Planar Chirality: Synthesis and Transannular Reactions of Unsaturated Optically Active Azoninones Bearing E-Olefins

Article abstract of DOI:10.1021/jo991484o

The zwitterionic aza-Claisen rearrangement of optically active trans 4-silyloxy-2-vinylpyrrolidines and carboxylic acid fluoride generated nine-membered ring lactams with high yields. The reaction proceeded with an almost complete 1,4-chirality transfer and the exclusive generation of the E-double bond in the medium sized rings to cause additional planar chiral information. The initially formed azoninones were characterized by a pS-arrangement of the olefin with respect to the ring. The rather kinetically stable conformation underwent a flipping of the double bond to give the pR-azoninones as the thermodynamically stable products. The planar diastereomers were subjected to regio- and diastereoselective transannular ring contractions to give indolizidinones. The stereochemical outcome was strongly dependent from the planar chiral information of the double bond and the lactam unit. The so-formed optically active bicycles bearing a defined substitution pattern should serve as versatile building blocks in alkaloid synthesis.

Full text of DOI:10.1021/jo991484o

1710
J . Org. Chem. 2000, 65, 1710-1720
P la n a r Ch ir a lity: Syn th esis a n d Tr a n sa n n u la r Rea ction s of
Un sa tu r a ted Op tica lly Active Azon in on es Bea r in g E-Olefin s
Alexander Sudau, Winfried Mu¨nch, and Udo Nubbemeyer*
Institut fu¨r Chemie/ Organische Chemie, Freie Universita¨t Berlin, Takustrasse 3,
D-14195 Berlin, Germany
J an W. Bats
Institut fu¨r Organische Chemie, J . W. Goethe Universita¨t Frankfurt, Marie-Curie-Strasse 11,
D-60439 Frankfurt/ Main, Germany
Received September 21, 1999
The zwitterionic aza-Claisen rearrangement of optically active trans 4-silyloxy-2-vinylpyrrolidines
and carboxylic acid fluoride generated nine-membered ring lactams with high yields. The reaction
proceeded with an almost complete 1,4-chirality transfer and the exclusive generation of the E-double
bond in the medium sized rings to cause additional planar chiral information. The initially formed
azoninones were characterized by a pS-arrangement of the olefin with respect to the ring. The
rather kinetically stable conformation underwent a flipping of the double bond to give the pR-
azoninones as the thermodynamically stable products. The planar diastereomers were subjected
to regio- and diastereoselective transannular ring contractions to give indolizidinones. The
stereochemical outcome was strongly dependent from the planar chiral information of the double
bond and the lactam unit. The so-formed optically active bicycles bearing a defined substitution
pattern should serve as versatile building blocks in alkaloid synthesis.
In tr od u ction
ment always induced the complete 1,3 chirality transfer
from an E-allylamine to the corresponding γ,δ-unsatur-
ated lactam.5a Furthermore, an almost complete simple
diastereoselection was operative, resulting from a defined
Z-enolate geometry in the hypothetical zwitterionic
intermediate.5b Finally, a regio- and diastereoselective
transannular reaction transferred the azoninones into
indolizidinones.4,5b
Here we report on the 1,4-chirality6 transfer of the
zwitterionic aza-Claisen rearrangement induced by the
defined enolate geometry in combination with a defined
transition state geometry, which had been sparsely
investigated up to now.7 The terminal unsubstituted
allylamine 1 served as the reactant and the so formed
azoninones 4-6 were used as the key intermediates in
the synthesis of the chiral indolizidinones 7-15.
The generation of nine-membered nitrogen hetero-
cycles (“azonines”) bearing defined constitutions and
configurations is still a challenge in organic synthesis.
On one hand, azonines are found as subunits in natural
and pharmaceutically important products (target mol-
ecules);1 on the other hand, the medium-sized constrained
ring systems can serve as key intermediates in the
synthesis of bicyclic amino compounds by selective tran-
sannular ring contractions.2 However, an intriguing
strategy to generate optically active medium-sized het-
erocycles is the ring enlargement of five- or six-membered
rings by means of Claisen rearrangements.3 Constrained
azonines bearing E double bonds were efficiently built
up by the so-called zwitterionic aza-Claisen rearrange-
ment, which had been developed from a ketene Claisen
reaction initially described for the synthesis of nine- or
ten-membered ring lactams by Edstrom in 1991.4 Start-
ing from chiral 2-vinylpyrrolidines, various substituted
nine-membered rings were formed.5 The highly ordered
chairlike transition state of the 3,3-sigmatopic rearrange-
Resu lts a n d Discu ssion
Allylamine 1 was efficiently generated via a six-step
sequence starting from trans-4-hydroxy-L-(-)-proline 2,6
the overall yield was about 50% (Scheme 1). After
esterification,8 the N-benzyl group was introduced by
treatment of the secondary amine with benzyl chloride
(1) Evans, P. A.; Holmes, A. B. Tetrahedron 1991, 47, 9131.
(2) Nubbemeyer, U. In Houben Weyl, Vol. E21c: Stereoselective
Synthesis; Helmchen, G., Hoffmann, R. W., Mulzer, J ., Schaumann,
E., Eds.; Thieme, Stuttgart, New York, 1995; p 2288.
(3) (a) Deur, C. J .; Miller, M. W.; Hegedus, L. S. J . Org. Chem. 1996,
61, 2871. (b) Evans, P. A.; Holmes, A. B.; McGeary, R. P.; Nadin, A.;
Russell, K.; O’Hanlon, P. J .; Pearson, N. D. J . Chem. Soc., Perkin Trans.
1 1996, 123. (c) Evans, P. A.; Holmes, A. B.; Collins, I.; Raithby, P. R.;
Russell, K. J . Chem. Soc., Chem. Commun. 1995, 2325. (d) Evans, P.
A.; Holmes, A. B.; Russell, K. Tetrahedron Lett. 1992, 33, 6857. (e)
Evans, P. A.; Collins, I.; Hamley, P.; Holmes, A. B.; Raithby, P. R.;
Russell, K. Tetrahedron Lett. 1992, 33, 6859.
(6) Sudau, A.; Nubbemeyer, U. Angew. Chem., Int. Ed. 1998, 37,
1140.
(7) Reviews on Claisen rearrangements: (a) Ziegler, F. E. Chem.
Rev. 1988, 88, 1429. (b) Frauenrath, H. In Houben Weyl, Vol. E21d:
Stereoselective Synthesis; Helmchen, G., Hoffmann, R. W., Mulzer, J .,
Schaumann, E., Eds.; Thieme, Stuttgart, New York, 1995; p 3301. (b)
Wipf, P. In Comprehensive Organic Synthesis; Trost, B. M., Flemming,
I., Paquette, L. A., Eds.; Pergamon Press: New York, 1991; Vol. 5, p
827. (d) Hill, R. K. In Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: New York, 1984; Vol. 3, p 503.
(4) (a) Edstrom, E. D. J . Am. Chem. Soc. 1991, 113, 6690. (b)
Edstrom, E. D. Tetrahedron Lett. 1991, 32, 5709.
(5) (a) Diederich, M.; Nubbemeyer, U. Angew. Chem., Int. Ed. Engl.
1995, 34, 1026. (b) Diederich, M.; Nubbemeyer, U. Chem. Eur. J . 1996,
2, 894. (c) Laabs, S.; Scherrmann, A.; Sudau, A.; Diederich, M.; Kierig,
C.; Nubbemeyer, U. Synlett 1999, 25.
(8) Tietze, L. F.; Eicher, T. Reaktionen und Synthesen im Organisch-
Chemischen Praktikum, 2nd ed.; Thieme: Stuttgart, 1991; p 135.
(9) Rosen, T.; Fesik, S. W.; Chu, D.; Pernet, T. W.; Andre, G.
Synthesis 1988, 40.
10.1021/jo991484o CCC: $19.00 © 2000 American Chemical Society
Published on Web 02/23/2000

Planar Chirality
J . Org. Chem., Vol. 65, No. 6, 2000 1711
Sch em e 1
Sch em e 2
in the presence of triethylamine.9 Neither any epimer-
ization to give the 2,4-cis material nor any further
benzylation of the tertiary amine or the hydroxyl group
was found, respectively. The high yield and the short
reaction time led to the replacement of the formerly used
reductive amination.5a,6 The protection of the alcohol as
a TBS ether (tert-butyldimethylsilyl) generated ester 3.10
The reduction of the carboxyl function with DIBALH
yielded the primary carbinol.11 A subsequent Swern
oxidation led to the corresponding aldehyde,12 which was
immediately converted into the vinylpyrrolidine 1 by a
Wittig olefination with methylenetriphenylphosphorane
to avoid any epimerization to the 2,4-cis product.13
Dia ster eoselective Aza -Cla isen Rea r r a n gem en t.
The vinylpyrrolidine 1 was now treated with a range of
carboxylic acid fluorides under the recently reported
standard conditions:5c The allylamine 1 was dissolved in
CH2Cl2 in the presence of solid K2CO3 at an ambient
temperature and treated with the acid fluoride.14 In
contrast to the reactions with carboxylic acid chlorides
described earlier, no formation of a corresponding N-
acylammonium salt was found! The rearrangement did
not start up until the addition of the Me3Al.15 Then, a
fast and highly chemoselective generation of the corre-
sponding azoninones was observed; in some cases the
addition of a further amount of the fluoride and some
Me3Al was useful to increase the yield. Overall, the
reaction was found to be completed after 2 to 12 h, and
the yield of isolated nine-membered ring lactams 4-6
varied between 70 and 95% (Scheme 2). In contrast to
the investigations involving the acid chlorides, no allyl
halides were formed, indicating that the competing von
Braun degradation16 had been almost efficiently sup-
pressed. Moreover, no deactivated in situ formed amine
hydrohalides decelerated the rate of the rearrange-
ment.5,6
All rearrangements led diastereoselectively to single
azoninones 4-6, respectively, considering the stereogenic
centers and the configurations of the olefins. Always, the
configuration of the double bond was E and the relative
configuration of the stereogenic centers C-3 and C-8 was
found to be trans as proved beyond doubt by NOE
analyses. Additionally, the complete description of the
stereochemical aspects of the lactams needed the careful
consideration of the relative arrangement of two planes
of chirality (double bond and lactam function).17 Right
after the isolation 3,8-trans-azoninones 4a -6a with
conformation a were identified, indicating the proximity
of the protons H-3, H-6, and H-9R, i.e., the double bond
was arranged pS with respect to the medium-sized ring.
The lactam unit showed a cis arrangement of C-3 and
C-9 (about 20% NOE amplification regarding H-3 and
H-9R) with respect to its partial double bond character
and a syn arrangement of the carbonyl O-atom and H-5.
The X-ray analysis of the R-chloro lactam 6a confirmed
these results.18 Analysis of the NOE spectra indicated
that irradiation at several peaks induced weak negative
peaks at different ppm values. Obviously, a transfer of
magnetization from the major compound to a minor
diastereomer was found indicating a potential equilibri-
(10) Corey, E. J .; Venkateswarlu, A. J . Am. Chem. Soc. 1972, 94,
6190.
(11) Winterfeldt, E. Synthesis 1975, 617.
(12) Mancuso, A. J .; Swern, D. Synthesis 1981, 165.
(13) (a) Corey, E. J .; Greenwald, R.; Chaykovsky, M. J . Org. Chem.
1963, 28, 1128. (b) Marshall, J . A.; Pike, M. T.; Carroll, R. D. Ibid.
1966, 31, 2933. (c) Marshall, J . A.; Huffmann, W. F.; Ruth, J . A.; J .
Am. Chem. Soc. 1972, 94, 4691. (d) Magnusson, G. Tetrahedron Lett.
1977, 2713.
(14) Preparation of the carboxylic acid fluorides: (a) Olah, G. A.;
Nojima, M.; Kerekes, I.; Synthesis 1973, 487. (b) Olah, G. A.; Kuhn,
S.; Beke, S. Chem. Ber. 1956, 89, 862.
(15) As known in the literature, tertiary amines and acid fluorides
do not react spontaneously: (a) Granitza, D.; Beyermann, M.; Wens-
chuh, H.; Haber, H.; Carpino, L. A.; Truran, G. A.; Bienert, M. J . Chem.
Soc., Chem. Commun. 1995, 2223. (b) Carpino, L. A.; Mansour, E.-S.
M. E.; El-Faham, A. J . Org. Chem. 1993, 58, 4162. (c) Carpino, L. A.;
Sadat-Aalaee, D.; Chao, H.-G.; DeSelms, R. H. J . Am. Chem. Soc. 1990,
112, 9651.
(17) The stereochemical terminology concerning the azoninones is
used according to Eliel, E. L.; Wilen, S. H.; Mander; L. N. Stereochem-
istry of Organic Compounds; J . Wiley: New York, 1994; p 1121
(nomenclature pS, pR) and p 1203 (trans cycloalkenes). Description of
trans cycloalkenes as planar chiral compounds: Schlo¨gl, K. Top. Curr.
Chem. 1984, 125, 27 and Nakazaki, M.; Yamamoto, K.; Naemura, K.
Top. Curr. Chem. 1984, 125, 1. Alternative description as axial chiral
compounds: Krow, G. Top. Stereochem. 1970, 5, 31.
(18) X-ray data of 6a : colorless, transparent prism, crystallized from
Et2O/n-hexane at -20 °C, C21H32NO2Cl Si (Mr ) 394.03); crystal
data: orthorhombic; P212121. For further data see Supporting Informa-
tion and Figure 2.
(16) Cooley, J . H.; Evain, E. J . Synthesis 1989, 1.

1712 J . Org. Chem., Vol. 65, No. 6, 2000
Sudau et al.
um of at least two conformations (planar configurations)
of the lactam function (partial double bond).19
All initially formed lactams 4a -6a were characterized
by conspicuous changes of their conformations, indicating
a defined change of the planar chirality:20 Keeping the
lactams 4a -6a at room temperature for 3-5 days or
heating them to 40-60 °C for an appropriate time led to
an almost complete relaxation to generate conformation
b.21 NOE analyses of 4b-6b proved that the 3,8-trans
configurations of the stereogenic centers and the E-double
bonds were maintained. In contrast to the prior described
lactams 4a -6a , the proximity of the protons H-3, H-5,
and H-9R was determined, indicating an almost complete
flipping of the olefin from the pS to the pR arrangement
in 4b-6b. Again, the lactam unit showed a cis arrange-
ment of C-3 and C-9 (about 20% NOE amplification
regarding H-3 and H-9R) with respect to its partial double
bond, but now a syn arrangement of the carbonyl O-atom
and H-6 was found. The X-ray analysis of the R-chloro
lactam 6b confirmed these results.22 Analysis of the NOE
spectra resulted in no evidence concerning further species
that improve almost rigid conformations of 4b-6b.
Mech a n istic Con clu sion s. The stereochemical out-
come of the zwitterionic aza-Claisen rearrangement could
be interpreted as follows (Figure 1): Initially, the acti-
vated carboxylic acid fluoride attacked the 2-vinylpyrro-
lidine anti with respect to the bulky TBSO substituent
to give the hypothetical 1,2-syn-configured zwitterion
with Z-enolate geometry as known for all amide eno-
lates.23 Then, the rearrangement proceeded diastereose-
lectively via a boatlike transition state to give the 3,8-
trans-lactam (Figure 1).24 Apparently, the reaction path
employing a chairlike transition state was disfavored
because of severe repulsive interactions (1,3 strain).25
Furthermore, the transition state effected initially the
formation of the medium-sized ring with pS-arrangement
F igu r e 1. Chair- and boatlike intermediates of the rearrange-
ment of allylamine 1 with carboxylic acid fluorides.
of the E-double bond. This planar diastereomer was
obviously unstable: NMR and NOE analyses indicated
the existence of one preferred (a ) and at least one
additional minor conformation (c?) as a highly flexible
equilibrium of some arrangements of the lactam function
(Figures 2, 4). Finally, the epimerization (flipping of the
E double bond) to give the pR arrangement of the olefin,
with respect to the ring, generated the most stable
conformation (b) (Figures 3, 4). Preliminary force field
calculations and molecular mechanics calculations of the
related E/ Z-1,5-nonadiene confirmed these observa-
tions.26 Nevertheless, a high activation barrier had to be
passed to achieve the change of the planar chiral infor-
mation.21,27 This fact allowed the isolation and the
characterization of the conformers of the nine-membered
rings. Furthermore, the reaction path starting from the
allylamine via the kinetically stable to the thermody-
namically stable lactam was a substantial argument that
the process followed a sigmatropic rearrangement pro-
tocol.
(19) The NMR spectra of lactam 5a showed a doubled set of peaks,
indicating the existence of two major diastereomeric species (ratio 3:1,
independent of the temperature), and an additional minor conformer
(about 5%). Several attempts to separate the compounds by means of
HPLC failed because of the rapid adjustment of the equilibrium state.
NOE analyses proved the conformation 5a (first major diastereomer).
The second major conformation might be the structure 5c as shown
in the Figure 4, but the NOE data left some doubts. The third
compound could have represented a further lactam with an anti
arrangement of C-3 and C-9 in respect to the partial double bond.
(20) Related effects had been reported investigating Xenicane diter-
penes: (a) Guella, G.; Chiasera, G.; N′Diaye, I.; Pietra, F. Helv. Chim.
Acta 1994, 77, 1203. (b) Pearson, W. H.; Hembre, E. J . J . Org. Chem.
1996, 61, 5546 (indolizidines).
(21) Preliminary kinetic investigations of the conversion of 4a into
4b: half-life period at 40 °C: 540 min, half-life period at 60 °C: 54
min, activation energy (∆G*) of the epimerization: about 24 kcal mol-1
((3). Preliminary kinetic investigations of the conversion of 6a into
6b: half-life period at 40 °C: 540 min, half-life period at 60 °C: 54
min, activation energy (∆G*) of the epimerization: about 23 kcal mol-1
((3).
(22) X-ray analysis of 6b: colorless, transparent blocks, crystallized
from Et2O/n-hexane at -20 °C. C21H32NO2Cl Si (Mr ) 394.03); crystal
data: orthorhombic; P212121. For further data see Supporting Informa-
tion and Figure 3. Residual density of about 0.84 e/A3 near the C-4/
C-5 double bond showed this bond to be slightly disordered. A careful
inspection of the data showed two possible orientations for this bond:
a major orientation with an occupancy factor of about 0.88 (6b in Figure
3) and a minor orientation with an occupancy factor of about 0.12
(resulting from cocrystallized 6a , Figure 2).
Tr a n sa n n u la r Rin g Con tr a ction s. Recent investi-
gations have shown that azoninones underwent regio-
(23) (a) Evans, D. A.; Bartoli, J .; Shih, T. L. J . Am. Chem. Soc. 1981,
103, 2127. (b) Richter, W.; Sucrow, W. Chem. Ber. 1971, 104, 3679.
(24) (a) Bu¨chi, G.; Powell, J . E.; J . Am. Chem. Soc. 1970, 92, 3162.
(b) Abelmann, M. M.; Funk, R. F.; Munger, J . D. Ibid. 1982, 104, 4030.
(25) (a) J ohnson, W. S.; Bauer, V. J .; Margrave, J . L.; Frisch, M. A.;
Dreger, L. H.; Hubbard, W. N. J . Am. Chem. Soc. 1961, 83, 606. (b)
Vittorelli, P.; Hansen, H.-J .; Schmid, H.; Helv. Chim. Acta 1975, 58,
1293. (c) Vance, R. L.; Rondan, N. G.; Houk, K. N.; J ensen, F.; Borden,
W. T.; Komornicki, A.; Wimmer, E. J . Am. Chem. Soc. 1988, 110, 2314.
(26) Force field calculations of cyclic 1,5-nonadienes were reported
by White, D. N. J .; Bowill, M. J . J . Chem. Soc., Perkin Trans. 2 1977,
1610.
(27) The activation energy (∆G*) of the racemisation of optically
active E-cyclononene is about 20 kcalmol-1, half-life period at 0 °C: 4
min. Cope, A. C.; Banholzer, K.; Keller, H.; Pawson, B. A.; Wang, J .
J .; Winkler, H. J . S. J . Am. Chem. Soc. 1965, 87, 3644. Compare:
E-cyclooctene: ∆G* ) 35 kcalmol-1, half-life period at 133 °C: 120 h.
Cope, A. C.; Pawson, B. A. Ibid. 1965, 87, 3649.

Planar Chirality
J . Org. Chem., Vol. 65, No. 6, 2000 1713
Ta ble 1. Da ta of th e Aza -Cla isen Rea r r a n gem en ts
and diastereoselective ring contractions to indolizidi-
nones.4-6 Predominantly, the rigid conformations of the
lactams involved caused a defined anti attack of an
external electrophile at the unshielded face of the double
bond and the intramolecular trapping of the nascent
cation by the lactam nitrogen; the so-formed intermediate
N-benzyl acylammonium ion underwent an immediate
von Braun degradation to give the indolizidinone.4,5
Preliminary investigations using the pS and the pR
azoninones as reactants in transannular ring contrac-
tions, respectively, gave different bicyclic lactams. Obvi-
ously, the transannular reaction required a significantly
lower activation energy than the epimerization pS into
pR (conformational relaxation), i.e., the process proceeded
in contrast to the dictates of the Curtin-Hammett
Principle.6
With the intention to investigate scope and limitations
of the transannular reactions, the azoninones 4-6 were
treated with I2, Br2, and PhSeBr. Most of the reactions
had been carried out in a NMR test tube scale to get the
information concerning regio- and stereochemistry of the
products 7-15; an adequate number of reactions had
been realized in a preparative scale to determine the
more exact yields.
In the first series the pR-lactams 4b-6b with the
stable conformations b were treated with the reagents
mentioned above. All attempts gave regio- and diaste-
reomerically pure the indolizidinones 7b-15b in accept-
able yields and short reaction times; no intermediate
acylammonium salts could be detected. The relative
configuration of the new stereogenic centers and the
position of the ring junction were proved by NOE
analyses and, if necessary, by HETCOR (heteronuclear
correlation). Detailed information is outlined in Table 3.
In the second series the pS-lactams 4a -6a with the
unstable conformations a were treated with the reagents
mentioned above. Again no intermediate acylammonium
salts could be detected; the reaction was found to be
completed within minutes, generating the indolizidinones
7a /c-15a /c in moderate to high yields. In contrast to the
first series, an alternative regio- and stereochemical
course was taken, and the products a /c were generated
in varying ratios. Furthermore, the course of the reaction
strongly depended on the reaction conditions: Adding
slowly a solution of the reagent at room temperature to
a solution of an azoninone (4a -6a ), the indolizidinones
7c-15c were built as the major products; the ratio of 7c-
15c and other diastereomers was 4:1 to >15:1. The
reaction was completed at that time when the color of
unreacted reagent remained. The reaction conditions
were changed so that a solution of the nine-membered
ring lactam 4a -6a was added to a solution of the reagent
at -20 °C. The regioisomeric indolizidinones 7a -15a
were isolated as the major products, and the ratios of 7a
to 15a and other diastereomers were found to be 3:1 to
>15:1.28 Again, the reaction was found to be completed
right after finishing the addition. The relative configu-
ration of the new stereogenic centers and the position of
the ring junction were proved by NOE analyses and, if
necessary, by HETCOR (heteronuclear correlation). The
results of the transannular ring contractions are sum-
marized in Table 3.
transannular distancea [Å]
NfC-5
NfC-6
azoninone
yield [%]
95
calcd
found
calcd
found
pS-4a
pR-4b
pS-5a
pR-5b
pS-6a
pR-6b
3.12
3.35
3.13
3.31
3.13
3.33
3.22
2.99
3.22
2.97
3.22
2.97
73
92
3.09
3.31
3.21
2.98
a
Calcd: MM+ optimized structure, found: X-ray analysis.
Ta ble 2. Nom en cla tu r e of th e In d olizid in on es
R2/R1
Ph
OBn
Cl
PhSe
I
Br
7
8
9
10
11
12
13
14
15
Mech a n istic Con clu sion s. The interpretation of the
results of the transannular reactions can be divided into
a stereo- and a regiochemical part. Apparently, the
stereochemical course of the ring contractions was quite
reasonable; all reactions underwent well-known electro-
philic anti additions of electrophile and nucleophile at
the olefin. Regarding the pS-lactams 4a -6a , the elec-
trophile attacked the unshielded Re-face (C-5 or C-6) of
the double bond, and the nascent cation was trapped by
a Si-face attack (C-6 or C-5) of the nitrogen to generate
the indolizidinones 7a /c-15a /c. Due to the changed
planar chirality, the double bond of the pR-lactams 4b-
6b suffered from a Si-face attack (C-5) of the electrophile
and, consequentially, from a Re-attack (C-6) of the
nitrogen to give 7b-15b. As expected, no mixtures of the
indolizidinones 7a /c-15a /c on one hand and 7b-15b on
the other hand were found. The activation energy of the
epimerization of the planar chiral information was
significantly higher than that of the transannular reac-
tion (anti Curtin-Hammett).27
The explanation of the regiochemical course of the
reaction is still somewhat speculative, but a preliminary
hypothesis should be submitted. All planar diastereo-
meric arrangements of the azoninones 4-6 were char-
acterized by defined transannular distances between the
nitrogen and C-5 and C-6 of the olefin (Table 1, Figure
3), respectively. The central assumption is that the
shortest distance between the nitrogen and C-5 or C-6
of the olefin, respectively, determined the regiochemical
outcome of the transannular reactions generating the
indolizidinones 7-15.
Transannular distances (Table 1, Figure 3) between
the nitrogen and C-5 and C-6 of the olefin in the
pR-lactams 4b-6b were determined by X-ray analysis
and some simple force field optimizations, and showed
that N-1 was positioned somewhat closer to C-6 than to
C-5.22,29 Considering the rigid conformations of these
lactams (no conformational mobility of both planes of
chirality according NMR and NOE experiments), the ring
contraction always proceeded regioselectively, the new
bond forming between N-1 and C-6 as found in the
indolizidinones 7b-15b. Apparently, an analogous argu-
ment explicate the formation of the indolizidinones 7a -
(29) Force field MM+ calculations had been carried out with
Hyperchem arranging C-3 and C-9 cis with respect to the double bond
character of the lactam unit. The structures are outlined in Figure 4.
Transannular distances of type-c-conformation (N-C-5/N-C-6, [Å]):
4c: 3.3/2.98, 5c: 3.35/3.03, 6c: 3.34/3.04.
(28) The transannular ring contraction of 5a and I2 followed an
exceptional path despite varying reaction conditions: The selective
formation of 11a failed; only varying mixtures of 11a and 11c have
been found to give predominantly lactam 11c.

1714 J . Org. Chem., Vol. 65, No. 6, 2000
Ta ble 3. Resu lts of th e Tr a n sa n n u la r Rin g Con tr a ction sa
Sudau et al.
ratio indolizidinones 7 to 15
entry
azoninone
reagent
method**
scale*
yield [%]
product
a
b
c
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
4a
4a
4a
4a
4a
4a
4b
4b
4b
5a
5a
5a
5a
5a
5b
5b
6a
6a
6a
6a
6a
6b
6b
PhSeBr
I2
Br2
PhSeBr
I2
Br2
PhSeBr
I2
Br2
PhSeBr
I2
Br2
PhSeBr
I2
PhSeBr
I2
PhSeBr
Br2
PhSeBr
I2
A
A
A
B
B
B
A or B
A or B
A or B
A
A
A
B
B
A or B
A or B
A
A
B
B
B
p
p
p
p
p
p
p
p
p
p
a
a
p
p
a
p
a
a
p
a
p
p
p
44
63
40
95
99
55
69
49
72
46
36
16
74
70
20
40
20.5
25
81
15
82
64[6]
64
7
8
9
7
8
9
7
8
9
10
11
12
10
11
10
11
13
15
13
14
15
13
14
1
3
1
-
-
1
-
-
-
5
-
-
-
-
-
-
1
-
1
-
1
1
4
-
-
-
1
1
1
-
-
-
-
-
1
1
1
1->3
-
1
1
-
-
1
-
1
1
1
-
-
-
-
13
1
-
-
-
-
-
1
-
-
-
-
-
1
s
t
u
v
w
Br2
PhSeBr
I2
A or B
A or B
-
-
1
a
*: a ) analytical scale, p ) preparative scale; **methods A and B as described in the Experimental Section.
the regioselective formation of the indolizidinones 7a -
15a (anti Curtin-Hammett). In contrast, the reaction led
to the regioisomer indolizidinones 7c-15c at room tem-
perature even though no further predominant conforma-
tion 4c-6c (planar diastereomer) could be detected (all
spectral data of the lactams 4a -6a , respectively, mea-
sured at -20 °C, 0 °C, and room temperature were almost
identical).19 Actually, the dictates of the Curtin-Ham-
mett Principle seemed to be the crucial point concerning
the relative arrangement of the lactam function with
respect to the ring. According to NOE and NMR data,
the pS-lactams show some conformational mobility. Thus,
a further conformation c (though sparsely populated)
must have been much more reactive in respect to the
transannular reaction than the predominant arrange-
ment of type a . Simple force field calculation optimized
structures resulted short transannular distances between
N-1 and C-6 (compared to that between N-1 and C-5) in
a pS-lactam showing a conformation of type c,26,29 but
severe repulsive interactions (f low concentration) might
have circumvented the occurrence of adequate peaks in
the spectral analyses. Figure 4 should clarify this argu-
ment. However, the selective formation of two regioiso-
meric products starting from one and the same reactant
presupposed the existence of at least two reactive con-
formations of the azoninones with (planar) diastereomeric
properties.30 Nevertheless, the exact reaction path is still
unproved.
F igu r e 2. ORTEP plots of azoninone 6a .
Con clu sion . The zwitterionic aza-Claisen rearrange-
ment of the trans 4-silyloxy-2-vinylpyrrolidine 1 to the
γ,δ-unsaturated lactams 4-6 proceeded with an almost
complete 1,4-chirality transfer and the formation of an
F igu r e 3. ORTEP plots of azoninone 6b.
15a starting from the pS-lactams 4a -6a : in this case
the transannular distances (Table 1, Figure 2) between
the nitrogen and C-5 were found to be somewhat shorter
than that to C-6 according to the X-ray analysis and some
simple force field calculation optimized structures.18,29
Considering the predominant conformation of lactams
4a -6a (rigid arrangement of the double bond according
NMR and NOE experiments) at -20 °C, the transannular
ring contraction was significantly faster than a confor-
mational relaxation of the lactam function resulting in
(30) Additionally, two corresponding (diastereomeric) trans arrange-
ments of the amide function are imaginable, but, as outlined in ref
25, such trans/trans nonadienes are thought to be less stable (4-6
kcal-1) than the trans/cis structures discussed above. Nevertheless,
the existence of such structures as reactive (and diastereomeric)
intermediates/transition states in the transannular ring contractions
yielding a or c type products could neither be excluded nor proven.
However, the presumption that diastereomeric properties caused the
formation of the different bicycles was left as is. The determination of
the transannular distances of N-C-5/N-C-6 would have allowed a very
similar argumentation.

Planar Chirality
J . Org. Chem., Vol. 65, No. 6, 2000 1715
F igu r e 4. Regio- and diastereoselective transannular ring contraction paths of the azoninones 4-6.
E-olefin in the medium-sized ring. In contrast to well-
known acyclic Claisen rearrangements, an unusual di-
astereoselectivity was observed yielding 3,8-trans-lac-
tams according to a boatlike transition state involved in
the 3,3 sigmatropic process. Furthermore, the medium-
sized rings were characterized by additional planar chiral
properties: Right after the reaction the lactams 4-6 with
conformations a (and c?) bearing a rigid pS-situation of
the olefin and an almost flexible arrangement of the
lactam unit were found. The relaxation from the kineti-
cally generated conformations a into the thermodynami-
cally stable forms b with almost rigid arrangements of
lactam and olefin with respect to the ring required a
significantly high activation energy.
The planar diastereomers a and b were subjected to
transannular reactions to give indolizidinones with a
complete stereoselectivity and a high regioselectivity. In
contrast to the Curtin-Hammett-Principle lactams 4-6
allowed defined additions to the double bond with respect
to the predominant conformation. The planar chiral
information of the nine-membered ring could be trans-
ferred into defined stereogenic centers by means of the
ring contraction. While the reactions of the rigid type-
b-azoninones yielded exclusively bicycles 7b-15b with
a δ-valerolactam function, the type-a -rings used different
reaction paths to generate two further products 7a /c-
15a /c. Obviously, the lactam function of the kinetically
formed azoninones a showed some flexibility to generate
at least two reactive conformations with diastereomeric
properties under the reaction conditions. The variation
of the transannular reaction conditions allowed us to pick
out predominantly one of these conformations yielding
either the series 7a -15a or series 7c-15c, respectively.
Further investigations concerning scope and limita-
tions of the regio- and diastereoseletive transannular
reactions and the use of an appropriate sequence in
natural product syntheses are in progress.
Exp er im en ta l Section
For general experimental data see ref 31. The 1H NMR
spectra of 5a , 9a and the NOEDS analyses of 5a , 9a were
recorded on a 500 MHz spectrometer. Satisfactory HRMS data-
(( 0.4%) are reported for all new compounds. X-ray analyses
were performed using MoKR-radiation (λ ) 0.71073 Å). The
structure was determined by direct methods using program
SHELXS. The H atoms were taken from a difference Fourier
synthesis and were refined with isotropic thermal parameters.
The non-H atoms were refined with anisotropic thermal
parameters. The structure was refined on F values using
weighting scheme: ω(F) ) 4F2/[ σ2(F2) + (0.03F2)2 ]. The final
difference density was between -0.29 and +0.36 e/A3.
Ben zyloxya cetyl F lu or id e. A solution of benzyloxyacetic
acid (3 g, 18 mmol) in dry CH2Cl2 (20 mL) was treated with
dry pyridine (0.72 mL, 0.72 g, 9 mmol) at room temperature.
After stirring for 10 min, cyanuric fluoride (0.77 mL, 1.22 g, 9
mmol) was added slowly. After a few minutes, a white solid
precipitated. The mixture was stirred for additional 2 h at
room temperature. Then the precipitate was removed by
filtration, and the solvent was evaporated. The residue was
dissolved in dry toluene, and the mixture was stored at -20
°C for 10 min to precipitate a further amount of the white salt.
After a final filtration and the removal of the solvent, the pure
benzyloxyacetyl fluoride was isolated as a clear oil, yield: 2.88
g (95%, 17.1 mmol): 1H NMR (270 MHz, CDCl3) δ 7.40-7.20
(m, 5 H), 4.65 (s, 2 H), 4.25 (d, J (19F,1H) ) 3.4 Hz, 2 H). 13C
NMR (67.9 MHz, CDCl3) δ 163.1 and 157.7 (d, J (19F,13C) )
366 Hz, CO), 136.1 (s), 128.6 (d), 128.4 (d), 128.1 (d), 73.4 (t),
64.9 and 63.9 (dd, J (19F,13C) ) 71 Hz).
St a n d a r d P r oced u r e for t h e Zw it t er ion ic Cla isen
Rea r r a n gem en t. Under argon, dry K2CO3 (70 mg, 0.5 mmol)
was suspended in dry CH2Cl2 (15 mL) and cooled to 0 °C.
N-Allylpyrrolidine 1 (320 mg, 1 mmol) and acid fluoride (3 to
6 mmol) were added subsequently by means of a syringe. After
about 15 min of stirring at 0 °C, a solution of Me3Al (0.75-1.5
mL, 1.5-3 mmol, 2 M in n-heptane) was added via syringe,
and CH4 evolved. The mixture was allowed to warm to room
temperature. The reaction was completed within hours (R1 )
Cl, Ph) or 1 to 2 days (R ) OBn). In several attempts the
addition of a second amount of acid fluoride and Me3Al was
necessary to achieve a complete conversion of the reactant.
Workup was started by dilution of the reaction mixture with
Et2O and filtration through a short silica gel column to remove
(31) Nubbemeyer, U. Synthesis 1993, 1120.

1716 J . Org. Chem., Vol. 65, No. 6, 2000
Sudau et al.
the polar impurities. The residual organic layer was washed
with saturated aqueous NaHCO3 and dried (MgSO4). The
solvent was removed below 20 °C to isolate the pS-lactams
4a -6a , heating to 40-60 °C led to a fast epimerization to give
the pR-lactams 4b-6b. The crude products were purified by
column chromatography. If necessary, the planar diastereo-
mers were separated via HPLC or column chromatography on
silica gel.
(d, J ) 12 Hz, 1 H), 4.57-4.55 (dd, J ) 5, 2 Hz, 1 H), 4.47-
4.44 (d, J ) 15 Hz, 1 H), 4.38-4.36 (m, 1 H), 4.33-4.30 (d, J
) 12 Hz, 1 H), 3.31-3.28 (dd, J ) 15, 4 Hz, 1 H), 2.60-2.55
(m, 1 H), 2.50-2.40 (m, 2 H), 2.34-2.30 (m, 1 H), 0.93 (s, 9
H), 0.09 (s, 6 H). 13C NMR (62.9 MHz, CDCl3) δ 173.3 (s),
140.0-126.0 (10 C), 76.6 (d), 71.7 (t), 51.9 (t), 48.5 (t), 41.9 (t),
34.3 (t), 25.9 (q), 17.9 (s), -4.6 (q), -4.8 (q).
(p R )E -3R ,8R -1-Be n zyl-3-b e n zyloxy-8-(t er t -b u t yld i-
m eth ylsilyloxy)-2,3,4,7,8,9-h exah ydr o-1H-azon in -2-on e 5b.
The pS-lactams 4a -6a had been stored at -20 °C without
a significant epimerization for several weeks. The crystals of
6a were found to be stable even at room temperature for days.
(pS)E-3S,8R-1-Ben zyl-8-(ter t-bu tyld im eth ylsilyloxy)-3-
p h en yl-2,3,4,7,8,9-h exa h yd r o-1H-a zon in -2-on e 4a .5c Reac-
tion of vinylpyrrolidine 1 (0.1 g, 0.32 mmol), phenylacetyl
fluoride (0.13 g, 0.95 mmol), and Me3Al (2 mL, 4 mmol)
following the standard procedure. Purification by column
chromatography on silica gel (hexane/EtOAc 5:1, Rf ) 0.53).
Heating of azoninone 5a to 40-60 °C yields conversion to 5b,
1
ratio 5b/5a : 7/1 to 10/1. [R]20 14.9 (c ) 1.3, CHCl3). H NMR
D
(270 MHz, CDCl3) δ 7.4-7.2 (m, 10 H), 5.65-5.50 (m, 1 H),
5.40-5.20 (m, 2 H), 4.60-4.55 (d, J ) 12 Hz, 1 H), 4.23-4.1.8
(d, J ) 12 Hz, 1 H), 4.10-4.05 (d, J ) 15 Hz, 1 H), 4.05-3.9
(m, 2 H), 3.60-3.50 (dd, J ) 14, 9 Hz, 1 H), 2.95-2.88 (d, J )
14 Hz, 1 H), 2.78-2.66 (ddd, J ) 11, 7, 4 Hz, 1 H), 2.55-2.45
(m, 2 H), 2.05-1.92 (ddd, J ) 12, 12, 8 Hz, 1 H), 0.80 (s, 9 H),
0.01 (s, 3 H), 0.05 (s, 3 H). 13C NMR (62.9 MHz, CDCl3) δ 171.6
(s), 137.5 (s), 137.4 (s), 130.2 (d), 129.7 (d), 128.5 (d), 128.4
(d), 128.2 (d), 128.0 (d), 127.7 (d), 127.4 (d), 76.7 (d), 71.1 (t),
69.4 (d), 53.7 (t), 49.0 (t), 42.8 (t), 36.8 (t), 25.6 (q), 17.8 (s),
-4.9 (q), -5.16 (q). IR (KBr) 2925 (s), 2885 (s), 2857 (s), 1646
(s), 1471 (s), 1452 (s) cm-1. MS (70 eV, EI, 130 °C): m/z 465
(7) [M+], 408 (7) [M+ - C4H9], 374 (41), 359 (16), 91 (100).
Yield: azoninone 4a (0.13 g, 95%) as crude oil. [R]20 -80.7 (c
D
) 1.5, CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.50-7.10 (m, 10
H), 5.92-5.77 (m, 1 H), 5.75-5.60 (m, 1 H), 5.08-5.00 (d, J )
14 Hz, 1 H), 4.30-4.22 (dd, J ) 10, 8 Hz, 1 H), 4.22-4.18 (d,
J ) 15 Hz, 1 H), 4.15-4.10 (m, 1 H), 3.95-3.90 (dd, J ) 16,
10 Hz, 1 H), 3.10-3.00 (dd, J ) 15, 4 Hz, 1 H), 2.70-2.60 (m,
2 H), 2.35-2.25 (dd, J ) 14, 2 Hz, 1 H), 2.22-2.10 (ddd, J )
14, 11, 5 Hz, 1 H), 0.81 (s, 9 H), -0.01 (s, 3 H), -0.07 (s, 3 H).
13C NMR (67.9 MHz, CDCl3) δ 174.2 (s), 139.8 (s), 137.4 (s),
134.4 (d), 128.7 (d), 128.5 (d), 128.4 (d), 128.2 (d), 127.5 (d),
127.0 (d), 67.9 (d), 52.2 (d), 52.1 (t), 48.9 (t), 39.2 (t), 34.4 (t),
25.7 (q), 18.0 (s), - 4.8 (q), - 4.9 (q). The NMR spectra show
a second species (equilibrium), witch might be in accordance
with azoninone 4c (NOE analysis). In some attempts some
degradation products of the phenylacetyl fluoride were found.
E(pR)-3S,8R-1-Ben zyl-8-(ter t-bu tyld im eth ylsilyloxy)-3-
p h en yl-2,3,4,7,8,9-h exa h yd r o-1H-a zon in -2-on e 4b.5c Heat-
ing of azoninone 4a to 40-60 °C yields conversion to 4b, ratio
HRMS: calcd for
C
28H39NO3Si: 465.26992 (M+), found
465.26532 (M+).
(pS)E-3R,8R-1-Ben zyl-8-(ter t-bu tyld im eth ylsilyloxy)-3-
ch lor o-2,3,4,7,8,9-h exa h yd r o-1H-a zon in -2-on e 6a .6 Reac-
tion of vinylpyrrolidine 1 (1 g, 3.15 mmol), chloroacetyl fluoride
(1.5 mL, 2 mmol), and Me3Al (2 mL, 4 mmol) following the
standard procedure. Purification by column chromatography
on silica gel (hexane/EtOAc 3:1, Rf ) 0.38). Yield: Azoninone
6a (1.14 g, 92%) as colorless crystals, mp 116 °C. [R]20 -79.8
D
1
(c ) 1.7, CHCl3). H NMR (270 MHz, CDCl3) δ 7.25 (m, 5 H),
5.76 (ddd, J ) 15, 11, 3 Hz, 1 H), 5.44 (ddd, J ) 16, 9 Hz, 6
Hz, 1 H), 5.05 (d, J ) 14 Hz, 1 H), 4.84 (dd, J ) 10, 8 Hz, 1 H),
4.17 (d, J ) 15 Hz, 1 H), 4.05 (m, 1 H), 3.55 (dd, J ) 16, 10
Hz, 1 H), 3.01 (dd, J ) 15, 4 Hz, 1 H), 2.90 (m, 1 H), 2.54 (ddd,
J ) 17,10, 6 Hz, 1 H), 2.28 (m, 1 H), 2.09 (ddd, J ) 17,11, 5
Hz, 1 H), 0.81 (s, 9 H), -0.01 (s, 3 H), -0.07 (s, 3 H). 13C NMR
(67.9 MHz, CDCl3) δ 169.6 (s), 136.8 (s), 131.2 (d), 130.7 (d),
128.5 (d), 127.7 (d), 66.3 (d), 55.2 (d), 51.6 (t), 49.3 (t), 39.0 (t),
36.9 (t), 25.5 (q), 17.8 (s), -4.9 (s), -5.1 (s).
4b/4a : 7/1 to 10/1. [R]20 -165.1 (c ) 0.6, CHCl3). 1H NMR
D
(270 MHz, CDCl3) δ 7.2-7.3 (m, 5 H), 5.84 (ddd, J ) 16, 11, 5
Hz, 1 H), 5.36 (ddd, J ) 16, 12, 4 Hz, 1 H), 5.20 (d, J ) 16 Hz,
1 H), 4.15-3.95 (m, 3 H), 3.84 (dd, J ) 12, 2 Hz, 1 H), 3.04 (d,
J ) 13 Hz, 1 H), 2.81 (ddd, J ) 12, 12, 12 Hz, 1 H), 2.75 (m,
1 H), 2.50 (dd, J ) 12, 5 Hz, 1 H), 2.08 (ddd, J ) 10, 10, 8 Hz,
1 H), 0.84 (s, 9 H), 0.05 (s, 3 H), 0.02 (s, 3 H). 13C NMR (67.9
MHz, CDCl3) δ 174.3 (s), 140.9 (s), 137.7 (s), 133.9 (d), 128.6
(d), 128.5 (d), 128.2 (d), 127.7 (d), 127.2 (d), 126.9 (d), 70.7 (d),
54.5 (d), 51.8 (t), 49.1 (t), 42.8 (t), 36.8 (t), 25.6 (q), 17.8 (s), -
4.4 (q), -4.9 (q). IR (KBr) 3063 (s), 3028 (s), 2953 (s), 2929 (s),
2887 (s), 2856 (s), 1775 (w), 1725 (w), 1637 (s, CdO), 1255 (s)
cm-1. MS (70 eV, EI, 60 °C): m/z 435 (22) [M+], 378 (32) [M+
- C4H9], 344 (31) [M+ - Bn], 91 (100). HRMS: Calcd for
(p R)E-3R,8R-1-Ben zyl-8-(ter t-b u t yld im et h ylsilyloxy)-
3-ch lor o-2,3,4,7,8,9-h exa h yd r o-1H-a zon in -2-on e 6b.6 [R]20
D
1
-122 (c ) 0.3, CHCl3). H NMR (270 MHz, CDCl3) δ 7.2-7.3
(m, 5 H), 5.67 (ddd, J ) 16, 10, 6 Hz, 1 H), 5.34 (ddd, J ) 15,
11, 3 Hz, 1 H), 5.22 (d, J ) 15 Hz, 1 H), 4.50 (dd, J ) 12, 3 Hz,
1 H), 4.09 (d, J ) 15 Hz, 1 H), 4.01 (m, 1 H), 3.62 (dd, J ) 14,
9 Hz, 1 H), 2.97 (d, J ) 14 Hz, 1 H), 2.60-2.80 (m, 3 H), 2.02
(ddd, J ) 12, 12, 9 Hz, 1 H), 0.81 (s, 9 H), 0.02 (s, 3 H), 0.00
(s, 3 H). 13C NMR (67.9 MHz, CDCl3) δ 169.6 (s), 136.8 (s),
131.2 (d), 130.1 (d), 128.6 (d), 127.9 (d), 127.6 (d), 69.5 (d), 56.2
(d), 54.3 (t), 49.7 (t), 42.8 (t), 40.1 (t), 25.6 (q), 17.8 (s), -4.5
C
27H37NO2Si: 435.25936 (M+), found 435.25747 (M+).
(p S )E -3R ,8R -1-Be n zyl-3-b e n zyloxy-8-(t er t -b u t yld i-
m eth ylsilyloxy)-2,3,4,7,8,9-h exah ydr o-1H-azon in -2-on e 5a.
Reaction of vinylpyrrolidine 1 (0.3 g, 0.95 mmol), benzyloxy-
acetyl fluoride (1 g, 5.7 mmol), and Me3Al (1.4 mL, 3 mmol)
following the standard procedure. Purification by column
chromatography on silica gel (hexane/EtOAc 3:1, Rf ) 0.51).
Yield: Inseparable 3:1 mixture of azoninones 5a (major
conformer) and 5c (minor conformer, structure had not been
undoubtedly proved) (0.32 g, 73%) as pale yellow oil. [R]20D 4.9
(c ) 1.1, CHCl3). Major compound 5a : 1H NMR (500 MHz,
CDCl3) δ 7.4-7.2 (m, 10 H), 5.65-5.55 (ddd, J ) 16, 11, 3 Hz,
1 H), 5.41-5.33 (ddd, J ) 16, 10, 6 Hz, 1 H), 5.20-5.15 (d, J
) 14 Hz, 1 H), 4.63-4.60 (d, J ) 12 Hz, 1 H), 4.42-4.38 (dd,
J ) 8, 8 Hz, 1 H), 4.33-4.30 (d, J ) 12 Hz, 1 H), 4.08-4.05 (d,
J ) 15 Hz, 1 H), 4.03-3.99 (m, 1 H), 3.43-3.35 (dd, J ) 15,
10 Hz, 1 H), 2.88-2.82 (dd, J ) 15, 5 Hz, 1 H), 2.75-2.68 (m,
1 H), 2.39-2.30 (m, 1 H), 2.27-2.20 (m, 1 H), 2.15-2.08 (ddd,
J ) 13, 11, 6 Hz, 1 H), 0.81 (s, 9 H), -0.02 (s, 3 H), -0.07 (s,
3 H). 13C NMR (62.9 MHz, CDCl3) δ 172.3 (s), 140.0-126.0
(10 C), 76.2 (d), 71.0 (t), 66.2 (d), 50.7 (t), 48.6 (t), 39.0 (t), 33.4
(t), 25.6 (q), 17.8 (s), -4.8 (q), -5.0 (q). Minor compound
(assignment as far as possible): 1H NMR (500 MHz, CDCl3) δ
7.4-7.2 (m, 10 H), 5.89-5.82 (ddd, J ) 16, 10, 5 Hz, 1 H),
5.81-5.74 (ddd, J ) 16, 10, 5 Hz, 1 H), 5.41-5.35 (d, J ) 14
Hz, 1 H), 4.65-4.62 (ddd, J ) 15, 1.4, 1.4 Hz, 1 H), 4.63-4.60
(s), -4.9 (s). IR (KBr) 2952 (s), 2879 (s), 1644 (s, CO) cm-1
.
MS (80 eV, EI, 100 °C): m/z 393 (6) [M+], 378 (2) [M+ -CH3],
358 (4) [M+ - Cl], 336 (18) [M+ - C4H9]. HRMS: calcd for
C
21H32NO2ClSi: 393.18909 (M+), found 393.18759 (M+).
Sta n d a r d P r oced u r e A. The electrophile (PhSeBr, I2 or
Br2, respectively, 1 mmol) was dissolved in dry CH2Cl2 (20 mL),
and the solution was cooled to -20 °C with stirring. Then a
solution of the azoninone 4, 5, or 6 (1 mmol) in dry CH2Cl2 (5
mL) was added slowly by means of a syringe. According to most
attempts, the reaction was found to be completed right after
the finish of the addition (TLC monitoring). The mixture was
stirred for a further 15 min at room temperature. Finally, the
solvent was evaporated, and the crude material was purified
by column chromatography.
Sta n d a r d P r oced u r e B. The azoninone 4, 5, or 6 (1 mmol)
was dissolved in dry CH2Cl2 (20 mL) at room temperature with
stirring. Then a solution of the electrophile (PhSeBr, I2, or Br2,
respectively, 1 mmol) in dry CH2Cl2 (5 mL) was added dropwise
by means of a syringe until the color of unreacted reagent
remained (quasi titration). According to most attempts, the
reaction was found to be completed right after the finish of

Planar Chirality
J . Org. Chem., Vol. 65, No. 6, 2000 1717
the addition (TLC monitoring). The mixture was stirred for a
further 15 min at room temperature. Finally, the solvent was
evaporated, and the crude material was purified by column
chromatography. (In most cases, method B was found to give
the higher yields of indolizidinones compared to method A.)
2S,6R,8R,8a S-6-(ter t-Bu tyld im eth ylsilyloxy)-2-p h en yl-
8-ph en ylselan yl-3-(8H)-in dolizidin on e 7a. Reaction of azon-
inone 4a (110 mg, 0.25 mmol) and PhSeBr following the
standard procedure A. Purification by column chromatography
on silica gel (hexane/EtOAc 3:1, Rf ) 0.38). Yield: indolizidi-
2.37 (m, 2 H), 2.29-2.18 (ddd, J ) 13, 11, 2 Hz, 1 H), 0.87 (s,
9 H), 0.07 (s, 3 H), 0.05 (s, 3 H). 13C NMR δ (67.9 MHz, CDCl3)
δ 174.3 (s), 139.7 (s), 128.7 (d), 127.6 (d), 126.9 (d), 67.4 (d),
62.7 (d), 46.6 (t), 46.5 (d), 45.5 (t), 34.8 (t), 27.9 (d), 25.7 (q),
17.9 (s), -4.9 (q), -5.16 (q). IR (KBr) 2949 (s), 2925 (s), 1697
(s, CO), 1257 (m) cm-1. MS (70 eV, EI, 150 °C) m/z 470 (0.1)
[M+], 456 (3) [M+ - CH3], 414 (100) [M+ - C4H9], 287 (14)
[M+ - C4H9 - I]. HRMS calcd for C19H27NO2ISi: 456.08559
(M+ - CH3), found 456.08212 (M+ - CH3).
2R,6S,8S,8a R-2-(ter t-Bu tyld im eth ylsilyloxy)-8-iod o-6-
p h en yl-5(8H)-in d olizid in on e 8b. Reaction of azoninone 4b
(100 mg, 0.23 mmol) with I2 following the standard procedure
B. Purification by column chromatography on silica gel (hex-
none 7a (56 mg, 44%) as a colorless oil. [R]20 -29.6 (c ) 0.5,
D
CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.53-7.56 (m, 2 H),
7.15-7.35 (m, 8 H), 4.06 (d, J ) 13 Hz, 1 H), 3.97 (m, 1 H),
3.71-3.65 (dd, J ) 10, 7 Hz, 1 H), 3.56-3.47 (ddd, J ) 5, 7,
11 Hz, 1 H), 3.41-3.31 (ddd, J ) 12, 12, 3 Hz, 1 H), 2.78-2.72
(dd, J ) 13, 1.5 Hz, 1 H), 2.54-2.32 (m, 2 H), 2.29-2.23 (m, 1
H), 1.78-1.68 (ddd, J ) 14, 13, 2 Hz, 1 H), 0.84 (s, 9 H), 0.05
(s, 3 H), 0.00 (s, 3 H). 13C NMR δ (67.9 MHz, CDCl3) 174.1 (s),
140.1 (s), 135.6 (d), 129.1 (d), 128.6 (d), 128.2 (d), 127.6 (d),
126.8 (d), 126.5 (s), 65.9 (d), 59.9 (d), 46.8 (d), 46.4 (t), 41.1
(d), 40.4 (t), 33.7 (t), 25.7 (q), 17.9 (s), -4.9 (q), -5.16 (q). IR
(KBr) 2951 (s), 1695 (s, CO), 1257 (m) cm-1. MS (80 eV, EI,
170 °C): m/z 501 (0.5) [M+], 486 (1.6) [M+ - CH3], 444 (100)
ane/EtOAc 6:1, Rf ) 0.34). Yield: indolizidinone 8b (53 mg,
1
49%) as a colorless oil. [R]20 73.4 (c ) 1.1, CHCl3). H NMR
D
(270 MHz, CDCl3) δ 7.4-7.1 (m, 5 H), 4.45 -4.35 (m, 1 H),
4.10-4.00 (ddd, J ) 11, 11, 3 Hz, 1 H), 4.00-3.90 (ddd, J )
11, 10, 5 Hz, 1 H), 3.78-3.70 (dd, J ) 12, 6 Hz, 1 H), 3.70-
3.65 (m, 1 H), 3.65-3.60 (dd, J ) 12, 6 Hz, 1 H), 2.92-2.80
(ddd, J ) 11, 7, 3 Hz, 1 H), 2.61-2.50 (ddd, J ) 12, 8, 7 Hz, 1
H), 2.50-2.35 (ddd, J ) 14, 14, 12 Hz, 1 H), 1.95-1.75 (ddd,
J ) 11, 9, 8 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H).
13C NMR (62.9 MHz, CDCl3) δ 168.4 (s), 139.9, 128.7, 128.0,
127.0, 67.7 (d), 64.6 (d), 54.7 (t), 50.6 (d), 44.9 (t), 43.8 (t), 25.7
(q), 24.0 (d), 17.9 (s), -4.9 (q). IR (KBr) 2953 (s), 2928 (s), 2856
(s), 1648 (s, CO), 1451 (s) 1431 (s), 1252 (m) cm-1. MS (70 eV,
EI, 160 °C) m/z 470 (0.5) [M+.- H+], 456 (3) [M+ - CH3], 414
(100) [M+ - C4H9], 287 (15) [M+ - I - C4H9]. HRMS calcd for
[M+ - C4H9], 344 (8) [M+ - PhSe]. HRMS calcd for C25H32
-
NO2SeSi: 486.13675 (M+ -CH3), found 486.13354 (M+ - CH3).
2R,6S,8S,8a R-2-(ter t-Bu tyld im eth ylsilyloxy)-6-p h en yl-
8-p h en ylsela n yl-5(8H)-in d olizid in on e 7b. Reaction of azon-
inone 4b (100 mg, 0.23 mmol) and PhSeBr following the
standard procedure B. Purification by column chromatography
on silica gel (hexane/EtOAc 3:1, Rf ) 0.28). Yield: indolizidi-
C
20H29NO2SiI 470.10124 (M+ - H), found 470.10574 (M+
H).
-
none 7b (79 mg, 69%) as a colorless oil. [R]20 106.9 (c ) 0.6,
2R,6S,8R,8a S-2-(ter t-Bu tyld im eth ylsilyloxy)-8-iod o-6-
p h en yl-5(8H)-in d olizid in on e 8c. Reaction of azoninone 4a
(120 mg, 0.28 mmol) and I2 following the standard procedure
B. Purification by column chromatography on silica gel (hex-
ane/EtOAc 3:1, Rf ) 0.28). Yield: indolizidinone 8c (132 mg,
D
CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.60-7.50 (m, 2 H), 7.5-
7.2 (m, 8 H), 4.45-4.35 (m, 1 H), 3.75-3.50 (m, 4 H), 3.25-
3.15 (ddd, J ) 13, 11, 3 Hz, 1 H), 2.60-2.40 (m, 2 H), 2.10-
1.95 (ddd, J ) 13, 13, 12 Hz, 1 H), 1.80-1.65 (ddd, J ) 12, 11,
8 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), -0.05 (s, 3 H). 13C NMR
(62.9 MHz, CDCl3) δ 168.7 (s), 140.7, 135.8, 129.2, 128.6, 128.5,
128.1, 126.8, 126.5, 68.7 (d), 62.4 (d), 53.6 (t), 49.7 (d), 42.4
(t), 42.4 (d), 40.0 (t), 25.7 (q), 17.9 (s), -4.8 (q). IR (KBr) 2951
(s), 2926 (s), 1643 (s), 1252 (m) cm-1. MS (80 eV, EI, 170 °C)
99%) as colorless crystals, mp 73 °C. [R]20 -15.3 (c ) 1.3,
D
CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.40-7.25 (m, 3 H),
7.10-7.00 (m, 2 H), 4.45-4.40 (dd, J ) 4, 4 Hz, 1 H), 4.22-
4.11 (ddd, J ) 11, 11, 4 Hz, 1 H), 4.00-3.92 (dd, J ) 13, 4 Hz,
1 H), 3.95-3.85 (ddd, J ) 13, 11, 4 Hz, 1 H), 3.80-3.76 (dd, J
) 6, 2 Hz, 1 H), 3.65-3.58 (d, J ) 13 Hz, 1 H), 2.86-2.73 (ddd,
J ) 14, 14, 7 Hz, 1 H), 2.65-2.55 (ddd, J ) 14, 4, 2 Hz, 1 H),
2.38-2.30 (dd, J ) 13, 5 Hz, 1 H), 1.72-1.60 (ddd, J ) 12, 12,
4 Hz, 1 H), 0.90 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C NMR
(67.9 MHz, CDCl3) δ 168.1 (s), 141.2 (s), 128.6 (d), 127.9 (d),
126.9 (d), 67.4 (d), 64.5 (d), 56.7 (t), 48.6 (d), 44.3 (t), 43.4 (t),
25.7 (q), 20.5 (d), 17.9 (s), -4.8 (q), -4.9 (q). IR (KBr) 2957 (s),
2925 (s), 2890 (s), 2851 (s), 1630 (s, CO), 1438 (s), 1254 (s)
cm-1. MS (80 eV, EI, 110 °C): m/z 470 (0.2) [M - H+], 456 (4)
m/z 500 (0.5) [M+], 486 (1.6) [M+ - CH3], 444 (100) [M+
-
C4H9], 344 (9) [M+ - PhSe], 287 (20) [M+ - C4H9 - PhSeH].
HRMS calcd for C25H32NO2Si 80Se: 486.13675 (M+ - CH3 ),
found 486.13281 (M+ - CH3).
2R,6S,8R,8a S-2-(ter t-Bu tyld im eth ylsilyloxy)-6-p h en yl-
8-p h en ylsela n yl-5(8H)-in d olizid in on e 7c. Reaction with
azoninone 4a (130 mg, 0.29 mmol) and PhSeBr following the
standard procedure B. Purification by column chromatography
on silica gel (hexane/EtOAc 3:1, Rf ) 0.25). Yield: indolizidi-
none 7c (141 mg, 95%) as colorless crystals, mp 109 °C. [R]20
[M+ - CH3], 444 (0.8), 414 (100) [M+ - C4H9], 344 (1) [M+
-
D
-12.1 (c ) 1.4, CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.50-
7.40 (m, 2 H), 7.40-7.25 (m, 6 H), 7.10-7.00 (m, 2 H), 4.45-
4.40 (dd, J ) 4, 4 Hz, 1 H), 4.00-3.90 (dd, J ) 13, 4 Hz, 1 H),
3.90-3.80 (m, 2 H), 3.50-3.40 (d, J ) 13 Hz, 1 H), 3.11-3.00
(ddd, J ) 11, 11, 5 Hz, 1 H), 2.38-2.22 (m, 3 H), 1.68-1.55
(ddd, J ) 12, 12, 4 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01
(s, 3 H). 13C NMR (67.9 MHz, CDCl3) δ 168.5 (s), 153.2 (s),
141.5 (s), 135.8 (d), 129.2 (d), 129.0 (d), 128.5 (d), 128.4 (d),
126.6 (d), 68.2 (d), 61.7 (d), 55.7 (t), 47.5 (d), 43.1 (t), 38.2 (t),
36.9 (d), 25.7 (q), 17.9 (s), -4.85 (q), -4.89 (q). IR (KBr) 3054
(s), 2929 (s), 2885 (s), 2855 (s), 1630 (s, CO), 1437 (s), 1265 (s)
I], 287 (19) [M+ - C4H9 - I]. HRMS calcd for C19H27INO2Si
456.08546 (M+ - CH3 ), found 456.08529 (M+ - CH3).
2S,6R,8R,8a S-8-Br om o-6-(ter t-bu tyld im eth ylsilyloxy)-
2-p h en yl-3(8H)-in d olizid in on e 9a. Reaction of azoninone 4a
(100 mg, 0.23 mmol) and Br2 following the standard procedure
A. Purification by column chromatography on silica gel (hex-
ane/EtOAc 5:1, Rf ) 0.38). Yield: indolizidine 9a (39 mg, 40%)
1
as a colorless oil. [R]20 -29.3 (c ) 1.9, CHCl3). H NMR (500
D
MHz, CDCl3) δ 7.4-7.2 (m, 5 H), 4.17-4.13 (dd, J ) 14, 4 Hz,
1 H), 4.14-4.10 (m, 1 H), 4.05-4.00 (m, 1 H), 3.75-3.69 (m, 2
H), 2.92-2.87 (dd, J ) 14, 2 Hz, 1 H), 2.53-2.46 (ddd, J ) 14,
10, 4 Hz, 1 H), 2.49 -2.42 (dddd, J ) 14, 4, 4, 2 Hz, 1 H),
2.43-2.35 (ddd, J ) 14, 7, 7 Hz, 1 H), 2.08-2.00 (ddd, J ) 14,
12, 2 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C
NMR (62.9 MHz, CDCl3) δ 174.2 (s), 139.7 (s), 128.7 (d), 127.6
(d), 126.9 (d), 66.9 (d), 61.8 (d), 48.8 (d), 46.4 (d), 46.4 (t), 43.3
(t), 32.9 (t), 25.6 (q), 17.9 (s), -4.9 (q), -5.16 (q). IR (KBr) 2952
(s), 1698 (s, CO), 1255 (m) cm-1. MS (70 eV, EI, 130 °C) m/z
424 (0.2) [M+], 410 (2.5) [M+ - CH3], 384 (1.1), 368 (100) [M+
cm-1. MS (80 eV, EI, 110 °C) m/z 501 (6) [M+], 486 (3) [M+
-
CH3], 444 (100) [M+ - C4H9]. HRMS calcd for C26H35NO2SiSe
501.16022 (M+), found 501.16038 (M+).
2S,6R,8R,8a S-6-(ter t-Bu tyld im eth ylsilyloxy)-8-iod o-2-
p h en yl-3-(8H)-in d olizid in on e 8a . Reaction of azoninone 4a
(110 mg, 0.25 mmol) and I2 following the standard procedure
A. Purification by column chromatography on silica gel (hex-
ane/EtOAc 3:1, Rf ) 0.41). Yield: indolizidinones 8a /c (72.5
mg, 63%, ratio 3:1) as a colorless oil. Separation 8a /8c via
- C4H9]. HRMS calcd for C19H2779BrNO2Si: 408.09944 (M+
CH3), found 408.10434 (M+ - CH3).
-
HPLC. [R]20 -26.0 (c ) 0.7, CHCl3). 1H NMR (270 MHz,
D
CDCl3) δ 7.33-7.19 (m, 5 H), 4.30-4.20 (ddd, J ) 12, 11, 4
Hz, 1 H), 4.21-4.14 (ddd, J ) 14, 2, 2 Hz, 1 H), 3.9-3.8 (m, 2
H), 3.74-3.67 (dd, J ) 9, 9 Hz, 1 H), 2.95-2.89 (dd, J ) 14,
1.5 Hz, 1 H), 2.59-2.50 (dddd, J ) 14, 4, 4, 2 Hz, 1 H), 2.43-
2R,6S,8S,8a R-8-Br om o-2-(ter t-bu tyld im eth ylsilyloxy)-
6-p h en yl-5(8H)-in d olizid in on e 9b. Reaction of azoninone 4b
(130 mg, 0.29 mmol) with Br2 following the standard procedure
B. Purification by column chromatography on silica gel (hex-

1718 J . Org. Chem., Vol. 65, No. 6, 2000
Sudau et al.
ane/EtOAc 3:1, Rf ) 0.25). Yield: indolizidinone 9b (90.5 mg,
127.9, 127.6, 126.5, 74.9 (d), 72.8 (t), 68.8 (d), 61.3 (d), 53.2
(t), 41.9 (t), 40.4 (d), 36.9 (t), 25.7 (q), 17.9 (s), -4.9 (q). IR
(KBr) 2927 (s), 2855 (s), 1654 (s, CO), 1258 (m) cm-1. MS (80
eV, EI, 170 °C) m/z 531(1.3) [M+], 516 (3) [M+ - CH3], 474
(40.2) [M+ - C4H9], 425 (90.1) [M+ - CH3 - C7H7], 374 (13.5)
[M+ - SePh]. HRMS calcd for C27H37NO3Si80Se: 531.17079
(M+), found 531.17552 (M+).
72%) as colorless crystals, mp 73 °C. [R]20 52.7 (c ) 1.8,
D
CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.40-7.20 (m, 5 H),
4.46-4.37 (m, 1 H), 4.04-3.93 (ddd, J ) 12, 10, 3 Hz, 1 H),
3.91-3.81 (ddd, J ) 10, 10, 6 Hz, 1 H), 3.76-3.68 (dd, J ) 11,
7 Hz, 1 H), 3.66-3.63 (m, 2 H), 2.83-2.72 (ddd, J ) 10, 6, 3
Hz, 1 H), 2.58-2.48 (ddd, J ) 13, 6, 6 Hz, 1 H), 2.40-2.25
(ddd, J ) 13, 12, 12 Hz, 1 H), 2.36-2.28 (ddd, J ) 13, 9, 7 Hz,
1 H), 0.90 (s, 9 H), 0.09 (s, 3 H), 0.05 (s, 3H). 13C NMR (67.9
MHz, CDCl3) δ 168.3 (s), 140.0 (s), 128.7 (s), 128.0 (s), 127.0
(s), 68.3 (d), 63.4 (d), 54.4 (t), 49.4 (d), 47.5 (d), 42.5 (t), 41.9
(t), 25.7 (q), 24.0 (d), 17.9 (s), -4.9 (q). IR (KBr) 2956 (s), 2928
(s), 1640 (s, CO), 1252 (m) cm-1. MS (70 eV, EI, 160 °C) m/z
425 (0.18) [M+], 424 (0.27) [M+ - H], 410 (4.17) [M+ - CH3],
368 (100) [M+ - C4H9]. HRMS calcd for C19H27NO2 79Br Si
408.09945 (M+ - CH3), found 408.09965 (M+ - CH3).
2R ,6R ,8R ,8a S -6-Be n zyloxy-2-(t er t -b u t yld im e t h ylsi-
lyloxy)-8-p h en ylsela n yl-5(8H)-in d olizid in on e 10c. Reac-
tion of azoninone 5a (960 mg, 2.06 mmol) and PhSeBr
following the standard procedure B. Purification by column
chromatography on silica gel (hexane/EtOAc 2:1, Rf ) 0.28).
Yield: indolizidinone 10c (820 mg, 74%) as colorless needles,
mp 77 °C (recrystallization from Et2O/hexane). [R]20 2.1 (c )
D
1.9, CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.60-7.50 (m, 2 H),
7.4-7.1 (m, 8 H), 4.90-4.85 (d, J ) 12 Hz, 1 H), 4.73-4.67 (d,
J ) 12 Hz, 1 H), 4.40-4.35 (dd, J ) 5, 5 Hz, 1 H), 3.85-3.80
(dd, J ) 4, 2 Hz, 1 H), 3.80-3.67 (m, 2 H), 3.78-3.73 (dd, J )
5, 2 Hz, 1 H), 3.37 -3.30 (d, J ) 13 Hz, 1 H), 3.32-3.20 (ddd,
J ) 13, 11, 4 Hz, 1 H), 2.50-2.40 (ddd, J ) 14, 3, 3 Hz, 1 H),
2.25-2.18 (dd, J ) 13, 4 Hz, 1 H), 1.98-1.85 (ddd, J ) 14, 13,
4 Hz, 1 H), 1.60-1.49 (ddd, J ) 12, 12, 4 Hz, 1 H), 0.80 (s, 9
H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C NMR (67.9 MHz, CDCl3) δ
166.6 (s), 138.1 (d), 136.1 (d), 129.1 (d), 128.4 (d), 128.2 (d),
127.8 (d), 127.5 (d), 125.9 (d), 73.9 (d), 72.8 (t, C-10), 68.1 (d),
61.6 (d), 55.4 (t), 42.7 (t), 37.2 (t), 37.1 (d), 25.7 (q), 17.9 (s),
-4.8 (q), -4.9 (q). IR (KBr) 2952 (s), 2883 (s), 1635 (s, CO),
1253 (s) cm-1. MS (80 eV, EI, 180 °C): m/z 531 (0.5) [M+], 516
(2.9) [M+ - CH3], 474 (90) [M+ - C4H9], 425 (45) [M+ - CH3
- Bn]. HRMS: calcd for C26H34NO3SeSi: 516.14731 (M+ - CH3
), found 516.14719 (M+ - CH3).
2R,6S,8R,8a S-8-Br om o-2-(ter t-bu tyld im eth ylsilyloxy)-
6-p h en yl-5(8H)-in d olizid in on e 9c: Reaction of azoninone 4a
(0.2 g, 0.45 mmol) and Br2 following the standard procedure
B. Purification by column chromatography on silica gel (hex-
ane/EtOAc 3:1, Rf ) 0.25). Yield: indolizidinone 9a /c (107 mg,
55%, ratio 1:4) as a colorless oil. Separation of 9a and 9c via
HPLC. [R]20 -28.3 (c ) 1.9, CHCl3). 1H NMR (270 MHz,
D
CDCl3) δ 7.40-7.25 (m, 3 H), 7.10-7.00 (m, 2 H), 4.48-4.43
(dd, J ) 4, 4 Hz, 1 H), 4.13-4.03 (ddd, J ) 11, 11, 4 Hz, 1 H),
3.95-3.88 (dd, J ) 13, 5 Hz, 1 H), 3.95-3.85 (m, 2 H), 3.58-
3.50 (d, J ) 14 Hz, 1 H), 2.73-2.60 (ddd, J ) 14, 14, 7 Hz, 1
H), 2.56-2.46 (ddd, J ) 14, 4, 2 Hz, 1 H), 2.36-2.28 (dd, J )
13, 5 Hz, 1 H), 1.75-1.62 (ddd, J ) 12, 12, 4 Hz, 1 H), 0.90 (s,
9 H), 0.09 (s, 3 H), 0.05 (s, 3 H). 13C NMR (67.9 MHz, CDCl3)
δ 168.1 (s), 141.1(s), 128.7 (d), 127.8 (d), 126.9 (d), 68.0 (d),
63.2 (d), 56.3 (t), 47.8 (d), 44.7 (d), 42.9 (t), 41.3 (t), 25.7 (q),
17.9 (s), -4.8 (q), -4.9 (q). IR (KBr) 2959 (s), 2883 (s), 2858
(s), 1645 (s, CO), 1257 (s) cm-1. MS (80 eV, EI, 130 °C) m/z
424 (0.45) [M+], 423 (0.2) [M+ - H], 408 (4.1) [M+ - CH3],
368 (100) [M+ - C4H9]. HRMS: calcd for C19H2779BrNO2Si:
408.09945 (M+ - CH3 ), found 408.09925 (M+ - CH3).
2R ,6R ,8R ,8a S-2-Be n zyloxy-6-(t er t -b u t yld im e t h ylsi-
lyloxy)-8-iod o-3-(8H)-in d olizid in on e 11a . Reaction of azon-
inone 5a (31 mg, 0.07 mmol) and I2 following the standard
procedure A. Purification by column chromatography on silica
gel (hexane/EtOAc 3:1, Rf ) 0.45). Yield: indolizidinone 11a /c
(12 mg, 36%, ratio 1:3) as a colorless oil. Separation of 11a
and 11c via HPLC. [R]20D -10° (c ) 0.3, CHCl3). 1H NMR (270
MHz, CDCl3) δ 7.4-7.2 (m, 5 H), 4.94-4.88 (d, J ) 12 Hz, 1
H), 4.74-4.66 (d, J ) 12 Hz, 1 H), 4.14-4.05 (m, 2 H), 4.03-
3.93 (ddd, J ) 12, 11, 4 Hz, 1 H), 3.90-3.85 (m, 1 H), 3.85-
3.75 (ddd, J ) 11, 7, 6 Hz, 1 H), 2.90-2.83 (dd, J ) 15, 2 Hz,
1 H), 2.51-2.42 (dddd, J ) 14, 6, 6, 3 Hz, 1 H), 2.41-2.30
(ddd, J ) 11, 7, 3 Hz, 1 H), 2.21-2.10 (m, 1 H), 2.09-1.98
(ddd, J ) 14, 8, 5 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s,
3 H). 13C NMR (62.9 MHz, CDCl3) δ 172.1, 137.7, 128.4, 128.0,
127.7, 74.5, 72.0, 67.0, 61.7, 46.1, 45.2, 34.2, 27.6, 25.6, -4.9,
-5.0. IR (KBr) 2952 (s), 2927 (s), 1700 (s), 1258 (m) cm-1. MS
2R ,6R ,8R ,8a S -2-Be n zyloxy-6-(t er t -b u t yld im e t h ylsi-
lyloxy)-8-p h en ylsela n yl-3-(8H)-in d olizid in on e 10a . Reac-
tion of azoninone 5a (100 mg, 0.21 mmol) and PhSeBr
following the standard procedure A. Purification by column
chromatography on silica gel (hexane/EtOAc 5:1, Rf ) 0.31).
Yield: indolizidinone 10a /c (52 mg, 46%, ratio 5:1) as a
colorless oil. Separation of 10a and 10c via HPLC. [R]20D -18.3
1
(c ) 1.1, CHCl3). H NMR (270 MHz, CDCl3) δ 7.6 (m, 2 H),
7.4-7.2 (m, 8 H), 4.94-4.88 (d, J ) 12 Hz, 1 H), 4.74-4.66 (d,
J ) 12 Hz, 1 H), 4.10-4.03 (dd, J ) 8, 4 Hz, 1 H), 4.02-3.95
(m, 2 H), 3.53-3.42 (ddd, J ) 11, 7, 6 Hz, 1 H), 3.18-3.07
(ddd, J ) 12, 11, 4 Hz, 1 H), 2.73-2.65 (dd, J ) 15, 2 Hz, 1
H), 2.40-2.28 (ddd, J ) 11, 7, 3 Hz, 1 H), 2.25-2.15 (dddd, J
) 14, 6, 6, 3 Hz, 1 H), 2.15-2.05 (ddd, J ) 14, 8, 5 Hz, 1 H),
1.70-1.60 (m, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H).
13C NMR (62.9 MHz, CDCl3) δ 171.8, 137.9, 135.8, 129.1, 128.3,
128.2, 128.0, 127.6, 126.4, 71.9, 65.6, 59.0, 45.9, 41.6, 40.0, 33.2,
25.6, 17.9, -4.9, -5.16. IR (KBr) 2953 (s), 2927 (s), 1699 (s,
CO), 1258 (m) cm-1. MS (80 eV, EI, 160 °C) m/z 516 (2.9) [M+
- CH3], 474 (100) [M+ - C4H9], 425 (45) [M+ - CH3 - Bn].
HRMS calcd for C26H34NO3SiSe: 516.14732 (M+ - CH3 ), found
516.14337 (M+ - CH3).
(70 eV, EI, 130 °C): m/z 500 (0.2) [M - H+ ], 486 (4) [M+
CH3], 444 (35) [M+ - C4H9], 395 (72) [M+ - C7H7 - CH3].
-
2R ,6R ,8S ,8a R -2-Be n zyloxy-6-(t er t -b u t yld im e t h ylsi-
lyloxy)-8-iod o-5(8H)-in d olizid in on e 11b. Reaction of azoni-
none 5b (130 mg, 0.28 mmol) with I2 following the standard
procedure B. Purification by column chromatography on silica
gel (hexane/EtOAc 7:1, Rf ) 0.4). Yield: indolizidinone 11b
(55.2 mg, 40%) as a colorless oil. [R]20 77.1 (c ) 1.8, CHCl3).
D
1H NMR (270 MHz, CDCl3) δ 7.4-7.1 (m, 5 H), 4.95-4.88 (d,
J ) 12 Hz, 1 H), 4.78-4.73 (d, J ) 12 Hz, 1 H), 4.40-4.30 (m,
1 H), 4.00-3.80 (m, 3 H), 3.65-3.55 (m, 2 H), 2.88-2.78 (ddd,
J ) 11, 7, 5 Hz, 1 H), 2.55-2.40 (m, 2 H), 1.95-1.75 (m, 1 H),
0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C NMR (62.9 MHz,
CDCl3) δ 167.8 (s), 137.7, 128.3, 127.9, 127.7, 74.9 (d), 72.7
(t), 68.1(d), 61.4 (d), 54.3 (t), 43.1 (t), 41.8 (t), 21.8 (d), 25.7
(q), 17.9 (s), -4.8 (q). IR (KBr) 2976 (s), 2926 (s), 1641 (s, CO),
1257 (m) cm-1. MS (80 eV, EI, 150 °C) m/z 500 (0.2) [M - H+],
2R ,6R ,8S ,8a R -2-Be n zyloxy-6-(t er t -b u t yld im e t h ylsi-
lyloxy)-8-p h en ylsela n yl-5(8H)-in d olizid in on e 10b. Reac-
tion of azoninone 5b (13 mg, 0.03 mmol) and PhSeBr following
the standard procedure B. Purification by column chromatog-
raphy on silica gel (hexane/EtOAc 7:1, Rf ) 0.38). Yield:
indolizidinone 10b (3.5 mg, 20%) as a colorless oil. [R]20 73.2
D
(c ) 2, CHCl3). H NMR (270 MHz, CDCl3) δ 7.60-7.50 (m, 2
486 (4) [M+ - CH3], 444 (100) [M+ - C4H9], 395 (84) [M+
-
1
H), 7.40-7.20 (m, 8 H), 4.95-4.85 (d, J ) 12 Hz, 1 H), 4.75-
4.65 (d, J ) 12 Hz, 1 H), 4.38-4.28 (m, 1 H), 3.98-3.80 (dd, J
) 8, 7 Hz, 1 H), 3.70-3.55 (ddd, J ) 10, 10, 6 Hz, 1 H), 3.56-
3.50 (dd, J ) 12, 6 Hz, 1 H), 3.50-3.43 (dd, J ) 12, 5 Hz, 1 H),
3.10-3.00 (ddd, J ) 11, 11, 5 Hz, 1 H), 2.58-2.48 (ddd, J )
11, 6, 4 Hz, 1 H), 2.45-2.35 (ddd, J ) 12, 6, 6 Hz, 1 H), 2.08-
1.95 (ddd, J ) 14, 12, 9 Hz, 1 H), 1.73-1.60 (ddd, J ) 13, 10,
7 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C NMR
(62.9 MHz, CDCl3) δ 168.1 (s), 138.0, 136.0, 129.2, 128.5, 128.3,
C7H7 - CH3], 268 (51) [M+ - J -CH3 - C7H7]. HRMS calcd
for C20H29INO3Si: 486.09615 (M+ - CH3 ), found 486.09378
(M+ - CH3).
2R ,6R ,8R ,8a S -2-Be n zyloxy-6-(t er t -b u t yld im e t h ylsi-
lyloxy)-8-iod o-5(8H)-in d olizid in on e 11c. Reaction of azoni-
none 5a (100 mg, 0.21 mmol) and I2 following the standard
procedure B. Purification by column chromatography on silica
gel (hexane/EtOAc 3:1, Rf ) 0.31). Yield: indolizidinone 11c
(80 mg, 70%) as colorless needles, mp 99 °C (recrystallization

Planar Chirality
J . Org. Chem., Vol. 65, No. 6, 2000 1719
1
from Et2O/hexane). [R]20 8.1 (c ) 0.8, CHCl3). H NMR (270
azoninone 6a (0.2 g, 0.51 mmol) and PhSeBr following the
standard procedure B. Purification by column chromatography
on silica gel (hexane/EtOAc 3:1, Rf ) 0.34). Yield: indolizidi-
D
MHz, CDCl3) δ 7.4-7.1 (m, 5 H), 4.94-4.89 (d, J ) 11 Hz, 1
H), 4.75-4.70 (d, J ) 11 Hz, 1 H), 4.40-4.35 (dd, J ) 4, 4 Hz,
1 H), 4.10-3.95 (m, 2 H), 3.87-3.78 (dd, J ) 13, 5 Hz, 1 H),
3.78-3.73 (dd, J ) 5, 2 Hz, 1 H), 3.73-3.65 (d, J ) 13 Hz, 1
H), 2.75-2.65 (ddd, J ) 14, 5, 2 Hz, 1 H), 2.50-2.38 (ddd, J )
14, 12, 5 Hz, 1 H), 2.33-2.25 (m, 1 H), 1.68-1.75 (ddd, J )
none 13c (187.7 mg, 81%) as a colorless oil. [R]20 -35.8 (c )
D
1.5, CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.70-7.60 (m, 2 H),
7.4-7.1 (m, 3 H), 4.40-4.35 (m, 2 H), 3.95-3.70 (m, 2 H),
3.40-3.35 (m, 2 H), 2.62-2.52 (ddd, J ) 15, 2, 2 Hz, 1 H),
2.35-2.20 (m, 2 H), 1.65-1.55 (ddd, J ) 12, 12, 4 Hz, 1 H),
0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C NMR (62.9 MHz,
CDCl3) δ 163.9 (s), 136.2, 129.3, 128.8, 125.2, 67.9 (d), 61.7
(d), 56.5 (t), 56.2 (d), 42.9 (t), 39.6 (t), 35.6 (d), 25.7 (q), 17.9
(s), -4.9 (q). IR (KBr) 2954 (s), 2855 (s), 1660 (s, CO), 1253 (s)
12, 11, 4 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13
C
NMR (62.9 MHz, CDCl3) δ 166.4, 137.8, 128.3, 128.0, 127.7,
74.3, 73.0, 67.4, 64.4, 56.4, 44.9, 42.5, 20.2, 25.7, 18.0, -4.7,
-4.8. IR (KBr) 2956 (s), 2926 (s), 1637 (s, CO), 1270 (s) cm-1
.
-
MS (70 eV, EI, 130 °C) m/z 500 (0.2) [M - H+], 486 (4) [M+
CH3], 444 (35) [M+ - C4H9], 395 (72) [M+ - C7H7 - CH3].
HRMS calcd for C20H29INO3Si: 486.09615 (M+ - CH3 ), found
486.09198 (M+ - CH3).
cm-1. MS (70 eV, EI, 150 °C) m/z 459 (3) [M+], 444 (3) [M+
-
CH3], 402 (100) [M+ - C4H9], 302 (10) [M+ - PhSe], 244 (14)
[M+ - C4H9 - PhSeH]. HRMS calcd for C20H30ClNO2SiSe:
459.08996 (M+), found 459.08975 (M+).
2R ,6R ,8R ,8a S -2-Be n zyloxy-8-b r om o-6-(t er t -b u t yld i-
m eth ylsilyloxy)-3-(8H)-in d olizid in on e 12a . Reaction of
azoninone 5a (10 mg, 0.02 mmol) with Br2 following the
standard procedure A. Purification by column chromatography
on silica gel (hexane/EtOAc 5:1, Rf ) 0.38). Yield: indolizidi-
2R,6R,8S,8a R-2-(ter t-Bu tyld im eth ylsilyloxy)-6-ch lor o-
8-iod o-5(8H)-in d olizid in on e 14b. Reaction of azoninone 6b
(300 mg, 0.75 mmol) and I2 following the standard procedure
B. Purification by column chromatography on silica gel (hex-
ane/EtOAc 10:1, Rf ) 0.5). Yield: indolizidinone 14b (150 mg,
none 12a (2.4 mg, 16%) as a colorless oil. [R]20 -4.4 (c ) 1.2,
D
CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.4-7.1 (m, 5 H), 4.95-
4.90 (d, J ) 12 Hz, 1 H), 4.75-4.70 (d, J ) 12 Hz, 1 H), 4.15-
4.08 (dd, J ) 8, 4 Hz, 1 H), 4.08-3.98 (m, 2 H), 3.95-3.85
(ddd, J ) 12, 11, 4 Hz, 1 H), 3.70-3.60 (ddd, J ) 11, 7, 4 Hz,
1 H), 2.88-2.79 (d, J ) 12 Hz, 1 H), 2.45-2.30 (m, 2 H), 2.22-
2.10 (ddd, J ) 13, 8, 5 Hz, 1 H), 2.04-1.94 (ddd, J ) 14, 13, 2
Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01 (s, 3 H). 13C NMR
(62.9 MHz, CDCl3) δ 128.3, 128.0, 127.7, 74.5, 72.0, 66.5, 60.0,
49.2, 46.0, 43.0, 32.4, 25.6, 17.0, -4.9, -5.16. IR (KBr) 2955
(s), 2929 (s), 1703 (s), 1259 (s) cm-1. MS (70 eV, EI, 110 °C):
m/z 440 (3.9) [M+ - CH3], 438 (3.7) [M+ - CH3], 398 (100)
64%) as a colorless oil. [R]20 47 (c ) 0.04, CHCl3). 1H NMR
D
(270 MHz, C6D6) δ 3.89 (dd, J ) 10, 7 Hz, 1 H), 3.76 (m, 1 H),
3.54 (dd, J ) 12, 6 Hz, 1 H), 3.40 (dd, J ) 12, 7 Hz, 1 H), 3.12
(ddd, J ) 10, 10, 5 Hz, 1 H), 3.01 (ddd, J ) 11, 11, 4 Hz, 1 H),
2.40 (ddd, J ) 12, 7, 4 Hz, 1 H), 2.30 (ddd, J ) 14, 12, 10 Hz,
1 H), 2.04 (ddd, J ) 12, 6, 6 Hz, 1 H), 1.38 (ddd, J ) 12, 9, 7
Hz, 1 H), 0.91 (s, 9 H), -0.04 (s, 3 H), -0.05 (s, 3 H). 13C NMR
(62.9 MHz, CDCl3) δ 163.2 (s), 67.9 (C-8), 63.5 (C-6), 54.9 (C-
3), 53.4 (C-9), 45.2 (C-4), 43.3 (C-7), 25.8 (q), 21.2 (C-5), 18.0
(s), -4.9 (q), -5.0 (q). IR (KBr) 2850 (m), 1649 (s, CO), 1273
(m) cm-1. MS (70 eV, EI, 150 °C) m/z 414 (3) [M+ - CH3], 372
(100) [M+ - C4H9], 244 (5) [M+ - C4H9 - HJ ]. HRMS calcd
for C13H22NO2ClISi 414.01519 (M+ - CH3 ), found 414.01514
(M+ - CH3).
[M+ - C4H9], 396 (96) [M+ - C4H9]. HRMS calcd for C20H29
-
BrNO3Si 438.11009 (M+ - CH3), found 438.10519 (M+ - CH3).
2R,6R,8R,8a S-6-(ter t-Bu tyld im eth ylsilyloxy)-2-ch lor o-
8-p h en ylsela n yl-3(8H)-in d olizid in on e 13a .6 Reaction of
azoninone 6a (23 mg, 0.06 mmol) and PhSeBr following the
standard procedure A. Purification by column chromatography
on silica gel (hexane/EtOAc 3:1, Rf ) 0.44). Yield: indolizidi-
none 13a /c (5.5 mg, 20.5%, ratio 13:1) as a colorless oil.
2R,6R,8R,8a S-2-(ter t-Bu tyld im eth ylsilyloxy)-6-ch lor o-
8-iod o-5(8H)-in d olizid in on e 14c. Reaction of azoninone 6a
(260 mg, 0.66 mmol) and I2 following the standard procedure
B. Purification by column chromatography on silica gel (hex-
ane/EtOAc 3:1, Rf ) 0.4). Yield: indolizidinone 14c (230 mg,
82%) as colorless needles, mp 94 °C (recrystallization from
Separation of 13a and 13c via HPLC. [R]20 -50.2 (c ) 1.3,
D
CHCl3). 1H NMR (270 MHz, CDCl3) δ 7.56-7.50 (m, 2 H),
7.35-7.26 (m, 3 H), 4.34 (dd, J ) 8, 3 Hz, 1 H), 4.03-3.93 (m,
2 H), 3.60-3.50 (ddd, J ) 11, 6, 6 Hz, 1 H), 3.22-3.10 (m, 1
H), 2.75 (d, J ) 12 Hz, 1 H), 2.63 (ddd, J ) 15, 6, 2 Hz, 1 H),
2.32-2.25 (m, 1 H), 2.25-2.15 (m, 1 H), 1.68 (m, 1 H), 0.81 (s,
9 H), 0.02 (s, 3 H), -0.03 (s, 3 H). 13C NMR (67.5 MHz, CDCl3)
δ 169.6 (s), 135.8 (d), 129.2 (d), 128.5 (d), 65.2 (d), 59.0 (d),
53.9 (d), 46.6 (t), 40.7 (d), 39.7(t), 36.7 (t), 25.5 (q), 17.9 (s),
-4.9 (q), -5.1 (q). IR (KBr) 2952 (s), 2927 (s), 1714 (s), 1257
(m) cm-1. MS (70 eV, EI, 150 °C) m/z 459 (0.1) [M+], 444 (2)
Et2O/hexane). [R]20 -26.5 (c ) 1.4, CHCl3). 1H NMR (270
D
MHz, CDCl3) δ 4.40-4.34 (dd, J ) 4, 4 Hz, 1 H), 4.32-4.26
(dd, J ) 4, 2 Hz, 1 H), 4.15-4.05 (ddd, J ) 11, 11, 4 Hz, 1 H),
4.08-3.99 (ddd, J ) 11, 11, 5 Hz, 1 H), 3.85-3.78 (dd, J ) 14,
5 Hz, 1 H), 3.53-3.45 (d, J ) 14 Hz, 1 H), 2.88-2.68 (m, 2 H),
2.32-2.25 (dd, J ) 13, 4 Hz, 1 H), 1.70-1.57 (ddd, J ) 11, 11,
4 Hz, 1 H), 0.80 (s, 9 H), 0.09 (s, 3 H), 0.05 (s, 3 H). 13C NMR
(67.9 MHz, CDCl3) δ 163.6 (s), 67.1 (d), 64.6 (d), 57.1 (t), 54.6
(d), 44.2 (t), 43.7 (t), 25.6 (q), 17.9 (s), 17.1 (d), -4.9 (s), -5.0
(s). IR (KBr) 2959 (s), 1659 (s, CO), 1651 (s), 1266 (m) cm-1
MS (80 eV, EI, 150 °C) m/z 414 (4) [M+ - CH3], 372 (100) [M+
.
[M+ - CH3], 402 (100) [M+ - C4H9], 244 (10) [M+ - C4H9
PhSeH]. HRMS calcd for C19H27ClNO2SiSe: 444.06647 (M+
CH3), found 444.06627 (M+ - CH3).
-
-
- C4H9], 245 (10) [M+ - C4H9 - HJ ]. HRMS calcd for C13H22
I
-
Cl NO2Si: 414.01519 (M+ - CH3), found 414.01514 (M+
2R,6R,8S,8a R-2-(ter t-Bu tyld im eth ylsilyloxy)-6-ch lor o-
8-p h en ylsela n yl-5(8H)-in d olizid in on e 13b.6 Reaction of
azoninone 6b (0.25 g, 0.65 mmol) and PhSeBr following the
standard procedure B. Purification by column chromatography
on silica gel (hexane/EtOAc 10:1, Rf ) 0.5). Yield: indolizidi-
CH3).
2R,6R,8R,8a S-8-Br om o-6-(ter t-bu tyld im eth ylsilyloxy)-
2-ch lor o-3-(8H)-in d olizid in on e 15a . Reaction of azoninone
6a (41 mg, 0.11 mmol) and Br2 following the standard
procedure A. Purification by column chromatography on silica
gel (hexane/EtOAc 6:1, Rf ) 0.44). Yield: indolizidinone 15a
(10 mg, 25%) as a colorless oil. [R]20D -44.9° (c ) 1.7, CH2Cl2).
1H NMR (270 MHz, CDCl3) δ 4.42-4.36 (dd, J ) 8, 3 Hz, 1
H), 4.08-4.02 (m, 1 H), 3.99-4.05 (ddd, J ) 11, 2, 2 Hz, 1 H),
3.98-3.87 (ddd, J ) 12, 10, 4 Hz, 1 H), 3.77-3.67 (ddd, J )
10, 6, 6 Hz, 1 H), 2.92-2.85 (dd, J ) 11, 2 Hz, 1 H), 2.65-2.55
(ddd, J ) 15, 7, 4 Hz, 1 H), 2.45-2.30 (m, 2 H), 2.05-1.95
(ddd, J ) 14, 13, 2 Hz, 1 H), 0.80 (s, 9 H), 0.05 (s, 3 H), 0.01
(s, 3 H). 13C NMR (62.9 MHz, CDCl3) δ 169.7 (s), 66.2 (d), 60.7
(d), 53.3 (d), 48.0 (d), 46.6 (t), 42.7 (t), 35.9 (t), 25.6 (q), 17.9
(s), -4.9 (q), -5.12 (q). IR (KBr) 2954 (s), 2928 (s), 1716 (s,
CO), 1258 (s) cm-1. MS (80 eV, EI, 110 °C) m/z 382 (0.12) [M+],
368 (3.2) [M+ - CH3], 326 (100) [M+ - C4H9]. HRMS calcd for
C13H2281Br 35ClNO2Si: 368.02718 (M+ - CH3), found 368.02520
(M+ - CH3).
none 13b (150 mg, 64%) as a colorless oil. [R]20 59.4 (c ) 0.4,
D
1
CHCl3). H NMR (270 MHz, C6D6) δ 7.40 (m, 2 H), 7.00-6.90
(m, 3 H), 4.00 (dd, J ) 9, 6 Hz, 1 H), 3.84 (m, 1 H), 3.55 (dd,
J ) 12, 6 Hz, 1 H), 3.37 (dd, J ) 12, 7 Hz, 1 H), 3.05 (ddd, J
) 10, 10, 5 Hz, 1 H), 2.53-2.4 (m, 2 H), 2.20-2.05 (m, 2 H),
1.47 (ddd, J ) 13, 10, 8 Hz, 1 H), 0.92 (s, 9 H), -0.02 (s, 3 H),
-0.03 (s, 3 H). 13C NMR (62.9 MHz, CDCl3) δ 164.2 (s), 136.3
(d), 129.5 (d), 125.8 (d), 125.9 (s), 68.8 (d), 61.8 (d), 54.1 (d),
53.9 (t), 42.0 (t), 40.7 (t), 40.7(d), 22.7 (q), 17.9 (s), -4.9 (q),
-5.0 (q). IR (KBr) 2855 (m), 1644 (s, CO) cm-1. MS (70 eV,
EI, 150 °C) m/z 459 (1) [M+], 444 (3) [M+ - CH3], 436 (2), 402
(100) [M+ - C4H9], 302 (11) [M+ - PhSe], 244 (22) [M+ - C4H9
- PhSeH]. HRMS calcd for C20H30ClNO2SiSe: 459.08996 (M+),
found 459.08773 (M+).
2R,6R,8R,8a S-2-(ter t-Bu tyld im eth ylsilyloxy)-6-ch lor o-
8-p h en ylsela n yl-5(8H)-in d olizid in on e 13c.6 Reaction of

1720 J . Org. Chem., Vol. 65, No. 6, 2000
Sudau et al.
2R,6R,8R,8a S-8-Br om o-2-(ter t-bu tyld im eth ylsilyloxy)-
6-ch lor o-5(8H)-in d olizid in on e 15c. Reaction of azoninone
6a (33 mg, 0.08 mmol) and Br2 following the standard
procedure B. Purification by column chromatography on silica
gel (hexane/EtOAc 3:1, Rf ) 0.38). Yield: indolizidinone 15c
(s), 2856 (s), 1665 (s, CO), 1253 (s) cm-1. MS (80 eV, EI, 100
°C) m/z 368 (4.8) [M+ - CH3], 326 (100) [M+ - C4H9]. HRMS
calcd for C13H2279Br35ClNO2Si 366.02918 (M+ - CH3 ), found
366.02905 (M+ - CH3).
(4.9 mg, 15%) as a colorless oil. [R]20 -30.4 (c ) 1.7, CHCl3).
D
Ack n ow led gm en t. We thank the DFG and Scher-
ing AG for support of this research.
1H NMR (270 MHz, CDCl3) δ 4.46-4.38 (m, 2 H), 4.13-4.03
(ddd, J ) 11, 11, 4 Hz, 1 H), 4.03-3.90 (ddd, J ) 11, 11, 5 Hz,
1 H), 3.83-3.76 (dd, J ) 14, 5 Hz, 1 H), 3.48-3.40 (d, J ) 14
Hz, 1 H), 2.80-2.72 (ddd, J ) 14, 4, 2 Hz, 1 H), 2.72-2.59
(ddd, J ) 12, 12, 5 Hz, 1 H), 2.32-2.25 (dd, J ) 13, 4 Hz, 1
H), 1.73-1.60 (ddd, J ) 11, 11, 4 Hz, 1 H), 0.80 (s, 9 H), 0.09
(s, 3 H), 0.05 (s, 3 H). 13C NMR (67.9 MHz, CDCl3) δ 163.6 (s),
67.7 (d), 63.4 (d), 56.8 (t), 53.9 (d), 42.5 (t), 42.3 (t), 42.3 (d),
25.7 (q), 17.9 (s), -4.9 (q), -4.8 (q). IR (KBr) 2954 (s), 2884
Su p p or tin g In for m a tion Ava ila ble: 13C NMR spectra,
NOEDS data for all new compounds, and crystallographic data
including ORTEP plots for 6a and 6b. This material is
available free of charge via the Internet at http://pubs.acs.org.
J O991484O