Intramolecular 1,3-dipolar cycloadditions of norbornadiene-tethered nitrile oxides

Article abstract of DOI:10.1021/jo005611o

Efficient routes to the synthesis of norbornadiene-tethered nitrile oxides have been developed, and their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in good yields for a variety of substrates and were found to be highly regio- and stereoselective, giving single regio- and stereoisomers in most cases.

Full text of DOI:10.1021/jo005611o

2
76
J . Org. Chem. 2001, 66, 276-286
In tr a m olecu la r 1,3-Dip ola r Cycloa d d ition s of
Nor bor n a d ien e-Teth er ed Nitr ile Oxid es
Carol Yip, Sean Handerson, Geoffrey K. Tranmer, and William Tam*
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, Department of Chemistry
and Biochemistry, University of Guelph, Guelph, Ontario, Canada N1G 2W1
wtam@uoguelph.ca
Received August 14, 2000
Efficient routes to the synthesis of norbornadiene-tethered nitrile oxides have been developed, and
their intramolecular 1,3-dipolar cycloadditions were studied. The cycloadditions occurred in good
yields for a variety of substrates and were found to be highly regio- and stereoselective, giving
single regio- and stereoisomers in most cases.
In tr od u ction
Cycloaddition reactions are among the most powerful
Sch em e 1. Gen er a l Ou tlin e for Con str u ction of
Tr icyclic a n d Sp ir ocyclic F r a m ew or k s via
In tr a m olecu la r Cycloa d d ition s of Nor bor n a d ien es
a n d Su bsequ en t Clea va ge of th e Cycloa d d u cts
methods for the construction of rings.1 In particular,
intramolecular cycloadditions with high regio- and ste-
reocontrol are important tools for the efficient assembly
of complex molecular structures. We have recently initi-
ated a program on the study of various types of intramo-
lecular cycloadditions of substituted norbornadienes. Our
long-term goal is to develop an efficient route for the
construction of angular fused tricyclic frameworks and
spirocyclic frameworks with high regio- and stereocontrol
(Scheme 1).
1
,3-Dipolar cycloadditions offer a convenient one-step
route for the construction of a variety of complex five-
membered heterocycles.2 1,3-Dipolar cycloadditions of
nitrile oxides are well-documented and provide efficient
3
entries to the synthesis of 2-isoxazolines. Reductive
cleavage of the N-O bond of 2-isoxazolines has proven
to be a useful routes to amino ketones, oxo alcohols, and
a number of natural products.2,3 Here we report our
results on the intramolecular 1,3-dipolar cycloadditions
of norbornadiene-tethered nitrile oxides.4
Sch em e 2. Syn th esis of Nor bor n a d ien e-Teth er ed
Nitr o Com p ou n d 7
a
Resu lts a n d Discu ssion
One of the most common methods to prepare nitrile
oxides is dehydration of the corresponding nitroalkanes.
An efficient route to the synthesis of norbornadiene-
tethered nitro compound 7 was developed, and 7 served
as a precursor of the required nitrile oxide for the
cycloaddition (Scheme 2). Deprotonation of norbornadiene
t
n
5
*
(
Ph: (519) 824-4120 (ext. 2268). Fax: (519) 766-1499.
1) (a) Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Paquette, L. A., Eds.; Pergamon: Oxford, 1991; Vol. 5, Chapters 1-9.
b) Advances in Cycloaddition; J AI Press: Greenwich, 1988-1999;
Vols. 1-6. (c) Lautens, M.; Klute, W.; Tam, W. Chem. Rev. 1996, 96,
9.
5 with Schlosser’s base ( BuOK/ BuLi) in THF at -78 °C,
followed by addition of the resulting norbornadienyl
anion to an excess of 1,4-dibromobutane, provided the
norbornadiene-tethered bromide 6. Displacement of the
2
bromide with NaNO in the presence of phloroglucinol
(
4
6
(2) (a) 1,3-Dipolar Cycloaddition Chemistry; Padwa, A., Ed.; J ohn
Wiley & Sons: New York, 1984; Vols. 1 and 2. (b) Gothelf, K. V.; J ø
rgensen, K. A. Chem. Rev. 1998, 98, 863.
in DMSO afforded the required nitro compound 7. As
-
NO
2
is an ambident anion, both nitrogen atom and
(3) (a) Kozikowski, A. P. Acc. Chem. Res. 1984, 17, 410. (b) Curran,
D. P. In Advances in Cycloaddition; Curran, D. P., Ed.; J AI Press:
Greenwich, 1988; Vol. 1, pp 129-189. (c) Nitrile Oxides, Nitrones, and
Nitronates in Organic Synthesis; Torssell, K. B. G., Ed.; VCH: New
York, 1988. (d) Kanemasa, S.; Tsuge, O. Heterocycles 1990, 30, 719.
oxygen atom could act as the nucleophile, leading to the
(5) (a) St a¨ ble, M.; Lehmann, R.; Kramar, J .; Schlosser, M. Chimia
1985, 39, 229. (b) Brandsma, L.; Verkuruijsse, H. D. Recl. Trav. Chim.
Pays-Bas 1986, 105, 66.
(6) Organic Functional Group Preparation; Sandler S. R., Karo, W.,
Eds.; Academic Press: New York, 1968; Vol. 1, pp 425-429.
(
4) (a) Preliminary results of this work have been published as a
communication: Yip, C.; Handerson, S.; J ordon, R.; Tam, W. Org. Lett.
999, 1, 791. (b) For a similar study on nitrone cycloaddition, see:
Tranmer, G. K.; Keech, P.; Tam, W. Chem. Commun. 2000, 863.
1
1
0.1021/jo005611o CCC: $20.00 © 2001 American Chemical Society
Published on Web 12/09/2000

Norbornadiene-Tethered Nitrile Oxides
J . Org. Chem., Vol. 66, No. 1, 2001 277
Ta ble 1. Con ver sion of Br om id e 6 to Nitr o Com p ou n d 7
Sch em e 3. P ossible Cycloa d d u cts
b
c
entry
solventa
temp (°C)
additive
none
phloroglucinol
phloroglucinol
none
yield (%)
1
2
3
4
5
6
DMF
DMF
DMF
DMSO
DMSO
DMSO
25
25
60
25
25
60
30d
44
e
e
48
d
37
e
phloroglucinol
phloroglucinol
56
55
e
a
Much lower yields were obtained with other solvents such as
Ta ble 3. Effect of Solven t
b
THF, CH2Cl2, and toluene. All reactions were stirred for 48 h.
c
d
Isolated yields after column chromatography. 20-30% of the
e
corresponding nitrite was obtained. <10% of the corresponding
nitrite was obtained.
Ta ble 2. Th r ee Differ en t Meth od s to Gen er a te Nitr ilie
Oxid e 8 a n d Cycloa d d u ct 9
b
entry
solvent
hexanes
THF
Et2O
DME
1,2-dichloroethane
CHCl3
tempa (°C)
yield (%)
1
2
3
4
5
6
7
60
60
35
90
80
60
90
50
76
39
72
67
61
86
solvent tempa (°C) yield (%)
b
entry
method
toluene
1
2
toluene
CHCl3
90
60
54
76
PhNCO, Et3N
a All reactions were carried out using the (BOC) O/DMAP
2
method and were stirred for 48 h. b Isolated yields after column
chromatography.
3
4
toluene
CHCl3
90
60
25
72
EtOCOCl, Et3N, DMAP
5
6
toluene
CHCl3
90
60
86
61
regio- and stereoselective, giving the exo cycloadduct 9
as a single regio- and stereosomer. It is noteworthy to
mention here that the intermolecular 1,3-dipolar cycload-
dition of norbornadiene with benzonitrile oxide is known
to produce a 4:1 exo/ endo cycloadducts.10
(
BOC)2O, DMAP
a
All reactions were stirred for 48 h. b Isolated yields after
column chromatography.
desired nitro compound (RNO
RONO). In the absence of phloroglucinol, a significant
amount of the corresponding nitrite was obtained and
the yield of nitro compound 7 was much lower (Table 1).
The most commonly used method for converting ni-
troalkanes to the corresponding nitrile oxides is the
Mukaiyama aromatic isocyanate method. Thus, treat-
ment of norbornadiene-tethered nitro compound 7 with
phenyl isocyanate and Et
the cycloadduct 9 in 54% and 76% yields (Table 2, entries
and 2). Two other methods were employed to generate
the corresponding nitrile oxide in situ from 7, the
Shimizu ethyl chloroformate method (Table 2, entries 3
and 4) and the Hassner (BOC)
, entries 5 and 6). The use of (BOC)
toluene at 90 °C was found to be the best method in our
system, giving the highest yield in the cycloaddition.
Four different cycloadducts are theoretically possible
in the cycloaddition (Scheme 3). Cycloaddition of the
tethered nitrile oxide on the C
exo and endo faces would provide the exo and endo
cycloadducts 9 and 10. Formation of the cycloadducts 11
2
) and the undesired nitrite
The regio- and stereochemistry of the cycloadduct 9
(
was proven by NMR techniques. The presence of two
1
olefinic protons in the H NMR spectrum eliminated the
possibilities of cycloadducts 11 and 12 (Scheme 3). The
exo and endo stereochemistry of the cycloadduct can
a
easily be distinguished by the coupling constant of H
7
b
1
11
and H in the H NMR. As the dihedral angle between
H and H in the exo cycloadduct 9 is close to 90°, the
coupling constant between H and H would be very small
a
b
3
N in toluene or CHCl
3
provided
a
b
(
J ≈ 0-2 Hz). In the endo cycloadduct 10, the dihedral
1
a b
angle between H and H is approximately 42° and would
12
give a doublet with J ≈ 5 Hz. NOESY NMR experiment
also provided an additional confirmation of the exo
8
2
O/DMAP method (Table
O and DMAP in
stereochemistry of the cycloadduct.
9
2
2
To optimize the yield of the cycloaddition, the effect of
different solvents and different reaction temperatures on
the cycloaddition of norbornadiene-tethered nitro com-
2
pound 7, using the (BOC) O and DMAP method, were
studied (Tables 3 and 4). Among various solvents tested,
toluene was found to be the best choice, giving the highest
yield in the cycloaddition (Table 3, entry 7). An increase
2
3
-C double bond from the
(
with the distal C
5
6
-C double bond) and 12 (with both
(
10) De Micheli, C.; Gandolfi, R.; Oberti, R. J . Org. Chem. 1980, 45,
209.
11) (a) Flautt, T. J .; Erman, W. F. J . Am. Chem. Soc. 1963, 85,
of the double bonds in the norbornadiene) are not very
likely as a result of the high strain in these resulting
molecules. The intramolecular cycloaddition of the nor-
bornadiene-tethered nitrile oxide 8 was found to be highly
1
(
3212. (b) 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.
(
12) The exo and endo cycloadducts 9 and 10 were modeled for
(
(
7) Mukaiyama, T.; Hoshino, T. J . Am. Chem. Soc. 1960, 82, 5339.
8) Shimizu, T.; Hayashi, T.; Shibafuchi, H.; Teramura, K. Bull.
energy minimization at the PM3 level (CS Chem 3D Pro Version 3.5.1)
using MOPAC for the assessment of the dihedral angles between H
and H . These dihedral angles were then compared to the Karplus
curve for the determination of the theoretical coupling constants.
a
b
Chem. Soc. J pn. 1986, 59, 2827.
9) Basel, Y.; Hassner, A. Synthesis 1997, 309.
(

2
78 J . Org. Chem., Vol. 66, No. 1, 2001
Yip et al.
Ta ble 4. Effect of Tem p er a tu r e
Sch em e 5. Syn th esis of Nitr o Com p ou n d s (27 a n d
2
8) w ith a n Oxygen Atom w ith in th e Teth er
tempa (°C)
yield (%)
b
entry
solvent
1
2
3
4
toluene
toluene
toluene
toluene
25
60
90
46
66
86
70
110
a
All reactions were carried out using the (BOC)2O/DMAP
b
method and were stirred for 48 h. Isolated yields after column
chromatography.
Sch em e 4. Syn th esis of All-Ca r bon Teth er ed
Nitr o Com p ou n d s 7, 15, 16, a n d 18
Sch em e 6. Syn th esis of Nitr o Com p ou n d (31)
w ith a Su lfu r Atom w ith in th e Teth er
in temperature from 25 to 90 °C led to an increase in
yield (Table 4, entries 1-3), but further increase in
temperature to 110 °C led to a lower yield, probably as a
result of decomposition of the cycloadduct 9. In two
control experiments, when pure cycloadduct 9 was re-
submitted to the cycloaddition conditions at 90 and 110
Two-carbon homologation of 19 and 20 to the alcohols
1
5
2
3 and 24 was achieved by a two-step sequence.
Conversion of the alcohols 23 and 24 to the corresponding
°
C for 48 h, 96% of the cycloadduct was recovered for the
1
6
iodides 25 and 26 using I
by displacement with NaNO
2
, PPh
3
, and imidazole followed
afforded the nitro com-
reaction at 90 °C but only 72% of the cycloadduct was
recovered for the reaction at 110 °C. This proved that
cycloadduct 9 tends to decompose slowly at temperature
above 90 °C. Thus, under the optimized conditions, by
2
pounds 27 and 28. Nitro compound 31, with a sulfur atom
within the tether, was prepared as in Scheme 6. Conver-
sion of the alcohol 19 to the corresponding thiol was
achieved using the Mitsunobu conditions followed by
hydrolysis of the thioacetate.17 Two-carbon homologation
of the thiol with 2-chloroethanol and NaOH produced
alcohol 29. Conversion of the alcohol 29 to the corre-
2
using the (BOC) O and DMAP method in toluene at 90
°
C for 48 h, norbornadiene-tethered nitro compound 7
was converted to the cycloadduct 9 as a single regio- and
stereoisomer in 86% yield.
To study the generality of the cycloaddition, a variety
of norbornadiene-tethered nitro compounds were synthe-
sized (Schemes 4-6) and subjected to the optimized
cycloaddition conditions (Table 5). Nitro compounds 15
and 16 were synthesized using the same protocol as nitro
compound 7 (Scheme 4). Nitro compound 18 with an
R-silyl ether substituent was synthesized through the
following sequence: hydration and Swern oxidation to
sponding iodide 30 using I
2
, PPh
3
, and imidazole followed
by displacement with NaNO
2
afforded the nitro com-
pound 31.
The results of the intramolecular 1,3-dipolar cycload-
ditions of norbornadiene-tethered nitrile oxides generated
from the nitro compounds 7, 15, 16, 18, 27, 28, and 31
are shown in Table 5. Similar to the 3-carbon tethered
nitrile oxide 8 (generated in situ from nitro compound
7), which provided cycloadduct 9 as the single cycloadduct
1
3
the corresponding aldehyde 17; addition of nitromethane
in the presence of alumina,14 followed by TBS-protection
(Table 5, entry 1), cycloaddition of the 4-carbon tethered
(Scheme 4). Nitro compounds with an oxygen atom within
nitrile oxide (generated in situ from nitro compound 15)
was also highly regio- and stereoselective, giving the exo
the tether were prepared as shown in Scheme 5. Nor-
bornadiene-tethered allylic and homoallylic alcohols 19
and 20 were prepared according to literature procedures.5b
(15) Heinze, I.; Knoll, K.; M o` ller, R.; Eberbach, W. Chem. Ber. 1989,
1
22, 2147.
(
13) Lautens M.; Edwards, L. G.; Tam, W.; Lough, A. J . J . Am.
Chem. Soc. 1995, 117, 10276.
14) Rosini, G.; Ballini, R.; Sorrenti, P. Synthesis 1983, 1014.
(16) Lange, G. L.; Gottardo, C. Synth. Commun. 1990, 20, 1473.
(17) McClure, K. F.; Renold, P.; Kemp, D. S. J . Org. Chem. 1995,
(
60, 454.

Norbornadiene-Tethered Nitrile Oxides
J . Org. Chem., Vol. 66, No. 1, 2001 279
Ta ble 5. In tr a m olecu la r 1,3-Dip ola r Cycloa d d ition of
Nor bor n a d ien e-teth er d Nitr ile Oxid es
Sch em e 7. Syn th e sis of Nitr o Com p ou n d s 46-49
a n d 51
Sch em e 8. Syn th esis of Nitr o Com p ou n d s 62-64
a
Typical cycloaddition conditions: (BOC)2O (2-3 equiv) in
toluene was added to the nitroalkane, DMAP (10 mol %) in toluene
,
and the reaction mixture was stirred at 90 °C for 24-96 h.
b
c
Isolated yields after column chromatograph. No cycloadduct was
d
obtained. Accompanied with an unidentified product (∼20%).
cycloadduct 32 as the only cycloadduct in good yield
(
Table 5, entry 2). However, no cycloadduct was formed
with the corresponding 5-carbon tethered nitrile oxide
Table 5, entry 3). In this case, only polymeric material
(
was obtained. As the length of the tether increases, the
rate of intramolecular cycloaddition decreases and side
reactions such as rearragement and dimerization of the
nitrile oxide, and polymerization could occur. Nitrile
oxide generated from nitro compound 18 with an R-silyl
ether substituent also provided the corresponding exo
cycloadduct 33 in good yield (Table 5, entry 4). Formation
of the five- and six-membered ring cycloadducts, 34 and
3
5, with an oxygen atom within the tether were also
found to be successful, giving moderate yields of the
cycloadducts (Table 5, entries 5 and 6). In case of the
cycloaddition with the nitrile oxide generated from nitro
compound 28, other than the exo cycloadduct 35, an
unidentified product (∼20%) was also detected. This is
the only case where we observed a product other than
the exo cycloadducts in the cycloadditions. Cycloaddition
of the nitrile oxide generated from nitro compound 31,
with a sulfur atom within the tether, was also found to
be successful, giving cycloadduct 36 in moderate yield
The regio- and stereochemistry of the cycloadducts
were confirmed by using NMR techniques as described
earlier with cycloadduct 9. The small coupling constant
a
b
between H and H (Scheme 3) of cycloadducts 9 and 32-
1
8
1
3
6 in H NMR (normally a singlet or a doublet with J <
.5 Hz) indicated the exo stereochemistry of the cycload-
1
ducts. NOESY NMR experiments also provided an ad-
ditional confirmation of the exo stereochemistry of the
cycloadducts.
To investigate the effect of a C3 subtitutent on the
norbornadiene in the cycloaddition, nitro compounds 46-
49, 51, and 62-64 were prepared (Schemes 7 and 8).
Monolithium-halide exchange of 2,3-dibromonorborna-
(Table 5, entry 7). Thus, except with nitro compound 28,
in all other cases, the cycloadditions were found to be
highly regio- and stereoselective, giving single regio- and
stereoisomers in moderate to good yields.
t
diene 37 with BuLi, followed by trapping the resulting
organolithiums with methyl iodide, hexyl iodide, TMSCl,
and TsCl, provided bromides 38-41 in good yields
(Scheme 7).19 A second lithium-halide exchange of these
18) Based on 1H NMR, the minor product is likely to be the endo
cycloadduct.
(

2
80 J . Org. Chem., Vol. 66, No. 1, 2001
Yip et al.
Ta ble 6. In tr a m olecu la r 1,3-Dip ola r Cycloa d d ition of
C3-Su bstitu ted Nor bor n a d ien e-Teth er ed Nitr ile Oxid es
to C
of norbornadiene, cycloadditions occurred smoothly
3
and provided cycloadducts 71 and 72 in moderate yields
Table 6, entries 8 and 9). The regio- and stereochemistry
(
of these cycloadducts were confirmed by using NMR
techniques (HCOSY, HSQC and NOESY experiments).
Furthermore, these assignments were also supported by
X-ray crystallography.20
entry
R
nitro compound cycloadducta yield (%)
b
Con clu sion
1
2
3
4
5
6
7
8
9
H
Me
hexyl
SiMe3
Cl
Br
I
COOMe
CH2OMe
7
46
47
48
49
51
62
63
64
9
65
66
67
68
69
70
71
72
86
82
83
0
89
69
5
We have demonstrated the first examples of the
intramolecular 1,3-dipolar cycloadditions of norborna-
diene-tethered nitrile oxides. Although four possible
cycloadducts could be formed in the cycloadditions, single
regio- and stereoisomers were formed. Thus, these cy-
cloadditions were found to be highly regio- and stereo-
selective, giving the exo cycloadducts in good yields.
Further investigations on subsequent cleavage reactions
of the cycloadducts (Scheme 1) for the construction of
angular-fused tricyclic and spirocyclic frameworks are
ongoing in our laboratory.
c
d
71
66
a
Typical cycloaddition conditions: (BOC)2O (2-3 equiv) in
toluene was added to the nitroalkane, DMAP (10 mol %) in toluene,
and the reaction mixture was stirred at 90 °C for 24-96 h.
Isolated yields after column chromatograph. No cycloadduct was
b
c
d
obtained. Cycloadduct 70 decomposed gradually on standing at
rt.
Exp er im en ta l Section
bromides followed by trapping with 1,4-dibromobutane
afforded norbornadiene-tethered bromides 42-45. Dis-
2 3
placement of these bromides with NaNO provided C -
Gen er a l. All reactions were carried out in an atmosphere
of dry nitrogen at ambient temperature unless otherwise
stated. Standard column chromatography was performed on
substituted norbornadiene-tethered nitro compounds 46-
9. Nitro compound 51 was synthesized by monolithium-
2
30-400 mesh silica gel (obtained from Silicycle) by use of
4
21
flash column chromatography techniques. Analytical thin-
layer chromatography (TLC) was conducted on Merck pre-
coated silica gel 60 F254 plates. All glassware was flame-dried
under an inert atmosphere of dry nitrogen. Chemical shifts
for 1H NMR spectra are reported in parts per million (ppm)
from tetramethylsilane with the solvent resonance as the
internal standard (deuteriochloroform, δ 7.26). Chemical shifts
for 13C NMR spectra are reported in parts per million (ppm)
from tetramethylsilane with the solvent as the internal
standard (deuteriochloroform, δ 77.0).
halide exchange of 2,3-dibromonorbornadiene 37 with
t
BuLi followed by trapping with 1,4-dibromobutane and
displacement of the resulting norbornadiene-tethered
bromide 50 with NaNO
with an I, COOMe, and CH
2
. Syntheses of nitro compounds
OMe group attached to C of
2
3
the norbornadiene are shown in Scheme 8. Monolithium-
halide exchange of 2,3-dibromonorbornadiene 37 with
t
BuLi followed by trapping with THP-protected 4-iodobu-
tanol produced 52. A second lithium-halide exchange of
Ma ter ia ls. Unless stated otherwise, commercial reagents
were used without purification. Solvents were purified by
distillation under dry nitrogen: from CaH
5
2 followed by trapping with iodine or methyl chlorofor-
2 2 2
(CH Cl , 1,2-
mate afforded 53 and 54. DIBAL reduction of ester 54
followed by methylation of the resulting alcohol provided
dichloroethane, chloroform, DMF, Et N, pyridine); from 4 Å
3
molecular sieves (DMSO, acetonitrile, nitromethane); from
sodium (toluene); from potassium/benzophenone (THF); and
from sodium/benzophenone (Et O). Norbornadiene (5), 1,5-
2
dibromopentane, 1,6-dibromohexane, and 2-chloroethanol were
purified by distillation from 4 Å molecular sieves under dry
nitrogen. Substituted norbornadienes 38-43, 50, 52, and 54
were prepared according to literature procedures. Norbor-
nadienes 6, 17, 19, and 20 are known compounds, and detailed
procedures for their preparation can be found in the Support-
ing Information.
P r ep a r a tion of 2-(5-Br om op en tyl)n or bor n a d ien e (13).
Norbornadiene 5 (24.0 mL, 222 mmol) was added to a flame-
dried three-neck flask containing potassium tert-butoxide (18.7
g, 167 mmol) and THF (220 mL) which was cooled at -78 °C
cryobath). n-Butyllithium (66.8 mL, 2.5M, 167 mmol) was
added dropwise through a dropping funnel to the solution over
h, and the temperature was maintained below -65 °C. The
reaction mixture was stirred at -65 °C for 30 min and at -40
C for 30 min. After cooling of the mixture to -78 °C, this light
5
5. Removal of the THP group in compounds 53-55 with
PPTS in MeOH, conversion of the resulting alcohols 56-
5
8 to the corresponding iodides 59-61 using I
2
, PPh
and imidazole, followed by displacement with NaNO
afforded C
3
2
,
,
1
6
3
-substituted norbornadiene-tethered nitro
1
9
compounds 62-64.
We anticipated that a C substitutent may retard the
3
cycloaddition because of steric hindrance, but in fact
cycloadditions of most of the nitrile oxides, generated
3
from the C -substituted norbornadiene-tethered nitro
compounds, occurred smoothly, giving the corresponding
exo cycloadducts as the only regio- and stereoisomers in
moderate to good yields (Table 6). With R ) H, Me, and
hexyl, cycloadducts 9, 65, and 66 were produced in the
cycloadditions with yields of 82-86% (Table 6, entries
(
1
1
-3). However, with a very bulky group at C
nadiene (48, R ) SiMe ), no cycloadduct was formed.
With halides at C of norbornadiene, R ) Cl gave a yield
of 89%, R ) Br gave 69% yield, and the R ) I gave only
% yield of the cycloadducts (Table 6, entries 5-7).
3
of norbor-
°
3
brown solution was added via cannula over 30 min to a cooled
flask containing 1,5-dibromopentane (100 mL, 734 mmol) in
THF (80 mL) at -65 °C. The reaction mixture was stirred at
3
-
40 °C for 2 h and at 0 °C for 2 h. After the reaction mixture
5
was quenched with saturated ammonium chloride (200 mL)
and water (200 mL), the aqueous layer was extracted with
diethyl ether (3 × 300 mL), and the combined organic layers
Cycloadduct 70 (with R ) I) was rather unstable and
decomposed gradually upon standing even at room tem-
perature. With an ester or an ether functionality attached
(
20) Tam, W.; Handerson, S.; Ferguson, G. Acta Crystallogr. 2000,
C56, e71.
(21) Still, W. C.; Kahn, M.; Mitra, A. J . Org. Chem. 1978, 43, 2923.
(19) Tranmer, G. K.; Yip, C.; Handerson, S.; J ordan, R. W.; Tam,
W. Can. J . Chem. 2000, 78, 527.

Norbornadiene-Tethered Nitrile Oxides
J . Org. Chem., Vol. 66, No. 1, 2001 281
were washed sequentially with water (400 mL) and brine (400
mL) and dried over magnesium sulfate. The solvent was
removed by rotary evaporation and the crude product was
purified by vacuum distillation to give three fractions. The first
fraction (3-5 Torr at 65 °C-80 °C) contained mainly the excess
3.6 Hz), 4.16 (ddd, 1H, J ) 13.1, 3.0, 1.4 Hz), 4.10 (dt, 1H, J
) 13.4, 1.7 Hz), 3.86-3.78 (m, 2H), 3.58-3.43 (m, 6H), 2.00
(m, 1H), 1.95 (dt, 1H, J ) 5.9, 1.4 Hz), 1.80 (m, 1H), 1.69 (m,
1H), 1.62-1.46 (m, 4H); 13C NMR (CDCl
, 100 MHz) δ 154.91,
3
154.87, 143.2, 142.50, 142.46, 138.43, 138.39, 98.71, 98.66,
73.54, 73.50, 69.44, 69.43, 68.7, 66.48, 66.46, 62.0, 51.2, 51.1,
1
7
,5-dibromopentane. The second fraction (1-3 Torr at 60 °C-
0 °C) contained 1,5-dibromopentane and product in a ratio
50.1, 30.4, 25.3, 19.3. Anal. Calcd for C15
8.86. Found C, 71.92; H, 8.89.
22 3
H O : C, 71.97; H,
1
of 3:1 as determined by H NMR. The third fraction (0.2-0.8
Torr at 70-85 °C) contained pure bromide 13 (32.5 g, 135
P r ep a r a tion of THP -P r otected Alcoh ol 22. To a flame-
dried flask containing alcohol 20 (2.87 g, 21.0 mmol), THP-
f
mmol, 81%) as a colorless oil: R 0.65 (hexanes); IR (neat,
NaCl) 3117 (w), 3064 (w), 2966 (s), 2933 (s), 2863 (m), 1622
22
protected 2-chloroethanol (6.97 g, 42.3 mmol), and tetrabu-
(
w), 1555 (w), 1460 (w), 1430 (w), 1301 (m), 1262 (w), 1246
tylammonium bromide (1.42 g, 4.28 mmol) was added 50%
-1 1
(w), 1184 (w) cm ; H NMR (CDCl
3
, 400 MHz) δ 6.75 (m, 2H),
.13 (m, 1H), 3.49 (m, 1H), 3.40 (t, 2H, J ) 6.8 Hz), 3.27 (m,
H), 2.20 (m, 2H), 1.98 (dt, 1H, J ) 5.7, 1.5 Hz), 1.94 (dm, 1H,
15
NaOH (6.50 g in 6.5 mL water, 163 mmol) at 0 °C. The
6
1
reddish-brown reaction mixture was stirred at 70 °C for 48 h.
After quenching of the reaction with saturated sodium chloride
1
3
J ) 5.7 Hz), 1.85 (m, 2H), 1.48-1.36 (m, 4H); C NMR (CDCl
1
3
3
,
(20 mL) and water (30 mL), the aqueous layer was extracted
00 MHz) δ 158.5, 143.8, 142.3, 133.6, 73.5, 53.4, 50.0, 33.9,
with diethyl ether (3 × 50 mL), and the combined organic
2.7, 31.2, 27.8, 26.3; HRMS calcd for C12 17Br m/z 240.0514,
H
layers were washed sequentially with water (50 mL) and brine
found m/z 240.0516.
(50 mL) and dried over magnesium sulfate. The solvent was
P r ep a r a tion of 2-(6-Br om oh exyl)n or bor n a d ien e (14).
Norbornadiene 5 (4.50 mL, 41.7 mmol) was added to a flame-
dried three-neck flask containing potassium tert-butoxide (3.42
g, 30.5 mmol) and THF (40 mL) which was cooled at -78 °C
removed by rotary evaporation and the crude product was
purified by column chromatography (EtOAc/hexanes 1:4) to
give 22 (4.88 g, 18.5 mmol, 88%) as a colorless oil: R
(
f
0.54
EtOAc/hexanes 1:4); IR (neat, NaCl) 3065 (w), 2938(s), 2867
s), 1556 (w), 1352 (w), 1307 (m), 1202 (m), 1184 (m), 1126 (s),
(
cryobath). n-Butyllithium (12.2 mL, 2.5M, 30.5 mmol) was
added dropwise through a dropping funnel to the solution over
h, and the temperature was maintained below -65 °C. The
reaction mixture was stirred at -65 °C for 30 min and at -40
C for 30 min. After cooling of the mixture to -78 °C, this light
(
-1
1
1
6
3
3
077 (s), 1037 (s), 1021 (s) cm ; H NMR (CDCl , 400 MHz) δ
1
.69 (m, 2H), 6.17 (m, 1H), 4.60 (m, 1H), 3.82 (m, 2H), 3.58-
.47 (m, 6H), 3.44 (m, 1H), 3.30 (m, 1H), 2.46 (m, 2H), 1.94
°
(
1
dm, 1H, J ) 5.6 Hz), 1.89 (dm, 1H, J ) 5.6 Hz), 1.80 (m, 1H),
brown solution was added via cannula over 30 min to a cooled
flask containing 1,6-dibromohexane (15.0 mL, 97.6 mmol) in
THF (30 mL) at -65 °C. The reaction mixture was stirred at
13
.68 (m, 1H), 1.58-1.46 (m, 4H); C NMR (CDCl
3
, 100 MHz)
δ 155.2, 143.6, 142.3, 134.9, 98.7, 73.5, 69.9, 69.5, 66.4, 61.9,
5
7
3.5, 50.0, 31.6, 30.4, 25.3, 19.3. Anal. Calcd for C16
2.69; H, 9.15. Found C, 72.78; H, 9.11.
24 3
H O : C,
-
40 °C for 2 h and at 0 °C for 2 h. After the reaction mixture
was quenched with saturated ammonium chloride (40 mL) and
water (40 mL), the aqueous layer was extracted with diethyl
ether (3 × 100 mL), and the combined organic layers were
washed sequentially with water (100 mL) and brine (100 mL)
and dried over magnesium sulfate. The solvent was removed
by rotary evaporation and the crude product was purified by
vacuum distillation to give three fractions. The first fraction
P r ep a r a tion of Alcoh ol 23. To a flame-dried flask con-
taining 21 (1.31 g, 5.22 mmol) in MeOH (43 mL) was added
pyridium p-toluenesulfonate (PPTS, 143 mg, 0.569 mmol) at
room temperature. The reaction mixture was stirred at 55 °C
for 45 min. After quenching of the reaction with water (30 mL),
the aqueous layer was extracted with diethyl ether (3 × 50
mL), and the combined organic layers were washed sequen-
tially with water (50 mL) and brine (50 mL) and dried over
magnesium sulfate. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes 1:4) to give 23 (754 mg, 4.54
(
4-6 Torr at 90-100 °C) contained mainly the excess 1,6-
dibromohexane. The second fraction (1-2 Torr at 90-100 °C)
contained 1,6-dibromohexane and product in a ratio of 5:1 as
determined by H NMR. The third fraction (0.2 Torr at 80 °C-
1
1
00 °C) contained pure bromide 14 (5.83 g, 22.9 mmol, 75%)
f
mmol, 87%) as a colorless oil: R 0.10 (EtOAc/hexanes 1:4);
IR (neat, NaCl) 3412 (s), 3065 (w), 2968 (s), 2934 (s), 2866 (s),
1556 (w), 1449 (w), 1351 (m), 1187 (w), 1129 (s), 1110 (s), 1064
as a colorless oil: R
f
0.35 (hexanes); IR (neat, NaCl) 3116 (w),
3
064 (m), 2966 (s), 2931 (s), 2857 (s), 1622 (s), 1555 (m), 1463
m), 1430 (m), 1302 (m), 1256 (m), 1184 (w) cm- ; H NMR
1
1
(
(
-
1 1
(
3
1
s) cm ; H NMR (CDCl
3
, 400 MHz) δ 6.77 (dd, 1H, J ) 5.2,
.1 Hz), 6.71 (dd, 1H, J ) 5.1, 3.0 Hz), 6.44 (m, 1H), 4.15 (dd,
H, J ) 13.0, 1.3 Hz), 4.09 (dd, 1H, J ) 13.0, 1.5 Hz), 3.67 (t,
CDCl
3
, 400 MHz) δ 6.75 (m, 2H), 6.12 (m, 1H), 3.49 (br. s,
H), 3.40 (t, 2H, J ) 6.9 Hz), 3.27 (br. s, 1H), 2.19 (m, 2H),
.96 (qt, 2H, J ) 5.7, 1.6 Hz), 1.85 (p, 2H, J ) 6.9 Hz), 1.47-
1
1
1
1
2
2
1
3
2H, J ) 4.5 Hz), 3.53 (m, 1H), 3.47-3.37 (m, 3H), 2.63 (br. s,
.36 (m, 4H), 1.28 (m, 2H); C NMR (CDCl
3
, 100 MHz) δ 158.7,
1
H), 2.00 (dt, 1H, J ) 5.9, 1.6 Hz), 1.96 (dm, 1H, J ) 5.9 Hz);
43.8, 142.3, 133.3, 73.4, 53.4, 50.0, 33.9, 32.7, 31.3, 28.4, 27.9,
1
3
C NMR (CDCl
3
, 100 MHz) δ 154.6, 143.2, 142.4, 138.7, 73.6,
: C, 72.26;
6.9; HRMS calcd for C13
54.0675.
H19Br m/z 254.0671, found m/z
7
0.9, 69.5, 61.6, 51.2, 50.1. Anal. Calcd for C10
14 2
H O
H, 8.49. Found C, 72.46; H, 8.43.
P r ep a r a tion of THP -P r otected Alcoh ol 21. To a flame-
dried flask containing alcohol 19 (1.03 g, 8.46 mmol), THP-
P r ep a r a tion of Alcoh ol 24. To a flame-dried flask con-
taining 22 (4.58 g, 17.3 mmol) in MeOH (140 mL) was added
pyridium p-toluenesulfonate (PPTS, 529 mg, 2.11 mmol) at
room temperature. The reaction mixture was stirred at 55 °C
for 45 min. Approximately 100 mL of MeOH was removed by
rotary evaporation. After quenching of the reaction with water
(100 mL), the aqueous layer was extracted with diethyl ether
(4 × 100 mL), and the combined organic layers were washed
sequentially with water (100 mL) and brine (100 mL) and dried
over magnesium sulfate. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes 1:4) to give 24 (1.61 g, 8.93
2
2
protected 2-chloroethanol (2.79 g, 17.0 mmol), and tetrabu-
tylammonium bromide (565 mg, 1.70 mmol) was added 50%
NaOH (2.6 g in 2.6 mL water, 65.0 mmol) at 0 °C.15 The
reaction mixture was stirred at 70 °C for 42 h. After quenching
of the reaction with saturated sodium chloride (25 mL) and
water (50 mL), the aqueous layer was extracted with diethyl
ether (3 × 100 mL), and the combined organic layers were
washed sequentially with water (100 mL) and brine (100 mL)
and dried over magnesium sulfate. The solvent was removed
by rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes 1:4) to give 21 (1.41
g, 5.63 mmol, 66%) as a colorless oil: R
f
0.47 (EtOAc/hexanes
:4); IR (neat, NaCl) 3065 (w), 2939 (s), 2868 (s), 1556 (w),
352 (m), 1260 (w), 1202 (m), 1185 (m), 1127 (s), 1077 (s), 1036
f
mmol, 52%) as a colorless oil: R 0.16 (EtOAc/hexanes 1:4);
1
1
IR (neat, NaCl) 3421 (s), 3064 (w), 2964 (s), 2933 (s), 2866 (s),
1686 (w), 1556 (w), 1457 (w), 1357 (w), 1306 (m), 1226 (w),
-
1
1
-1 1
(s), 1021 (s) cm ; H NMR (CDCl
3
, 400 MHz) δ 6.76 (m, 1H),
3
1122 (s), 1057 (s) cm ; H NMR (CDCl , 400 MHz) δ 6.73 (m,
6
.69 (dd, 1H, J ) 5.0, 3.0 Hz), 6.43 (m, 1H), 4.61 (t, 1H, J )
2H), 6.20 (m, 1H), 3.67 (m, 2H), 3.53 (t, 2H, J ) 6.9 Hz), 3.50
(
m, 2H), 3.48 (m, 1H), 3.30 (m, 1H), 2.53-2.41 (m, 3H), 1.96
13
(dm, 1H, J ) 5.8 Hz), 1.92 (dm, 1H, J ) 5.7 Hz); C NMR
, 100 MHz) δ 155.1, 143.7, 142.3, 135.2, 73.6, 71.6, 69.2,
(
22) Miyashita, M.; Yoshikoshi, A.; Grieco, P. A. J . Org. Chem. 1977,
4
2, 3772.
(CDCl
3

2
82 J . Org. Chem., Vol. 66, No. 1, 2001
Yip et al.
6
8
1.6, 53.5, 50.0, 31.6. Anal. Calcd for C11
.95. Found C, 73.12; H, 8.99.
H
16
O
2
: C, 73.30; H,
6 using diluted HCl, the aqueous layer was extracted with
diethyl ether (3 × 25 mL). The combined organic layers were
washed sequentially with water (25 mL) and brine (25 mL)
and dried over magnesium sulfate. The solvent was removed
by rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes 1:4) to give alcohol
P r ep a r a tion of Iod id e 25. To a flame-dried flask contain-
ing PPh (296 mg, 1.13 mmol), imidazole (170 mg, 2.49 mmol),
acetonitrile (1.5 mL), and THF (0.5 mL) was added I (318 mg,
.51 mmol) at 0 °C. The reddish-brown reaction mixture was
3
2
2
stirred for 15 min at 0 °C. Alcohol 23 (93.1 mg, 0.560 mmol)
in acetonitrile (1 mL) was added via a cannula at 0 °C. The
reaction mixture was stirred at room temperature for 5.5 h.
f
29 (826 mg, 4.53 mmol, 54%) as a clear yellow oil: R 0.27
(EtOAc/hexanes 1:4); IR (neat, NaCl) 3372 (br. s), 3116 (w),
3064 (m), 2978 (s), 2934 (s), 2866 (s), 1555 (m), 1417 (m), 1305
-
1 1
The reaction mixture was diluted with CH
2
Cl
2
(15 mL) and
3
(s), 1047 (s), 1016 (s) cm ; H NMR (CDCl , 400 MHz) δ 6.80
quenched with water (15 mL). The aqueous layer was ex-
tracted with diethyl ether (3 × 20 mL), and the combined
organic layers were washed sequentially with water (20 mL)
and brine (20 mL) and dried over magnesium sulfate. The
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography (EtOAc/
hexanes 1:19) to give iodide 25 (151 mg, 0.55 mmol, 98%) as
(m, 1H), 6.65 (dd, 1H, J ) 4.2, 2.8 Hz), 6.28 (s, 1H), 3.59 (m,
2H), 3.52 (br. s, 1H), 3.37 (br. s, 1H), 3.31 (m, 2H), 2.44 (m,
1
3
2H), 2.31 (br. s, 1H), 1.98 (m, 1H), 1.95 (m, 1H); C NMR
(CDCl , 100 MHz) δ 152.5, 142.5, 142.2, 137.9, 73.0, 59.8, 52.7,
3
50.2, 33.4, 31.8. Anal. Calcd for C10
Found C, 65.91; H, 7.73.
H14SO: C, 65.89; H, 7.74.
P r ep a r a tion of Iod id e 30. To a flame-dried flask contain-
ing PPh (2.35 g, 8.97 mmol), imidazole (1.37 g, 20.1 mmol),
acetonitrile (20 mL), and THF (9 mL) was added I (2.63 g,
a colorless oil: R
f
0.40 (EtOAc/hexanes 1:19); IR (neat, NaCl)
3
3
1
064 (w), 2934 (m), 2866 (m), 1556 (w), 1350 (w), 1261 (w),
2
-1 1
187 (m), 1126 (m), 1085 (s), 1059 (m), 1019 (w) cm ; H NMR
, 400 MHz) δ 6.78 (dd, 1H, J ) 5.1, 3.2 Hz), 6.71 (dd,
H, J ) 5.0, 3.0 Hz), 6.46 (m, 1H), 4.16 (dd, 1H, J ) 12.9, 1.2
20.7 mmol) at 0 °C. The reaction mixture was stirred for 15 m
at 0 °C. Alcohol 29 (801 mg, 4.39 mmol) in acetonitrile (5 mL)
was added via a cannula at 0 °C. The reaction mixture was
stirred at room temperature for 3 h. After the reaction mixture
was quenched with saturated sodium thiosulfate (25 mL), the
aqueous layer was extracted with diethyl ether (3 × 25 mL),
and the combined organic layers were washed sequentially
with water (25 mL) and brine (25 mL) and dried over
magnesium sulfate. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes 1:19) to give iodide 30 (689
(CDCl
3
1
Hz), 4.10 (dd, 1H, J ) 12.9, 1.5 Hz), 3.59-3.53 (m, 3H), 3.46
m, 1H), 3.20 (t, 2H, J ) 6.8 Hz), 2.01 (dt, 1H, J ) 5.9, 1.5
(
1
3
Hz), 1.97 (dm, 1H, J ) 5.9 Hz); C NMR (CDCl
1
3
, 100 MHz) δ
54.3, 143.1, 142.3, 138.9, 73.5, 70.0, 69.0, 51.1, 50.0, 3.17;
HRMS calcd for C10H13IO m/z 276.0013, found m/z 276.0009.
P r ep a r a tion of Iod id e 26. To a flame-dried flask contain-
ing PPh (4.38 g, 16.7 mmol), imidazole (2.51 g, 36.9 mmol),
acetonitrile (15 mL), and THF (7.5 mL) was added I (4.76 g,
7.5 mmol) at 0 °C. The reddish-brown reaction mixture was
3
2
3
mg, 2.36 mmol, 54%) as a colorless oil: R
1:4); IR (neat, NaCl) 3115 (w), 3063 (m), 2979 (s), 2933 (s),
f
0.85 (EtOAc/hexanes
stirred for 15 min at 0 °C. Alcohol 24 (1.50 g, 8.33 mmol) in
acetonitrile (23 mL) was added via a cannula at 0 °C. The
reaction mixture was stirred at room temperature for 4 h. The
-1 1
2865 (m), 1554 (m), 1424 (m), 1304 (s), 1156 (s) cm ; H NMR
(CDCl , 400 MHz) δ 6.82 (m, 1H), 6.69 (m, 1H), 6.33 (m, 1H),
3
reaction mixture was diluted with CH
2
Cl
2
(25 mL) and
3.57 (br. s, 1H), 3.38 (br. s, 1H), 3.40 (dAB, 1H, J ) 14.0 Hz),
3.33 (dAB, 1H, J ) 14.0 Hz), 3.18 (m, 2H), 2.69 (m, 2H), 2.02
quenched with water (25 mL). The aqueous layer was ex-
tracted with diethyl ether (3 × 50 mL), and the combined
organic layers were washed sequentially with water (50 mL)
and brine (50 mL) and dried over magnesium sulfate. The
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography (EtOAc/
hexanes 1:19) to give iodide 26 (1.85 g, 6.38 mmol, 76%) as a
1
3
(m, 1H), 1.98 (m, 1H); C NMR (CDCl , 100 MHz) δ 152.4,
3
142.7, 142.3, 138.3, 73.1, 52.8, 50.4, 33.1, 32.4, 3.1.
P r ep a r a tion of 2-(4-Br om obu tyl)-3-ch lor on or bor n a -
d ien e (45). tert-Butyllithium (12.5 mL, 1.7 M, 21.3 mmol) was
added to a flame-dried flask containing 2-bromo-3-chloronor-
bornadiene 4119 (2.07 g, 10.1 mmol) in THF (50 mL) at -78
°C. After the reaction mixture stirred for 1 h, the resulting
yellow mixture was added to a flame-dried flask containing
1,4-dibromobutane (3.5 mL, 29.3 mmol) in THF (52 mL) at
-78 °C. The reaction mixture was stirred at -78 °C for 1 h
and at room temperature for 19 h. After quenching of the
reaction mixture with water (150 mL), the aqueous layer was
extracted with diethyl ether (4 × 150 mL), and the combined
organic layers were washed sequentially with water (150 mL)
and brine (150 mL) and dried over magnesium sulfate. The
solvent was removed by rotary evaporation and the crude
product was purified by vacuum distillation to give two
fractions. The first fraction (2-5.5 Torr at 70-80 °C) contained
mainly the excess 1,4-dibromobutane. The second fraction (0.5
Torr at 70-80 °C) contained pure 45 (2.40 g, 9.17 mmol, 91%)
colorless oil: R
3
1
f
0.39 (EtOAc/hexanes 1:19); IR (neat, NaCl)
064 (w), 2968 (m), 2932 (m), 2865 (m), 1555 (w), 1357 (w),
306 (m), 1262 (w), 1168 (w), 1118 (s), 1098 (s), 1040 (w) cm-1
;
1
H NMR (CDCl , 400 MHz) δ 6.74 (m, 2H), 6.22 (m, 1H), 3.68
3
(
(
)
1
5
t, 2H, J ) 7.0 Hz), 3.55 (t, 2H, J ) 7.0 Hz), 3.49 (m, 1H), 3.33
m, 1H), 3.22 (t, 2H, J ) 7.0 Hz), 2.48 (m, 2H), 1.99 (dt, 1H, J
5.7, 1.6 Hz), 1.93 (dt, 1H, J ) 5.7, 1.6 Hz); 13C NMR (CDCl
,
3
00 MHz) δ 154.9, 143.7, 142.2, 135.3, 73.6, 71.3, 69.1, 53.5,
0.0, 31.6, 3.0; HRMS calcd for C11 15IO m/z 290.0169, found
H
m/z 290.0164.
P r ep a r a tion of Alcoh ol 29. To a flame-dried flask con-
taining PPh (2.65 g, 10.1 mmol) in THF (25 mL) was added
3
diisopropyl azodicarboxylate (DIAD, 1.80 mL, 9.14 mmol)
dropwise at 0 °C. The pasty white reaction mixture was stirred
for 30 min at 0 °C. A solution of alcohol 19 (1.03 g, 8.40 mmol)
and thiolacetic acid (0.70 mL, 9.8 mmol) in THF (20 mL) was
added via a cannula at 0 °C. The reaction mixture was stirred
at 0 °C for 2 h and at room temperature for 1 h. The solvent
was removed by rotary evaporation and the crude reaction
mixture was purified by column chromatography (EtOAc/
hexanes 1:19). To the crude product was added MeOH (20 mL),
followed by a saturated solution of ammonia in MeOH (20 mL).
The reaction mixture was stirred at room temperature for 18
h. The solvent was removed by rotary evaporation and the
cloudy brown oil, 2-norbornadienylmethanethiol, was used in
the next step of the procedure without further purification.
To a flask containing the crude thiol was added sodium
hydroxide (0.362 g, 9.18 mmol), which was dissolved in a
as a colorless oil: R
f
0.63 (hexanes); IR (neat, NaCl) 2974 (s),
2938 (s), 2867 (m), 1639 (w), 1558 (w), 1452 (m), 1297 (s), 1267
-
1 1
3
(m), 1249 (m), 1225 (m), 1093 (w) cm ; H NMR (CDCl , 400
MHz) δ 6.86 (dd, 1H, J ) 5.0, 3.0 Hz), 6.78 (dd, 1H, J ) 5.0,
3.0 Hz), 3.45 (br. s, 1H), 3.40 (t, 2H, J ) 6.7 Hz), 3.38 (br. s,
1H), 2.28-2.14 (m, 3H), 2.03 (dm, 1H, J ) 6.0 Hz), 1.76 (m,
2H), 1.56 (m, 2H); 13C NMR (CDCl
, 100 MHz) δ 146.4, 142.2,
3
141.8, 140.8, 71.2, 56.3, 52.9, 33.7, 31.9, 26.6, 25.0.
P r ep a r a tion of 2-Iod o-3-(4-tetr a h yd r op yr a n yloxybu -
tyl)n or bor n a d ien e (53). tert-Butyllithium (8.4 mL, 1.7 M,
14.3 mmol) was added to a flame-dried flask containing
bromide 5219 (2.12 g, 6.48 mmol) in THF (15 mL) at -78 °C.
After the reaction mixture stirred for 30 min, the resulting
yellow mixture was added via a cannula to a flame-dried flask
deoxygenated mixture of H
2
O (10 mL) and THF (14 mL), via
2
containing I (1.73 g, 13.6 mmol) in THF (18 mL) at -78 °C.
a cannula at 0 °C. After 20 min, 2-chloroethanol (0.75 mL, 11.2
mmol) was added dropwise to the solution. The reaction
mixture was stirred at 0 °C for 30 min and at room temper-
ature for 9 h. After adjusting the reaction mixture to a pH of
The reaction mixture was stirred at -78 °C for 3 h and at room
temperature for 30 min. After quenching of the reaction
mixture with water (50 mL), the aqueous layer was extracted
with diethyl ether (4 × 50 mL), and the combined organic

Norbornadiene-Tethered Nitrile Oxides
J . Org. Chem., Vol. 66, No. 1, 2001 283
layers were washed sequentially with water (50 mL) and brine
(4 × 50 mL), and the combined organic layers were washed
sequentially with water (50 mL) and brine (50 mL) and dried
over magnesium sulfate. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes 1:4) to give 56 (1.36 g, 4.69
(50 mL) and dried over magnesium sulfate. The solvent was
removed by rotary evaporation and the crude product was
purified by column chromatography (EtOAc/hexanes 1:19) to
give 53 (2.03 g, 5.42 mmol, 84%) as a colorless oil: R
f
0.70
(
(
(
EtOAc/hexanes 1:4); IR (neat, NaCl) 2938 (s), 2866 (m), 1557
f
mmol, 91%) as a colorless oil: R 0.25 (EtOAc/hexanes 1:4);
w), 1453 (w), 1440 (w), 1352 (w), 1323 (w), 1297 (m), 1259
w), 1200 (m), 1137 (m), 1120 (m), 1077 (m), 1034 (s), 1023 (s)
IR (neat, NaCl) 3334 (s), 3066 (w), 2971 (s), 2935 (s), 2865 (s),
1653 (w), 1617 (w), 1557 (m), 1456 (m), 1296 (s), 1259 (w), 1224
-
1
1
-1
1
cm ; H NMR (CDCl
3
, 400 MHz) δ 6.83 (dd, 1H, J ) 5.0, 2.9
(m), 1160 (w), 1052 (s), 1023 (m), 1000 (m) cm
;
H NMR
Hz), 6.70 (dd, 1H, J ) 5.0, 2.9 Hz), 4.56 (m, 1H), 3.85 (m, 1H),
3
3
(CDCl
3
, 400 MHz) δ 6.82 (dd, 1H, J ) 5.0, 2.9 Hz), 6.70 (dd,
.72 (m, 1H), 3.57 (br. s, 1H), 3.49 (m, 1H), 3.42 (br. s, 1H),
.38 (m, 1H), 2.25 (m, 1H), 2.17-2.10 (m, 2H), 1.99 (dm, 1H,
1H, J ) 5.0, 2.9 Hz), 3.63-3.57 (m, 3H), 3.41 (br. s, 1H), 2.25
(m, 1H), 2.16-2.08 (m, 2H), 2.00 (m, 1H), 1.53-1.40 (m, 5H);
1
3
J ) 6.0 Hz), 1.82 (m, 1H), 1.70 (m, 1H), 1.60-1.44 (m, 8H);
3
C NMR (CDCl , 100 MHz) δ 158.4, 142.0, 141.4, 101.2, 72.1,
1
3
C NMR (CDCl
3
, 100 MHz) δ 158.5, 142.0, 141.4, 101.0, 98.8,
62.5, 60.9, 53.4, 32.0, 31.8, 22.6. Anal. Calcd for C11
45.54; H, 5.21. Found C, 45.84; H, 5.05.
H15IO: C,
9
2
8.7, 72.1, 67.3, 67.2, 62.2, 60.95, 60.88, 53.4, 31.8, 30.7, 29.1,
5.4, 23.2, 19.6.
P r ep a r a tion of Alcoh ol 57. To a flame-dried flask con-
taining 54 (412 mg, 1.34 mmol) in MeOH (11.2 mL) was added
pyridium p-toluenesulfonate (PPTS, 69.3 mg, 0.276 mmol) at
room temperature. The reaction mixture was stirred at 55 °C
for 1 h. After quenching of the reaction mixture with water
(10 mL), the aqueous layer was extracted with diethyl ether
(4 × 25 mL), and the combined organic layers were washed
sequentially with water (25 mL) and brine (25 mL) and dried
over magnesium sulfate. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes 2:3) to give 57 (265 mg, 1.19
P r ep a r a tion of 2-Meth oxym eth yl-3-(4-tetr a h yd r op y-
r a n yloxybu tyl)n or bor n a d ien e (55). To a flame-dried flask
containing 2-methoxycarbonyl-3-(4-tetrahydropyranyloxybu-
tyl) norbornadiene 54 (1.84 g, 6.00 mmol) in CH Cl (10 mL)
2 2
was added DIBAL (16.0 mL, 1.0 M, 16.0 mmol) at -78 °C.
The reaction mixture was stirred at -78 °C for 50 min. After
quenching of the reaction mixture with water (10 mL), the
1
9
aqueous layer was extracted with CH
2
Cl
2
(4 × 25 mL), and
the combined organic layers were washed sequentially with
water (30 mL) and brine (30 mL) and dried over magnesium
sulfate. The solvent was removed by rotary evaporation and
the crude product was purified by column chromatography
f
mmol, 89%) as a colorless oil: R 0.35 (EtOAc/hexanes 2:3);
IR (neat, NaCl) 3393 (m), 2938 (s), 2867 (m), 1700 (s), 1695
(s), 1683 (s), 1653 (m), 1628 (m), 1558 (w), 1436 (m), 1345 (m),
(
EtOAc/hexanes 1:4) to give the corresponding alcohol (1.17
g, 4.20 mmol, 70%) as a colorless oil: R 0.16 (EtOAc/hexanes
:4); IR (neat, NaCl) 3423 (m), 3062 (w), 2939 (s), 2865 (s),
658 (w), 1556 (w), 1453 (m), 1441 (m), 1353 (m), 1323 (w),
-1
f
1295 (s), 1239 (s), 1193 (m), 1160 (m), 1103 (m), 1070 (m) cm ;
1
1
1
1
3
H NMR (CDCl , 400 MHz) δ 6.85 (dd, 1H, J ) 5.0, 3.0 Hz),
6.68 (dd, 1H, J ) 5.0, 3.2 Hz), 3.86 (br. s, 1H), 3.69 (s, 3H),
3.63 (t, 2H, J ) 5.9 Hz), 3.50 (br. s, 1H), 2.77-2.63 (m, 2H),
2.01 (dm, 1H, J ) 6.4 Hz), 1.95 (dm, 1H, J ) 6.4 Hz), 1.79 (br.
-1 1
201 (m), 1137 (m), 1120 (m), 1076 (m), 1023 (s) cm ; H NMR
, 400 MHz) δ 6.78 (dd, 1H, J ) 5.0, 2.9 Hz), 6.71 (dd,
(CDCl
3
1
4
3
2
H, J ) 5.0, 2.9 Hz), 4.54 (m, 1H), 4.23 (dAB, 1H, J ) 12.2 Hz),
.11 (dABd, 1H, J ) 12.2, 2.0 Hz), 3.85 (m, 1H), 3.71 (m, 1H),
.53 (br. s, 1H), 3.49 (m, 1H), 3.39-3.33 (m, 2H), 2.25 (m, 1H),
.15 (m, 1H), 1.93 (dm, 1H, J ) 5.8 Hz), 1.88 (dm, 1H, J ) 5.8
s, 1H), 1.61-1.24 (m, 4H); 13C NMR (CDCl
3
, 100 MHz) δ 173.6,
166.3, 143.8, 140.7, 138.6, 71.2, 62.4, 56.0, 51.0, 50.9, 32.0, 29.7,
23.0. Anal. Calcd for C13
70.39; H, 8.13.
18 3
H O : C, 70.24; H, 8.16. Found C,
1
3
Hz), 1.80 (m, 1H), 1.67 (m, 1H), 1.56-1.38 (m, 9H); C NMR
CDCl , 100 MHz) δ 152.1, 145.7, 143.0, 142.13, 142.11, 98.79,
8.76, 71.4, 67.3, 62.34, 62.31, 58.8, 53.5, 51.87, 51.85, 30.7,
8.94, 28.92, 27.8, 25.4, 23.9, 19.62, 19.60. This alcohol (1.01
P r ep a r a tion of Alcoh ol 58. To a flame-dried flask con-
taining 55 (690 mg, 2.36 mmol) in MeOH (20 mL) was added
pyridium p-toluenesulfonate (PPTS, 149 mg, 0.593 mmol) at
room temperature. The reaction mixture was stirred at 55 °C
for 1 h. After quenching of the reaction mixture with water
(20 mL), the aqueous layer was extracted with diethyl ether
(4 × 40 mL), and the combined organic layers were washed
sequentially with water (40 mL) and brine (40 mL) and dried
over magnesium sulfate. The solvent was removed by rotary
evaporation and the crude product was purified by column
chromatography (EtOAc/hexanes 1:4) to give 58 (466 mg, 2.24
(
9
2
3
g, 3.63 mmol) in THF (1.3 mL) was added via a cannula to a
flame-dried flask containing NaH (212 mg, 8.83 mmol) in THF
(4 mL). The reaction mixture was stirred at room temperature
for 30 min and at 30 °C for 1.5 h. Iodomethane (1.20 mL, 19.3
mmol) was then added, and the reaction mixture was allowed
to stir at room temperature for 3 h. After quenching of the
reaction mixture with water (20 mL), the aqueous layer was
extracted with diethyl ether (4 × 20 mL), and the combined
organic layers were washed sequentially with water (20 mL)
and brine (20 mL) and dried over magnesium sulfate. The
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography (EtOAc/
hexanes 1:9) to give 55 (831 mg, 2.84 mmol, 78%) as a colorless
f
mmol, 95%) as a colorless oil: R 0.30 (EtOAc/hexanes 2:3);
IR (neat, NaCl) 3394 (m), 3064 (w), 2975 (s), 2934 (s), 2864
(s), 2819 (m), 1556 (w), 1451 (m), 1376 (m), 1355 (m), 1307
-
1
1
(m), 1190 (m), 1141 (m), 1073 (s), 1025 (m) cm
(CDCl , 400 MHz) δ 6.75 (dd, 1H, J ) 4.8, 3.0 Hz), 6.67 (dd,
1H, J ) 4.8, 3.0 Hz), 4.01 (dAB, 1H, J ) 11.8 Hz), 3.85 (dAB
; H NMR
3
,
oil: R
936 (s), 2865 (s), 2815 (m), 1658 (w), 1557 (w), 1453 (m), 1441
f
0.55 (EtOAc/hexanes 1:4); IR (neat, NaCl) 3064 (w),
1H, J ) 11.8 Hz), 3.56 (t, 2H, J ) 6.2 Hz), 3.46 (br. s, 1H),
3.34 (br. s, 1H), 3.18 (s, 3H), 2.28 (br. s, 1H), 2.19-2.26 (m,
2H), 1.91 (dm, 1H, J ) 5.8 Hz), 1.85 (dm, 1H, J ) 5.8 Hz),
2
(
(
m), 1376 (m), 1353 (m), 1323 (w), 1305 (w), 1260 (w), 1229
w), 1200 (m), 1191 (m), 1160 (m), 1139 (s), 1120 (s), 1077 (s),
1.34-01.55 (m, 4H); 13C NMR (CDCl
, 100 MHz) δ 153.3, 143.3,
142.9, 141.8, 71.2, 68.0, 62.4, 57.3, 53.5, 51.9, 32.1, 27.9, 23.5.
3
1
1
1
3
2
035 (s), 1023 (s) cm-1; 1H NMR (CDCl
3
, 400 MHz) δ 6.73 (dd,
H, J ) 5.0, 3.0 Hz), 6.65 (dd, 1H, J ) 5.0, 3.1 Hz), 4.50 (m,
H), 3.99 (dAB, 1H, J ) 11.8 Hz), 3.83 (dAB, 1H, J ) 11.8 Hz),
.79 (m, 1H), 3.67 (m, 1H), 3.47-3.41 (m, 2H), 3.32-3.30 (m,
H), 3.16 (s, 3H), 2.21 (m, 1H), 2.11 (m, 1H), 1.89 (dm, 1H, J
Anal. Calcd for C13
H, 9.79.
20 2
H O : C, 74.96; H, 9.68. Found C, 74.77;
P r ep a r a tion of Iod id e 59. To a flame-dried flask contain-
ing PPh (4.20 g, 16.0 mmol), imidazole (2.52 g, 37.0 mmol),
acetonitrile (12 mL), and THF (8.1 mL) was added I (4.30 g,
3
)
5.8 Hz), 1.83 (dm, 1H, J ) 5.8 Hz), 1.77 (m, 1H), 1.66 (m,
2
1
3
1
1
5
H), 1.55-1.35 (m, 8H); C NMR (CDCl
3
, 100 MHz) δ 153.1,
33.9 mmol) at 0 °C. The reddish-brown reaction mixture was
stirred for 15 m at 0 °C. Alcohol 56 (1.06 g, 3.65 mmol) in
acetonitrile (6 mL) was added via a cannula at 0 °C. The
reaction mixture was stirred at room temperature for 4 h. After
the reaction mixture was quenched with water (20 mL), the
aqueous layer was extracted with diethyl ether (4 × 20 mL),
and the combined organic layers were washed sequentially
with water (20 mL), saturated sodium thiosulfate (20 mL) and
brine (20 mL) and dried over magnesium sulfate. The solvent
was removed by rotary evaporation and the crude product was
43.4, 142.8, 141.8, 98.62, 98.60, 71.1, 67.9, 67.1, 62.1, 57.3,
3.5, 51.9, 30.6, 29.1, 27.9, 25.3, 23.9, 19.5. Anal. Calcd for
C
18
H
28
O
3
: C, 73.93; H, 9.65. Found C, 73.96; H, 9.64.
P r ep a r a tion of Alcoh ol 56. To a flame-dried flask con-
taining 53 (1.93 g, 5.15 mmol) in MeOH (43 mL) was added
pyridium p-toluenesulfonate (PPTS, 332 mg, 1.28 mmol) at
room temperature. The reaction mixture was stirred at 55 °C
for 1 h. After quenching of the reaction mixture with water
(50 mL), the aqueous layer was extracted with diethyl ether

2
84 J . Org. Chem., Vol. 66, No. 1, 2001
Yip et al.
purified by column chromatography (hexanes) to give iodide
9 (1.13 g, 2.82 mmol, 77%) as a colorless oil: R 0.80 (EtOAc/
hexanes 1:4); IR (neat, NaCl) 3065 (w), 2971 (s), 2934 (s), 2864
and dried over magnesium sulfate. The solvent was removed
by rotary evaporation and the crude product was purified by
column chromatography.
5
f
(
m), 1616 (w), 1557 (m), 1449 (m), 1426 (m), 1295 (s), 1260
Nitr o Com p ou n d 7. Bromide 6 (4.00 g, 17.6 mmol) in
DMSO (10 mL) was added via cannula to a flask containing
NaNO (3.01 g, 43.6 mmol) and phloroglucinol (3.55 g, 21.9
2
-
1 1
3
(m), 1216 (s), 1181 (m), 1163 (m) cm ; H NMR (CDCl , 400
MHz) δ 6.85 (dd, 1H, J ) 5.1, 2.9 Hz), 6.73 (dd, 1H, J ) 5.1,
.9 Hz), 3.60 (br. s, 1H), 3.43 (br. s, 1H), 3.20 (t, 2H, J ) 6.8
Hz), 2.27 (m, 1H), 2.17 (dm, 1H, J ) 6.0 Hz), 2.15 (m, 1H),
2
mmol) in DMSO (8 mL). The light brown reaction mixture was
stirred at room temperature for 48 h. After quenching of the
reaction with water (100 mL), the aqueous layer was extracted
with diethyl ether (4 × 40 mL) and the combined organic layers
were washed with water (100 mL) and brine (100 mL) and
dried over magnesium sulfate. The solvent was removed by
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes 1:9) to give 7 (1.91
2
(
3
.02 (dm, 1H, J ) 6.0 Hz), 1.73 (m, 2H), 1.53 (m, 2H); 13C NMR
CDCl , 100 MHz) δ 158.0, 142.0, 141.4, 101.6, 72.2, 61.0, 53.4,
3
2.5, 30.9, 27.2, 7.1.
P r ep a r a tion of Iod id e 60. To a flame-dried flask contain-
ing PPh
acetonitrile (2.9 mL), and THF (2 mL) was added I
.30 mmol) at 0 °C. The reddish-brown reaction mixture was
3
(1.10 g, 4.19 mmol), imidazole (651 mg, 9.56 mmol),
2
(1.18 g,
9
g, 9.88 mmol, 56%) as a colorless viscous oil: R
f
0.40 (EtOAc/
stirred for 15 min at 0 °C. Alcohol 57 (216 mg, 0.970 mmol) in
acetonitrile (2 mL) was added via a cannula at 0 °C. The
reaction mixture was stirred at room temperature for 21 h.
hexanes 1:9); IR (neat, NaCl) 3065 (w), 2969 (s), 2933 (s), 2866
-1
1
(
(
)
(
m), 1553 (s), 1434 (m), 1382 (m), 1301 (m) cm
CDCl , 400 MHz) δ 6.73 (m, 2H), 6.15 (m, 1H), 4.35 (t, 2H, J
7.0 Hz), 3.49 (m, 1H), 3.25 (m, 1H), 2.24 (m, 2H), 1.97-1.90
; H NMR
3
2 2
The reaction mixture was diluted with CH Cl (20 mL) and
quenched with water (20 mL). The aqueous layer was ex-
tracted with diethyl ether (3 × 40 mL), and the combined
organic layers were washed sequentially with water (40 mL),
saturated sodium thiosulfate (40 mL), and brine (40 mL) and
dried over magnesium sulfate. The solvent was removed by
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes 1:9) to give iodide 60
13
m, 4H), 1.51 (m, 2H); C NMR (CDCl
3
, 100 MHz) δ 157.2,
43.7, 142.1, 134.4, 75.4, 73.4, 53.2, 50.0, 30.4, 26.7, 23.6;
m/z 193.1103, found m/z 193.1105.
: C, 68.37; H, 7.82; N, 7.25. Found
1
HRMS calcd for C11
Anal. Calcd for C11
C, 68.59; H, 7.79; N, 7.20.
Nitr o Com p ou n d 15. R
neat, NaCl) 3065 (w), 2969 (m), 2932 (m), 2864 (m), 1553 (s),
H
15NO
2
H
15NO
2
f
0.43 (EtOAc/hexanes 1:19); IR
(
1
(
)
(
(
272 mg, 0.82 mmol, 84%) as a colorless oil: R
hexanes 1:4); IR (neat, NaCl) 3067 (w), 2970 (s), 2937 (s), 2867
m), 1694 (s), 1682 (m), 1626 (s), 1558 (m), 1433 (s), 1340 (s),
294 (s), 1249 (s), 1239 (s), 1191 (s), 1155 (s), 1102 (s), 1068
f
0.68 (EtOAc/
-1 1
461 (w), 1435 (m), 1383 (m), 1301 (m), 1185 (w) cm ; H NMR
, 400 MHz) δ 6.73 (m, 2H), 6.12 (m, 1H), 4.35 (t, 2H, J
7.0 Hz), 3.48 (m, 1H), 3.25 (m, 1H), 2.20 (m, 2H), 2.02-1.92
CDCl
3
(
1
13
m, 4H), 1.46 (m, 2H), 1.33 (m, 2H); C NMR (CDCl
3
, 100
-
1
1
(m), 1038 (w), 1019 (w) cm ; H NMR (CDCl
3
, 400 MHz) δ
MHz) δ 157.9, 143.7, 142.1, 133.8, 75.5, 73.4, 53.3, 49.9, 30.9,
7.1, 26.2, 25.7; HRMS calcd for C12 m/z 207.1259,
found m/z 207.1258. Anal. Calcd for C12 : C, 69.54; H,
.27; N, 6.76. Found C, 69.39; H, 8.29; N, 6.79.
Nitr o Com p ou n d 16. R 0.57 (EtOAc/hexanes 1:9); IR
neat, NaCl) 3117 (w), 3064 (m), 2968 (s), 2931 (s), 2862 (s),
653 (w), 1622 (w), 1561 (s), 1556 (s), 1231 (w), 1184 (w), 1150
6
3
6
1
.87 (dd, 1H, J ) 5.0, 3.0 Hz), 6.71 (dd, 1H, J ) 5.0, 3.2 Hz),
2
H
H
17NO
17NO
2
.88 (br. s, 1H), 3.71 (s, 3H), 3.51 (br. s, 1H), 3.19 (t, 2H, J )
.8 Hz), 2.71 (m, 2H), 2.03 (dm, 1H, J ) 6.4 Hz), 1.97 (dm,
H, J ) 6.4 Hz), 1.75 (p, 2H, J ) 7.1 Hz), 1.67-1.50 (m, 2H);
2
8
1
3
f
C NMR (CDCl
1.2, 55.9, 51.1, 51.0, 32.6, 28.9, 27.5, 6.8. Anal. Calcd for
: C, 47.01; H, 5.16. Found C, 46.87; H, 5.18.
P r ep a r a tion of Iod id e 61. To a flame-dried flask contain-
ing PPh (2.56 g, 9.86 mmol), imidazole (1.54 g, 22.6 mmol),
acetonitrile (8 mL), and THF (5 mL) was added I (2.76 g, 21.7
3
, 100 MHz) δ 172.6, 166.1, 143.8, 140.7, 139.0,
(
1
(
1
(
(
5
7
13 2
C H17IO
-
1 1
w) cm ; H NMR (CDCl
3
, 400 MHz) δ 6.75 (m, 2H), 6.11 (m,
H), 4.36 (t, 2H, J ) 7.1 Hz), 3.49 (m, 1H), 3.26 (m, 1H), 2.18
3
1
3
m, 2H), 2.03-1.93 (m, 4H), 1.47-1.26 (m, 6H); C NMR
CDCl , 100 MHz) δ 158.4, 143.8, 142.3, 133.5, 75.6, 73.5, 53.4,
0.0, 31.2, 28.4, 27.3, 26.7, 26.0. Anal. Calcd for C13
C, 70.56; H, 8.65; N, 6.33. Found C, 70.71; H, 8.64; N, 6.35.
Nitr o Com p ou n d 18. R 0.43 (EtOAc/hexanes 1:19); IR
neat, NaCl) 3066 (w), 2958 (s), 2932 (s), 2859 (m), 1557 (s),
2
3
mmol) at 0 °C. The reddish-brown reaction mixture was stirred
for 15 m at 0 °C. Alcohol 58 (466 mg, 2.24 mmol) in acetonitrile
2
H19NO :
(3 mL) was added via a cannula at 0 °C. The reaction mixture
f
was stirred at room temperature for 3 h. After the reaction
mixture was quenched with water (20 mL), the aqueous layer
was extracted with diethyl ether (4 × 20 mL), and the
combined organic layers were washed sequentially with water
(
1
1
(
(
(
472 (w), 1463 (w), 1386 (w), 1362 (w), 1301 (w), 1258 (m),
-
1
1
112 (m), 1021 (w) cm ; H NMR (CDCl , 400 MHz) δ 6.74
3
m, 2H), 6.14 (m, 1H), 4.39-4.30 (m, 3H), 3.50 (m, 1H), 3.26
(40 mL), saturated sodium thiosulfate (40 mL), and brine (40
m, 1H), 2.20 (m, 2H), 1.96 (m, 2H), 1.55-1.41 (m, 4H), 0.85
mL) and dried over magnesium sulfate. The solvent was
removed by rotary evaporation and the crude product was
purified by column chromatography (EtOAc/hexanes 1:9) to
give iodide 61 (584 mg, 1.84 mmol, 82%) as a colorless oil: R
0
2
s, 9H), 0.06 (s, 3H), 0.01 (s, 3H); 13C NMR (CDCl
, 100 MHz)
3
δ 157.7, 153.6, 143.84, 143.80, 142.15, 142.09, 134.2, 134.1,
8
2
1.01, 80.99, 73.5, 70.0, 69.9, 53.3, 50.0, 34.7, 34.6, 31.2, 31.1,
5.6, 22.4, 22.1, 17.8, -4.7, -5.2, -5.3; HRMS calcd for C18
m/z 337.2073, found m/z 337.2078.
Nitr o Com p ou n d 27. R 0.44 (EtOAc/hexanes 1:4); IR
(neat, NaCl) 3066 (w), 2980 (m), 2936 (m), 2868 (m), 1557 (s),
f
31
H -
.44 (EtOAc/hexanes 1:9); IR (neat, NaCl) 3062 (w), 2968 (s),
931 (s), 2863 (s), 2814 (m), 1556 (w), 1449 (m), 1376 (w), 1354
SiNO
3
(w), 1307 (m), 1288 (m), 1216 (m), 1189 (m), 1170 (m), 1141
f
-
1 1
(m), 1098 (s) cm ; H NMR (CDCl , 400 MHz) δ 6.79 (dd, 1H,
3
1
1
(
466 (w), 1421 (m), 1372 (m), 1309 (w), 1300 (w), 1283 (w),
J ) 5.0, 3.0 H), 6.73 (dd, 1H, J ) 5.0, 3.0 Hz), 4.02 (dAB, 1H,
J ) 11.8 Hz), 3.88 (dAB, 1H, J ) 11.8 Hz), 3.50 (br. s, 1H),
-1 1
218 (m), 1187 (w), 1129 (m), 1091 (m), 1032 (w) cm ; H NMR
, 400 MHz) δ 6.77 (dd, 1H, J ) 5.2, 3.1 Hz), 6.72 (dd,
CDCl
3
3
1
.38 (br. s, 1H), 3.23 (s, 3H), 3.17 (t, 2H, J ) 6.8 Hz), 2.26 (m,
H), 2.15 (m, 1H), 1.95 (dm, 1H, J ) 5.8 Hz), 1.89 (dm, 1H, J
1
H, J ) 5.1, 3.0 Hz), 6.49 (m, 1H), 4.49 (t, 2H, J ) 4.9 Hz),
5.8 Hz), 1.72 (m, 2H), 1.51 (m, 2H); 1 C NMR (CDCl
3
4.17 (dd, 1H, J ) 12.9, 1.3 Hz), 4.10 (dd, 1H, J ) 12.9, 1.5
)
3
, 100
Hz), 3.82 (m, 2H), 3.55 (m, 1H), 3.40 (m, 1H), 2.01 (m, 1H),
MHz) δ 152.6, 144.0, 143.0, 141.9, 71.4, 68.1, 57.6, 53.6, 52.1,
1
1
.97 (m, 1H); 13C NMR (CDCl
3
, 100 MHz) δ 153.8, 143.2, 142.4,
39.7, 75.1, 73.7, 69.5, 64.8, 51.1, 50.1. Anal. Calcd for C10
: C, 61.53; H, 6.71; N, 7.17. Found C, 61.44; H, 6.70; N,
.31.
Nitr o Com p ou n d 28. R
3
6
2.8, 28.1, 27.1, 6.9. Anal. Calcd for C13
.02. Found C, 48.91; H, 6.23.
H17IO: C, 49.07; H,
13
H -
NO
3
Gen er a l P r oced u r e for th e Con ver sion of Nor bor n a -
7
d ien e-Teth er ed Br om id es or Iod id es to Nor bor n a d ien e-
Teth er ed Nitr o Com p ou n d s (7, 15, 16, 27, 28, 31, 46, 47,
f
0.45 (EtOAc/hexanes 1:4); IR
4
(
9, 51, a n d 62-64). Norbornadiene-tethered bromide or iodide
1 equiv) in DMSO was added via cannula to a flask containing
NaNO (2.5-3.5 equiv) and phloroglucinol (1.2-1.5 equiv) in
(neat, NaCl) 3065 (w), 2969 (m), 2933 (m), 2867 (m), 1559 (s),
1421 (w), 1380 (m), 1364 (m), 1307 (w), 1219 (w), 1125 (m),
1042 (w) cm ; H NMR (CDCl , 400 MHz) δ 6.70 (m, 2H), 6.17
3
-1 1
2
DMSO. The light brown reaction mixture was stirred at room
temperature for 8-69 h. After quenching of the reaction with
water, the aqueous layer was extracted with diethyl ether and
the combined organic layers were washed with water and brine
(m, 1H), 4.48 (t, 2H, J ) 5.0 Hz), 3.91 (t, 2H, J ) 5.1 Hz), 3.52
(t, 2H, J ) 6.9 Hz), 3.45 (m, 1H), 3.27 (m, 1H), 2.44 (m, 2H),
1
3
1.94 (dt, 1H, J ) 5.7, 1.6 Hz), 1.90 (dm, 1H, J ) 5.7 Hz);
NMR (CDCl
C
3
, 100 MHz) δ 154.7, 143.6, 142.1, 135.3, 75.0, 73.5,

Norbornadiene-Tethered Nitrile Oxides
J . Org. Chem., Vol. 66, No. 1, 2001 285
6
2
9.5, 65.9, 53.4, 50.0, 31.3; HRMS calcd for C11
09.1052, found m/z 209.1051.
H
15NO
3
m/z
143.9, 140.6, 139.7, 75.2, 71.4, 55.8, 51.1, 51.0, 28.9, 26.5, 23.3.
Anal. Calcd for C13
H
17NO
4
: C, 62.14; H, 6.82. Found C, 63.56;
Nitr o Com p ou n d 31. R
f
0.67 (EtOAc/hexanes 1:4); IR
H, 6.74.
(
1
neat, NaCl) 2977 (m), 2935 (m), 2867 (w), 1554 (s), 1430 (m),
376 (m), 1306 (m), 1184 (w) cm ; H NMR (CDCl , 400 MHz)
3
Nitr o Com p ou n d 64. R 0.73 (EtOAc/hexanes 2:3); IR
f
-1
1
(neat, NaCl) 3064 (w), 2969 (s), 2932 (s), 2865 (s), 2818 (m),
1660 (w), 1552 (s), 1452 (m), 1435 (m), 1382 (s), 1355 (m) 1306
(m), 1288 (w), 1247 (w), 1230 (w), 1190 (m), 1141 (m), 1095 (s)
δ 6.83 (dd, 1H, J ) 5.0, 3.1 Hz), 6.69 (dd, 1H, J ) 5.0, 3.0 Hz),
6
(
.37 (dm, 1H, J ) 1.6 Hz), 4.43 (td, 2H, J ) 7.2, 1.1 Hz), 3.58
-
1 1
dm, 1H, J ) 1.2 Hz), 3.40 (dAB, 1H, J ) 14.0 Hz), 3.38 (br. s,
3
cm ; H NMR (CDCl , 400 MHz) δ 6.79 (dd, 1H, J ) 5.1, 3.0
1
4
6
1
H), 3.35 (dABd, 1H, J ) 14.0, 1.1 Hz), 2.80 (td, 2H, J ) 7.2,
.8 Hz), 2.02 (dABt, 1H, J ) 6.0, 1.5 Hz), 1.99 (dABm, 1H, J )
Hz), 6.70 (dd, 1H, J ) 5.1, 3.0 Hz), 4.35 (t, 2H, J ) 6.9 Hz),
4.02 (dAB, 1H, J ) 11.8 Hz), 3.88 (dAB, 1H, J ) 11.8 Hz), 3.50
(br. s, 1H), 3.34 (br. s, 1H), 3.23 (s, 3H), 2.29 (m, 1H), 2.19 (m,
1H), 1.94 (dm, 1H, J ) 5.9 Hz), 1.89 (dm, 1H, J ) 5.9 Hz),
1
3
.0 Hz); C NMR (CDCl
38.9, 74.2, 73.1, 52.8, 50.5, 32.7, 26.6. Anal. Calcd for C10
: C, 56.85; H, 6.20. Found C, 56.87; H, 6.19.
Nitr o Com p ou n d 46. R 0.40 (EtOAc/hexanes 1:9); IR
neat, NaCl) 3063 (w), 2964 (s), 2932 (s), 2863 (m), 1556 (s),
436 (m), 1382 (m), 1302 (m) cm-1; 1H NMR (CDCl
, 400 MHz)
3
, 100 MHz) δ 152.0, 142.7, 142.3,
13
H -
1.87 (m, 2H), 1.45 (m, 2H); 13C NMR (CDCl
, 100 MHz) δ 151.8,
44.7, 143.1, 141.8, 75.4, 71.5, 68.1, 57.7, 53.5, 52.2, 27.3, 26.7,
3.9; HRMS calcd for C13 m/z 237.1365, found m/z
SNO
2
3
1
2
f
H
19NO
3
(
1
237.1367.
3
Gen er a l P r oced u r e for in Situ F or m a tion of Nitr ile
Oxid es fr om th e Cor r esp on d in g Nitr o Com p ou n d s a n d
Su bsequ en t In tr a m olecu la r 1,3-Dip ola r Cycloa d d ition s
δ 6.73 (m, 1H), 6.70 (m, 1H), 4.33 (t, 2H, J ) 7.0 Hz), 3.26 (br.
s, 1H), 3.21 (br. s, 1H), 2.18 (m, 1H), 2.10 (m, 1H), 1.90-1.81
1
3
3
(m, 4H), 1.68 (s, 3H), 1.45 (m, 2H); C NMR (CDCl , 100 MHz)
(
(
9, 32-36, 65, 66, 68-72). Di-tert-butyl dicarbonate, (BOC)
2
O
δ 144.6, 144.2, 142.5, 142.1, 75.5, 70.9, 55.2, 52.9, 27.0, 26.7,
2
2
2-3 equiv) in toluene was added via a cannula to a flame-
3.9, 14.1; HRMS calcd for C12
07.1255.
2
H17NO m/z 207.1259, found m/z
dried flask containing the nitro compound (1 equiv) and
-(dimethylamino)pyridine (DMAP, 10-20 mol %) in toluene.
4
Nitr o Com p ou n d 47. R
f
0.76 (EtOAc/hexanes 1:9); IR
The reaction mixture was stirred at 90 °C for 18-96 h. The
solvent was removed by rotary evaporation and the crude
product was purified by column chromatography to provide
the pure cycloadducts.
(neat, NaCl) 3063 (w), 2960 (s), 2929 (s), 2859 (s), 1555 (s),
1
1
465 (m), 1457 (m), 1435 (m), 1381 (m), 1303 (m), 1229 (w),
-1 1
200 (w) cm ; H NMR (CDCl , 400 MHz) δ 6.70 (m, 2H), 4.35
3
(t, 2H, J ) 7.0 Hz), 3.32 (m, 1H), 3.27 (m, 1H), 2.23-1.97 (m,
2
Cycloa d d u ct 9. Di-tert-butyl dicarbonate, (BOC) O (274
4
0
1
2
2
H), 1.92-1.83 (m, 4H), 1.50-1.33 (m, 4H), 1.30-1.17 (m, 6H),
.87 (t, 3H, J ) 6.8 Hz); 1 C NMR (CDCl
45.0, 142.6, 142.2, 75.6, 71.1, 53.2, 52.9, 31.7, 29.0, 28.2, 27.5,
3
mg, 1.25 mmol) in toluene (2.5 mL) was added via a cannula
to a flame-dried flask containing the nitro compound 7 (100
mg, 0.518 mmol) and 4-(dimethylamino)pyridine (DMAP, 12.4
mg, 0.101 mmol) in toluene (2.5 mL). The reaction mixture
was stirred at 90 °C for 96 h. The solvent was removed by
rotary evaporation and the crude product was purified by
column chromatography (EtOAc/hexanes 1:9) to give cycload-
duct 9 (77.6 mg, 0.443 mmol, 86%) as white crystals. Recrys-
tallization with 10% EtOAc/hexanes provided colorless needle-
3
, 100 MHz) δ 148.3,
2
7.2, 26.8, 24.1, 22.6, 14.1; HRMS calcd for C17H27NO m/z
77.2042, found m/z 277.2047.
Nitr o Com p ou n d 49. R
f
0.63 (EtOAc/hexanes 1:4); IR
(neat, NaCl) 2976 (m), 2939 (m), 2869 (m), 1639 (w), 1553 (s),
1
1
(
453 (m), 1434 (m), 1382 (m), 1297 (m), 1226 (w), 1097 (w),
045 (m), 1015 (w) cm-1; H NMR (CDCl
, 400 MHz) δ 6.86
1
3
dd, 1H, J ) 5.0, 2.7 Hz), 6.76 (dd, 1H, J ) 5.0, 2.9 Hz), 4.36
like crystals: R
f
0.25 (EtOAc/hexanes 1:9); mp 67.5 °C; IR
(
t, 2H, J ) 6.9 Hz), 3.39 (br.s, 2H), 2.25 (m, 2H), 2.17 (dm,
(
(
CH
w), 1320 (m), 1256 (m), 1246 (m) cm ; H NMR (CDCl
2 2
Cl ) 3073 (w), 2979 (s), 2949 (s), 1647 (w), 1446 (w), 1430
1
7
1
H, J ) 6.0 Hz), 2.03 (dm, 1H, J ) 6.0 Hz), 1.89 (p, 2H, J )
-1 1
3
, 400
.3 Hz), 1.50 (m, 2H); 13C NMR (CDCl
42.1, 141.9, 141.4, 75.3, 71.3, 56.4, 52.9, 26.7, 26.5, 23.2. Anal.
14ClNO : C, 58.03; H, 6.20. Found C, 58.01; H,
, 100 MHz) δ 145.8,
3
MHz) δ 6.27 (dd, 1H, J ) 5.7, 3.0 Hz), 6.00 (dd, 1H, J ) 5.7,
.2 Hz), 4.33 (s, 1H), 3.18 (m, 1H), 2.75 (br. s, 1H), 2.34 (t, 2H,
J ) 7.8 Hz), 2.16-1.96 (m, 2H), 1.77 (m, 1H), 172 (d, 1H, J )
.3 Hz), 1.57 (dd, 1H, J ) 9.1 Hz, J ) 1.1 Hz), 1.31 (ddd, 1H,
3
Calcd for C11
.21.
Nitr o Com p ou n d 51. R
neat, NaCl) 3067 (w), 2975 (m), 2938 (m), 2867 (m), 1633 (w),
H
2
6
9
f
0.68 (EtOAc/hexanes 1:9); IR
13
J ) 12.8, 7.9, 2.3 Hz); C NMR (CDCl
3
, 100 MHz) δ 167.5,
(
1
38.0, 135.3, 92.6, 76.2, 50.5, 46.7, 44.4, 32.0, 24.0, 20.2; HRMS
1
1
5
553 (s), 1455 (w), 1434 (m), 1383 (m), 1297 (m), 1261 (w),
calcd for C11
Calcd for C11
H
H
13NO m/z 175.0997, found m/z 175.0999. Anal.
13NO: C, 75.40; H, 7.48; N, 7.99. Found C, 75.60;
-
1 1
225 (w) cm ; H NMR (CDCl
3
, 400 MHz) δ 6.84 (dd, 1H, J )
.1, 3.3 Hz), 6.73 (dd, 1H, J ) 5.1, 2.9 Hz), 4.35 (t, 2H, J ) 2.0
H, 7.55; N, 7.88.
Cycloa d d u ct 32. R 0.23 (EtOAc/hexanes 1:9); IR (neat,
f
NaCl) 3062 (w), 2975 (s), 2936 (s), 2859 (m), 1626 (w), 1448
m), 1354 (w), 1326 (m), 1255 (w), 1232 (w), 1148 (w), 1049
Hz), 3.46 (m, 1H), 3.40 (br. s, 1H), 2.29-2.14 (m, 3H), 2.02
(
(
5
2
dt, 1H, J ) 6.0, 1.6 Hz), 1.89 (m, 2H), 1.49 (m, 2H); 13C NMR
CDCl , 100 MHz) δ 149.7, 141.9, 141.6, 130.4, 75.2, 71.6, 57.9,
3.2, 28.1, 26.4, 22.9; HRMS calcd for C11 14BrNO m/z
71.0208, found m/z 271.0207.
Nitr o Com p ou n d 62. R 0.61 (EtOAc/hexanes 1:4); IR
neat, NaCl) 3066 (w), 2973 (m), 2936 (m), 2866 (m), 1560 (s),
556 (s), 1549 (s), 1453 (m), 1434 (m), 1382 (m), 1296 (m), 1258
3
(
(
3
H
2
-1 1
w) cm ; H NMR (CDCl , 400 MHz) δ 6.29 (dd, 1H, J ) 5.8,
3
.0 Hz), 5.97 (dd, 1H, J ) 5.7, 3.2 Hz), 4.02 (t, 1H, J ) 1.3
f
Hz), 3.16 (m, 1H), 2.90 (m, 1H), 2.59 (dm, 1H, J ) 13.6 Hz),
(
1
2.08 (td, 1H, J ) 13.3, 5.3 Hz), 1.98 (m, 1H), 1.72-1.65 (m,
2H), 1.61-1.52 (m, 3H), 1.49-1.40 (m, 2H); 13C NMR (CDCl ,
3
-
1 1
(
w), 1225 (w), 1190 (w), 1163 (w), 1131 (w), 1022 (w) cm ; H
NMR (CDCl , 400 MHz) δ 6.85 (dd, 1H, J ) 5.0, 2.9 Hz), 6.71
dd, 1H, J ) 5.0, 2.9 Hz), 4.38 (t, 2H, J ) 6.8 Hz), 3.60 (br. s,
100 MHz) δ 160.8, 137.9, 133.9, 90.9, 67.8, 50.7, 44.7, 44.3,
36.7, 27.4, 23.8, 22.6; HRMS calcd for C H15NO m/z 189.1154,
3
1
2
(
1
found m/z 189.1159.
Cycloa d d u cts 33. Two separable diasteromers 33a and
H), 3.41 (br. s, 1H), 2.31 (m, 1H), 2.18 (m, 1H), 2.16 (dm, 1H,
J ) 6.1 Hz), 2.03 (dm, 1H, J ) 6.1 Hz), 1.90 (m, 2H), 1.52 (m,
33b. Cycloadduct 33a : R 0.31 (EtOAc/hexanes 1:19); IR (neat,
f
1
3
2
7
INO
H); C NMR (CDCl
5.4, 72.3, 61.0, 53.4, 31.1, 26.5, 23.1. Anal. Calcd for C11
: C, 41.40; H, 4.42. Found C, 41.75; H, 4.32.
Nitr o Com p ou n d 63. R 0.75 (EtOAc/hexanes 2:3); IR
neat, NaCl) 3068 (w), 2972 (s), 2949 (s), 2869 (m), 1704 (s),
699 (s), 1683 (s), 1626 (s), 1563 (s), 1557 (s), 1549 (s), 1455
m), 1435 (s), 1384 (s), 1295 (s), 1239 (s), 1193 (m), 1162 (s),
135 (w), 1103 (s), 1072 (s), 1019 (w), 1004 (w) cm-1; 1H NMR
CDCl , 400 MHz) δ 6.87 (dd, 1H, J ) 4.9, 3.1 Hz), 6.69 (dd,
3
, 100 MHz) δ 157.4, 142.2, 141.2, 102.3,
NaCl) 3064 (w), 2934 (s), 2857 (m), 1555 (w), 1361 (w), 1257
H
14
-
(m), 1115 (m), 1063 (m), 1027 (m) cm-1
; H NMR (CDCl , 400
1
3
2
MHz) δ 6.34 (dd, 1H, J ) 5.7, 3.0 Hz), 6.00 (dd, 1H, J ) 5.7,
3.2 Hz), 4.68 (t, 1H, J ) 2.4 Hz), 4.07 (s, 1H), 3.36 (br. s, 1H),
3.20 (t, 1H, J ) 1.4 Hz), 2.07-1.94 (m, 2H), 1.73-1.46 (m, 4H),
f
(
1
(
1
1
3
0.89 (br. s, 9H), 0.10 (br. s, 3H), 0.06 (br. s, 3H); C NMR
(CDCl , 100 MHz) δ 160.4, 138.8, 134.0, 92.2, 67.1, 64.7, 50.7,
46.6, 44.6, 37.1, 36.2, 25.7, 17.7, -5.0, -5.2. Cycloadduct 33b.
0.23 (EtOAc/hexanes 1:19); IR (neat, NaCl) 3064 (w), 2934
(s), 2857 (m), 1555 (w), 1361 (w), 1257 (m), 1115 (m), 1063
3
(
3
R
f
1
3
6
1
H, J ) 4.9, 3.3 Hz), 4.39 (t, 2H, J ) 6.9 Hz), 3.89 (br. s, 1H),
.71 (s, 3H), 3.48 (br. s, 1H), 2.75 (m, 2H), 2.03 (dm, 1H, J )
.5 Hz), 1.98 (dm, 1H, J ) 6.5 Hz), 1.93 (p, 2H, J ) 7.2 Hz),
-
1
1
(m), 1027 (m) cm ; H NMR (CDCl , 400 MHz) δ 6.29 (dd,
3
1H, J ) 5.7, 3.0 Hz), 6.01 (dd, 1H, J ) 5.7, 3.2 Hz), 4.43-4.39
(m, 1H), 4.14-4.13 (m, 1H), 3.22 (t, 1H, J ) 1.4 Hz), 2.85 (m,
1
3
.65-1.50 (m, 2H); C NMR (CDCl , 100 MHz) δ 171.9, 166.0,
3

2
86 J . Org. Chem., Vol. 66, No. 1, 2001
Yip et al.
2
0.28 (EtOAc/hexanes 1:9); IR (CH Cl )
1
H), 2.17 (m, 1H), 1.80-1.59 (m, 4H), 1.42 (m, 1H), 0.94 (br.
Cycloa d d u ct 69. R
f
2
1
3
s, 1H), 0.91 (m, 8H), 0.14 (br. s, 3H), 0.09 (m, 3H); C NMR
3074 (w), 3025 (m), 3011 (s), 2980 (s), 2879 (m), 1648 (w), 1463
(m), 1456 (m), 1452 (m), 1434 (m), 1252 (m), 1218 (w), 1180
(
CDCl
5.3, 44.4, 38.1, 36.2, 25.8, 22.1, -4.9, -5.4.
Cycloa d d u ct 34. R 0.28 (EtOAc/hexanes 1:4); IR (neat,
NaCl) 3055 (m), 2986 (m), 2878 (w), 1422 (w), 1348 (w), 1325
3
, 100 MHz) δ 162.1, 137.8, 134.2, 91.8, 69.4, 68.4, 50.9,
-
1 1
4
3
(m), 1130 (m), 1103 (w), 1059 (m) cm ; H NMR (CDCl , 400
f
MHz) δ 6.36 (dd, 1H, J ) 5.7, 3.0 Hz), 6.21 (dd, 1H, J ) 5.6,
3.1 Hz), 3.68 (m, 1H), 3.03 (m, 1H), 2.58-2.53 (m, 2H), 2.28-
2.12 (m, 3H), 1.83 (dm, 1H, J ) 9.5 Hz), 1.75 (dm, 1H, J ) 9.6
-1 1
(
(
(
3
w), 1266 (s), 1012 (m) cm ; H NMR (CDCl , 400 MHz) δ 6.39
dd, 1H, J ) 5.8, 3.0 Hz), 6.15 (dd, 1H, J ) 5.7, 3.3 Hz), 4.68
t, 1H, J ) 1.5 Hz), 4.40 (m, 2H), 3.88 (d, 1H, J ) 8.6 Hz),
Hz), 1.37 (m, 1H); 13C NMR (CDCl
, 100 MHz) δ 171.0, 137.4,
136.0, 114.1, 79.1, 58.5, 47.1, 44.0, 34.1, 25.9, 21.6. Anal. Calcd
for C11 12BrNO: C, 51.99; H, 4.76; N, 5.51; Found C, 51.79;
3
3
1
1
4
7
.51 (d, 1H, J ) 8.5 Hz), 3.36 (m, 1H), 3.08 (m, 1H), 1.91 (dm,
H
H, J ) 9.4 Hz), 1.77 (dm, 1H, J ) 9.4 Hz); 13C NMR (CDCl
00 MHz) δ 164.6, 138.2, 136.7, 92.9, 76.7, 73.2, 61.0, 50.6,
7.1, 44.7. Anal. Calcd for C10 : C, 67.78; H, 6.26; N,
.90. Found C, 68.02; H, 6.23; N, 7.86.
Cycloa d d u ct 35. R 0.23 (EtOAc/hexanes 1:4); IR (neat,
NaCl) 2976 (m), 2853 (w), 1460 (w), 1326 (w), 1094 (s), 1081
,
3
H, 4.79; N, 5.54.
Cycloa d d u ct 70. Unstable, gradually decomposed upon
H
11NO
2
standing at room temperature (>80% pure by NMR): R
f
0.69
) 2967 (m), 2884 (w), 1748 (s),
721 (s), 1716 (s), 1453 (w), 1405 (w), 1371 (w), 1320 (w), 1274
(
1
(
2 2
EtOAc/hexanes 2:3); IR (CH Cl
f
-1 1
3
m), 1148 (m) cm ; H NMR (CDCl , 400 MHz) δ 6.63 (dd, 1H,
-
1 1
(
s), 1054 (m) cm ; H NMR (CDCl
J ) 5.8, 3.0 Hz), 6.06 (dd, 1H, J ) 5.7, 3.3 Hz), 4.50 (d, 1H, J
12.6 Hz), 4.19 (s, 1H), 4.10 (d, 1H, J ) 12.6 Hz), 3.92 (ddd,
H, J ) 12.0, 4.6, 1.5 Hz), 3.70 (td, 1H, J ) 12.3, 2.0 Hz), 3.26
m, 1H), 3.09 (m, 1H), 2.18 (td, 1H, J ) 13.3, 4.6 Hz), 1.64-
3
, 400 MHz) δ 6.34 (dd, 1H,
J ) 5.5, 2.8 Hz), 6.24 (dd, 1H, J ) 5.4, 3.4 Hz), 3.11 (dd, 1H,
J ) 3.1, 1.5 Hz), 3.03 (m, 1H), 2.93 (dm, 1H, J ) 9.7 Hz), 2.45-
)
1
(
2
1
6
.30 (m, 2H), 2.17-2.04 (m, 3H), 1.87 (m, 1H), 1.73-1.66 (m,
13
H); C NMR (CDCl
0.7, 56.0, 47.8, 46.1, 39.3, 36.7, 19.6.
Cycloa d d u ct 71. R 0.25 (EtOAc/hexanes 1:4); IR (neat,
NaCl) 3070 (w), 2979 (s), 2956 (s), 2882 (m), 2847 (w), 1732
s), 1571 (w), 1456 (m), 1435 (s), 1325 (s), 1286 (s), 1256 (s),
3
, 100 MHz) δ 215.3, 211.8, 142.1, 134.0,
1
1
4
.63 (m, 2H), 1.45 (dm, 1H, J ) 13.6 Hz); 13C NMR (CDCl
00 MHz) δ 156.2, 137.8, 134.5, 91.4, 69.7, 64.8, 62.3, 50.1,
4.7, 44.4, 38.3; HRMS calcd for C11H13NO : (CI, [M + H] )
2
3
,
f
+
(
m/z 192.1025, found m/z 192.1032.
Cycloa d d u ct 36. R 0.50 (EtOAc/hexanes 1:4); IR (neat,
NaCl) 3065 (m), 2979 (s), 2946 (s), 2881 (m), 1758 (w), 1694
1
1
5
(
2
)
(
5
193 (m), 1168 (w), 1129 (m), 1104 (m), 1081 (s), 1054 (w),
f
-
1 1
008 (w) cm ; H NMR (CDCl
3
, 400 MHz) δ 6.32 (dd, 1H, J )
.6, 3.2 Hz), 6.25 (dd, 1H, J ) 5.6, 3.1 Hz), 3.72 (s, 3H), 3.37
-
1
1
(
(
s), 1633 (w), 1459 (m), 1326 (s), 1298 (m) cm
CDCl , 400 MHz) δ 6.40 (dd, 1H, J ) 5.7, 3.0 Hz), 6.14 (dd,
H, J ) 5.7, 3.0 Hz), 4.48 (s, 1H), 3.57 (dAB, 1H, J ) 13.2 Hz),
; H NMR
m, 1H), 2.98 (br. s, 1H), 2.54-2.41 (m, 2H), 2.29-2.10 (m,
3
H), 1.83 (dm, 1H, J ) 9.4 Hz), 1.81 (m, 1H), 1.61 (dm, 1H, J
1
3
1
1
1
3
9.4 Hz), 1.22 (ddd, 1H, J ) 12.9, 7.5, 2.6 Hz); C NMR
, 100 MHz) δ 170.2, 168.9, 137.4, 134.5, 99.4, 81.4, 52.7,
2.2, 48.9, 44.5, 30.4, 25.8, 20.7. Anal. Calcd for C13
.48 (dAB, 1H, J ) 13.2 Hz), 3.37 (tm, 1H, J ) 1.6 Hz), 3.08 (d,
H, J ) 10.8 Hz), 3.06 (br. s, 1H), 2.35 (d, 1H, J ) 10.8 Hz),
.80 (dAB, 1H, J ) 9.6 Hz), 1.72 (dABd, 1H, J ) 9.6, 1.2 Hz);
CDCl
3
H
15NO
3
:
C, 66.94; H, 6.84. Found C, 66.71; H, 6.49.
Cycloa d d u ct 72. R 0.50 (EtOAc/hexanes 2:3); IR (neat,
NaCl) 3072 (w), 2998 (m), 2973 (s), 2950 (s), 2876 (m), 2816
1
3
C NMR (CDCl , 100 MHz) δ 162.9, 138.1, 135.9, 93.3, 77.1,
3
f
5
6
1.4, 46.5, 44.7, 34.9, 23.4. Anal. Calcd for C10
2.15; H, 5.74. Found C, 62.17; H, 5.73.
H11SNO: C,
(
(
w), 2752 (w), 1637 (w), 1475 (w), 1450 (m), 1391 (w), 1329
m), 1299 (w), 1271 (w), 1254 (w), 1247 (m), 1202 (m), 1148
Cycloa d d u ct 65. R
IR (CH Cl ) 3055 (w), 2975 (m), 2881 (w), 2307 (w), 1638 (w),
448 (w), 1374 (w), 1326 (w), 1266 (s), 1139 (w), 1101 (w) cm
f
0.49 (EtOAc/hexanes 1:9); mp 83 °C;
2
2
-
1
1
-1
3
(w), 1129 (m), 1111 (s), 1098 (s) cm ; H NMR (CDCl , 400
1
;
1
MHz) δ 6.21 (dd, 1H, J ) 5.7, 3.0 Hz), 6.17 (dd, 1H, J ) 5.6,
H NMR (CDCl , 400 MHz) δ 6.17 (m, 2H), 3.01 (br. s, 1H),
3
3
1
.1 Hz), 3.36 (s, 3H), 3.27 (d, 1H, J ) 10.5 Hz), 3.21 (br. s,
H), 3.16 (d, 1H, J ) 10.5 Hz), 2.94 (br. s, 1H), 2.46-2.42 (m,
2
.92 (br. s, 1H), 2.43 (t, 2H, J ) 8.5 Hz), 2.26-2.06 (m, 2H),
.73 (d, 1H, J ) 9.0 Hz), 1.58 (m, 1H), 1.49 (d, 1H, J ) 9.1
1
1
3
2H), 2.22 (m, 1H), 2.11 (m, 1H), 1.76 (dm, 1H, J ) 9.2 Hz),
Hz), 1.09 (s, 3H), 1.05 (ddd, 1H, J ) 13.0, 7.8, 2.4 Hz);
NMR (CDCl , 100 MHz) δ 169.1, 136.5, 135.1, 97.9, 74.6, 54.9,
C
1
1
1
.71 (m, 1H), 1.54 (dm, 1H, J ) 9.2 Hz), 0.96 (ddd, 1H, J )
2.7, 7.7, 2.5 Hz); 13C NMR (CDCl
, 100 MHz) δ 169.5, 136.3,
35.3, 99.5, 75.5, 74.9, 59.6, 51.6, 49.1, 44.4, 28.5, 25.7, 21.1.
3
4
8.9, 44.4, 29.3, 25.6, 21.3, 21.0. Anal. Calcd for C12
C, 76.16; H, 7.99; N 7.40; Found C, 76.29; H, 7.93; N, 7.55.
Cycloa d d u ct 66. R 0.33 (EtOAc/hexanes 1:9); IR (CH Cl
135 (w), 3062 (m), 2956 (s), 2857 (s), 1638 (m), 1569 (w), 1455
s), 1436 (m), 1378 (w), 1326 (s), 1264 (m), 1212 (w), 1145 (w)
H15NO:
3
Anal. Calcd for C13
H, 7.84.
2
H17NO : C, 71.21; H, 7.81. Found C, 70.87;
f
2
2
)
3
(
-
1 1
cm ; H NMR (CDCl , 400 MHz) δ 6.15 (dd, 1H, J ) 5.7, 2.9
Hz), 6.11 (dd, 1H, J ) 5.5, 3.1 Hz), 3.16 (br. s, 1H), 2.91 (br.
s,1H), 2.41 (t, 2H, J ) 6.9 Hz), 2.19 (m, 1H), 2.09 (m, 1H),
1
7
6
1
2
3
Ack n ow led gm en t. We thank the Natural Science
and Engineering Research Council (NSERC) of Canada
and the University of Guelph for the generous financial
support of our program. Mr. Robert W. J ordan is
thanked for preliminary studies of this work. Professor
George Ferguson and Ms. Valerie Robinson are thanked
for X-ray structure determination and NMR experi-
ments.
.70-1.31 (m, 6H), 6.12-6.10 (m, 6H), 1.01 (ddd, 1H, J ) 12.8,
.7, 2.4 Hz), 0.90 (dd, 1H, J ) 12.9, 4.0 Hz), 0.84 (t, 3H, J )
1
3
.0 Hz); C NMR (CDCl , 100 MHz) δ 169.3, 136.0, 135.2,
3
00.2, 75.1, 51.9, 48.9, 44.1, 35.3, 31.6, 29.7, 29.0, 25.6, 24.4,
2.5, 21.2, 14.0; HRMS calcd for C17 25NO m/z 259.1936, found
H
m/z 259.1932.
f 2 2
Cycloa d d u ct 68. R 0.47 (EtOAc/hexanes 1:4); IR (CH Cl )
3
073 (w), 2979 (s), 2883 (m), 1454 (m), 1429 (m), 1326 (s), 1251
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
-
1
1
3
(m), 1062 (m), 1013 (s) cm ; H NMR (CDCl , 400 MHz) δ
cedures for preparation of all cycloadducts and their precursors
6
3
2
.35 (dd, 1H, J ) 5.7, 3.0 Hz), 6.25 (dd, 1H, J ) 5.7, 3.1 Hz),
.54 (dm, 1H, J ) 1.4 Hz), 3.08 (br. s, 1H), 2.61-2.48 (m, 2H),
.33-2.17 (m, 2H), 2.10-2.02 (m, 1H), 1.81 (dm, 1H, J ) 9.6
1
13
that are not included in the Experimental Section; H and
C
NMR spectra for compounds 13, 14, 25, 26, 30, 45, 53, 59;
nitro compounds 18, 28, 46, 47, 51, 64; and all cycloadducts
, 32-36, 65, 66, 68-72. This material is available free of
charge via the Internet at http://pubs.acs.org.
Hz), 1.73 (dm, 1H, J ) 9.6 Hz), 1.39 (ddd, 1H, J ) 13.1, 7.0,
3
1
9
1
3
.0 Hz); C NMR (CDCl
18.3, 78.9, 57.0, 47.9, 44.3, 31.3, 26.0, 21.6. Anal. Calcd for
12ClNO: C, 63.01; H, 5.77; Found C, 63.00; H, 5.74.
3
, 100 MHz) δ 171.0, 136.6, 135.9,
11
C H
J O005611O