by this lack of chelating unity, we also wondered whether
the Grignard reagent was involved in a Schlenk equilibrium [57] (Eqn. 18).
2 RMgX > MgX2 þ R2Mg
(18)
Since iodo Grignard reagents are known for rarely forming aggregates [58], we first
tested the addition of 2.2 mol-equiv. of BuMgI to 2d, at ꢀ 788 in Et2O26). The
conversion was very poor, and the diastereoselectivity reached only 29% d.e. A firm
conclusion is nevertheless difficult to reach, since substrate 2d is extremely insoluble in
Et2O, particularly at ꢀ 788, so that the heterogeneity of the reaction could also be at the
origin of this ambivalent result27). In a second control experiment, we added 1.1 mol-
equiv. of anh. MgBr2 (generated in situ by addition of BrCH2CH2Br to Mg/THF) to a
THF solution of 2d, before adding, at ꢀ 788, 1.1 mol-equiv. of commercially available
Bu2Mg28). This experiment worked perfectly well, and after complete conversion, 5d
was isolated in 83% yield and 72% d.e. This MgBr2 chelating experiment was repeated,
but with 1.1 mol-equiv. of BuMgCl as nucleophile, thus affording 5d in 96% yield and
72% d.e. We also treated 2d with 1.1 mol-equiv. of anh. ZnBr2 in THF, prior to the
addition of 1.1 mol-equiv. of BuMgCl at ꢀ 788. In this case, the partial, ca. 50%
conversion allowed the isolation of 5d in 22% yield and 41% d.e. [59]. Finally, we also
added 2.2 mol-equiv. of Bu2Mg to a THF solution of 2d at ꢀ 788 and obtained, after
4 h, 5d in 85% yield and 59% d.e. It is noteworthy that the addition of EtMgCl (2.5 mol-
equiv., THF, ꢀ 788) in the presence of 2.5 mol-equiv. of either LiCl or [18]crown-6
ether [60] did not influence significantly the aggregation since 2d was isolated in 55 or
59% yield and 74 or 67% d.e., respectively. A different coordinating solvent such as
chiral tetrahydro-2-methylfuran seems to be more influent as 5d was obtained in 69%
yield but only 40% d.e. during the addition of 2.5 mol-equiv of BuMgCl at ꢀ 788.
Oppolzer and Kingma reported that the sense of induction was inverted when the alkyl
Grignard reagent was additionally complexed with CuI [10a]. Curiously, he only
reported C(a) substituted Michael acceptors and rationalized this reverse selectivity by
Cu aggregation involving the easily interconverted s-trans conformer [10a]. It was only
ten years later that Huang et al. reported, in an obscure journal [10b], a similar
25
)
Furthermore, in a later article, only 1.25 mol-equiv. of Grignard reagent were employed, according
to the Exper. Part (vs. 1.4 mol-equiv. according to the discussion) published in [9c]. This inversion of
chelation is questionable since compounds 266 and 268 in [46a] possess an identical configuration,
and epimerization was not excluded.
26
27
)
)
Due to the Schlenk equilibrium, the catalytic presence of MgI2 is known to catalyze the attack and
opening of THF during the preparation of the Grignard reagent.
When the Grignard reagent was prepared in Et2O and added to a clear THF soln. of 2d at ꢀ 788, a
d.e. of 24% was observed. Similarly, addition of 2.2 mol-equiv. of BuMgBr to 2d in Et2O at ꢀ 788
afforded 5d in 20% yield and 50% d.e. after 4 h. Alternatively, addition of 2.2 mol.-equiv. of EtMgI
to 2d in Et2O at ꢀ 788 afforded 3d in 25% yield and 31% d.e.
28
)
In heptane soln. containing 1% of Et3Al as a viscosity reducer. The supplier is unable to either
infirm or confirm the presence of any traces of either MgX2 or HgX2.

Helvetica Chimica Acta – Vol. 94 (2011)
2153
comparative inversion between alkyl MgBr and alkyl MgBr/CuI 1,4-additions to N-
crotonoylbornane-10,2-sultam, thus suggesting that, in some instances, and certainly
depending on either the C(b) or metal coordinating substituents, even C(a)-
unsubstituted Michael acceptors may eventually also adopt a s-trans reactive
conformation29). At this point, it is also noteworthy that we need to take into account
two further exceptions, namely the allyl MgCl/CuBr· DMS/LiCl/Me3SiCl conditions
[10c – 10f], as well as the Me2CuLi/PBu3 1,4-addition to N-crotonoylbornane-10,2-
sultam [11i][11j]30), which both favor the particularly rare C(a)-si face attack31). We
thus became convinced that our arguments, based on alkyl Grignard 1,4-additions,
could be biased due to a possible transfer of steric chiral information from the bornane
skeleton to the C(b) position through a conformationally rigid bimetallic aggregate,
directing its coordinating ligands in thermodynamically preferred directions. It was thus
necessary to focus our attention on nonchelating/nonaggregating conditions, such as
those employed for the addition of MeNO2 to N-crotonoylbornane-10,2-sultam [6]. We
similarly treated the N-(p-methoxycinnamoyl) substrate 2b with MeNO2/DBU, to
afford 9b in 65% yield and 59% d.e. Under the same conditions, the p-facial selectivity
diminished for both the N-cinnamoyl acceptor 2d (! 9d; 58%, 52% d.e.), 2g (! 9g;
48%, 51% d.e.), as well as the electronically deficient and planar N-p-nitrocinnamoyl)
derivative 2m (! 9m; 18%, 24% d.e.). The extent of induction was measured and
1
13
confirmed by H- and C-NMR analyses, respectively32), while the absolute config-
uration was based on both mechanistic considerations, with respect to X-ray analyses
reported for analogous substrates [6][61], as well as on 1H- and 13C-NMR comparisons
with an authentic sample of 9d33), obtained independently.
Although the four adducts 9 obtained under nonchelating conditions are in full
agreement with our initial hypothesis, we considered it would be useless to apply these
conditions to all the series of electronically modified acceptors 2, due to the following
considerations. Indeed, paralleling the experimental approach, we also wondered about
the reliability of our calculations. We thus decided to compare them with the known X-
29
)
In our case, addition of 2.5 mol-equiv. of EtMgCl/CuI to 2d at ꢀ 788 afforded 3d in 54% yield and
70% d.e. It is noteworthy that the anti-s-trans and syn-s-trans conformations are 3.39 and 6.21 kcal/
mol higher in energy as compared to the ground state, respectively. This is a substantial difference
as compared to the N-crotonoyl analogue [5].
30
31
32
)
)
)
We are indebted to Prof. C. L. Willis for scrupulous control and confirmation of the absolute
configuration of her adduct (9th Nov. 2010). In our case, addition of Bu2CuLi · Bu3P to 2d in THF at
ꢀ 788 afforded 5d in 23% yield and 44% d.e.
In the first case, the sense of induction was based on an optical rotation of ꢀ 1.6 [10c] and
confirmed, after removal of the auxiliary, by the asymmetric Flack indexes of three intermediate X-
ray analyses [10d][10e].
Here again, the minor diastereoisomer 9 exhibits its Me(8) signal by ca. 0.03 ppm at higher field in
1
the H-NMR spectrum, while in the 13C-NMR spectrum C(2) and C(9) also resonate by ca. 0.26 –
0.37 ppm at higher field. We found log(d.r.) ¼ 0.354spara þ 0.514 (n ¼ 4, R2 ¼ 0.94, s.d. ¼ 0.044), or
log(d.r.) ¼ ꢀ0.314sInductive ꢀ 0.44sResonance þ 0.498 (n ¼ 4, R2 ¼ 0.98, s.d. ¼ 0.044).
1
)
Because we were unable to obtain the original H- and 13C-NMR analyses of 9d from the main
33
author of [61] (10th Nov. 2010), we scrupulously repeated the addition of (2R)-N-acetylbornane-
10,2-sultam to trans-b-nitrostyrene (TiCl4, Et3N, THF, ꢀ 788) and could isolate 9d in 83% yield and
83% d.e. after purification by CC (SiO2), in slight contrast with the original report in which the
adduct was purified by crystallization [61].

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ray structure analysis of the pyramidalized electron-donating p-MeO substrate 2b [24]
and of the unreported analogue 2d (Fig. 5), as well as the electron-poor p-nitro-
cinnamoyl derivative 2m (Fig. 6). First of all, comparison of the crystal structures of 2b
and 2m confirmed that, for electron-withdrawing substituents, the N-atom tends to
become more planar. Interestingly, and we can even say surprisingly for us, the case of
the unsubstituted N-cinnamoyl derivative 2d is noteworthy since it is even more
pyramidalized than expected. The SꢀNꢀC¼O dihedral angle is well correlated with
DhN or, alternatively, with the sum of all three N-substituent angles (C(2)ꢀNꢀS þ
C(2)ꢀNꢀC(11) þ C(11)ꢀNꢀS [62]). Furthermore, to demonstrate the qualitative
predictive properties of our calculations34), we also prepared the unreported N-
(benzoxazolylcarbonyl) derivative 10 (NaH, toluene, benzoxazole-2-carbonyl chloride
[63]; yield 79%). As we anticipated, it co-adopts both an anti-s-syn-clinal and syn-s-
anti-clinal disposition as shown in Fig. 7 and Table 4.
Fig. 5. ORTEP Diagram of 2d. Arbitrary atom numbering. Ellipsoids are represented at the 50%
probability level.
Fig. 6. ORTEP Diagram of 2m. Arbitrary atom numbering. Ellipsoids are represented at the 50%
probability level.
34
)
See footenote 6 in [55] for solid-state SO2/C¼O syn conformations not exceeding 1.8 kcal/mol. The
conformational analysis of 10 suggests the following energies in kcal/mol: anti-s-syn-clinal 0.00; anti-
s-anti-clinal 0.77; syn-s-syn-clinal 1.63; syn-s-anti-clinal 4.58.

Helvetica Chimica Acta – Vol. 94 (2011)
2155
Fig. 7. ORTEP Diagram of syn-/anti-10. Arbitrary atom numbering. Ellipsoids are represented at the
50% probability level.
Table 4. Selected Bond Lengths [ꢄ] and Angles [8] of 2b, 2d, 2m, and 10
2d
2b [24]
1.408
2m
10anti
10syn
S¼O(1)
1.4307(15)
1.4359(15)
1.7051(17)
1.783(2)
1.476(2)
1.403(2)
1.213(2)
1.485(3)
1.323(3)
1.4283(12)
1.4302(12)
1.7022(13)
1.7835(16)
1.4820(17)
1.3927(19)
1.2154(18)
1.481(2)
1.4239(13)
1.4289(13)
1.7170(14)
1.7782(17)
1.485(2)
1.4250(13)
1.4310(13)
1.7136(14)
1.7797(18)
1.488(2)
S¼O(2)
1.421
1.677
1.771
1.458
1.393
1.206
1.460
1.323
SꢀN
SꢀC(10)
NꢀC(2)
NꢀC(11)
1.385(2)
1.218(2)
1.356(2)
1.213(2)
C(11)ꢀO(3)
C(11)ꢀC(12)
C(12)¼C(13)
O(1)¼S¼O(2)
C(2)ꢀNꢀS
1.486(2)
1.496(2)
1.320(2)
1.302(2)a)
1.292(2)a)
117.66(9)
107.78(13)
117.55(16)
119.71(13)
117.0
116.56(7)
112.82(9)
119.33(12)
123.09(11)
118.35(8)
112.63(11)
115.46(13)
122.52(12)
119.58(8)
113.67(11)
129.57(14)
116.34(12)
110.3
118.4
120.4
C(2)ꢀNꢀC(11)
C(11)ꢀNꢀS
C(2)ꢀNꢀS¼O(1)
C(2)ꢀNꢀS¼O(2)
C(3)-C(2)ꢀNꢀS
SꢀNꢀC(11)¼O(3)
ꢀ 147.74(13) ꢀ 140.8 ꢀ 121.08(11)
ꢀ 116.49(12) ꢀ 123.32(13)
82.24(14)
153.89(15)
142.37(18)
89.8
149.6
148.2
109.42(11)
136.58(12)
160.58(13)
ꢀ 6.7(3)
113.19(12)
135.54(13)
158.16(15)
ꢀ 38.8(3)b)
105.01(13)
139.20(14)
ꢀ 4.2(2)
O(3)¼C(11)ꢀC(12)¼C(13) ꢀ 18.6(3)
ꢀ 18.8
118.4(2)b)
C(12)¼C(13)ꢀC(14)¼Co
C(12)¼C(13)ꢀC(14)¼Co’
DhN [ꢄ]
ꢀ 14.8(3)
164.4(2)
0.341
0.417
43.95
ꢀ 14.4
2.6(3)
165.0 ꢀ 178.27(17)
0.285
0.390
57.28
0.191
0.321
101.91
0.271
0.299
107.83
0.056
0.363
96.78
Puckering parameter q2
SꢀNꢀC(2)ꢀC(1)ꢀC(10) F2
a) C(12)¼N(2). b) O(3)¼C(11)ꢀC(12)¼N(2).

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Comparison of both 10anti and 10syn also confirmed that the syn conformers are more
planar, as calculated in Table 3. Both DhN and the SꢀNꢀC¼O torsional angle of 10syn
constitute new extreme values, as compared to the previous records for such a
conformation (0.066 ꢄ [55], and ꢀ 8.88 [64]). Another salient structural characteristic
is the pseudo-axial orientation of the S¼O(2) substituent, particularly marked for the
electron-donating analogues 2b and 2d, or the conformer 10syn as compared to 10anti, as
expressed by the small dihedral C(2)ꢀNꢀS¼O(2) angles. This pseudo-axial orientation
is also evident from the F2 puckering parameter which, for both 2b and 2d, are the
smallest ever reported for an SO2/C¼O anti disposition (usually comprised inbetween
778 [55] and 1408 [65]). We thus can be confident in our gas-phase calculations and can
envisage three possible rationalizations. In the first one, a conformational equilibrium
implicates both the most-stable less-reactive mismatching anti-s-cis and the minor more
reactive steric/stereoelectronic matching syn-s-cis conformers. In that option, the more
planar N, resulting from electron-withdrawing p-substituents, induces more difficulties
to reach a syn-s-cis cooperative disposition, and thus results in lower d.e. This
intuitively postulated dependence of the diastereoselectivity on the conformational
energy was opposed by a multilinear correlation of log(d.r.) with respect to sInductive
,
sResonance, and DE, which increased insignificantly the square of the correlation
coefficient R2 from 0.87 to 0.88 only, thus rendering this hypothesis less attractive as the
main origin for substrates of type 2. In the second option, the stereoelectronic influence
is stronger for pyramidalized electron-rich conformers, thus explaining that, for
electron-poor, more planar substrates, the p-facial discrimination diminishes. Finally,
we can also imagine the absence of any stereoelectronic effect. The p-substituent would
electronically modify the tilting of the N-atom, and thus, the puckering of the sultam
ring. As a result, for a strongly pyramidalized N-atom, both S¼O(2) and HꢀC(2)
substituents would adopt a pseudo-axial orientation, while for electron-attracting p-
substituted cinnamoyl derivatives, the more planar N-atom would rather direct these
two substituents in a less pseudo-axial direction, thus diminishing their p-facial
directing abilities. The steric directing influence of the sultam substituents would thus
be indirectly a colateral consequence of the electronic effect of the p-substituent at the
cinnamoyl moiety. One could argue that this geometry optimizes the steric influence on
C(a), and to a lesser extent on C(b), thus explaining their higher diastereoselectivities
in the SO2/C¼O anti-s-cis disposition. In both stereoelectronic or S¼O(2)/C(2)ꢀ(C3)
steric differential interactions, one would expect a better diastereoselectivity for
2d as compared to 2b. This argument is nevertheless moderated by the fact that the
conformation in solution may be quite different from that in the solid state. A
cumulative interaction between two or three of these hypotheses is also not ex-
cluded.
The steric influence of the chiral promoter is significantly more important on the
proximate C(a) atom, as compared to the stereoelectronic effect. The situation could
be inverted for the C(b) atom, especially for sterically nondemanding nucleophiles.
When the bulkiness of the incoming Grignard reagent increases, the steric directing
influence gains in importance and, consequently, the diastereoselectivity decreases due
to the poor steric differentiation of the chiral auxiliary on the remote C(b) atom. This
logical explanation does not constitute a proof of the stereoelectronic influence on

Helvetica Chimica Acta – Vol. 94 (2011)
2157
small nucleophiles but at least does not constitute a disproof of our postulate35).
Finally, by fixing the C(3)ꢀC(2)ꢀNꢀC(11) torsional angle, we calculated both the
stereoelectronic and geometric influence of the SꢀNꢀC¼O conformation at ca. ꢂ1.58,
and ꢂ38 around the minimum syn-s-cis and anti-s-cis conformers, respectively. We thus
found that the most-reactive conformations in terms of LUMO and atomic coefficient
levels are not necessarily those in the thermodynamically most-favored orientation. A
very slight conformational change may even invert the stereoelectronic p-facial
preference.
Conclusions. – For electron-rich pyramidalized substrates of type 2, the ꢂbananaꢃ
bond rationalization is statistically well corroborated by the Hꢁckel representation. We
showed that the alkyl Grignard reagent may be used in an equimolar amount, provided
that the sultam moiety is chelated with a Lewis acid such as MgBr2. The Schlenk
equilibrium (Eqn. 18) may also be used to generate the appropriate conditions for
effective 1,4-addition. Further developments to determine the scope, the limitations,
and the effects of the nature of the Lewis acid are actually under study and shall be
disclosed in due course. Addition of poorly aggregating iodo Grignard alkyl reagents
resulted in both poor conversions and diastereoselectivities, thus allowing, as ration-
alization, a possible transmission of the chiral information of the bornane skeleton to
the C(b) reactive center through a rigidified bimetallic chelated-(mixed Mg or Cu)-
aggregated species, as earlier suggested by Oppolzer and co-workers. Even under
nonchelating MeNO2 1,4-addition conditions, the concomitant electronic influence on
both the N-pyramidalization and the ring puckering modifies the orientation of both
the sterically directing S¼O(2) and HꢀC(2) substituents, thus precluding any evident
demonstration of a pure and dissociated stereoelectronic effect on the diastereose-
lectivity. These calculated geometries are consistent with the new X-ray structure
analyses of 2d and 2m. It is noteworthy that when S¼O(1) becomes more pseudo-axial,
the pseudo-C2 symmetry of the chiral auxiliary is lost [2][67]. Furthermore, theoretical
calculations (Table 5) suggest that the LUMO atomic coefficients on both C(a) and
C(b) strongly depend on very slight modifications of the reactive conformation, so that
the effective stereoelectronic effect should be calculated and compared with the
transition state, rather than on extreme SO2/C¼O anti or syn reactive conformations.
Several typical NMR displacements (of C¼O, C(a), C(b), and Cipso), as well as
conformational or energy properties (SꢀNꢀC¼O dihedral angle, DE syn/anti; HOMO/
LUMO) could nevertheless be very well correlated with the electronic parameters.
Finally, from the synthetic point of view, this methodology may also be extended to give
access to natural products and medicinal intermediates [68]. Amazingly, neither
uncatalyzed nor Lewis acid mediated [4 þ 2] cycloadditions of 1,3-dienes to dienophiles
of type 2 have been reported. Their study could bring some interesting insights, as the
C(a) and C(b) LUMO coefficients are strongly dependent on the electronic nature of
35
)
The increasing mismatching steric influence was also observed for the counter anions or
substituents of the Grignard reagent at ꢀ 788; for example: EtMgCl/THF (78% d.e.), EtMgBr/
THF (73% d.e.), EtMgI/Et2O (31% d.e.), BuMgCl/THF (72% d.e.), BuMgBr/THF (57% d.e.), and
BuMgI/Et2O (29% d.e.). For an inverse trend in the Mg cuprate addition to Michael acceptors
connected to Evansꢃ chiral auxiliaries, see [66].

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Helvetica Chimica Acta – Vol. 94 (2011)
the aryl substituent, and hence may cooperatively influence the same face in some
instances36), thus leading to subtle predictable differences. The knowledge acquired
during this study could eventually help us in redesigning a modified set of experiments,
to bring to the fore this hypothetical stereoelectronic effect. Indeed, if 1,4-additions are
ideal in minimizing the steric influence of the sultam skeleton on the C(a) position, the
Michael acceptor should also maintain constant its sultam ring puckering, thus
minimizing the S¼O(2) and C(2)ꢀC(3) steric influence on the remote C(b) position.
Moreover, the electronically tunable nucleophiles chosen should have the same steric
impact. All these requirements suggest the use of conjugated additions, at a constant
temperature, of adequately p-substituted thiophenols or methyl thiosalicylates [8] to
strongly pyramidalized sultam acceptors of type 2b, 2c, or 2d, and comparison of the
general trend with more planar counterparts of type 2k or 2m, or alternatively with the
more isosteric 2i, 2j, or 2f analogues, respectively.
Table 5. Calculated Influences of the N-Pyramidalization on the Geometry and the MO Parameters of 2d
SO2/C¼O anti-periplanar
SO2/C¼O syn-periplanar
C(3)ꢀC(2)ꢀNꢀC(11) [8]
DE [kcal/mol]
DhN [ꢄ]
SꢀNꢀC¼O [8]
C(2)ꢀNꢀS¼O(1) [8]
C(2)ꢀNꢀS¼O(2) [8]
lpꢀNꢀS¼O(2) [8]
O¼CꢀC(a)¼C(b) [8]
C(a)¼C(b)ꢀCipso¼Co [8]
HOMO [eV]
LUMO [eV]
C(11) up
C(11) down
C(a) up
C(a) down
C(b) up
C(b) down
ꢀ 69.4
ꢀ 64.4
ꢀ 59.4
0.33
0.202
153.5
ꢀ 130.0
97.5
ꢀ 67.8
ꢀ 64.8
ꢀ 61.8
6.25
0.148
ꢀ 18.7
ꢀ 119.1
105.5
0.07
0.00
6.30
6.23
0.278
147.7
ꢀ 129.5
98.2
0.240
150.8
ꢀ 129.5
98.1
0.199
0.175
ꢀ 21.3
ꢀ 120.8
103.8
ꢀ 19.8
ꢀ 120.2
104.5
ꢀ 156.2
ꢀ 158.5
ꢀ 161.2
ꢀ 154.8
ꢀ 155.7
ꢀ 156.0
ꢀ 7.8
ꢀ 8.0
ꢀ 7.9
ꢀ 4.0
ꢀ 4.5
ꢀ 6.4
0.4
0.2
0.3
ꢀ 3.1
ꢀ 1.3
ꢀ 4.2
ꢀ 0.2304
ꢀ 0.0656
0.155
0.143
0.151
0.146
0.196
0.198
ꢀ 0.2304
ꢀ 0.0652
0.155
0.137
0.153
0.149
0.196
0.197
ꢀ 0.2302
ꢀ 0.0648
0.150
0.144
0.153
0.155
0.195
0.193
ꢀ 0.2376
ꢀ 0.0708
0.126
ꢀ 0.2375
ꢀ 0.0705
0.128
ꢀ 0.2374
ꢀ 0.0703
0.131
0.136
0.156
0.153
0.196
0.133
0.158
0.154
0.196
0.135
0.162
0.158
0.196
0.191
0.190
0.191
The X-Ray measurements were performed in the Structural Research Laboratory at the Chemistry
Department of the University of Warsaw. We are indebted to Prof. A. Eschenmoser for stimulating
discussions after the presentation of our matching/mismatching stereoelectronic concept at the IXth Eur.
Symp. Org. Chem. in Warsaw, 18 – 23 June 1995.
36
)
For example, the C(a)-re face is electronically favored for both anti-s-cis and syn-s-cis 2e, as well as
anti-s-cis 2m and syn-s-cis 2j, in contrast to syn-s-cis 2l, suggesting a C(a)-si face stereoelectronic
preference in the latter case (see Table 3). Recently, double diastereoselection was used for
determining the reactive conformation of Evansꢃ N-enoyloxazolidin-2-ones in case of conjugate
additions [69]. For 1,4-additions with Evansꢃ derivatives, see ref. cited in [70].

Helvetica Chimica Acta – Vol. 94 (2011)
2159
Experimental Part
1. General. See [19a]. For 13C-NMR attributions, see Table 6. All crystal measurements were
performed with a KM4CCD k-axis diffractometer and graphite-monochromated MoKa radiation, see
Table 7. The crystal was positioned at 61.2 mm from the CCD camera; 2224 frames were measured at 18
intervals with a counting time of 10 s for 2d, 1392 frames were measured at 18 intervals with a counting
time of 20 s for 2m, and 2221 frames were measured at 18 intervals with a counting time of 3 s for 10. The
data were corrected for Lorentz and polarization effects. Empirical correction for absorption was applied
[71]. Data reduction and analysis were carried out with the Oxford Diffraction programs [72]. The
structure was solved by direct methods [73] and refined with SHELXL [74]. The refinement was based
on F2 for all reflections, except for 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 F2o > 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 in [75]. The known configurations of the
asymmetric centers were confirmed by the Flack-parameter refinement [76]. CCDC-779696, -779697,
and -793873 contain the supplementary crystallographic data (excluding structural factors) for 2d, 2m,
and 10, resp. These data can be obtained free of charge via http://www.ccdc.cam.ac.uk/data_request/cif.
Table 6. 13C-NMR Assignments of 2a – 2m
2a
48.7
2b
2c
2d
2e
2f
2g
2h
2i
2j
2k
2l
2m
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
C(9)
48.7 48.7 48.6 48.7 48.7
65.4 65.4 65.3 65.4 65.4
38.7 38.7 38.6 38.7 38.7
44.9 44.9 44.8 44.9 44.9
26.7 26.7 26.6 26.7 26.7
33.0 33.0 32.9 33.0 33.0
48.0 48.0 47.9 48.0 48.0
20.1 20.1 20.0 20.1 20.1
21.1 21.1 20.9 21.1 21.0
53.4 53.4 53.2 53.4 53.4
164.7 164.6 164.3 164.5 164.3
115.1 116.5 117.5 116.5 116.4
145.5 145.8 145.6 145.2 144.4
127.3 131.7 134.3 131.0 130.8
48.7 48.8 48.8 48.8
65.4 65.4 65.4 65.4
38.6 38.7 38.7 38.6
44.9 44.9 44.9 44.9
26.7 26.7 26.7 26.7
33.0 33.0 33.0 33.0
48.0 48.0 48.0 48.1
20.1 20.1 20.1 20.1
21.0 21.0 21.0 21.0
53.3 53.4 53.3 53.3
164.2 164.2 164.1 163.9
118.1 118.2 118.6 120.1
144.2 144.3 143.8 143.7
132.9 133.4 133.1 137.9
48.9 48.9 48.7
65.5 65.4 65.3
38.6 38.6 38.4
44.8 44.8 44.7
26.7 26.7 26.5
33.0 33.0 32.9
48.1 48.0 47.9
20.1 20.1 19.9
21.0 21.0 20.8
53.4 53.3 53.2
163.6 163.6 163.3
121.1 121.3 121.6
143.1 142.9 142.3
138.7 139.7 140.4
129.1 129.3 129.2
132.8 128.1 124.1
113.8 141.8 148.6
65.4
38.8
44.9
26.7
33.0
48.0
20.1
21.1
C(10) 53.4
C¼O 164.7
C(a) 115.2
C(b) 145.5
Cipso
Co
Cm
Cp
R1
127.5
130.6
115.4
161.1
130.6 128.9 128.7 129.2 130.7a) 129.3 130.2 130.2 128.9
114.5 129.8 128.9 126.0 116.2a) 130.0 132.3 121.3 126.0
161.9 141.4 130.7 142.7 117.4
15.3
136.7 125.2 158.8 131.3
150.8 123.9c) 118.6 44.6
70.3b) 55.6 21.7
a) Co (d, J ¼ 34.8 Hz); Cm (J ¼ 86.8 Hz). b) 127.7 (2d), 128.4 (d), 128.9 (2d), and 136.6 (s). c) q, J ¼
270 Hz.
2. Acylation of 1: General Procedure A. To a suspension of 60% NaH in mineral oil (1.2 equiv.) in
dry toluene (10 ml) under Ar was added at 08 a soln. of 1 (1.1 equiv.) in dry toluene (20 ml). After 30 min.
at 208, the suspension was cooled to 08 and a soln. of the appropriate acyl chloride (2.2 mmol) in toluene
(20 ml) was added dropwise. The mixture was stirred at 208 for 18 h. Then H2O (10 ml) was added, and
the aq. phase was extracted with CH2Cl2. The org. layer was dried (MgSO4) and concentrated. The crude
material was purified by CC (SiO2, toluene/AcOEt 95 :5) to afford products 2a – 2j or 10.

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Helvetica Chimica Acta – Vol. 94 (2011)
Table 7. Crystal Data and Structure Refinement of Compounds 2d, 2m, and 10
2d
2m
10
Empirical formula
Mr
C19H23NO3S
345.44
C19H22N2O5S
390.45
C18H20N2O4S
360.42
Temp. [K]
Wavelength [ꢄ]
Crystal system
Space group
Unit-cell dimensions
a [ꢄ]
100(2)
0.71073
triclinic
P1
100(2)
100(2)
0.71073
monoclinic
P21
0.71073
monoclinic
P21
7.3497(3)
7.6149(2)
8.6919(3)
101.544(3)
111.169(3)
96.679(3)
434.89(3)
1
7.8294(3)
7.1339(3)
16.9557(7)
7.07460(10)
13.1149(2)
18.1568(4)
b [ꢄ]
c [ꢄ]
a [8]
b [8]
99.398(4)
93.239(2)
g [8]
V [ꢄ3]
934.33(7)
2
1681.95(5)
4
Z
Density [Mg/m3]
Absorpt. coeff. [mmꢀ1
F(000) electrons
Crystal size [mm]
q Range for data [8]
Index ranges
1.319
0.203
184
1.388
0.207
412
0.44 ꢃ 0.08 ꢃ 0.06
3.08 to 26.36
ꢀ 9 ꢁ h ꢁ 9
ꢀ 8 ꢁ k ꢁ 8
ꢀ 21 ꢁ l ꢁ 21
20835/3816
0.0339
1.423
0.219
760
0.28 ꢃ 0.20 ꢃ 0.16
2.73 to 26.36
ꢀ 8 ꢁ h ꢁ 8
ꢀ 16 ꢁ k ꢁ 16
ꢀ 22 ꢁ l ꢁ 22
55240/6854
0.0433
]
0.35 ꢃ 0.13 ꢃ 0.08
2.79 to 26.37
ꢀ 9 ꢁ h ꢁ 9
ꢀ 9 ꢁ k ꢁ 9
ꢀ 10 ꢁ l ꢁ 10
14163/3549
0.0283
full-matrix least-squares on F2
R(F) (I > 2s(I))
3549, 3, 259
1.065
Reflections collected, unique
R(int)
Refinement method
Criterion for observed
Data, restraints, parameters
Goodness-of-fit on F2
R1 (GT)
3816, 1, 285
0.914
0.0263
6854, 1, 455
0.928
0.0363
0.0280
wR2 (all)
0.0735
0.0497
0.0527
Abs. struct. parameter
Largest peak and holes [ꢄꢀ3
ꢀ 0.04(6)
ꢀ 0.04(5)
0.02(4)
0.216, ꢀ 0.259
]
0.233, ꢀ 0.178
0.237, ꢀ 0.259
(ꢀ)-(2R)-N-[4-(Benzyloxy)cinnamoyl]bornane-10,2-sultam (¼(–)-(2E)-3-[4-(Benzyloxy)phenyl]-
1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-
prop-2-en-1-one; 2a); Yield 83%. M.p. 115 – 1208. [a]2D0 ¼ ꢀ60.9 (c ¼ 1.0, CHCl3). IR: 3030, 2984, 2966,
2874, 1669, 1614, 1596, 1510, 1468, 1455, 1422, 1388, 1375, 1328, 1303, 1262, 1248, 1235, 1209, 1174, 1131,
1110, 1081, 1062, 1042, 1004, 984, 885, 828, 776, 758, 748, 698, 612, 548, 529, 497. 1H-NMR: 0.98 (s, 2 H);
1.20 (s, 3 H); 1.40 – 1.49 (m, 2 H); 1.89 – 1.91 (m, 3 H); 2.08 – 2.20 (m, 2 H); 3.45, 3.54 (AB, J ¼ 13.8, 2 H);
3.98 (t, J ¼ 6.8, 1 H); 5.08 (s, 2 H); 7.04 (d, J ¼ 15.4, 1 H); 6.94 – 7.40 (m, 7 H); 7.53 (d, J ¼ 8.8, 2 H); 7.75 (d,
J ¼ 15.4, 1 H). ESI-MS: 474.2 ([M þ Na]þ). HR-ESI-MS: 474.1715 (C26H29NNaO4Sþ; calc. 474.1690).
(ꢀ)-(2R)-N-(4-Methylcinnamoyl)bornane-10,2-sultam
(¼(ꢀ)-(2E)-3-(4-Methylphenyl)-1-
[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]prop-
2-en-1-one; 2c): Yield 95%. M.p. 204 – 2108. [a]2D0 ¼ ꢀ95.9 (c ¼ 1.0, CHCl3). IR: 3009, 2991, 2968, 2941,
2908, 2879, 1676, 1623, 1606, 1570, 1514, 1480, 1457, 1417, 1393, 1369, 1331, 1316, 1285, 1267, 1233, 1209,
1184, 1165, 1132, 1113, 1062, 989, 882, 815, 772, 717, 618, 548, 523, 497, 436. 1H-NMR: 0.99 (s, 3 H); 1.21 (s,
3 H); 1.38 – 1.45 (m, 2 H); 1.91 – 1.94 (m, 3 H); 2.14 – 2.17 (m, 2 H); 2.37 (s, 3 H); 3.46, 3.55 (AB, J ¼ 13.7,

Helvetica Chimica Acta – Vol. 94 (2011)
2161
2 H); 3.99 (t, J ¼ 6.8, 1 H); 7.12 (d, J ¼ 15.4, 1 H); 7.16 – 7.24 (m, 2 H); 7.46 – 7.50 (m, 2 H); 7.77 (d, J ¼ 15.4,
1 H). ESI-MS: 382.1 ([M þ Na]þ). HR-ESI-MS: 382.1453 (C20H25NNaO3Sþ; calc. 382.1450).
(ꢀ)-(2R)-N-[4-(Methylthio)cinnamoyl]bornane-10,2-sultam (¼(ꢀ)-(2E)-3-[4-(Methylthio)phenyl]-
1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-
prop-2-en-1-one; 2e): Yield 87%. M.p. 153 – 1588. [a]2D0 ¼ ꢀ86.6 (c ¼ 1.0, CHCl3). IR: 3006, 2986, 2963,
2940, 2878, 1671, 1614, 1589, 1550, 1494, 1456, 1407, 1368, 1336, 1315, 1275, 1230, 1206, 1187, 1164, 1132,
1112, 1093, 1062, 1042, 988, 882, 815, 762, 615, 546, 537, 500, 480, 463, 404. 1H-NMR: 0.99 (s, 3 H); 1.20 (s,
3 H); 1.38 – 1.50 (m, 2 H); 1.85 – 1.95 (m, 3 H); 2.13 – 2.18 (m, 2 H); 2.50 (s, 3 H); 3.47, 3.56 (AB, J ¼ 14,
2 H); 3.99 (t, J ¼ 5,4, 1 H); 7.11 (d, J ¼ 15.4, 1 H); 7.18 – 7.27 (m, 2 H); 7.47 – 7.51 (m, 2 H); 7.74 (d, J ¼ 15.4,
1 H). ESI-MS: 414,1 ([M þ Na]þ). HR-ESI-MS: 414.1174 (C11H16NaOþ3 ; calc. 414.1187).
(ꢀ)-(2R)-N-(4-Fluorocinnamoyl)bornane-10,2-sultam (¼(ꢀ)-(2E)-3-(4-Fluorophenyl)-1-[(3aS,
6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]prop-2-en-
1-one; 2f): Yield 89%. M.p. 178 – 1868. [a]2D0 ¼ ꢀ90.2 (c ¼ 1.0, CHCl3). IR: 3008, 2993, 2946, 2904, 1678,
1626, 1598, 1509, 1459, 1416, 1394, 1366, 1332, 1283, 1265, 1232, 1206, 1159, 1130, 1112, 1063, 1042, 987,
940, 883, 830, 777, 548, 526, 499, 455, 439. 1H-NMR: 0.99 (s, 3 H); 1.21 (s, 3 H); 1.39 – 1.50 (m, 2 H); 1.91 –
1.96 (m, 3 H); 2.14 – 2.18 (m, 2 H); 3.46, 3.57 (AB, J ¼ 14, 2 H); 4.0 (t, J ¼ 7.2, 1 H); 7.07 (d, J ¼ 15.4, 1 H);
7.03 – 7.13 (m, 2 H); 7.54 – 7.61 (m, 2 H); 7.75 (d, J ¼ 15.4, 1 H). ESI-MS: 386.1 ([M þ Na]þ). HR-ESI-
MS: 386.1202 (C19H22FNNaO3Sþ; calc. 386.1216).
(ꢀ)-(2R)-N-(4-Chlorocinnamoyl)bornane-10,2-sultam (¼(ꢀ)-(2E)-3-(4-Chlorophenyl)-1-[(3aS,
6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]prop-2-en-
1-one; 2g): Yield 79%. M.p. 207 – 2128. [a]2D0 ¼ ꢀ98.8 (c ¼ 1.0, CHCl3). IR: 3007, 2991, 2941, 2880, 1676,
1628, 1593, 1494, 1410, 1373, 1343, 1325, 1311, 1296, 1281, 1236, 1219, 1165, 1132, 1116, 1092, 1064, 1013,
992, 885, 829, 819, 782, 762, 730, 547, 536, 499, 491, 405. 1H-NMR: 0.99 (s, 3 H); 1.20 (s, 3 H); 1.34 – 1.51
(m, 2 H); 1.85 – 1.98 (m, 3 H); 2.14 – 2.18 (m, 2 H); 3.47, 3.54 (AB, J ¼ 13.8, 2 H); 3.99 (t, J ¼ 6.8, 1 H);
7.14 (d, J ¼ 15.5, 1 H); 7.10 – 7.37 (m, 2 H); 7.49 – 7.54 (m, 2 H); 7.73 (d, J ¼ 15.5, 1 H). ESI-MS: 402.1
([M þ Na]þ). HR-ESI-MS: 402.0907 (C19H22ClNNaO3Sþ; calc. 402.0924).
(ꢀ)-(2R)-N-(4-Bromocinnamoyl)bornane-10,2-sultam (¼(ꢀ)-(2E)-3-(4-Bromophenyl)-1-[(3aS,
6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]prop-2-en-
1-one; 2h): Yield 76%. M.p. 208 – 2108. [a]2D0 ¼ ꢀ79.8 (c ¼ 1.0, CHCl3). IR: 3006, 2989, 2939, 2879, 1676,
1628, 1587, 1565, 1490, 1459, 1417, 1405, 1392, 1374, 1343, 1325, 1296, 1275, 1236, 1219, 1165, 1132, 1115,
1064, 1039, 1009, 991, 884, 826, 817, 781, 760, 727, 546, 535, 497, 445. 1H-NMR: 0.99 (s, 3 H); 1.20 (s, 3 H);
1.38 – 1.51 (m, 2 H); 1.92 – 1.98 (m, 3 H); 2.14 – 2.18 (m, 2 H); 3.47, 3.57 (AB, J ¼ 13.7, 2 H); 3.99 (t, J ¼ 5.8,
1 H); 7.15 (d, J ¼ 15.4, 1 H); 7.11 – 7.50 (m, 4 H); 7.71 (d, J ¼ 15.4). ESI-MS: 446.0 ([M þ Na]þ). HR-ESI-
MS: 446.0412 (C19H19BrN4NaO3Sþ; calc. 446.0424).
(ꢀ)-(2R)-N-[4-(Trifluoromethoxy)cinnamoyl]bornane-10,2-sultam (¼(ꢀ)-(2E)-1-[(3aS,6R,7aR)-
Tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-3-[4-(trifluorome-
thoxy)phenyl]prop-2-en-1-one; 2i): Yield 91%. M.p. 120 – 1258. [a]2D0 ¼ ꢀ81.3 (c ¼ 1.0, CHCl3). IR: 3000,
2963, 2883, 1682, 1634, 1508, 1457, 1418, 1408, 1374, 1337, 1288, 1272, 1259, 1214, 1147, 1135, 1112, 1069,
995, 982, 880, 833, 796, 776, 757, 546, 536, 498. 1H-NMR: 0.99 (s, 3 H); 1.20 (s, 3 H); 1.39 – 1.51 (m, 2 H);
1.91 – 1.96 (m, 3 H); 2.14 – 2.19 (m, 2 H); 3.48, 3.57 (AB, J ¼ 13.8, 2 H); 4.00 (t, J ¼ 5.6, 1 H); 7.14 (d, J ¼
15.5, 1 H); 7.10 – 7.27 (m, 2 H); 7.58 – 7.64 (m, 2 H); 7.75 (d, J ¼ 15.5, 1 H). ESI-MS: 452.1 ([M þ Na]þ).
HR-ESI-MS: 452.1119 (C20H22F3NNaO4Sþ; calc. 452.1139).
(ꢀ)-(2R)-N-[4-(Trifluoromethyl)cinnamoyl]bornane-10,2-sultam (¼(ꢀ)-(2E)-1-[(3aS,6R,7aR)-
Tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-3-[4-(trifluorome-
thyl)phenyl]prop-2-en-1-one; 2j): Yield 75%. M.p. 164 – 1688. [a]2D0 ¼ ꢀ76.5 (c ¼ 0.26, CHCl3). IR: 2992,
2966, 2939, 2904, 1683, 1632, 1418, 1335, 1321, 1285, 1233, 1214, 1169, 1127, 1113, 1070, 1060, 1045, 1015,
987, 883, 833, 769, 545, 486, 457. 1H-NMR: 1.00 (s, 3 H); 1.21 (s, 3 H); 1.34 – 1.60 (m, 2 H); 1.93 – 2.05 (m,
3 H); 2.15 – 2.19 (m, 2 H); 3.48, 3.58 (AB, J ¼ 13.9, 2 H); 4.00 (t, J ¼ 7, 1 H); 7.23 (d, J ¼ 15.4, 1 H); 7.28 –
7.71 ( m, 4 H); 7.78 (d, J ¼ 15.4, 1 H). ESI-MS: 436.1 ([M þ Na]þ). HR-ESI-MS: 436.1170
(C20H22F3NNaO3Sþ; calc. 436.1129).
3. EtMgBr Addition to 2: General Procedure B. A soln. of substrate 2a – 2m (1 mmol) in anh. THF
(5 ml) under Ar was cooled to ꢀ 788. Then alkylmagnesium halide (1m or 2m soln. in THF, 2.2 equiv.) was

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Helvetica Chimica Acta – Vol. 94 (2011)
added dropwise along the cold wall of a long reaction flask37). The wall of the flask was then rinsed by
dropwise addition of THF (0.5 ml). The mixture was stirred at ꢀ 788 for 4h and then quenched with aq.
sat. NH4Cl soln. The aq. phase was extracted with Et2O (2 ꢃ 10 ml) and the combined org. layer washed
with brine (10 ml), dried (MgSO4), and concentrated. Both the conversion and d.e. [%] were measured
1
by H-NMR integration. Pure material 3 was obtained after purification by CC (SiO2, hexane/AcOEt
9 :1).
(2R)-N-{(3R)-3-[4-(Benzyloxy)phenyl]pentanoyl}bornane-10,2-sultam (¼(3R)-3-[4-(Benzyloxy)-
phenyl]-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-
1(4H)-yl]pentan-1-one; 3a): IR: 3088, 3065, 3030, 3006, 2960, 2947, 2926, 2886, 2869, 2081, 1986, 1966,
1923, 1886, 1822, 1681, 1608, 1583, 1512, 1498, 1486, 1456, 1415, 1378, 1357, 1332, 1310, 1271, 1255, 1234,
1208, 1180, 1164, 1132, 1114, 1083, 1065, 1041, 1026, 990, 962, 945, 911, 878, 865, 848, 834, 817, 796, 775,
743, 698, 649, 639, 625, 602, 564, 549, 532, 496, 466, 447, 420. 1H-NMR: 0.81 (t, J ¼ 7, 3 H); 0.96 (s, 3 H);
1.15 (s, 3 H); 1.28 – 1.33 (m, 2 H); 1.56 – 1.61 (m, 3 H); 1.82 – 1.88 (m, 3 H); 2.01 – 2.03 (m, 2 H); 3.00 –
3.10 (m, 2 H); 3.39, 3.49 (AB, J ¼ 13.8, 2 H); 3.80 (t, J ¼ 6.2, 1 H); 5.02 (s, 2 H); 6.85 – 6.95 (m, 2 H);
7.10 – 7.14 (m, 2 H); 7.35 – 7.45 (m, 5 H). 13C-NMR: 12.1 (q); 20.1 (q); 21.1 (q); 26.6 (t); 29.6 (t); 33.0 (t);
38.7 (t); 42.4 (t); 42.7 (d); 44.8 (d); 47.9 (s); 48.5 (s); 53.2 (t); 65.4 (d); 70.2 (t); 114.8 (2d); 127.7 (2d);
128.1 (d); 128.7 (2d); 128.8 (2d); 136.3 (s); 137.4 (s); 157.5 (s); 170.9 (s). ESI-MS: 504.2 ([M þ Na]þ).
HR-ESI-MS: 504.2185 (C28H35NNaO4Sþ; calc. 504.2189).
(2R)-N-{(3R)-3-[4-(Methylthio)phenyl]pentanoyl}bornane-10,2-sultam (¼(3R)-3-[4-(Methylthio)-
phenyl]-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-
1(4H)-yl]pentan-1-one; 3e): IR: 3075, 3023, 2962, 2922, 2885, 1898, 1692, 1598, 1494, 1458, 1444, 1426,
1409, 1388, 1377, 1327, 1287, 1267, 1251, 1242, 1213, 1164, 1133, 1111, 1099, 1085, 1068, 1040, 989, 954, 926,
907, 878, 828, 806, 781, 762, 751, 723, 675, 609, 566, 552, 537, 494, 438. 1H-NMR: 0.79 (t, J ¼ 7, 3 H); 0.95 (s,
3 H); 1.15 (s, 3 H); 1.30 – 1.34 (m, 3 H); 1.62 – 1.68 (m, 2 H); 1.83 – 1.89 (m, 3 H); 2.15 – 2.19 (m, 2 H);
2.44 (s, 3 H); 3.05 – 3.11 (m, 2 H); 3.39, 3.49 (AB, J ¼ 13.8, 2 H); 3.79 (t, J ¼ 6.4, 1 H); 7.12 – 7.20 (m, 4 H).
13C-NMR: 12.1 (q); 15.3 (q); 20.1 (q); 21.0 (q); 26.6 (t); 29.4 (t); 32.9 (t); 38.6 (t); 41.9 (t); 42.9 (d); 44.8
(d); 47.9 (s); 48.5 (s); 53.1 (t); 65.3 (d); 127.0 (2d); 128.4 (d); 128.6 (d); 136.0 (s); 141.0 (s); 170.6 (s). ESI-
MS: 444.2 ([M þ Na]þ). HR-ESI-MS: 444.1643 (C22H31NNaO3Sþ2 ; calc. 444.1608).
(2R)-N-[(3R)-3-(4-Bromophenyl)pentanoyl]bornane-10,2-sultam (¼(3R)-3-(4-Bromophenyl)-1-
[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]pen-
tan-1-one; 3h): IR: 3005, 2992, 2973, 2930, 2887, 1908, 1689, 1589, 1485, 1459, 1412, 1406, 1384, 1328, 1287,
1253, 1242, 1211, 1180, 1165, 1134, 1120, 1108, 1072, 1041, 1008, 990, 927, 909, 878, 832, 820, 807, 781, 759,
1
727, 716, 675, 613, 603, 566, 549, 535, 498, 452, 425. H-NMR: 0.79 (t, J ¼ 7, 3 H); 0.96 (s, 3 H); 1.15 (s,
3 H); 1.30 – 1.34 (m, 2 H); 1.57 – 1.70 (m, 3 H); 1.84 – 1.89 (m, 3 H); 2.01 (d, J ¼ 6.4, 2 H); 2.99 – 3.13 (m,
2 H); 3.40 3.50 (AB, J ¼ 13.9, 2 H); 3.79 (t, J ¼ 6.2, 1 H); 7.07 – 7.41 (m, 4 H). 13C-NMR: 12.0 (q); 20.1 (q);
21.0 (q); 26.6 (t); 29.4 (t); 33.0 (t); 38.6 (t); 41.9 (t); 42.8 (d); 44.8 (d); 47.9 (s); 48.5 (s); 53.2 (t); 65.4 (d);
120.2 (s); 129.7 (2d); 131.6 (2d); 143.0 (s); 170.5 (s). ESI-MS: 478.1 ([M þ Na]þ). HR-ESI-MS: 476.0871
(C21H28BrN4NaO3Sþ; calc. 476.0851).
(2R)-N-{(3R)-3-[4-Trifluoromethoxy)phenyl]pentanoyl}bornane-10,2-sultam (¼(3R)-1-[(3aS,
6R,7aR)-Tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-3-[4-(tri-
fluoromethoxy)phenyl]pentan-1-one; 3i): IR: 3047, 3016, 3000, 2966, 2936, 2879, 2463, 1897, 1692, 1610,
1595, 1511, 1481, 1418, 1392, 1331, 1299, 1285, 1259, 1223, 1212, 1164, 1133, 1109, 1069, 1039, 1017, 988,
944, 928, 878, 839, 821, 808, 781, 754, 720, 694, 665, 611, 594, 555, 538, 509, 490, 452, 423. 1H-NMR: 0.78 (t,
J ¼ 7.6, 3 H); 0.96 (s, 3 H); 1.15 (s, 3 H); 1.30 – 1.36 (m, 2 H); 1.61 – 1.67 (m, 3 H); 1.82 – 1.90 (m, 3 H);
2.01 (d, J ¼ 6.2, 2 H); 3.01 – 3.07 (m, 2 H); 3.40, 3.51 (AB, J ¼ 14, 2 H); 3.80 (t, J ¼ 6.4, 1 H); 7.09 – 7.15 (m,
2 H); 7.21 – 7.27 (m, 2 H). 13C-NMR: 12.0 (q); 20.0 (q); 21.0 (q); 26.6 (t); 29.5 (t); 33.0 (t); 38.6 (t); 41.9
37
)
In view of both the high reactivity of N-alkenoylbornane-10,2-sultam derivatives, and their high
conformational dependence on temperature, this experimental detail is primordial for the good
reproducibility of the results, as earlier already emphasized in the experimental part of [77]. Thus,
for example, differences of up to 29% d.e. were reported by the Chinese authors between both
enantiomers of bornane-10,2-sultam derivatives 2, after 1,4-addition of alkyl Grignard reagents
[20b]!

Helvetica Chimica Acta – Vol. 94 (2011)
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(t); 42.7 (d); 44.8 (d); 47.9 (s); 48.5 (s); 53.1 (t); 65.4 (d); 119.0 (s); 121.0 (2d); 129.2 (2d); 142.7 (s); 147.8
(s); 170.5 (s). ESI-MS: 482.2 ([M þ Na]þ). HR-ESI-MS: 482.1589 (C22H28F3NNaO4Sþ; calc. 482.1577).
(2R)-N-{(3R)-3-[4-(Trifluoromethyl)phenyl]pentanoyl}bornane-10,2-sultam (¼(3R)-1-[(3aS,
6R,7aR)-Tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]-3-[4-(tri-
fluoromethyl)phenyl]pentan-1-one; 3j): IR: 3018, 3005, 2971, 2938, 2904, 1924, 1692, 1617, 1585, 1482,
1418, 1392, 1324, 1287, 1267, 1243, 1213, 1166, 1124, 1111, 1068, 1041, 1015, 989, 954, 879, 845, 821, 807, 781,
755, 715, 665, 613, 604, 550, 536, 506, 490, 454. 1H-NMR: 0.72 (t, J ¼ 7, 3 H); 0.90 (s, 3 H); 1.09 (s, 3 H);
1.23 – 1.30 (m, 2 H); 1.57 – 1.64 (m, 2 H); 1.78 – 1.85 (m, 3 H); 1.97 (d, J ¼ 6.4, 2 H); 3.02, 3.39 (AB, J ¼
13.9, 2 H); 3.05 – 3.34 (m, 2 H); 3.73 (t, J ¼ 5.6, 1 H); 7.23 – 7.30 (m, 2 H); 7.43 – 7.50 (m, 2 H).
13C-NMR: 12.0 (q); 20.0 (q); 21.0 (q); 26.6 (t); 29.4 (t); 32.9 (t); 38.6 (t); 41.6 (t); 43.1 (d); 44.8 (d); 47.9
(s); 48.5 (s); 53.1 (t); 65.4 (d); 124.4 (q, J ¼ 1500); 125.4 (d); 125.5 (d); 128.1 (d); 128.2 (d); 129.0 (s);
148.2 (s); 170.2 (s). ESI-MS: 466.2 ([M þ Na]þ). HR-ESI-MS: 466.1640 (C22H28F3NNaO3Sþ; calc.
466.1653).
(2R)-N-[(3R)-3-(4-Cyanophenyl)pentanoyl]bornane-10,2-sultam (¼4-{(1R)-1-Ethyl-3-oxo-3-
[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]pro-
pyl}benzonitrile; 3k): IR: 3003, 2967, 2935, 2888, 2875, 2227, 1920, 1687, 1607, 1504, 1481, 1460, 1417, 1384,
1328, 1285, 1268, 1244, 1227, 1213, 1166, 1136, 1113, 1087, 1071, 1042, 991, 954, 928, 909, 879, 837, 808, 782,
755, 732, 683, 642, 611, 571, 540, 495, 437. 1H-NMR: 0.79 (t, J ¼ 7.6, 3 H); 0.96 (s, 3 H); 1.17 (s, 3 H); 1.39 –
1.45 (m, 2 H); 1.72 – 1.85 (m, 3 H); 1.97 – 2.04 (m, 3 H); 2.13 (d, J ¼ 6.4, 2 H); 3.18 – 3.32 (m, 2 H); 3.39,
3.49 (AB, J ¼ 13.9, 2 H); 3.90 (t, J ¼ 6.2, 1 H); 7.40 – 7.47 (m, 2 H); 7.67 – 7.73 (m, 2 H). 13C-NMR: 12.0
(q); 20.0 (q); 21.0 (q); 26.6 (t); 29.3 (t); 33.0 (t); 38.6 (t); 41.4 (t); 43.4 (d); 44.8 (d); 47.9 (s); 48.6 (s); 53.1
(t); 65.4 (d); 110.4 (s); 119.3 (s); 128.8 (2d); 132.4 (2d); 149.8 (s); 170.1 (s). ESI-MS: 423.2 ([M þ Na]þ).
HR-ESI-MS: 423.1685 (C22H31NNaO3Sþ2 ; calc. 423.1598).
(2R)-N-{(3R)-3-[4-Methylthio)phenyl]pentanoyl}bornane-10,2-sultam (¼(3R)-3-[4-(Methylthio)-
phenyl]-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-
1(4H)-yl]pentan-1-one; 3l): IR: 2961, 2926, 2878, 2855, 1923, 1695, 1637, 1598, 1575, 1459, 1414, 1384,
1328, 1313, 1250, 1214, 1150, 1134, 1113, 1089, 1064, 1039, 989, 955, 909, 876, 836, 807, 778, 724, 686, 649,
617, 565, 536, 511, 496, 456, 419. 1H-NMR: 0.79 (t, J ¼ 7, 3 H); 0.97 (s, 3 H); 1.15 (s, 3 H); 1.26 – 1.43 (m,
2 H); 1.61 – 1.78 (m, 3 H); 1.86 – 1.93 (m, 3 H); 2.01 (d, J ¼ 6.5, 2 H); 3.05 (s, 3 H); 3.12 – 3.50 (m, 2 H);
3.40, 3.51 (AB, J ¼ 14, 2 H); 3.78 (t, J ¼ 6, 1 H); 7.42 (d, J ¼ 8.4, 2 H); 7.86 (d, J ¼ 8.4, 2 H). 13C-NMR: 12.0
(q); 20.0 (q); 21.1 (q); 26.6 (t); 29.3 (t); 33.0 (t); 38.6 (t); 41.5 (t); 43.2 (d); 44.8 (d); 45.0 (q); 47.6 (s); 48.6
(s); 53.2 (t); 65.4 (d); 121.0 (2d); 127.7 (d); 128.9 (d); 138.3 (s); 152.2 (s); 170.1 (s). ESI-MS: 444.2 ([M þ
Na]þ). HR-ESI-MS: 444.1608 (C22H31NNaO3Sþ2 ; calc. 444.1643).
(2R)-N-[(3R)-3-(4-Nitrophenyl)pentanoyl]bornane-10,2-sultam (¼(3R)-3-(4-Nitrophenyl)-1-
[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]pen-
tan-1-one; 3m): IR: 3079, 2960, 2881, 2850, 1676, 1626, 1597, 1520, 1482, 1458, 1413, 1393, 1374, 1341, 1288,
1265, 1235, 1215, 1176, 1165, 1134, 1113, 1083, 1065, 1038, 982, 940, 910, 882, 856, 838, 754, 712, 615, 547,
536, 500, 451. 1H-NMR: 0.88 (t, J ¼ 7.5, 3 H); 0.97 (s, 3 H); 1.15 (s, 3 H); 1.26 – 1.43 (m, 2 H); 1.82 – 1.92
(m, 6 H); 2.05 – 2.20 (m, 2 H); 2.70 – 3.25 (m, 2 H); 3.39 – 3.59 (m, 2 H); 3.84 (t, J ¼ 6, 1 H); 7.24 – 8.15 (m,
4 H). 13C-NMR: 12.2 (q); 20.1 (q); 21.0 (q); 26.6 (t); 29.3 (t); 33.0 (t); 38.6 (t); 41.4 (t); 43.2 (d); 44.8 (d);
47.8 (s); 48.6 (s); 53.2 (t); 65.4 (d); 123.7 (2d); 130.4 (2d); 145.8 (s); 146.3 (s); 170.1 (s). ESI-MS: 443.2
([M þ Na]þ). HR-ESI-MS: 443.1624 (C21H28N2NaO5Sþ; calc. 443.1617).
4. (3R)-3-(4-Methoxyphenyl)-4-nitro-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-
3a,6-methano-2,1-benzisothiazol-1(4H)-yl]butan-1-one (9b). A soln. of 2b (375 mg, 1.00 mmol), DBU
(914 mg, 6.0 mmol), and MeNO2 (366 mg, 6.0 mmol) in THF (17 ml) and DMPU (3.45 ml) was stirred
under N2 for 24 h at 208. The mixture was then diluted with Et2O and extracted with H2O. The org. phase
was dried (MgSO4) and concentrated and the residue purified by CC (SiO2, cyclohexane/AcOEt 95 :5 !
8 :2): 9b (65%); 59% d.e. IR: 2959, 1691, 1551, 1514, 1457, 1413, 1376, 1327, 1249, 1213, 1178, 1165, 1133,
1113, 1064, 1034, 989, 909, 830, 761, 728. 1H-NMR: 0.95 (s, 3 H); 1.11 (s, 3 H); 1.26 – 1.42 (m, 3 H); 1.70 –
1.90 (m, 3 H); 2.02 (br. d, J ¼ 6.6, 1 H); 3.15 (dd, J ¼ 4.2, 7.6, 2 H); 3.46 (dd, J ¼ 13.8, 19.8, 2 H); 3.76 (t,
J ¼ 7.5, 1 H); 3.76 (s, 3 H); 4.07 (quint., J ¼ 7.4, 1 H); 4.64 (dq, J ¼ 5.2, 12.4, 2 H); 6.83 (d, J ¼ 8.6, 2 H);
7.17 (d, J ¼ 8.6, 2 H). 13C-NMR: 20.0 (q); 20.6 (q); 26.6 (t); 32.9 (t); 38.5 (t); 38.8 (t); 39.0 (d); 44.8 (d);

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Helvetica Chimica Acta – Vol. 94 (2011)
47.9 (s); 48.7 (s); 53.0 (t); 55.4 (q); 65.4 (d); 79.9 (t); 114.5 (2d); 128.8 (2d); 130.4 (s); 159.3 (s); 168.9 (s).
HR-ESI-MS: 437.1717 ([M þ H]þ, C21H29N2O6Sþ; calc. 437.1741).
(3R)-4-Nitro-3-phenyl-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-
benzisothiazol-1(4H)-yl]butan-1-one (9d). As described for 9b, with 2d (100 mg, 0.29 mmol), DBU
(265 mg, 1.74 mmol), MeNO2 (106 mg, 1.74 mmol), THF (5 ml), and DMPU (1 ml): 9d (58%); 52% d.e.
IR: 2975, 2925, 2851, 1689, 1551, 1455, 1376, 1326, 1279, 1237, 1215, 1164, 1133, 1066, 1039, 989, 867, 765,
1
699. H-NMR: 0.96 (s, 3 H); 1.12 (s, 3 H); 1.25 – 1.41 (m, 3 H); 1.97 – 1.99 (m, 3 H); 3.03 (br. d, J ¼ 6.8,
1 H); 3.20 (dd, J ¼ 4.2, 7.2, 2 H); 3.45 (q, J ¼ 6.8, 2 H); 3.80 (t, J ¼ 6.2, 1 H); 4.13 (quint., J ¼ 7.5, 1 H); 4.67
(dq, J ¼ 3.4, 7.5, 2 H); 7.2 – 7.4 (m, 5 H). 13C-NMR: 20.0 (q); 21.0 (q); 26.6 (t); 33.0 (t); 38.5 (t); 38.6 (t);
39.7 (d); 44.8 (d); 48.0 (s); 48.7 (s); 53.1 (t); 65.4 (d); 79.7 (t); 127.7 (2d); 128.1 (d); 129.2 (2d); 138.5 (s);
168.8 (s). HR-ESI-MS: 407.1661 ([M þ H]þ, C20H27N2O5Sþ; calc. 407.1635).
(3R)-3-(4-Chlorophenyl)-4-nitro-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-
methano-2,1-benzisothiazol-1(4H)-yl]butan-1-one (9g). As described for 9b, with 2g: 9g (48%); 51% d.e.
IR: 2961, 2886, 1693, 1553, 1494, 1414, 1377, 1328, 1278, 1238, 1215, 1165, 1135, 1119, 1094, 1063, 1040,
1014, 990, 830, 775, 736, 537. 1H-NMR: 0.96 (s, 3 H); 1.11 (s, 3 H); 1.24 – 1.45 (m, 3 H); 1.8 – 2.04 (m, 3 H);
2.04 (br. s, 1 H); 3.17 (dd, J ¼ 4.2, 7.4, 2 H); 3.45 (dd, J ¼ 13.8, 20.2, 2 H); 3.79 (t, J ¼ 6.2, 1 H); 4.04 – 4.19
(m, 1 H); 4.69 (dq, J ¼ 7, 7.8, 2 H); 7.20 – 7.34 (m, 4 H). 13C-NMR: 20.0 (q); 21.0 (q); 26.6 (t); 32.9 (t); 38.4
(2t); 39.1 (d); 44.8 (d); 48.0 (s); 48.8 (s); 53.0 (t); 65.4 (d); 79.4 (t); 129.2 (2d); 129.4 (2d); 134.0 (s); 137.0
(s); 168.5 (s). HR-ESI-MS: 463.1069 (C20H25ClN2NaO5Sþ; calc. 463.1070).
(3R)-4-Nitro-3-(4-nitrophenyl)-1-[(3aS,6R,7aR)-tetrahydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-
methano-2,1-benzisothiazol-1(4H)-yl]butan-1-one (9m). As described for 9b, with 2m (390 mg,
1.00 mmol), DBU (914 mg, 6.0 mmol), MeNO2 (366 mg, 6.0 mmol), THF (17 ml), and DMPU
(3.45 ml): 9m (18%); 24% d.e. IR: 2959, 1674, 1622, 1595, 1518, 1342, 1325, 1279, 1233, 1209, 1164,
1132, 1113, 1069, 1046, 1040, 998, 849, 770, 753, 693, 613. 1H-NMR: 0.95 (s, 3 H); 1.09 (s, 3 H); 1.29 – 2.0
(m, 7 H); 3.09 – 3.15 (m, 2 H); 3.30 – 3.36 (m, 1 H); 3.46 (q, J ¼ 7, 2 H); 3.75 (t, J ¼ 7, 1 H); 5.01 (dq, J ¼ 4,
12.4, 2 H); 7.50 (d, J ¼ 4, 2 H); 8.16 (d, J ¼ 4, 2 H). 13C-NMR: 19.8 (q); 20.6 (q); 26.3 (t); 29.7 (t); 32.7 (t);
38.3 (t); 41.8 (d); 44.5 (d); 47.7 (s); 48.4 (s); 52.9 (t); 65.2 (d); 83.2 (t); 123.8 (2d); 127.0 (2d); 146.9 (s);
149.6 (s); 168.0 (s). HR-ESI-MS: 436.5042 ([M þ H]þ, C20H26N3O6Sþ; calc. 436.5019).
5. (2R)-N-(Benzoxazol-2-ylcarbonyl)bornane-10,2-sultam (¼ Benzoxazol-2-yl[(3aS,6R,7aR)-tetra-
hydro-8,8-dimethyl-2,2-dioxido-3H-3a,6-methano-2,1-benzisothiazol-1(4H)-yl]methanone; 10). Ob-
tained in 79% yield according to Procedure A. M.p. 163 – 1668. [a]2D0 ¼ ꢀ113.8 (c ¼ 0.69, CHCl3).IR:
3097, 2993, 2958, 2939, 2881, 2850, 1936, 1819, 1680, 1606, 1560, 1478, 1453, 1407, 1391, 1374, 1352, 1328,
1317, 1261, 1251, 1237, 1220, 1197, 1167, 1141, 1120, 1107, 1085, 1062, 1038, 1027, 1004, 975, 938, 917, 908,
892, 859, 829, 806, 783, 755, 695, 665, 634, 617, 578, 568, 543, 531, 509, 490, 452, 445, 430. 1H-NMR: 1.03 (s,
3 H); 1.31 (s, 3 H); 1.50 (t, J ¼ 7, 2 H); 1.90 – 2.15 (m, 5 H); 3.57 (q, J ¼ 13.6, 2 H); 4.44 (dd, J ¼ 7, 5, 1 H ) ;
7.18 – 7.27 (m, 1 H); 7.41 – 7.56 (m, 1 H); 7.68 (d, J ¼ 7, 1 H); 7.95 (d, J ¼ 7, 1 H ) . 13C-NMR: 20.2 (q); 22.0
(q); 26.4 (t); 33.7 (t); 39.5 (t); 45.7 (d); 48.1 (s); 49.2 (s); 53.7 (t); 66.8 (d); 111.9 (d); 122.5 (d); 125.9 (d);
128.3 (d); 129.2 (s); 140.4 (s); 150.7 (s); 156.7 (s). ESI-MS: 383.1 ([M þ Na]þ). HR-ESI-MS: 383.0995
(C18H20N2NaO4Sþ; calc. 383.1041).
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