1,3-Dipolar cycloaddition of nitrile oxides with unsymmetrically substituted norbornenes

Article abstract of DOI:10.1016/S0040-4020(01)00573-7

1,3-Dipolar cycloadditions of nitrile oxides with unsymmetrically substituted norbornenes were investigated. The cycloadditions were found to be completely stereoselective, giving only the exo cycloadducts in moderate to good yields. Regioselectivities in the cycloadditions ranging from 50:50 to 100:0 were observed with various unsymmetrically substituted norbornenes.

Full text of DOI:10.1016/S0040-4020(01)00573-7

TETRAHEDRON
Pergamon
Tetrahedron 57 62001) 5931±5941
1,3-Dipolar cycloaddition of nitrile oxides with unsymmetrically
substituted norbornenes
Peter Mayo, Tiffany Hecnar and William Tamp
Department of Chemistry and Biochemistry, Guelph-Waterloo Center for Graduate Work in Chemistry and Biochemistry,
University of Guelph, Guelph, Ontario, Canada N1G 2W1
Received 13 March 2001; accepted 17 May 2001
AbstractÐ1,3-Dipolar cycloadditions of nitrile oxides with unsymmetrically substituted norbornenes were investigated. The cycloadditions
were found to be completely stereoselective, giving only the exo cycloadducts in moderate to good yields. Regioselectivities in the
cycloadditions ranging from 50:50 to 100:0 were observed with various unsymmetrically substituted norbornenes. q 2001 Elsevier Science
Ltd. All rights reserved.
1. Introduction
cycloaddition. Other than generation from the correspond-
ing hydroimoyl chlorides, another widely used method to
generate nitrile oxides is the dehydration of the correspond-
ing nitroalkanes. The two most commonly used methods for
converting nitroalkanes to the corresponding nitrile oxides
are the Mukaiyama aromatic isocyanate method and the
Shimizu ethyl chloroformate method.8,9 All the above
mentioned methods suffer from a limitation: a high reaction
temperature 6above 808C) is usually required, sometimes
leading to lower yields and lower stereoselectivities. More
recently Hassner and co-workers have reported an improved
procedure to generate nitrile oxides from the corresponding
nitroalkanes at room temperature using di-tert-butyl dicar-
bonate, 6BOC)2O, in the presence of a catalytic amount of 4-
dimethylaminopyridine 6DMAP).10 Under these reaction
conditions, we obtained excellent yields of single regio-
and stereoisomers in our intramolecular 1,3-dipolar
cycloadditions of norbornadiene-tethered nitrile oxides
6Scheme 2).
1,3-Dipolar cycloadditions offer a convenient one-step route
for the construction of a variety of complex ®ve-membered
heterocycles.1 1,3-Dipolar cycloadditions of nitrile oxides
are well-documented and provide ef®cient entries to the
synthesis of 2-isoxazolines.2 Reductive cleavage of the
N±O bond of 2-isoxazolines has proven to be a useful
route to amino ketones, oxo alcohols, and a number of
natural products.1,2 1,3-Dipolar cycloadditions of nitrile
oxides with bicyclic alkenes have also been studied.3,4 For
example, norbornadiene 1a 6XˆH) or 1b 6XˆCl) reacted
with benzonitrile oxide 2a or phenylglyoxynitrile oxide 2b
to provide a mixture of exo and endo cycloadducts 3 and 4 in
a ratio of about 80:20 6Scheme 1). These nitrile oxides were
generated from the corresponding hydroimoyl chlorides by
dehydrohalogenation with the removal of HCl using Et3N.5
During our studies on the intramolecular cycloadditions of
norbornadiene-tethered nitrile oxides,6,7 we noticed that
using different methods and different conditions to generate
the nitrile oxides could affect the stereoselectivity of the
To our knowledge, all the bicyclic alkenes that have been
studied in the intermolecular nitrile oxide cycloadditions are
Scheme 2. Intramolecular 1,3-dipolar cycloadditions of norbornadiene-
tethered nitrile oxides.
Scheme 1.
Keywords: 1,3-dipolar cycloadditions; nitrile oxides; bicyclic alkenes; norbornenes; regioselectivity; stereoselectivity; remote substituent effects.
Corresponding author. Tel.: 1519-824-4120, ext. 2268; fax: 1519-766-1499; e-mail: tam@chembio.uoguelph.ca
p
0040±4020/01/$ - see front matter q 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020601)00573-7

5932
P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
symmetrical and thus no regiochemistry questions could be
addressed. In this paper we report our studies on the 1,3-
dipolar cycloadditions of nitrile oxides with unsym-
metrically substituted norbornenes 8±11 6Fig. 1). We
would like to address both the questions of regiochemistry
and stereochemistry.
Figure 1. Unsymmetrically substituted norbornenes.
Scheme 5. Nitrile oxide cycloadditions of 2-substituted-2-norbornenes.
2. Results and discussion
2.1. Nitrile oxide cycloadditions of norbornene #8a) and
2-substituted-2-nornornenes #8b±8d)
Figure 2. Assignment of regiochemistry of cycloadducts 14a±d.
Several 2-substituted-2-norbornenes 8b±8d were prepared
as shown in Scheme 3. Deprotonation of norbornene 68a)
with Schlosser's base 6tBuOK/nBuLi) in THF at 2788C,11
followed by trapping with hexyl bromide, TMSCl or ethyl
chloroformate provided the 2-substituted-2-norbornenes
8b±8d. Four different cycloadducts 614±17) could be
formed from a 2-substituted-2-norbornene 8 reacting with
benzonitrile oxide 2a 6Scheme 4). Cycloaddition could
occur with the oxygen of the nitrile oxide attached to C2
of the norbornene 8 to produce exo-cycloadduct 14 or
endo-cycloadduct 16, or the oxygen of the nitrile oxide
attached to C3 to give exo-cycloadduct 15 or endo-cyclo-
adduct 17. The benzonitrile oxide 2a was generated from
nitromethylbenzene 618)12 using Hassner's method
66BOC)2O and DMAP) and its cycloadditions with norbor-
nene 68a) and 2-substituted-2-norbornenes 8b±8d were
studied 6Scheme 5).
These cycloadditions were found to be completely regio-
and stereoselective, giving single regio- and stereoisomers
14a±14d in moderate to good yields. Only the exo-cyclo-
adducts were formed, and regardless of the electronic nature
of the substituent at C2 of the 2-norbornene 8, only the
regioisomers with the oxygen of the nitrile oxide attached
to C2 of the norbornene 8 were produced. The complete
control of the regiochemistry by the substitutent at C2 of
the 2-norbornene 8 was expected as similar regiochemical
control was observed previously in acyclic systems.13a,b
Usually the oxygen of the nitrile oxide becomes bonded to
the most substituted carbon of the ole®n regardless of the
electronic nature of the substituent. The lower yields of the
cycloadditions of substituted norbornenes 8b±8d 650±55%)
can be explained by the fact that these substituted norbor-
nenes are less reactive than the unsubstituted norbornene
68a), and the nitrile oxide 62a) is prone to undergo dimer-
ization, rearrangement and polymerization when reacted
with less reactive dipolarophiles.1a,2b In fact, for the
cycloadditions of substituted norbornenes 8b±8d, we
obtained a signi®cant amount of polymeric material at the
end of the reactions.
The regio- and stereochemistry of the cycloadducts 14a±
1
14d were easily assigned by H and 13C NMR. For cyclo-
adduct 14a 6XˆH), the exo stereochemistry was proven by
the coupling pattern of Ha and Hb in the H NMR spectra
1
6Fig. 2). As the dihedral angles between Ha and Hd, and Hb
and Hc in the exo cycloadducts are close to 908, their
coupling constants would be very small 6Jˆ,0±2 Hz).
The corresponding dihedral angles of the endo cycloadducts
would be approximately 428 and would give coupling
constants of ,5 Hz. In 14a, both Ha and Hb are doublets
6coupled only with each other but not with Hc or Hd), there-
fore this cycloadduct must possess exo stereochemistry.14
Similarly for cycloadducts 14b±14d 6X±H), the singlet of
Scheme 3. Synthesis of 2-substituted-2-norbornenes 8b±8d.
1
Hb in the H NMR 6does not couple with Hc) indicated the
exo stereochemistry of the cycloadducts. The regiochemis-
try of cycloadducts 14b±14d were proven by the fact that in
the APT-13C NMR,15 the carbons attached to the oxygen in
the isoxazoline rings 6Ca) are quaternary carbons.
Scheme 4. Possible cycloadducts.

P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
5933
2.2. Nitrile oxide cycloadditions of 1-substituted-2-nor-
bornene #9b)
major cycloadduct, Hb 64.62 ppm, the proton next to the
carbon adjacent to the CvN in the isoxazoline ring) showed
positive NOE effect with Ha 65.10 ppm), Hc 62.80 ppm) and
the phenyl ring. Ha 6the proton attached to the carbon next to
the oxygen in the isoxazoline ring) in the major cycloadduct
showed positive NOE only with Hb. In the minor cyclo-
adduct, Ha showed positive NOE effect with Hb and Hc;
and Hb showed positive NOE effect with Ha and the phenyl
ring.
1-Substituted-2-norbornene 9b was prepared as shown in
Scheme 6. Deprotonation of freshly cracked cyclopenta-
diene 15 with BuLi followed by trapping of the resulting
n
anion with methyl chloroformate afforded 1-methoxycarbo-
nylcyclopentadiene 616).16,17 Diels±Alder reaction of 16
with freshly recrystallized maleic anhydride provided 1-
substituted-2-norbornene 9a.17 As 9a is not quite soluble
in most organic solvents such as THF, Et2O, toluene and
CHCl3 6the solvent that we used to carried out the 1,3-di-
polar cycloadditions), we decided to convert 9a to 9b before
studying the nitrile oxide cycloaddition. Thus, treatment of
9a with sodium methoxide in methanol at 08C, followed by
trapping with methyl iodide provided 9b. Benzonitrile oxide
62a) was generated from nitromethylbenzene 618) using
6BOC)2O and DMAP and its cycloaddition with 1-substi-
tuted-2-norbornene 9b was studied 6Scheme 7). Similar to
the nitrile oxide cycloadditions with 2-substituted-2-norbor-
nenes 8b±8d, cycloaddition of nitrile oxide 2a with 1-
substituted-2-norbornene 9b was also completely stereo-
selective, only the exo cycloadducts were obtained. Two
regioisomers 18a and 18b were obtained in a ratio of
80:20 with an overall isolated yield of 87%. The major
regioisomer was found to be the one with the oxygen of
the nitrile oxide attached to C2 of the norbornene 9b.
2.3. Nitrile oxide cycloadditions of 2-substituted-5-nor-
bornenes #10 and 11)
Although the substituents 6Z1 and Z2) in 2-substituted-5-
norbornenes 10 and 11 6Fig. 1) are far away from the reac-
tion center 6the double bond), previous examples in the
literature have shown that these remote substituents could
have a signi®cant effect on the regiochemical control in
cycloaddition reactions.19±22 We have recently reported
the remote substituent effects on the regioselectivity of the
ruthenium-catalyzed [212] cycloadditions and Pauson±
Khand [21211] cycloadditions of 2-substituted-5-norbor-
nenes.19,20 Regioselectivities of up to 88:12 were observed
in the ruthenium-catalyzed [212] cycloadditions 6Scheme
8), and regioselectivities of up to 74:26 were observed in the
Pauson±Khand reactions 6Scheme 9).
exo-2-Substituted-5-norbornenes 10a±10g and endo-2-
substituted-5-norbornenes 11a±11f were prepared accord-
ing to our previously reported procedures.20,21 Benzonitrile
oxide 62a) was generated from nitromethylbenzene 618)
using 6BOC)2O and DMAP and its cycloaddition with
exo- and endo-2-substituted-5-norbornenes are shown in
Table 1. Similar to norbornenes 8 and 9, the cycloadditions
of 10 and 11 were completely stereoselective, giving only
the exo cycloadducts. Generally the yields of the cyclo-
additions were good but the regioselectivities were very
low. Unlike the ruthenium-catalyzed [212] cycloadditions
and Pauson±Khand [21211] cycloadditions in which the
remote substituents showed a signi®cant effect on the
regioselectivity of the cycloadditions, very little remote
substituent effects were observed in the 1,3-dipolar nitrile
oxide cycloadditions. The highest regioselectivity observed
The stereochemistry of the cycloadducts 18a and 18b were
proven by the coupling pattern of Ha and Hb in the 1H NMR
spectra, similar to 14a as described earlier. The regiochem-
istry of the cycloadducts were determined by GOESY
experiments 6gradient NOE experiments), Fig. 3.18 In the
Scheme 6. Synthesis of 1-substituted-2-norbornene 9b.
Scheme 8. Ruthenium-catalyzed [212] cycloadditions of 2-substituted-5-
norbornenes.
Scheme 7. Nitrile oxide cycloadditions of 1-substituted-2-norbornene 9b.
Scheme 9. Cobalt-catalyzed Pauson-Khand reactions of 2-substituted-5-
norbornenes.
Figure 3. Assignment of regiochemistry of cycloadducts 18a/18b.

5934
P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
Table 1. Nitrile oxide cycloadditions of 2-substituted-5-norbornenes
Exo-substituents 6Z2ˆH)
Endo-substituents 6Z1ˆH)
Yield 6%)a Cycloadducts 25:2b
Entry Norbornene Z1
Yield 6%)a Cycloadducts 25:26 Entry Norbornene Z2
1
2
3
4
5
6
7
10a
10b
10c
10d
10e
10f
COOMe
OH
OTBS
OMEM
OBn
OAc
79
82
82
94
95
95
89
25a/26a
25b/26b
25c/26c
25d/26d
25e/26e
25f/26f
25g/26g
54:46
50:50
8
9
11a
11b
11c
11d
11e
11f
COOMe
OH
PTBS
OMEM
OBn
46
72
90
86
76
95
25h/26h
25i/26i
25j/26j
25k/26k
25l/26l
50:50
58:42
50:50
55:45
51:49
55:45
50:50 10
50:50 11
53:47 12
62:38 13
57:43
OAc
25m/26m
10g
XˆYˆO 6ketone)
a
Isolated yields of pure products after column chromatography.
Measured by integration on 400 MHz H NMR spectra.
b
1
was 62:38 with the exo-OAc norbornene 10f. We have also
studied the effect of different solvents on the regioselectivity
of the cycloadditions between exo-OAc norbornene 10f with
benzonitrile oxide 62a). Very little changes on the regio-
selectivity were observed using different solvents, but
different solvents have signi®cant effect on the chemical
yields. The highest yields were observed using CHCl3 as
solvent 695%). In toluene, the yield was 65%, in THF
46%, in Et2O 47%, in DME 49%, in hexanes 53%, and in
DMF 16%. We have also studied the effect of different
nitrile oxides on the regioselectivity of the cycloadditions.
The nitrile oxide cycloadditions of exo-OAc norbornene 10f
with three different nitrile oxides 6generated from the corre-
sponding nitroalkanes using the 6BOC)2O/DMAP method))
are shown in Table 2. Both phenylglyoxynitrile oxide 62b)
and methyl nitrile oxide 62c) are less reactive than benzo-
nitrile oxide 62a), giving lower chemical yields in the
cycloadditions. In case of methyl nitrile oxide 62c), very
little reaction was observed when the reaction was carried
out at room temperature. Both the cycloadditions of 10f with
nitrile oxide 2a and 2c gave regioselectivities of 62:38 while
the cycloadditions of 10f with nitrile oxide 2b was non-
selective, giving a 50:50 ratio of the regioisomers.
nenes using the gaussian 98 suite of programs 6Scheme
10).23,24 Natural population analysis shows that the charges
on the C5 and C6 atoms of the 2-substituted norbornenes 10
are slightly negative and slightly different. With Z1ˆOAc,
OCH3 6used to model the experimentally used OCH2Ph) or
OH, C6 is always more `negative' than C5. This explains the
regiochemistry of the cycloadditions that we observed: the
major isomers formed 6cycloadduct 25) are the isomers with
the oxygen of the nitrile oxide 6the `negative' end of the 1,3-
dipole) attached to C5 6the less negatively charged carbon of
the double bond) and the carbon of the nitrile oxide 6the
`positive' end of the 1,3-dipole) attached to C6 6the more
negatively charged carbon of the double bond). For the
regioselectivity in the cycloadditions, one would expect
the greater the difference of the charges between C5 and
C6 in 10, the higher the regioselectivity. This is exactly
what we observed. When Z1ˆOAc, the difference in the
charges between C5 and C6 6qC5-C6) is 0.015 and the regio-
selectivity is 62:38. Changing Z1 from OAc to OCH3
6Z1ˆOCH3 was used to model the experimentally used
OCH2Ph), the difference in the charges between C5 and C6
is smaller 60.007) and the regioselectivity decreased to
53:47. For Z1ˆOH, the difference in the charges between
C5 and C6 is very small 60.003) and the cycloaddition is non-
selective 650:50).
In order to explain the regiochemistry of the cycloadditions
and the observed trend of regioselectivity, we have
performed theoretical calculations of some of the norbor-
We observed stronger remote substituent effects on the
regioselectivity in the ruthenium-catalyzed [212] cyclo-
additions19 and Pauson±Khand [21211] cycloadditions20
than the 1,3-dipolar nitrile oxide cycloadditions. The 1,3-
dipolar cycloadditions of nitrile oxides with alkenes are
usually concerted processes and their regioselectivities are
determined by the ground state of the reaction partners. As
indicated in the theoretical calculations shown in Scheme
10, although there is a slight difference in the charge distri-
bution between C5 and C6 in 10, the difference is in fact very
small and this account for the low levels of the regio-
selectivity in the 1,3-dipolar cycloadditions. Unlike 1,3-dipolar
cycloadditions of nitrile oxides, metal-catalyzed cycloaddition
reactions are normally stepwise processes and the regio-
selectivity is not only governed by the ground state of the
reaction partners but also controlled by the relative stability
of the metallacycles involved in the stepwise process.20
Table 2. Cycloadditions of 2-substituted-5-norbornene 10f with different
nitrile oxides
Entry Nitrile oxide
R
Temperature 68C) Yield 6%)a 27:28b
1
2
3
2a
2b
2c
Ph
COPh
CH3
25
25
60
95
30
54
62:38
50:50
62:38
a
Isolated yields of prue products after column chromatography.
Measured by integration on 400 MHz 1H NMR spectra of the crude
reaction mixtures.
b

P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
5935
Scheme 10. Explanation of the regiochemistry and regioselectivity of the cycloadditions.
The stereochemistry of the cycloadducts 25 and 26 were
4. Experimental
4.1. General information
1
proven by the coupling pattern of Ha and Hb in the H
NMR spectra, similar to 14a, 18a and 18b as described
earlier. The regiochemistry of the cycloadducts were deter-
mined by 1H NMR and GOESY experiments 6Fig. 4). From
1H NMR, Hd in all the minor cycloadducts is more down-
®eld than Hd and Hc in the major cycloadducts as it is next to
two adjacent C±O bonds instead of one. Also, Hc in the
major cycloadducts 6next to an adjacent C±O bond) is
always more down®eld than Hc in the minor cycloadducts
6next to an adjacent C±CvN group). From GOESY experi-
ments, in the major cycloadducts Ha 6the proton attached to
the carbon next to the oxygen in the isoxazoline ring)
showed positive NOE effect with Hb and Hc but not with
Hd while in the minor cycloadducts, Ha showed positive
NOE effect with Hb and Hd but not with Hc.
All reactions were carried out in an atmosphere of dry nitro-
gen at ambient temperature unless otherwise stated.
Standard column chromatography was performed on 230±
400 mesh silica gel 6obtained from Silicycle) by use of ¯ash
column chromatography techniques.25 Analytical thin-layer
chromatography 6TLC) was conducted on Merck precoated
silica gel 60 F254 plates. All glassware was ¯ame dried under
an inert atmosphere of dry nitrogen. Infrared spectra were
1
taken on a Bomem MB-100 FTIR spectrophotometer. H
and 13C NMR spectra were recorded on a Bruker-400 spec-
trometer. Chemical shifts for H NMR spectra are reported
1
in parts per million 6ppm) from tetramethylsilane with the
solvent resonance as the internal standard 6chloroform: d
7.26). Chemical shifts for 13C NMR spectra are reported in
parts per million 6ppm) from tetramethylsilane with the
solvent as the internal standard 6deuterochloroform: d
77.0). High resolution mass spectra were done by McMaster
Regional Centre for Mass Spectrometry at McMaster
University, Hamilton, Ontario. Elemental analyses were
performed by Canadian Microanalytical Service Ltd.,
British Columbia or by Quantitative Technologies Inc.,
New Jersey.
Figure 4. Assignment of regiochemistry of cycloadducts 25/26.
4.2. Materials
3. Conclusions
Unless stated otherwise, commercial reagents were used
without puri®cation. Solvents were puri®ed by distillation
under dry nitrogen: from CaH2 6CH2Cl2, 1,2-dichloroethane,
We have studied the 1,3-dipolar cyloadditions of nitrile
oxides with various unsymmetrical bicyclic norbornenes.
Cycloadditions of all the substituted norbornenes were
found to be highly stereoselective, giving only exo cyclo-
adducts in moderate to excellent yields. Cycloadditions of
2-substituted-2-norbornenes 8b±8d with benzonitrile oxide
62a) were completely regioselective, and regardless of the
electronic nature of the substitutent at C2 on 2-norbornenes
8, only the regioisomers with the oxygen of the nitrile oxide
attached to C2 of the norbornenes 8 were produced. For
1-substituted-2-norbornene 9b, the cycloaddition was also
regioselective, giving two regioisomers in a ratio of 80:20.
2-Substituted-5-norbornenes 10 and 11 showed very little
remote substituent effect on the regioselectivity of the nitrile
oxide cycloaddition, and low levels of regioselectivity
650:50 to 62:38) were observed.
Ê
chloroform, DMF, Et3N, pyridine); from 4 A molecular
sieves 6DMSO); from sodium 6toluene); from potassium/
benzophenone 6THF); and from sodium/benzophenone
6Et2O). Nitromethylbenzene 618),12 2-substituted-2-norbor-
nane 8d,11b 1-substituted-2-norbornene 9a,17 and exo-2-
substituted-5-nornornenes 10a±10g20,21 and endo-2-substi-
tuted-5-nornornenes 11a±11f20,21 were prepared according
to literature procedures.
4.2.1. 2-Hexylbicyclo[2.2.1]hept-2-ene #8b). A solution of
norbornene 62.57 g, 27.3 mmol) in THF 66 mL) was added
via a cannula to a ¯ame-dried ¯ask containing KOtBu
61.01 g, 9.00 mmol) in THF 65 mL) at 2788C. The tempera-
n
ture was kept below 2608C during this addition. BuLi

5936
P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
65.60 mL, 8.96 mmol, 1.6 M in hexanes) was added to the
reaction mixture over 15 min, with the temperature kept
below 2708C. The reaction mixture was warmed to
2408C and stirred for 1 h, then cooled to 2788C. Hexyl
bromide 61.50 mL, 10.7 mmol) was added to the reaction
mixture, and the reaction mixture was warmed to room
temperature and stirred for 17 h. After quenching with
water 620 mL), the layers were separated and the aqueous
layer was extracted with Et2O 62£30 mL). The combined
organic layers were washed with brine 630 mL), dried
6MgSO4), and the solvent was removed by rotary evapo-
ration. The crude product was puri®ed by column chroma-
tography 6hexanes) to give 8b 61.1983 g, 6.72 mmol, 75%)
as a clear, transparent liquid. Rf 0.93 6hexanes); IR
6neat, NaCl) 3048 6w), 2958 6s), 2926 6s), 2869 6s),
2858 6s), 1621 6w), 1467 6m), 1378 6w), 1274 6w),
6CH2Cl2) 3063 6m), 2998 6s), 2954 6s), 2880 6w), 2847 6w),
1724 6s), 1437 6m), 1368 6s), 1202 6s), 1121 6s), 1074 6s)
1
cm21; H NMR 6CDCl3, 400 MHz) d 6.47 6d, 1H, Jˆ
5.6 Hz), 6.23 6dd, 1H, Jˆ5.6, 3.0 Hz), 3.75 6s, 3H), 3.70
6d, 1H, Jˆ10.4 Hz), 3.60 6s, 6H), 3.52 6dd, 1H, Jˆ10.4,
3.5 Hz), 3.25 6m, 1H), 1.75 6dABd 1H, Jˆ8.5, 1.7 Hz),
1.68 6br. d, 1H, Jˆ8.5 Hz); 13C NMR 6APT, CDCl3,
100 MHz) d 172.6, 171.9, 171.5, 134.74, 134.71, 61.2,
53.1, 52.2, 51.7, 51.0, 49.3, 47.1. HRMS calcd for
C13H16O6: m/z 268.0947, found m/z 268.0950.
4.2.4. Cycloaddition of norbornene 8a with benzonitrile
oxide #2a). A solution of 18 649.2 mg, 0.359 mmol) in tolu-
ene 61 mL) was added to a ¯ame-dried ¯ask containing
norbornene 8a 6187 mg, 1.99 mmol), 6BOC)2O 6124 mg,
0.569 mmol), DMAP 65.2 mg, 0.043 mmol), and toluene
62 mL) via a cannula. The reaction mixture was stirred at
room temperature for 24 h. The solvent was removed by
rotary evaporation, and the crude product was puri®ed by
column chromatography 6EtOAc/hexanesˆ1:19) to give
14a 655.2 mg, 0.259 mmol, 72%) as a light yellow solid.
Rf 0.24 6EtOAc/hexanesˆ1:19); IR 6CH2Cl2) 3066 6w),
3044 6w), 2969 6s), 2878 6m), 1594 6w), 1500 6w), 1446
1120 6w) cm21 1H NMR 6CDCl3, 400 MHz) d 5.50
;
6d, 1H, Jˆ0.5 Hz), 2.76 6m, 1H), 2.65 6br. s, 1H), 2.06
6m, 2H), 1.60 6m, 2H), 1.43±1.27 6m, 10H), 1.00 6m, 2H),
0.89 6t, 3H, Jˆ6.6 Hz); 13C NMR 6APT, CDCl3, 100 MHz)
d 150.1, 126.8, 48.3, 45.0, 42.0, 31.7, 29.8, 29.1, 27.5, 26.6,
24.5, 22.6, 14.0. HRMS calcd for C13H22: m/z 178.1722,
found m/z 178.1718.
1
6m), 1354 6s) cm21; H NMR 6CDCl3, 400 MHz) d 7.71
4.2.2. 2-#Trimethylsilyl)bicyclo[2.2.1]hept-2-ene #8c). A
solution of norbornene 62.50 g, 26.6 mmol) in THF
66 mL) was added via a cannula to a ¯ame-dried ¯ask
containing KOtBu 61.51 g, 13.5 mmol) in THF 620 mL) at
2788C. The temperature was kept below 2608C during this
6m, 2H), 7.39 6m, 3H), 4.64 6d, 1H, Jˆ8.4 Hz), 3.50 6d,
1H, Jˆ8.4 Hz), 2.63 6m, 1H) 2.53 6m, 1H), 1.51±1.61 6m,
3H), 1.36 6m, 1H), 1.20 6m, 2H); 13C NMR 6APT, CDCl3,
100 MHz) d 156.8, 129.6, 129.3, 128.6, 126.8, 87.8, 57.0,
43.0, 39.2, 32.3, 27.4, 22.7. Anal. Calcd for C14H15NO: C,
78.84; H, 7.09. Found C, 78.80; H, 7.23.
n
addition. BuLi 68.40 mL, 13.4 mmol, 1.6 M in hexanes)
was added to the reaction mixture over 15 min, with the
temperature kept below 2708C. The reaction mixture was
warmed to 2408C and stirred for 1 h, then cooled to 2788C.
TMSCl 61.10 mL, 8.70 mmol) was added to the reaction
mixture, and the reaction mixture was warmed to room
temperature and stirred for 18 h. After quenching with
water 620 mL), the layers were separated and the aqueous
layer was extracted with Et2O 63£30 mL). The combined
organic layers were washed with brine 630 mL) and dried
6MgSO4). The solvent was removed by rotary evaporation
and the crude product was puri®ed by column chroma-
tography 6hexanes) to give 8c 61.27 g, 7.63 mmol, 88%)
as a clear, transparent liquid. Rf 0.98 6hexanes); IR 6neat,
NaCl) 3033 6m), 2959 6s), 2918 6s), 2900 6m), 2870 6s), 1557
6s), 1448 6m), 1403 6w), 1299 6m), 1248 6s), 1215 6w), 1170
6w), 1122 6m), 1040 6s), 1019 6m) cm21; 1H NMR 6CDCl3,
400 MHz) d 6.29 6d, 1H, Jˆ2.8 Hz), 2.96 6s, 1H), 2.86 6s,
1H), 1.59 6m, 2H), 1.27 6m, 1H), 1.11 6dm, 1H, Jˆ1.8 Hz),
0.95 6td, 1H, Jˆ9.4, 2.1 Hz), 0.83 6td, 1H, Jˆ9.4, 2.2 Hz),
0.07 6s, 9H); 13C NMR 6APT, CDCl3, 100 MHz) d 148.8,
145.0, 48.8, 44.5, 43.2, 24.7, 24.6, 21.6.
4.2.5. Cycloaddition of 2-substituted-2-norbornene 8b
with benzonitrile oxide #2a). A solution of 18 617.9 mg,
0.131 mmol) in CHCl3 60.2 mL) was added to a ¯ame-dried
vial containing norbornene 8b 620.3 mg, 0.114 mmol),
6BOC)2O 683.8 mg, 0.384 mmol), DMAP 65.5 mg,
0.045 mmol), and CHCl3 61.6 mL) via a cannula and rinsed
with CHCl3 60.2 mL). The reaction mixture was stirred at
608C for 6 days. The solvent was removed by rotary
evaporation, and the crude product was puri®ed by column
chromatography 6Et2O/hexanesˆ1:49) to give 14b
616.9 mg, 0.0568 mmol, 50%) as a clear, transparent liquid.
Rf 0.16 6EtOAc/hexanesˆ1:49); IR 6neat) 3060 6w), 2961
6s), 2930 6s), 2872 6s), 2858 6s), 1705 6w), 1592 6m), 1563
6m), 1464 6s), 1445 6s), 13257 9s), 1326 6m), 1310 6m), 1266
6m), 1235 6w), 1073 6w), 1025 6w) cm21; 1H NMR 6CDCl3,
400 MHz) d 7.69 6m, 2H), 7.37 6m, 3H), 2.90 6d, 1H, Jˆ
1.6 Hz), 2.55 6d, 1H, Jˆ4.0 Hz), 2.49 6d, 1H, Jˆ4.3 Hz),
1.24±1.74 6m, 15H), 1.19 6dd, 1H, Jˆ10.4, 1.5 Hz), 0.87 6t,
3H, Jˆ6.9 Hz); 13C NMR 6APT, CDCl3, 100 MHz) d 157.0,
129.8, 129.4, 128.6, 126.6, 96.7, 61.1, 45.6, 40.8, 35.0, 34.5,
31.7, 29.7, 27.4, 24.1, 23.1, 22.6, 14.1. Anal. Calcd for
C20H27NO: C, 80.76; H, 9.15. Found C, 80.88; H, 9.01.
4.2.3. 1,5,6-Tris#methoxycarbonyl)bicyclo[2.2.1]hept-2-
ene #9b). NaOMe 624.3 mg, 0.450 mmol) was added to a
solution of norbornene 9a 6114 mg, 0.513 mmol) in MeOH
61 mL) cooled to 08C, and the reaction mixture was stirred
for 15 min. Methyl iodide 60.150 mL, 2.41 mmol) was
added to the reaction mixture at 08C, and the reaction
mixture was warmed to room temperature and stirred for
24 h. The solvent was removed by rotary evaporation and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ2:3) to give 9b 681.4 mg, 0.303 mmol,
67%) as a white solid. Rf 0.20 6EtOAc/hexanesˆ2:3); IR
4.2.6. Cycloaddition of 2-substituted-2-norbornene 8c
with benzonitrile oxide #2a). A solution of 18 618.9 mg,
0.138 mmol) in CHCl3 60.2 mL) was added to a ¯ame-dried
vial containing norbornene 8c 68.9 mg, 0.0535 mmol),
6BOC)2O 641.6 mg, 0.191 mmol), DMAP 64.9 mg,
0.040 mmol), and CHCl3 61.6 mL) via a cannula and rinsed
with CHCl3 60.2 mL). The reaction mixture was stirred at
room temperature for 48 h. The solvent was removed by
rotary evaporation, and the crude product was puri®ed by

P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
5937
column chromatography 6Et2O/hexanesˆ1:49) to give 14c
68.4 mg, 0.0294 mmol, 55%) as white crystals. Rf 0.15
6Et2O/hexanesˆ1:49); IR 6CH2Cl2) 1965 6s), 2878 6w),
51.9, 51.8, 47.9, 46.4, 42.3, 35.7; visible peaks of minor
isomer 18b: 128.7, 126.5, 85.0, 52.29, 52.2, 51.1, 46.0,
45.4, 44.8, 37.8. HRMS calcd for C20H21NO7: m/z
387.1318, found m/z 387.1290.
1594 6w), 1445 6w), 1351 6m), 1260 6s), 1005 6w) cm21
;
1H NMR 6CDCl3, 400 MHz) d 7.72 6m, 2H), 7.38 6m, 3H),
3.29 6s, 1H), 2.68 6d, 1H, Jˆ4.4 Hz), 2.52 6d, 1H, Jˆ
4.3 Hz), 1.62 6m, 2H), 1.48 6tt, 1H, Jˆ12.8, 4.7 Hz), 1.37
6m, 1H), 1.26 6m, 1H), 1.19 6ddd, 1H, Jˆ10.4, 2.7, 1.3 Hz),
0.13 6s, 9H); 13C NMR 6APT, CDCl3, 100 MHz) d 156.6,
129.8, 129.4, 128.0, 126.8, 91.3, 59.3, 46.3, 40.8, 34.4, 26.9,
22.6, 22.8. Anal. Calcd for C17H23SiNO: C, 71.53; H, 8.12.
Found C, 71.94; H, 7.84.
4.2.9. Cycloaddition of exo-2-substituted-5-norbornene
10a with benzonitrile oxide #2a). A solution of 18
650.6 mg, 0.369 mmol) in CHCl3 61 mL) was added to a
¯ame-dried vial containing norbornene 10a 639.3 mg,
0.258 mmol) and DMAP 65.3 mg, 0.043 mmol) via a
cannula and rinsed with CHCl3 61 mL). 6BOC)2O
685.2 mg, 0.390 mmol) was then added to the reaction
mixture. The reaction mixture was stirred at room tempera-
ture for 72 h. The solvent was removed by rotary evapora-
tion, and the crude product was puri®ed by column
chromatography 6EtOAc/hexanesˆ1:4) to give an insepar-
able mixture of 25a and 26a 655.3 mg, 0.204 mmol, 79%,
25a:26aˆ54:46 measured by 400 MHz 1H NMR) as a light
yellow solid. Rf 0.22 6EtOAc/hexanesˆ1:19); IR 6neat)
3000 6m), 2966 6s), 2952 6s), 2887 6w), 1733 6s), 1593
6w), 1565 6w), 1497 6w), 1355 6s), 1290 6w), 1213 6s),
4.2.7. Cycloaddition of 2-substituted-2-norbornene 8d
with benzonitrile oxide #2a). A solution of 18 637.1 mg,
0.271 mmol) in CHCl3 61.2 mL) was added to a ¯ame-dried
vial containing norbornene 8d 619.3 mg, 0.116 mmol),
6BOC)2O 6124.5 mg, 0.570 mmol), DMAP 610.8 mg,
0.088 mmol), and CHCl3 61.6 mL) via a cannula and rinsed
with CHCl3 60.2 mL). The reaction mixture was stirred at
608C for 10 days. The solvent was removed by rotary
evaporation, and the crude product was puri®ed by column
chromatography 6EtOAc/hexanesˆ1:19) to give 14d
618.1 mg, 0.0634 mmol, 55%) as white crystals. Rf 0.22
6EtOAc/hexanesˆ1:19); IR 6CH2Cl2) 3065 6w), 2976 6s),
2883 6m), 1733 6s), 1446 6m), 1358 6m), 1324 6w), 1290
6s), 1210 6s), 1180 6m), 1156 6m), 1050 6m) cm21; 1H NMR
6CDCl3, 400 MHz) d 7.72 6m, 2H), 7.40 6m, 3H), 4.26 6m,
2H), 3.90 6d, 1H, Jˆ1.7 Hz), 2.83 6d, 1H, Jˆ3.6 Hz), 2.60
6d, 1H, Jˆ4.0 Hz), 1.47±1.75 6m, 4H), 1.33 6t, 3H,
Jˆ7.1 Hz), 1.32 6m, 1H), 1.29 6m, 1H); 13C NMR 6APT,
CDCl3, 100 MHz) d 169.6, 157.5, 130.0, 128.7, 127.0, 96.5,
61.7, 58.7, 45.5, 40.7, 34.6, 26.7, 22.2, 14.1. Anal. Calcd for
C17H19NO3: C, 71.56; H, 6.71. Found C, 71.24; H, 6.85.
1
1159 6m), 1058 6m), 1040 6m), 1025 6m) cm21; H NMR
6CDCl3, 400 MHz) d 7.71 6m, 2H), 7.40 6m, 3H), 4.72 6d,
0.46H, Jˆ8.9 Hz), 4.69 6d, 0.54H, Jˆ8.6 Hz), 3.71 6s,
1.38H), 3.69 6s, 1.62H), 3.60 6d, 0.54H, Jˆ8.2 Hz), 3.56
6d, 0.46H, Jˆ8.2 Hz), 2.90 6s, 0.46H), 2.80 6s, 0.54H),
2.71 6d, 0.54H, Jˆ4.7 Hz), 2.61 6d, 0.46H, Jˆ3.6 Hz),
2.51 6ddd, 0.54H, Jˆ8.8, 4.8, 1.4 Hz), 2.34 6dd, 0.46H,
Jˆ8.8, 5.7 Hz), 2.00 6m, 1H), 1.67 6ddd, 0.54H, Jˆ11.4,
8.9, 2.4 Hz), 1.54±1.43 6m, 2.46 Hz); 13C NMR 6APT,
CDCl3, 100 MHz) d major isomer 25a: 175.0, 156.0,
129.86, 128.9, 128.74, 126.8, 87.3, 57.0, 51.99, 43.0, 42.8,
39.1, 30.49, 27.4; minor isomer 26a: 174.9, 156.6, 129.87,
128.9, 128.71, 126.8, 87.1, 56.9, 52.05, 47.1, 44.5, 40.3,
32.0, 30.53. Anal. Calcd for C16H17NO3: C, 70.83; H,
6.32. Found C, 70.54; H, 6.46.
4.2.8. Cycloaddition of 1-substituted-2-norbornene 9b
with benzonitrile oxide #2a). A solution of 18 651.6 mg,
0.376 mmol) in CHCl3 61.2 mL) was added to a ¯ame-dried
vial containing norbornene 9b 632.7 mg, 0.122 mmol),
6BOC)2O 6182.8 mg, 0.838 mmol), DMAP 610.0 mg,
0.082 mmol), and CHCl3 61.6 mL) via a cannula and rinsed
with CHCl3 60.2 mL). The reaction mixture was stirred at
608C for 7 days. The solvent was removed by rotary
evaporation, and the crude product was puri®ed by column
chromatography 6EtOAc/hexanesˆ2:3) to give an insepar-
able mixture of 18a and 18b 641.3 mg, 0.107 mmol, 87%,
18a:18bˆ80:20 measured by 400 MHz 1H NMR) as a light
yellow solid. Rf 0.43 6EtOAc/hexanesˆ2:3); IR 6CH2Cl2)
3065 6m), 2998 6m), 2954 6m), 2848 6m), 1740 6s), 1499
6m), 1437 6s), 1366 6s), 1213 6s), 1175 6m), 1125 6m), 1069
4.2.10. Cycloaddition of exo-2-substituted-5-norbornene
10b with benzonitrile oxide #2a). A solution of 18
650.6 mg, 0.369 mmol) in CHCl3 61 mL) was added to a
¯ame-dried vial containing norbornene 10b 630.3 mg,
0.275 mmol) via a cannula and rinsed with CHCl3
62£0.5 mL). Et3N 60.020 mL, 0.143 mmol) and phenyl-
isocyanate 60.090 mL, 0.828 mmol) were added. The reac-
tion mixture was stirred at room temperature for 24 h. The
solvent was removed by rotary evaporation, and the crude
product was puri®ed by column chromatography 6EtOAc/
hexanesˆ2:3) to give an inseparable mixture of 25b and
26b 652.0 mg, 0.227 mmol, 82%, 25b:26bˆ50:50 measured
1
by 400 MHz H NMR) as white crystals. Rf 0.14 6EtOAc/
1
6m) cm21; H NMR 6CDCl3, 400 MHz) d 7.90 6m, 1.6H),
hexanesˆ2:3); IR 6CH2Cl2) 3412 6br. s), 3060 6m), 2971 6s),
7.69 6m, 0.4H), 7.40 6m, 3H), 5.23 6dd, 0.2H, Jˆ8.3,
1.4 Hz), 5.10 6dd, 0.8H, Jˆ8.1, 1.3 Hz), 4.96 6d, 0.2H,
Jˆ8.2 Hz), 4.62 6dd, 0.8H, Jˆ8.1, 1.3 Hz), 3.80 6s, 2.4H),
3.76 6s, 0.6H), 3.72 6s, 2.4H), 3.71 6s, 2.4H), 3.70 6s, 0.6H),
3.49 6d, 0.8H, Jˆ11.9 Hz), 3.41 6dd, 0.2H, Jˆ12.2, 4.8 Hz),
3.18 6d, 0.2H, Jˆ12.3 Hz), 3.14 6dd, 0.8H, Jˆ11.9, 3.6 Hz),
3.06 6dd, 0.2H, Jˆ2.9, 1.0 Hz), 2.88 6s, 0.6H), 2.81 6m,
0.8H), 2.21 6dd, 0.2H, Jˆ11.1, 1.5 Hz), 2.02 6dd, 0.8H,
Jˆ11.2, 1.6 Hz), 1.71 6dd, 0.8H, Jˆ11.2, 1.4 Hz), 1.61
6dd, 0.2H, Jˆ11.1, 1.4 Hz),; 13C NMR 6APT, CDCl3,
100 MHz) d major isomer 18a: 171.3, 170.7, 170.6,
157.5, 130.1, 128.8, 128.4, 127.1, 84.2, 61.4, 52.4, 52.34,
2939 6s), 1648 6m), 1593 6m), 1498 6w), 1445 6s), 1356 6s),
1
1316 6m), 1265 6m), 1071 6s), 1027 6m) cm21; H NMR
6CDCl3, 400 MHz) d 7.70 6m, 2H), 7.38 6m, 3H), 4.63 6d,
0.5H, Jˆ8.4 Hz), 4.60 6d, 0.5H, Jˆ8.3 Hz), 3.99 6d, 0.5H,
Jˆ6.3 Hz), 3.89 6d, 0.5H, Jˆ6.1 Hz), 3.47 6d, 0.5H, Jˆ
8.3 Hz), 3.43 6d, 0.5H, Jˆ8.2 Hz), 2.65 6d, 0.5H, Jˆ
4.6 Hz), 2.63 6s, 0.5H), 2.58 6d, 0.5H, Jˆ3.8 Hz), 2.47 6s,
0.5H), 1.91 6ddd, 0.5H, Jˆ13.3, 6.9, 2.4 Hz), 1.80±1.61 6m,
2.5H), 1.53±1.48 6m, 1H), 1.44 6ddd, 0.5H, Jˆ13.4, 4.3,
2.8 Hz), 1.37 6ddd, 0.5H, Jˆ13.9, 5.0, 1.5 Hz); 13C NMR
6APT, CDCl3, 100 MHz) d 156.6, 155.9, 129.8, 128.8,
128.7, 126.7, 87.3, 84.6, 72.6, 69.3, 56.8, 53.2, 51.8, 47.1,

5938
P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
42.0, 40.3, 38.6, 35.7, 28.8, 28.5. HRMS calcd for
C14H15NO2: m/z 229.1103, found m/z 229.1100.
10e with benzonitrile oxide #2a). A solution of 18
629.7 mg, 0.217 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 10e 633.5 mg,
0.167 mmol), 6BOC)2O 654.2 mg, 0.248 mmol), DMAP
64.9 mg, 0.040 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ1:4) to give an inseparable mixture of 25e
and 26e 650.8 mg, 0.159 mmol, 95%, 25e:26eˆ53:47
4.2.11. Cycloaddition of exo-2-substituted-5-norbornene
10c with benzonitrile oxide #2a). A solution of 18
625.1 mg, 0.183 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 10c 631.6 mg,
0.141 mmol), 6BOC)2O 647.5 mg, 0.218 mmol), DMAP
65.1 mg, 0.042 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ1:9) to give an inseparable mixture of 25c
and 26c 640.0 mg, 0.116 mmol, 82%, 25c:26cˆ50:50
1
measured by 400 MHz H NMR) as a clear, transparent
liquid. Rf 0.22 6EtOAc/hexanesˆ1:9); IR 6neat) 3062 6w),
3030 6s), 2938 6s), 2881 6m), 1592 6w), 1564 6w), 1497 6m),
1446 6s), 1356 6s), 1318 6w), 1266 6w), 1208 6w), 1173 6w),
1
1
measured by 400 MHz H NMR) as a white solid. Rf 0.31
1093 6s), 1028 6m) cm21; H NMR 6CDCl3, 400 MHz) d
6EtOAc/hexanesˆ1:19); IR 6CH2Cl2) 2956 6s), 1931 6s),
6w), 1274 6s), 1173 6w), 1094 6s) cm21; H NMR 6CDCl3,
7.69 6m, 2H), 7.41 6m, 3H), 7.35 6m, 5H), 4.61 6d, 0.53H,
Jˆ8.2 Hz), 4.60 6d, 0.47H, Jˆ8.2 Hz), 4.52 6AB, 2H), 3.66
6d, 0.53H, Jˆ6.5 Hz), 3.57 6dd, 0.47H, Jˆ6.8, 1.5 Hz), 3.48
6d, 0.47H, Jˆ8.2 Hz), 3.37 6d, 0.53H, Jˆ8.2 Hz), 2.88 6s,
0.47H), 2.66 6d, 0.53H, Jˆ4.4 Hz), 2.65 6s, 0.53H), 2.59 6d,
0.47H, Jˆ4.0 Hz), 1.86 6ddd, 0.53H, Jˆ13.2, 6.9, 2.4 Hz),
1.50±1.69 6m, 3.47H); 13C NMR 6APT, CDCl3, 100 MHz) d
156.6, 155.8, 138.2, 129.8, 129.0, 128.9, 128.71, 128.68,
128.4, 127.63, 127.61, 127.58, 126.8, 126.7, 87.7, 84.9,
79.7, 76.3, 70.73, 70.70, 57.1, 53.3, 48.0, 43.6, 41.9, 38.4,
38.1, 33.3, 29.3, 29.0. HRMS calcd for C21H21NO2: m/z
319.1572, found m/z 319.1570.
2887 6m), 2852 6m), 1472 6m), 1446 6m), 1357 6m), 1330
1
400 MHz) d 7.69 6m, 2H), 7.40 6m, 3H), 4.59 6d, 0.5H,
Jˆ8.2 Hz), 4.57 6d, 0.5H, Jˆ8.2 Hz), 3.87 6d, 0.5H, Jˆ
6.3 Hz), 3.77 6d, 0.5H, Jˆ6.2 Hz), 3.43 6d, 0.5H, Jˆ
8.2 Hz), 3.37 6d, 0.5H, Jˆ8.2 Hz), 2.61 6d, 0.5H, Jˆ
4.8 Hz), 2.54 6s, 0.5H), 2.53 6d, 0.5H, Jˆ4.7 Hz), 2.36 6s,
0.5H), 1.83 6ddd, 0.5H, Jˆ13.0, 6.7, 2.3 Hz), 1.31±1.69 6m,
3.5H), 0.88 6s, 4.5H), 0.87 6s, 4.5H), 0.08 6s, 3H), 0.07 6s,
1.5H), 0.06 6s, 1.5H); 13C NMR 6APT, CDCl3, 100 MHz) d
156.6, 155.9, 129.8, 129.2, 129.1, 128.73, 128.69, 126.8,
126.7, 87.7, 84.8, 73.0, 69.7, 57.0, 53.1, 52.0, 47.4, 42.0,
41.5, 38.5, 36.5, 29.0, 28.6, 25.80, 25.76, 18.02, 17.98,
24.66, 24.73, 24.8. Anal. Calcd for C20H29SiNO2: C,
69.92; H, 8.51. Found C, 69.54; H, 8.40.
4.2.14. Cycloaddition of exo-2-substituted-5-norbornene
10f with benzonitrile oxide #2a). A solution of 18
637.0 mg, 0.270 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 10f 628.6 mg,
0.188 mmol), 6BOC)2O 667.0 mg, 0.307 mmol), DMAP
65.5 mg, 0.045 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ1:4) to give an inseparable mixture of 25f
and 26f 648.3 mg, 0.178 mmol, 95%, 25f:26fˆ62:38
4.2.12. Cycloaddition of exo-2-substituted-5-norbornene
10d with benzonitrile oxide #2a). A solution of 18
629.8 mg, 0.217 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 10d 631.1 mg,
0.157 mmol), 6BOC)2O 653.9 mg, 0.247 mmol), DMAP
65.2 mg, 0.043 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ2:3) to give an inseparable mixture of
25d and 26d 646.8 mg, 0.147 mmol, 94%, 25d:26dˆ50:50
1
measured by 400 MHz H NMR) as a clear, transparent
liquid. Rf 0.35 6EtOAc/hexanesˆ1:4); IR 6neat) 3060 6w),
2978 6s), 2944 6s), 2888 6m), 1750 6s), 1593 6w), 1565 6w),
1498 6w), 1446 6m), 1376 6m), 1359 6s), 1320 6w), 1247 6s),
1
measured by 400 MHz H NMR) as a clear, transparent
1207 6m), 1062 6s), 1017 6s) cm21 1H NMR 6CDCl3,
;
liquid. Rf 0.41 6EtOAc/hexanesˆ2:3); IR 6neat) 3060 6w),
2972 6s), 2920 6s), 2886 6s), 2818 6m), 1592 6m), 1565 6m),
1497 6m), 1446 6s), 1357 6s), 1241 6w), 1190 6w), 1047 6s)
cm21; 1H NMR 6CDCl3, 400 MHz) d 7.68 6m, 2H), 7.38 6m,
3H), 7.47 62ABq, 2H), 4.62 6d, 0.5H, Jˆ8.3 Hz), 4.59 6d,
0.5H, Jˆ8.3 Hz), 3.85 6d, 0.5H, Jˆ6.8 Hz), 3.76 6dd, 0.5H,
Jˆ7.0, 2.1 Hz), 3.65±3.74 6m, 2H), 3.52±3.59 6m, 2H), 3.46
6d, 0.5H, Jˆ8.3 Hz), 3.41 6d, 0.5H, Jˆ8.3 Hz), 3.40 6s,
1.5H), 3.36 6s, 1.5H), 2.77 6s, 0.5H), 2.62 6d, 0.5H, Jˆ
5.1 Hz), 2.61 6s, 0.5H), 2.56 6d, 0.5H, Jˆ3.9 Hz), 1.86
6ddd, 0.5H, Jˆ13.3, 7.0, 2.2 Hz), 1.67 6ddd, 0.5H, Jˆ
13.9, 6.9, 2.1 Hz), 1.43±1.58 6m, 3H); 13C NMR 6APT,
CDCl3, 100 MHz) d 156.5, 155.8, 129.8, 129.0, 128.9,
128.70, 128.66, 126.74, 126.72, 94.2, 94.0, 87.6, 84.8,
77.4, 73.9, 71.7, 67.0, 66.9, 59.0, 58.95, 57.0, 53.2, 48.9,
44.2, 41.8, 38.4, 38.1, 33.4, 29.4, 28.9. HRMS calcd for
C18H23NO4: m/z 317.1627, found m/z 317.1630.
400 MHz) d 7.66 6m, 2H), 7.35 6m, 3H), 4.74 6dm, 0.62H,
Jˆ5.3 Hz), 4.62±4.67 6m, 0.76H), 4.58 6d, 0.62H, Jˆ
8.2 Hz), 3.50 6d, 1H, Jˆ8.2 Hz), 2.71 6s, 0.38H), 2.63 6d,
0.62H, Jˆ4.8 Hz), 2.57 6s, 0.62H), 2.56 6d, 0.38H, Jˆ
4.2 Hz), 2.00 6s, 1.14H), 1.98 6s, 1.86H), 1.73 6ddd,
0.62H, Jˆ14.2, 6.9, 1.2 Hz), 1.44±1.55 6m, 3.38H); 13C
NMR 6APT, CDCl3, 100 MHz) major isomer 25f: d
170.4, 155.4, 129.7, 128.6, 128.2, 126.55, 87.0, 74.6, 52.8,
44.2, 41.9, 32.8, 29.1, 21.0; minor isomer 26f: d 170.3,
156.3, 129.7, 128.5, 127.1, 126.58, 84.1, 71.7, 56.6, 48.7,
38.4, 37.9, 29.5, 21.0. Anal. Calcd for C16H17NO3: C, 70.83;
H, 6.32. Found C, 70.67; H, 6.38.
4.2.15. Cycloaddition of 2-substituted-5-norbornene 10g
with benzonitrile oxide #2a). A solution of 18 648.1 mg,
0.351 mmol) in CHCl3 60.8 mL) was added to a ¯ame-dried
vial containing norbornene 10g 630.1 mg, 0.278 mmol),
6BOC)2O 689.7 mg, 0.411 mmol), DMAP 65.0 mg, 0.041
mmol), and CHCl3 60.7 mL) via a cannula. The reaction
4.2.13. Cycloaddition of exo-2-substituted-5-norbornene

P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
5939
mixture was stirred at room temperature for 1 days. The
solvent was removed by rotary evaporation, and the crude
product was puri®ed by column chromatography 6EtOAc/
hexanesˆ1:4) to give an inseparable mixture of 25g and 26g
656.0 mg, 0.246 mmol, 89%, 25g:26gˆ57:43 measured by
400 MHz 1H NMR) as a white solid. Rf 0.22 6EtOAc/
hexanesˆ1:4); IR 6CH2Cl2) 3063 6w), 2950 6w), 1752 6s),
1447 6m), 1409 6w), 1355 6m), 1263 6m), 1156 6w) cm21; 1H
NMR 6CDCl3, 400 MHz) d 7.70 6m, 2H), 7.41 6m, 3H), 4.90
6d, 1H, Jˆ8.2 Hz), 3.90 6d, 0.57H, Jˆ8.2 Hz), 3.86 6d,
0.43H, Jˆ8.2 Hz), 3.06 6s, 0.43H), 3.05 6d, 0.57H, Jˆ
2.5 Hz), 3.01 6d, 0.43H, Jˆ2.4 Hz), 2.81 6s, 0.57H), 2.09±
2.26 6m, 1H), 1.87±2.03 6m, 2H), 1.74 6m, 1H); 13C NMR
6APT, CDCl3, 100 MHz) major isomer 25g: d 213.5, 154.5,
130.2, 128.9, 128.0, 126.7, 86.5, 58.1, 52.2, 42.6, 39.9, 31.4;
minor isomer 26g: d 212.8, 156.6, 130.2, 128.9, 128.2,
126.8, 82.8, 56.8, 51.8, 44.4, 39.6, 32.0. Anal. Calcd for
C14H13NO2: C, 73.99; H, 5.77. Found C, 73.65; H, 5.86.
2971 6s), 2890 6w), 2868 6m), 1594 6w), 1471 6w), 1446
6m), 1357 6w), 1244 6w), 1152 6m), 1121 6w), 1072 6m)
1
cm21; H NMR 6CDCl3, 400 MHz) d 7.71 6m, 2H), 7.38
6m, 3H), 5.27 6d, 0.42H, Jˆ8.4 Hz), 4.74 6d, 0.58H, Jˆ
8.3 Hz), 4.33 6m, 1H), 4.30 6d, 0.58H, Jˆ8.3 Hz), 3.74 6d,
0.42H, Jˆ8.4 Hz), 2.77 6d, 0.42H, Jˆ4.5 Hz), 2.56 6d,
0.58H, Jˆ5.4 Hz), 2.54 6d, 0.58H, Jˆ4.2 Hz), 2.49 6dd,
0.42H, Jˆ4.5 Hz), 2.41 6br. s, 0.58H), 2.25 6br. s, 0.42H),
2.04 6m, 1H), 1.54 6m, 0.84H), 1.28 6m, 1.16H), 1.18 6dt,
0.42H, Jˆ13.2, 3.4 Hz), 0.88 6dt, 0.58H, Jˆ13.2, 3.4 Hz);
13C NMR 6APT, CDCl3, 100 MHz) major isomer 25i: d
157.5, 129.8, 129.07, 128.66, 126.9, 87.4, 70.5, 48.4, 45.4,
43.8, 33.5, 31.2; minor isomer 26i: d 157.0, 129.8, 129.06,
128.70, 126.8, 82.7, 69.7, 57.1, 49.2, 40.2, 37.7, 31.9. Anal.
Calcd for C14H15NO2: C, 73.34; H, 6.59. Found C, 73.65; H,
6.48.
4.2.18. Cycloaddition of endo-2-substituted-5-norbor-
nene 11c with benzonitrile oxide #2a). A solution of 18
625.5 mg, 0.186 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 11c 630.5 mg,
0.136 mmol), 6BOC)2O 645.1 mg, 0.207 mmol), DMAP
65.3 mg, 0.043 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ1:9) to give an inseparable mixture of 25j
and 26j 642.0 mg, 0.122 mmol, 90%, 25j:26jˆ50:50
4.2.16. Cycloaddition of endo-2-substituted-5-norbor-
nene 11a with benzonitrile oxide #2a). A solution of 18
649.4 mg, 0.360 mmol) in CHCl3 61 mL) was added to a
¯ame-dried vial containing norbornene 11a 642.8 mg,
0.281 mmol) and 6BOC)2O 687.5 mg, 0.401 mmol) via a
cannula and rinsed with CHCl3 62£0.5 mL). DMAP
65.4 mg, 0.044 mmol) was added to the reaction mixture.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ1:4) to give an inseparable mixture of
25h and 26h 634.8 mg, 0.128 mmol, 46%, 25h:26hˆ50:50
measured by 400 MHz 1H NMR) as a clear, transparent oil.
Rf 0.42 6EtOAc/hexanesˆ1:4); IR 6neat) 3056 6m), 2973 6s),
2953 6s), 2886 6m), 2843 6w), 1734 6s), 1593 6w), 1564 6w),
1499 6m), 1446 6m), 1436 6m), 1356 6s), 1309 6m), 1267
1
measured by 400 MHz H NMR) as a white solid. Rf 0.35
6EtOAc/hexanesˆ1:19); IR 6CH2Cl2) 2957 6s), 2885 6s),
2857 6s), 1593 6w), 1565 6m), 1472 6s), 1446 6m), 1359
6s), 1275 6s), 1154 6s), 1122 6s), 1093 6s), 1071 6s) cm21
;
1H NMR 6CDCl3, 400 MHz) d 7.70 6m, 2H), 7.38 6m, 3H),
5.24 6d, 0.5H, Jˆ8.4 Hz), 4.71 6d, 0.5H, Jˆ8.3 Hz), 4.27 6d,
0.5H, Jˆ8.3 Hz), 4.20 6m, 1H), 3.71 6d, 0.5H, Jˆ8.4 Hz),
2.69 6d, 0.5H, Jˆ4.5 Hz), 2.55 6d, 0.5H, Jˆ5.1 Hz), 2.46 6d,
0.5H, Jˆ4.4 Hz), 2.43 6d, 0.5H, Jˆ3.9 Hz), 1.93 6m, 1H),
1.50 6m, 1H), 1.23 6m, 1H), 1.12 6dt, 0.5H, Jˆ12.9, 3.2 Hz),
0.95 6s, 4.5H), 0.90 6s, 4.5H), 0.83 6dt, 0.5H, Jˆ13.3,
3.3 Hz), 0.12 6s, 1.5H), 0.081 6s, 1.5H), 0.079 6s, 1.5H),
0.06 6s, 1.5H); 13C NMR 6APT, CDCl3, 100 MHz) d
157.5, 156.9, 129.6, 129.4, 129.3, 128.6, 126.77, 126.76,
87.5, 83.1, 70.9, 70.0, 57.0, 49.5, 48.6, 45.9, 43.7, 40.1,
38.8, 34.2, 31.5, 30.7, 25.8, 18.02, 17.99, 24.7, 24.89,
24.94. HRMS calcd for C20H29SiNO2: m/z 343.1968,
found m/z 343.1965.
1
6m), 1197 6m), 1116 6m), 1041 6m), 1023 6w) cm21; H
NMR 6CDCl3, 400 MHz) d 7.70 6m, 2H), 7.39 6m, 3H),
4.67 6d, 0.5H, Jˆ8.3 Hz), 4.66 6d, 0.5H, Jˆ8.3 Hz), 3.81
6s, 1.5H), 3.72 6s, 1.5H), 3.70 6dd, 0.5H, Jˆ8.3, 1.4 Hz),
3.66 6dd, 0.5H, Jˆ8.4, 0.9 Hz), 2.95 6d, 0.5H, Jˆ4.8 Hz),
2.88±2.81 6m, 1.5H), 2.68 6d, 0.5H, Jˆ5.2 Hz), 2.567 6d,
0.5H, Jˆ3.7 Hz), 1.91±1.78 6m, 1.5H), 1.67±1.62 6m, 1H),
1.56 6ddd, 0.5H, Jˆ13.4, 4.8, 2.4 Hz), 1.35 6dd, 0.5H, Jˆ
2.9, 1.4 Hz), 1.33 6dd, 0.5H, Jˆ2.9, 1.4 Hz); 13C NMR
6APT, CDCl3, 100 MHz) d 174.3, 174.1, 156.9, 156.5,
129.9, 129.8, 129.0, 128.75, 128.73, 126.8, 126.7, 87.1,
84.3, 56.7, 52.3, 51.9, 46.2, 43.8, 43.6, 42.3, 41.3, 40.1,
34.0, 33.4, 30.3, 26.0. Anal. Calcd for C16H17NO3: C,
70.83; H, 6.32. Found C, 70.43; H, 6.37.
4.2.19. Cycloaddition of endo-2-substituted-5-norbor-
nene 11d with benzonitrile oxide #2a). A solution of 18
628.1 mg, 0.205 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 11d 632.6 mg,
0.164 mmol), 6BOC)2O 659.0 mg, 0.270 mmol), DMAP
65.2 mg, 0.043 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ2:3) to give an inseparable mixture of
25k and 26k 644.6 mg, 0.141 mmol, 86%, 25k:26kˆ55:45
4.2.17. Cycloaddition of endo-2-substituted-5-norbor-
nene 11b with benzonitrile oxide #2a). A solution of 18
655.6 mg, 0.405 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 11b 635.6 mg,
0.323 mmol), 6BOC)2O 6106.5 mg, 0.488 mmol), DMAP
65.1 mg, 0.042 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ3:2) to give an inseparable mixture of 25i
and 26i 653.6 mg, 0.234 mmol, 72%, 25i:26iˆ58:42
1
measured by 400 MHz H NMR) as a clear, transparent
liquid. Rf 0.40 6EtOAc/hexanesˆ2:3); IR 6neat) 3060 6w),
2969 6s), 2940 6s), 2887 6s), 2818 6m), 1592 6w), 1564 6w),
1498 6w), 1446 6s), 1355 6w), 1307 6w), 1244 6w), 1177 6s),
1085 6s), 1048 6s) cm21; 1H NMR 6CDCl3, 400 MHz) d 7.70
1
measured by 400 MHz H NMR) as a white solid. Rf 0.33
6EtOAc/hexanesˆ2:3); IR 6CH2Cl2) 3608 6s), 3061 6m),

5940
P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
6m, 2H), 7.37 6m, 3H), 5.13 6d, 0.45H, Jˆ8.4 Hz), 4.80 6AB,
1.1H), 4.73 6AB, 0.9H), 4.70 6d, 0.55H, Jˆ8.0 Hz), 4.10±
4.19 6m, 1.55H), 3.67±3.77 6m, 2.45H), 3.56±3.59 6m, 2H),
3.40 6s, 1.35H), 3.38 6s, 1.65H), 2.87 6d, 0.45H, Jˆ4.4 Hz),
2.64 6d, 0.55H, Jˆ3.8 Hz), 2.57 6d, 0.55H, Jˆ5.2 Hz), 2.49
6d, 0.45H, Jˆ4.5 Hz), 2.05 6ddd, 0.45H, Jˆ13.2, 10.2,
4.8 Hz), 1.99 6ddd, 0.55H, Jˆ13.6, 10.4, 5.4 Hz), 1.55 6d,
0.45H, Jˆ16 Hz), 1.52 6d, 0.55H, Jˆ1.6 Hz), 1.24 6m,
1.45H), 0.97 6dt, 0.55H, Jˆ13.6, 3.5 Hz); 13C NMR 6APT,
CDCl3, 100 MHz) d 157.1, 156.8, 129.7, 129.2, 129.1,
128.65, 128.62, 126.8, 126.7, 94.9, 94.8, 87.4, 82.8, 75.8,
74.3, 71.7, 67.4, 67.2, 59.0, 57.1, 49.1, 47.2, 43.30, 43.25,
39.6, 35.6, 31.4, 31.1, 30.8. HRMS calcd for C18H23NO4:
m/z 317.1627, found m/z 317.1620.
0.55H, Jˆ10.1, 4.0 Hz), 4.73 6d, 0.55H, Jˆ8.3 Hz), 4.04
6d, 0.55H, Jˆ8.3 Hz), 3.72 6d, 0.45H, Jˆ8.4 Hz), 2.93 6d,
0.45H, Jˆ4.5 Hz), 2.79 6d, 0.55H, Jˆ3.8 Hz), 2.62 6d,
0.55H, Jˆ5.2 Hz), 2.54 6d, 0.45H, Jˆ4.2 Hz), 2.17 6m,
1H), 2.14 6s, 1.65H), 2.06 6s, 1.35H), 1.57 6m, 1H), 1.33
6m, 1H), 1.23 6dt, 0.45H, Jˆ13.6, 3.4 Hz), 1.00 6dt, 0.55H,
Jˆ14.0, 3.5 Hz); 13C NMR 6APT, CDCl3, 100 MHz) major
isomer 25m: d 170.8, 156.5, 129.9, 128.87, 128.73, 126.67,
87.1, 73.3, 49.2, 43.2, 43.0, 31.4, 31.2, 21.1; minor isomer
26m: d 170.7, 156.6, 129.8, 128.91, 128.71, 126.74, 82.4,
71.7, 57.0, 46.8, 39.6, 35.6, 30.9, 20.9. Anal. Calcd for
C16H17NO3: C, 70.83; H, 6.32. Found C, 70.47; H, 6.41.
4.2.22. Cycloaddition of exo-2-substituted-5-norbornene
10f with nitrile oxide 2b. A solution of benzoylnitro-
methane 635.0 mg, 0.212 mmol) in CHCl3 60.8 mL) was
added to a ¯ame-dried vial containing norbornene 10f
624.9 mg, 0.164 mmol), 6BOC)2O 656.2 mg, 0.258 mmol),
DMAP 65.4 mg, 0.044 mmol), and CHCl3 60.7 mL) via a
cannula. The reaction mixture was stirred at room tempera-
ture for 24 h. The solvent was removed by rotary evapora-
tion, and the crude product was puri®ed by column
chromatography 6EtOAc/hexanesˆ1:9) to give an insepar-
able mixture of 27b and 28b 614.8 mg, 0.0494 mmol, 30%,
27b:28bˆ50:50 measured by 400 MHz 1H NMR) as a clear,
transparent liquid. Rf 0.31 6EtOAc/hexanesˆ1:4); IR 6neat)
3062 6w), 2977 6s), 2890 6w), 1742 6s), 1651 6s), 1582 6m),
1567 6m), 1468 6w), 1448 6m), 1361 6s), 1246 6s), 1211 6m),
4.2.20. Cycloaddition of endo-2-substituted-5-norbor-
nene 11e with benzonitrile oxide #2a). A solution of 18
649.9 mg, 0.364 mmol) in CHCl3 61 mL) was added to a
¯ame-dried vial containing norbornene 11e 655.0 mg,
0.275 mmol) and DMAP 65.3 mg, 0.043 mmol) via a
cannula and rinsed with CHCl3 62£0.5 mL). 6BOC)2O
688.9 mg, 0.407 mmol) was added then to the reaction
mixture. The reaction mixture was stirred at room tempera-
ture for 72 h. The solvent was removed by rotary evapora-
tion, and the crude product was puri®ed by column
chromatography 6EtOAc/hexanesˆ1:9) to give an insepar-
able mixture of 25l and 26l 667.1 mg, 0.210 mmol, 76%,
25l:26lˆ51:49 measured by 400 MHz 1H NMR) as a
clear, transparent liquid. Rf 0.25 6EtOAc/hexanesˆ1:9); IR
6neat) 3062 6w), 3031 6w), 2968 6s), 2875 6m), 1592 6w),
1564 6m), 1498 6m), 1475 6m), 1353 6s), 1310 6w), 1267 6m),
1207 6w), 1155 6s), 1121 6w), 1095 6s), 1072 6s), 1027 6w)
1
1149 6m), 1055 6s), 1017 6m) cm21; H NMR 6CDCl3,
400 MHz) d 8.13 6m, 2H), 7.58 6m, 1H), 7.46 6t, 2H,
Jˆ7.7 Hz), 4.76 6d, 0.5H, Jˆ8.4 Hz), 4.74 6d, 0.5H, Jˆ
8.5 Hz), 4.67 6d, 1H, Jˆ7.7 Hz), 4.19 6dd, 1H, Jˆ8.4,
2.0 Hz), 2.80 6s, 0.5H), 2.72±2.75 6m, 1.5H), 2.04 6s,
1.5H), 2.02 6s, 1.5H), 1.98 6ddd, 0.5H, Jˆ14.0, 7.2,
2.5 Hz), 1.81 6ddd, 0.5H, Jˆ14.4, 6.9, 2.3 Hz), 1.43±1.68
6m, 3H); 13C NMR 6APT, CDCl3, 100 MHz) d 186.3,
186.1, 170.5, 170.3, 157.7, 156.8, 136.1, 133.54, 133.52,
130.3, 128.3, 88.7, 86.0, 74.5, 71.7, 56.3, 52.6, 49.0,
44.3, 42.3, 38.7, 37.9, 33.7, 29.7, 29.6, 21.13, 21.11. Anal.
Calcd for C17H17NO4: C, 68.22; H, 5.72. Found C, 67.88; H,
5.83.
1
cm21; H NMR 6CDCl3, 400 MHz) d 7.73±7.66 6m, 2H),
7.41±7.30 6m, 8H), 5.20 6d, 0.49H, Jˆ8.4 Hz), 4.75 6d,
0.51H, Jˆ8.4 Hz), 4.61±4.46 6m, 2H), 4.21 6d, 0.49H, Jˆ
8.3 Hz), 4.04±3.96 6m, 1H), 3.74 6d, 0.51H, Jˆ8.5 Hz), 2.97
6d, 0.49H, Jˆ4.3 Hz), 2.70 6d, 0.51H, Jˆ3.7 Hz), 2.55 6m,
1H), 2.18±1.95 6m, 1H), 1.60±1.55 6m, 1H), 1.34±1.24 6m,
1.49H), 1.04 6dt, 0.51H, Jˆ13.6, 3.5 Hz); 13C NMR 6APT,
CDCl3, 100 MHz) d 157.2, 156.9, 138.1, 138.0, 129.7,
129.3, 129.2, 128.69, 128.65, 128.5, 128.4, 127.8, 127.7,
127.6, 127.5, 126.8, 126.7, 87.5, 82.7, 77.9, 76.6, 71.6,
71.5, 57.1, 48.9, 46.4, 43.2, 42.8, 39.6, 35.7, 31.5, 31.2,
30.9. Anal. Calcd for C21H21NO2: C, 78.97; H, 6.63.
Found C, 78.62; H, 6.44.
4.2.23. Cycloaddition of exo-2-substituted-5-norbornene
10f with nitrile oxide 2c. A solution of nitroethane
625.1 mg, 0.334 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 10f 639.5 mg,
0.260 mmol), 6BOC)2O 686.6 mg, 0.397 mmol), DMAP
65.0 mg, 0.041 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at 608C for 24 h. The
solvent was removed by rotary evaporation, and the crude
product was puri®ed by column chromatography 6EtOAc/
hexanesˆ1:4) to give an inseparable mixture of 27c and 28c
629.2 mg, 0.140 mmol, 54%, 27c:28cˆ62:38 measured by
4.2.21. Cycloaddition of endo-2-substituted-5-norbor-
nene 11f with benzonitrile oxide #2a). A solution of 18
635.1 mg, 0.256 mmol) in CHCl3 60.8 mL) was added to a
¯ame-dried vial containing norbornene 11f 632.0 mg,
0.210 mmol), 6BOC)2O 670.4 mg, 0.323 mmol), DMAP
65.1 mg, 0.042 mmol), and CHCl3 60.7 mL) via a cannula.
The reaction mixture was stirred at room temperature for
24 h. The solvent was removed by rotary evaporation, and
the crude product was puri®ed by column chromatography
6EtOAc/hexanesˆ1:4) to give an inseparable mixture of
25m and 26m 654.2 mg, 0.200 mmol, 95%, 25m:26mˆ
1
400 MHz H NMR) as a clear, transparent liquid. Rf 0.42
6EtOAc/hexanesˆ2:3); IR 6neat) 2975 6s), 2888 6w), 1737
6s), 1627 6w), 1467 6m), 1439 6s), 1386 6s), 1360 6s), 1334
6m), 1314 6m), 1248 6s), 1197 6m), 1173 6m), 1059 6s), 1018
1
1
55:45 measured by 400 MHz H NMR) as a white solid.
6s), 1033 6m) cm21; H NMR 6CDCl3, 400 MHz) d 4.63
Rf 0.34 6EtOAc/hexanesˆ1:4); IR 6CH2Cl2) 3064 6w),
2980 6m), 2947 6w), 1731 6s), 1446 6m), 1376 6m), 1356
6m), 1247 6s), 1146 6w), 1047 6w) cm21; 1H NMR 6CDCl3,
400 MHz) d 7.71 6m, 2H), 7.39 6m, 3H), 5.10 6d, 0.45H,
Jˆ8.4 Hz), 5.05 6dt, 0.45H, Jˆ10.1, 4.0 Hz), 4.98 6dt,
6dm, 0.62H, Jˆ7.0 Hz), 4.57 6dd, 0.38H, Jˆ7.1, 1.8 Hz),
4.47 6d, 0.38H, Jˆ8.2 Hz), 4.40 6d, 0.62H, Jˆ8.2 Hz),
2.99 6d, 0.62H, Jˆ8.2 Hz), 2.97 6d, 0.38H, Jˆ8.2 Hz),
2.63 6s, 0.38H), 2.56 6d, 0.62H, Jˆ4.9 Hz), 2.43 6s,
0.62H), 2.42 6d, 0.38H, Jˆ5.0 Hz), 2.02 6s, 1.86H), 2.01

P. Mayo et al. / Tetrahedron 57 *2001) 5931±5941
5941
13. 6a) Houk, K. M.; Sims, J.; Duke, Jr., R. E.; Strozier, R. W.;
George, J. K. J. Am. Chem. Soc. 1973, 95, 7287. 6b) Houk,
K. M.; Sims, J.; Watts, C. R.; Luskus, L. J. J. Am. Chem. Soc.
1973, 95, 7301.
6s, 1.14H), 1.895 6s, 1.14H), 1.894 6s, 1.86H), 1.85 6ddd,
0.38H, Jˆ13.8, 7.2, 2.6 Hz), 1.74 6m, 0.38H), 1.67 6ddd,
0.62H, Jˆ14.3, 7.1, 2.3 Hz), 1.41±1.57 6m, 2.62H); 13C
NMR 6APT, CDCl3, 100 MHz) major isomer 27c: d
170.5, 154.0, 85.5, 74.9, 56.5, 43.2, 41.9, 32.9, 29.0, 21.2,
11.9; minor isomer 28c: d 170.6, 155.0, 82.6, 71.8, 60.3,
48.7, 38.0, 37.3, 29.4, 21.1, 11.7. HRMS calcd for
C11H15NO3: m/z 209.1052, found m/z 209.1050.
14. Similar method has been used for the assignment of exo and
endo stereochemistry of bicyclic alkenes, see: 6a) Flautt, T. J.;
Erman, W. F. J. Am. Chem. Soc. 1963, 85, 3212.
6b) Mazzocchi, P. H.; Stahly, B.; Dodd, J.; Rondan, N. G.;
Domelsmith, L. N.; Rozeboom, M. D.; Caramella, P.; Houk,
K. N. J. Am. Chem. Soc. 1980, 102, 6482. See also Refs. 6 and
7.
Acknowledgements
15. Silverstein, R. M.; Bassler, G. C.; Morrill, T. C. Spectrometric
Identi®cation of Organic Compounds, 5th ed; Wiley: New
York, 1991 6A.P.T.: Attached Proton Test); p 276.
We thank the Natural Sciences and Engineering Research
Council 6NSERC) of Canada, Boehringer Ingelheim
6Canada) Ltd and the University of Guelph for the generous
®nancial support of our program. Peter Mayo thanks
NSERC for postgraduate scholarships 6PGS A and PGS
B). Ms Valerie Robertson is thanked for NMR experiments
and discussion of NMR data. Professor John D. Goddard
and Dr Galina Orlova are thanked for theoretical calcula-
tions.
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È
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