The lithium amide induced rearrangement of epoxysulfones derived from bicyclo[2.2.1]heptane system

Article abstract of DOI:10.1016/S0040-4020(00)00294-5

Lithium amides induce rearrangement of the title compounds 1 to afford nortricyclanones 4 via a ketocarbene intermediate. Compounds 4 undergo hydride transfer reduction and imino aldol condensation to afford the other observed reaction products. (C) 2000

Full text of DOI:10.1016/S0040-4020(00)00294-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 3901±3907
The Lithium Amide Induced Rearrangement of Epoxysulfones
Derived from Bicyclo[2.2.1]heptane System
*
 Â
Odon Arjona, Roberto Menchaca and Joaquõn Plumet
  Â
Departamento de Quõmica Organica I, Facultad de Quõmica, Universidad Complutense, 28040 Madrid, Spain
Received 2 February 2000; accepted 17 April 2000
AbstractÐLithium amides induce rearrangement of the title compounds 1 to afford nortricyclanones 4 via a ketocarbene intermediate.
Compounds 4 undergo hydride transfer reduction and imino aldol condensation to afford the other observed reaction products. q 2000
Elsevier Science Ltd. All rights reserved.
Oxiranes constitute an important family of strained small
ring heterocyclic compounds widely recognized as being
extremely useful synthetic intermediates.1 Among functio-
nalized epoxides, a,b-epoxysulfones have been proved to
be versatile synthons in the presence of nucleophilic
reagents.2 However, the chemistry of bicyclic a,b-epoxy-
sulfones such as 1 and in particular their reaction with orga-
nolithium bases remains unexplored.3 In these cases the
conformational rigidity of the bicyclic skeleton should
permit a more accurate study of the reaction, because the
evolution of the reactive intermediates would follow a
predictable and well established reaction pathway. In this
paper we wish to report our results concerning the reaction
of a,b-epoxysulfones 1 with lithium amides as nucleophilic
reagents.
There is considerable evidence about the nature of the two
®rst steps in the reaction of bicyclic epoxides with lithium
amides. For instance, in the reaction of bicyclo[2.2.1]hep-
tane-exo-oxide with lithium diethylamide Crandall and co-
workers8 showed that carbene 6 or its carbenoid equivalent9
is a key intermediate formed via 7, the metalated epoxide
ring10 (Scheme 3a). Further evidence arises from transannu-
lar insertion experiments11 (Scheme 3b). Thus, compound 8
affords, by reaction with LDA, alcohol 9 in 82% yield.
Similar results have been obtained for others bicyclic epox-
ides.3 Formation of nortricyclanone 4a or aldol adduct 5a
was not observed in these experiments.
Very different results have been obtained in the case of
monosubstituted bicyclic epoxides. Thus, McDonald and
co-workers12 showed that the chloroepoxide 10 reacted
with lithium diethylamide in ether±benzene to give a 10:1
mixture of 4a:3a. No traces of aldols 5b were observed. For
these authors, the major compound 4a arises from the
generation of anion 11 followed by carbene insertion in
12, whereas the origin of 3a should be the lithium amide
induced reduction of C2±Cl bond to give anion 13 followed
by evolution to carbene 14 (Scheme 4).
Results and Discussion
The a,b-epoxysulfones 1 were prepared from the related
vinylsulfones 2a,4 2b5 and 2c6 by reaction with t-BuOOLi7
(Scheme 1).
Reaction of 1 with LDA and lithium diethylamide in ether at
2788C afforded, after puri®cation, a mixture of the related
nortricyclanols 3, nortricyclanones 4 and aldol adducts 5 in
yields that can be reproduced fairly well (Scheme 2, Table
1).
With these precedents in mind, we speculated with the
possibility that in the case of the epoxysulfones 1, the
In the cases of reaction of 1a and 1b with LDA, a more
accurate distribution of products have been obtained when
the reaction crudes were examined by coupled GLC±MS.
The resulting data are collected in Table 2.
Keywords: bicyclic aliphatic compounds; carbenes and carbenoids; epox-
ides; lithium amides.
* Corresponding author. Tel./fax: 134-1-3944100;
e-mail: plumety@eucmax.sim.ucm.es
Scheme 1.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00294-5

3902
O. Arjona et al. / Tetrahedron 56 (2000) 3901±3907
Scheme 2.
Table 1. Reaction of 1 with lithium amides
Starting materiala
R
Compd
Yield (%)
Compd
Yield (%)
Compd
Yield (%)
1a
1a
1b
1b
1c
1c
Me
H
Me
H
Me
H
3a
3a
3b
3b
3c
3c
50±53b
43±50c
49±55b
48±53c
30±34c
32±37c
5a
5b
5c
5d
5e
5f
20±26b
20±25c
7±8b
4a
4a
4b
4b
4c
4c
0b
0c
7±11b
0c
24±26c
20±22c
10±16c
0c
0c
a All reactions were conducted in ether at 2788C. The ratio 1: (CH3CHR)2NLi was 1:5 equiv. in all cases. Concentrations of 1 were 0.1 M in ether with the
exception of the 7-aza derivative 1c, in which the concentrations used were 0.03 M due to the lower solubility of the starting material in ether.
b Isolated yields. The indicated yields are the average of three independent experiments.
c Isolated yields. The indicated yields are the average of two independent experiments.
Table 2. GLC±MS analysis of the crudes obtained from reaction of 1a and
1b with LDA
Reaction
Ratio of products (3:4:5)
1a1LDA
1b1LDA
1: 0.13: 1.3a
4.5: 1: 1.2b,c
a Ratio 3a:4a:5a.
b Ratio 3b:4b:5c.
c Traces of dimeric structure 19b were also observed. See Scheme 7.
Scheme 4.
work-up, compounds 16 and 18 affords 3 and 5, respec-
tively.
It should be noted that LDA is known to be able to perform
hydride transfer reduction of ketones,14 although an electron
transfer mechanism has also been proposed.15 In this case,
isolation of compounds 5 arising from the indicated reaction
pathway seems to con®rm the hydride transfer mechanism.
On the other hand, it is known that the imine, resulted from
hydride transfer, is deprotonated by the amide and the result
anion can act as a nucleophile.16 An alternative pathway
should be the reduction of the C±S bond by the action of
the lithium amide and further evolution of the epoxyanion
Scheme 3.
compounds 5 and, at least partially, 3 could arise from
ketone 413 (Scheme 5). Thus, nucleophilic addition of
lithium amide to 4 gives 15 which undergoes b-hydride
transfer reaction to 16 with concomitant formation of
imine 17. The iminoaldol reaction of 17 with ketone 4
promoted by lithium amide yields intermediate 18. After

O. Arjona et al. / Tetrahedron 56 (2000) 3901±3907
3903
Scheme 5.
according to Crandall's mechanism8a (Scheme 3). However,
although the reaction of sulfones with lithium naphthalenide
has been proved to involve a desulfonylation process, the
same reaction with lithium amides does not work in the
same way.17
The result of the reaction was also dependent on the
temperature. Thus, when epoxysulfones 1 were treated
with 5 equiv. of LDA in ether at 215 to 08C, a new distribu-
tion of products was observed (Scheme 7, Table 3).
The formation of compounds 19 can be explained via an
iminoaldol condensation between intermediate 18 (Scheme
5) and nortricyclanones 4 (Scheme 8).
Two independent experiments gave further support for this
hypothesis. Thus, reaction of epoxysulfone 1 with lithium
bis(trimethylsilyl)-amide (LHMDS) afforded only the
ketones 4 in moderate yields (Scheme 6a). With this base
no hydride ion can be transferred to 4. Considering that the
remaining products obtained were always starting materials,
we can conclude that nortricyclanols are not primary
products in these processes, but products arising from the
reduction of the related nortricyclanones 4. Thus, a mechan-
ism involving intermediates 13 and 14 (Scheme 4) can be
ruled out in this case. The second experiment concerned the
independent reaction of nortricyclanone 4a with LDA under
the same conditions of 1a. In this case, products 3a (47%)
and 5a (26%) were isolated (Scheme 6b).
Conclusions
The reaction of bicyclic epoxysulfones 1 with lithium amide
derivatives shows a different behavior to other substituted
bicyclic epoxides when treated with these reagents. From
these results we can conclude that nortricyclanones 4 are the
main products of the reaction being formed probably via
ketocarbene intermediates. Nortricyclanones react concur-
rently with lithium amides via hydride transfer reduction to
give the corresponding nortricyclanols. The other observed
Scheme 6.

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O. Arjona et al. / Tetrahedron 56 (2000) 3901±3907
Scheme 7.
matograph coupled with a mass spectrometer with quadru-
pole ®lter. Elemental analyses were performed at the
Universidad Complutense de Madrid.
Table 3. Reaction of epoxides 1 with LDA at 215 to 08C. All reactions
were conducted in ether at 215 to 08C. The ratio 1: LDA was 1:5 equiv. in
all cases. Concentrations of 1 were 0.1 M in ether with the exception of the
7-aza derivative 1c, in which the concentrations used were 0.03 M due to
the lower solubility of the starting material in ether
General procedure for epoxidation of vinyl sulfones
2a±c.7 A solution containing t-BuOOH (2.2 equiv.) in dry
THF, was cooled at 2788C under argon. n-BuLi (2.2 equiv.)
was added dropwise and the resulting solution was stirred at
2788C for 15 min. Then, 1 equiv. of 2 dissolved in THF was
added dropwise. The reaction was warmed to rt and stirred
overnight. The reaction mixture was quenched with brine,
the organic layer was extracted with ether and dried over
anhydrous magnesium sulfate. Evaporation of the solvent
under reduced pressure followed by puri®cation via ¯ash
chromatography eluting with an ethyl acetate:hexanes
system of appropriate polarity, afforded the corresponding
epoxysulfones (1a±c).
Epoxide Nortricyclanol (%) 3 Aldol (%) 5
Dimeric aldol (%) 19
1a
1b
1c
23 (3a)
20 (3b)
11 (3c)
50 (5a)
45 (5c)
43 (5e)
20 (19a)
8 (19b)
Not observed
products arise from iminoaldol condensations of the
proposed intermediates.
Experimental
General. Reagents and solvents were handled by using stan-
dard syringe techniques. Tetrahydrofuran and diethyl ether
were distilled from sodium and benzophenone; methylene
chloride, diethylamine and diisopropylamine from calcium
hydride, all under argon. The remaining solvents and chemi-
cals were commercial and used as received. All products
were puri®ed by ¯ash chromatography using 230±400 mesh
silica gel. Analytical TLC was carried out on silica gel
2-Phenylsulfonylbicyclo[2.2.1]hept-2-ene-exo-oxide (1a).
mp: 71±728C. IR (KBr): n 2980, 1580, 1340, 1100 cm21. 1H
NMR (CDCl3, 300 MHz): d 7.91 (dd, 2H, Jˆ8.8, 1.9 Hz),
7.69±7.50 (m, 3H), 3.64 (s, 1H), 2.64 (d, 1H, Jˆ1.5 Hz),
2.55 (d, 1H, Jˆ1.5 Hz), 2.28 (td, 1H, Jˆ8.9, 2.3 Hz), 1.64±
1.55 (m, 2H), 1.40 (m, 1H), 1.36 (br s, 1H), 0.86 (dd, 1H,
Jˆ9.0, 1.2 Hz). 13C NMR (CDCl3, 75 MHz): d 138.7,
134.0, 129.1, 128.8, 72.5, 58.6, 38.7, 37.6, 29.9, 25.7,
23.3. Anal. Calcd for C13H14O3S (MW: 250): C, 62.40; H,
5.60. Found: C, 62.31; H, 5.56.
1
plates. Melting points are uncorrected. H NMR and 13C
NMR were recorded in CDCl3 at 300 and 75 MHz, respec-
tively. When peak multiplicities are reported, the following
abbreviations are used: s (singlet); d (doublet); t (triplet); m
(multiplet); dd (doublet of doublets); dt (doublet of triplets).
Chemical shifts (d) are reported in ppm from (CH3)4Si as
internal standard and J values are given in hertz. IR spectra
were recorded on a FT-IR spectrometer as thin ®lms or KBr
disks. GC±MS analyses were performed using a gas chro-
2-Phenylsulfonyl-7-oxabicyclo[2.2.1]hept-2-ene-exo-oxide
1
(1b). IR (CCl4): n 2980, 1570, 1210, 860 cm21. H NMR
(CDCl3, 300 MHz): d 7.93 (dd, 2H, Jˆ8.4, 1.3 Hz), 7.73±
7.55 (m, 3H), 4.57 (d, 1H, Jˆ4.6 Hz), 4.50 (d, 1H,
Jˆ4.4 Hz), 3.87 (s, 1H), 2.55 (dd, 1H, Jˆ10.2, 6.3 Hz),
Scheme 8.

O. Arjona et al. / Tetrahedron 56 (2000) 3901±3907
3905
1.85 (td, 1H, Jˆ10.2, 4.6 Hz), 1.83±1.73 (m, 1H), 1.68±
1.63 (m, 1H). 13C NMR (CDCl3, 75 MHz): d 134.6,
129.4, 129.3, 128.7, 75.3, 74.9, 71.3, 57.6, 27.8, 25.0.
Anal. Calcd for C12H12O4S (MW: 252): C, 57.14; H, 4.76.
Found: C, 57.31; H, 4.63.
acetate:hexanes system of appropriate polarity to afford the
titled compounds shown in Table 1.
General procedure for the reaction of epoxysulfones
1a±c with lithium bis(trimethylsilyl)-amide (LHMDS) in
ether18
N-(t-Butyloxycarbonyl)-2-p-tolylsulfonyl-7-azabicyclo-
[2.2.1]hept-2-ene-exo-oxide (1c). mp: 148±1498C. IR
A solution containing HMDS (5 equiv.) in ether (10 ml
ether/mmol HMDS) was cooled at 08C, n-BuLi (5 equiv.,
1.6 M solution in hexane) was added dropwise. After stir-
ring for 20 min, the appropriate epoxysulfone 1a±c
dissolved in ether was added and the solution was stirred
at 08C for 1 h. The reaction was quenched with a saturated
NaCl solution and extracted with ether. The organic layer
was dried over MgSO4 and evaporated under reduced pres-
sure. The resulting crude was puri®ed by silica gel chroma-
tography eluting with an ethyl acetate:hexanes system of
appropriate polarity to afford the corresponding compounds
(see Scheme 6a).
1
(KBr): n 3080, 1660, 1580, 1150 cm21. H NMR (CDCl3,
300 MHz): d 7.81 (d, 2H, Jˆ5.5 Hz), 7.39 (d, 2H,
Jˆ5.5 Hz), 4.39 (d, 1H, Jˆ3.3 Hz), 4.17 (d, 1H,
Jˆ2.8 Hz), 3.89 (s, 1H), 2.44 (s, 3H), 2.40±2.31 (m, 1H),
2.02±1.83 (m, 2H), 1.51 (ddd, 1H, Jˆ7.0, 5.9, 2.8 Hz), 1.13
(s, 9H). 13C NMR (CDCl3, 75 MHz): d 156.9, 129.9, 129.7,
128.6, 128.3, 80.1, 71.5, 58.4, 57.7, 27.9, 27.6, 26.8, 23.3,
21.5. Anal. Calcd for C18H23O5NS (MW: 365): C, 59.18; H,
6.30; N, 3.83. Found: C, 59.31; H, 6.22; N, 3.52.
General procedure for the reaction of epoxysulfones
1a±c with lithium diisopropylamide in ether18
Tricyclo[2.2.1.02,6]heptan-3-ol (3a). mp: 111±1128C. IR
(KBr): n 3500±3300, 2860, 1120, 970 cm21 1H NMR
.
Method A: at 2788C. A solution containing diisopropyla-
mine (5 equiv.) in ether was cooled at 2788C under argon.
Then, n-BuLi (5 equiv., 1.6 M solution in hexane) was
added dropwise. After stirring for 20 min, 1a±c (1 equiv.)
dissolved in ether (see Table 1) was added under argon and
the resulting yellow solution was stirred at 2788C for 1 h.
The reaction was quenched with a saturated NaCl solution
and extracted with ether. The organic layer was dried over
MgSO4 and evaporated under reduced pressure. The result-
ing crude was puri®ed by silica gel chromatography eluting
with an ethyl acetate:hexanes system of appropriate polarity
to afford the title compounds shown in Table 1.
(CDCl3, 300 MHz): d 3.84 (s, 1H), 1.78 (d, 1H,
Jˆ10.8 Hz), 1.75 (s, 1H), 1.60 (s, 1H), 1.36 (dd, 1H,
Jˆ10.8, 1.2 Hz), 1.25±1.21 (m, 3H), 1.18 (s, 1H), 1.06
(td, 1H, Jˆ5.1, 1.3 Hz). 13C NMR (CDCl3, 75 MHz): d
77.3, 35.7, 30.7, 29.4, 16.3, 13.7, 10.7. MS m/z 110 (M1).
Anal. Calcd for C7H10O (MW: 110): C, 76.36; H, 9.09.
Found: C, 76.41; H, 10.01.
7-Oxatricyclo[2.2.1.02,6]heptan-3-exo-ol (3b). IR (CCl4):
n
3600, 2980, 1210, 1180 cm21 1H NMR (CDCl3,
.
300 MHz): d 3.98 (t, 1H, Jˆ4.1 Hz), 3.92 (d, 1H,
Jˆ1.9 Hz), 3.90 (dd, 1H, Jˆ2.6, 1.9 Hz), 2.19±2.10 (m,
1H), 2.02 (dd, 1H, Jˆ10.7, 0.7 Hz), 1.45 (t, 1H,
Jˆ4.1 Hz), 1.38 (dt, 1H, Jˆ10.7, 1.8 Hz), 1.23 (td, 1H,
Jˆ4.1, 1.8 Hz). 13C NMR (CDCl3, 75 MHz): d 75.5, 71.8,
55.5, 29.1, 15.7, 11.8. MS m/z 112 (M1). Anal. Calcd for
C6H8O2 (MW: 112): C, 64.28; H, 7.14. Found: C, 64.40; H,
7.19.
Method B: at 215 to 08C. A solution of diisopropylamine
(5 equiv.) in ether was placed in a ¯ask previously cooled to
2158C. n-BuLi (5 equiv.) was injected by syringe over a
period of 10 min with vigorous stirring. After 5 min, a solu-
tion of the appropriate epoxysulfone dissolved in ether (see
Table 3) was added over a period of 10 min at 2158C. The
¯ask was placed in an ice bath and the contents were stirred
for 1 h. The reaction was quenched with ice water and the
layers were allowed to separate. The aqueous layer was
extracted with ether and the combined ether extracts were
dried over MgSO4 and ®ltered. The solvent was removed
under vacuum and puri®cation via ¯ash-column chromato-
graphy on silica gel eluting with an ethyl acetate:hexanes
system of appropriate polarity afforded the corresponding
products (see Table 3).
7-Oxatricyclo[2.2.1.02,6]heptan-3-one (4b). IR (CCl4): n
2990, 1710, 1210, 1150 cm21
.
1H NMR (CDCl3,
300 MHz): d 3.95 (t, 1H, Jˆ4.1 Hz), 3.93 (dd, 1H, Jˆ2.2,
0.9 Hz), 2.27 (dd, 1H, Jˆ10.7, 0.9 Hz), 1.48 (td, 1H, Jˆ4.1,
1.0 Hz), 1.35 (dt, 1H, Jˆ10.7, 2.2 Hz), 0.91 (t, 1H,
Jˆ4.1 Hz). 13C NMR (CDCl3, 75 MHz): d 216.7, 66.6,
54.9, 32.6, 29.5, 14.1. MS m/z 110 (M1). Anal. Calcd for
C6H6O2 (MW: 110): C, 65.45; H, 5.45. Found: C, 65.38; H,
5.40.
General procedure for the reaction of epoxysulfones
1a±c with lithium diethylamide in ether
(3-exo-Hydroxytricyclo[2.2.1.02,6]hept-3-yl)acetone (5a).
IR (CCl4): n 3500, 1720, 1470, 1150 cm21 1H NMR
.
A solution containing diethylamine (5 equiv.) in ether was
cooled at 2788C under argon. Then, n-BuLi (5 equiv.,
1.6 M solution in hexane) was added dropwise. After stir-
ring for 20 min, 1a±c (1 equiv.) dissolved in ether (see
Table 1) was added under argon and the resulting yellow
solution was stirred at 2788C for 1 h. The reaction was
quenched with a saturated NaCl solution and extracted
with ether. The organic layer was dried over MgSO4 and
evaporated under reduced pressure. The resulting crude was
puri®ed by silica gel chromatography eluting with an ethyl
(CDCl3, 300 MHz): d 3.43 (s, 1H), 2.72 (d, 2H,
Jˆ2.5 Hz), 2.19 (s, 3H), 2.09 (dd, 1H, Jˆ10.1, 1.3 Hz),
1.75 (s, 1H), 1.47 (dd, 1H, Jˆ10.1, 1.2 Hz), 1.30 (s, 1H),
1.27±1.21 (m, 3H), 1.13 (td, 1H, Jˆ4.7, 1.0 Hz). 13C NMR
(CDCl3, 75 MHz): d 210.7, 82.0, 47.1, 38.4, 31.5, 31.4,
31.2, 19.8, 12.7, 11.8. MS m/z 166 (M1). Anal. Calcd for
C10H14O2 (MW: 166): C, 72.29; H, 8.43. Found: C, 72.35;
H, 8.50.
(3-exo-Hydroxytricyclo[2.2.1.02,6]hept-3-yl)acetaldehyde

3906
O. Arjona et al. / Tetrahedron 56 (2000) 3901±3907
(5b). IR (CCl4): n 3600, 2780, 1730, 1110 cm21. H NMR
(CDCl3, 300 MHz): d 9.99 (s, 1H), 2.70 (d, 2H, Jˆ1.8 Hz),
2.48 (d, 1H, Jˆ2.9 Hz), 2.02 (dd, 1H, Jˆ10.2, 1.2 Hz), 1.81
(s, 1H), 1.52 (dd, 1H, Jˆ10.2, 1.3 Hz), 1.35 (s, 1H), 1.33±
1.15 (m, 4H). 13C NMR (CDCl3, 75 MHz): d 203.1, 82.3,
48.4, 38.8, 31.5, 31.3, 20.2, 12.1, 11.9. Anal. Calcd for
C9H12O2 (MW: 152): C, 71.05; H, 7.89. Found: C, 71.08;
H, 7.93.
1180 cm21. H NMR (CDCl3, 300 MHz): d 3.99 (t, 2H,
1
1
Jˆ4.4 Hz), 3.95 (dd, 2H, Jˆ4.1, 1.7 Hz), 2.58 (syst. AB,
2H, JABˆ15.8 Hz), 2.04 (d, 2H, Jˆ10.2 Hz), 1.78±1.63 (m,
2H), 1.50 (t, 2H, Jˆ4.4 Hz), 1.41 (dt, 2H, Jˆ10.2, 1.7 Hz),
1.25±1.22 (m, 2H). 13C NMR (CDCl3, 75 MHz): d 216.4,
75.6, 71.8, 55.6, 29.1, 15.7, 14.2, 13.0. MS m/z 276
(M122). Anal. Calcd for C15H18O5 (MW: 278): C, 64.75;
H, 6.47. Found: C, 64.61; H, 6.30.
(3-exo-Hydroxy-7-oxatricyclo[2.2.1.02,6]hept-3-yl)acetone
Reaction of nortricyclanone 4a with lithium diisopropyl-
amide
1
(5c). IR (CCl4): n 3500, 1710, 1470, 1150 cm21. H NMR
(CDCl3, 300 MHz): d 3.83 (s, 1H), 3.75 (d, 1H, Jˆ1.1 Hz),
2.81 (syst. AB, 2H, JABˆ12.2 Hz), 2.29 (d, 1H, Jˆ7.2 Hz),
2.19 (s, 3H), 1.90 (br s, 1H), 1.41 (dd, 1H, Jˆ7.2, 1.1 Hz),
1.26±1.24 (m, 2H). 13C NMR (CDCl3, 75 MHz): d 211.4,
81.1, 74.3, 54.5, 45.5, 31.1, 30.2, 18.9, 12.8. MS m/z 169
(MH1). Anal. Calcd for C9H12O3 (MW: 168): C, 64.28; H,
7.14. Found: C, 64.36; H, 7.23.
To a solution containing 0.16 ml of diisopropylamine
(1.1 mmol) in 1.5 ml of ether cooled at 2788C under
argon, 0.74 ml of a 1.6 M n-BuLi solution in hexane
(5 equiv.) was added dropwise. After stirring for 20 min,
4a (25 mg, 0.23 mmol) dissolved in 2 ml of ether was
added under argon and the resulting yellow solution was
stirred at 2788C for 1 h. The reaction was quenched with
a saturated NaCl solution and extracted with ether. The
organic layer was dried over MgSO4 and removal of the
solvent under vacuum followed by silica gel chromato-
graphy (25:1, hexane:ethyl acetate) afforded 12 mg of 3a
(47%) and 10 mg of 5a (26%).
(3-exo-Hydroxy-7-oxatricyclo[2.2.1.02,6]hept-3-yl)acetal-
dehyde (5d). IR (CCl4): n 3600±3300, 1710, 1200,
1
1180 cm21. H NMR (CDCl3, 300 MHz): d 9.98 (s, 1H),
3.94 (t, 1H, Jˆ4.1 Hz), 3.79 (d, 1H, Jˆ2.2 Hz), 2.86 (syst.
AB, 2H, JABˆ18.0 Hz), 2.27 (d, 1H, Jˆ10.7 Hz), 1.51 (m,
1H), 1.42 (dd, 1H, Jˆ10.7, 2.2 Hz), 1.29±1.24 (m, 2H). 13C
NMR (CDCl3, 75 MHz): d 205.6, 74.4, 54.7, 47.0, 39.7,
30.2, 19.0, 12.9. Anal. Calcd for C8H10O3 (MW: 154): C,
62.34; H, 6.49. Found: C, 62.26; H, 6.33.
Acknowledgements
Financial support was obtained from the Ministerio de
Â
(N-(t-Butyloxycarbonyl)-3-exo-hydroxy-7-azatricyclo-
[2.2.1.02,6]hept-3-yl)acetone (5e). IR (CCl4): n 3500, 1730,
1650, 1200 cm21. 1H NMR (CDCl3, 300 MHz): d 3.91 (m,
1H), 3.81 (m, 1H), 3.54 (m, H), 2.73 (d, 1H, Jˆ8.6 Hz), 2.42
(d, 1H, Jˆ8.6 Hz), 2.23 (d, 1H, Jˆ7.5 Hz), 2.19 (s, 3H),
1.99 (d, 1H, Jˆ7.5 Hz), 1.59±1.57 (m, 2H), 1.45 (s, 9H).
13C NMR (CDCl3, 75 MHz): d 205.6, 155.9, 80.0, 71.7,
60.9, 50.9, 45.2, 34.7, 31.3, 29.0, 28.4, 20.3. Anal. Calcd
for C14H21O4N (MW: 267): C, 62.92; H, 7.86; N, 5.24.
Found: C, 63.01; H, 7.93; N, 5.25.
Educacion y Cultura, Spain, through grant no. 96-0641.
Roberto Menchaca thanks Universidad Complutense de
Madrid for a predoctoral fellowship. Prof L. Bennasar
(Universidad Central de Barcelona) and Prof P. Vogel
(ICO-Lausanne) are gratefully acknowledged for critical
comments to this manuscript.
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1
1200 cm21. H NMR (CDCl3, 300 MHz): d 3.32 (s, 2H),
2.73 (d, 4H, Jˆ2.6 Hz), 2.07 (d, 2H, Jˆ10.0 Hz), 1.76 (s,
2H), 1.49 (d, 2H, Jˆ10.0 Hz), 1.30 (d, 2H, Jˆ1.2 Hz),
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Scheme 9.
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5. Vinyl sulfone 2b was synthesized from bisulfone 22, the Diels±
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Hydrogenation of the double bond in 22 using CH3CN as solvent
and further elimination of one of the phenylsulfonyl groups
employing t-BuOK in equimolecular amount lead to 2b in high
yields (Scheme 10).
6. Giblin, G. M. P.; Jones, C. D.; Simpkins, N. S. J. Chem. Soc.,
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