Intramolecular Ene Reactions. Stereo- And Enantioselective Synthesis of Spirolactams through Thermolysis of Enamino Carboxamides

Article abstract of DOI:10.1021/jo970257o

A new and facile access to spirolactams based on the thermal rearrangement of tertiary and secondary enamino carboxamides has been developed. The enamine group of an enamino carboxamide, in which no electron-withdrawing group is present in the enophile, c

Full text of DOI:10.1021/jo970257o

7106
J . Org. Chem. 1997, 62, 7106-7113
In tr a m olecu la r En e Rea ction s. Ster eo- a n d En a n tioselective
Syn th esis of Sp ir ola cta m s th r ou gh Th er m olysis of En a m in o
Ca r boxa m id es
J anine Cossy,* Abdelrrahim Bouzide, and Michel Pfau
Laboratoire de Chimie Organique associe´ au CNRS (URA 476), ESPCI, 10 rue Vauquelin,
75231 Paris Cedex 05, France
Received February 12, 1997X
A new and facile access to spirolactams based on the thermal rearrangement of tertiary and
secondary enamino carboxamides has been developed. The enamine group of an enamino carbox-
amide, in which no electron-withdrawing group is present in the enophile, can be involved in the
ene reaction and the enamino carboxamide can be transformed into enamino or imino spirolactams.
In the case of secondary carboxamido enamines, the diastereoselectivity is higher than 98%. If
chiral nonracemic analogs are utilized, 50-54% enantiomeric excesses can be achieved in the final
products.
The ene reaction occurs between an alkene having an
hetero-ene components with the exception of the Conia
reaction6 in which a thermal cyclization of an olefinic
ketone through an intramolecular ene reaction of the
corresponding enol occurs generally at very high tem-
perature. More recently, hetero-ene reactions of N-
sulfinyl-p-toluenesulfonamides,7 hydrazones,8 and thiols9
with electron-rich olefins have been reported.
allylic hydrogen (an “ene”) and a compound containing
an electron-deficient double bond (an “enophile”) to form
a σ-bond with migration of the ene double bond and a
1,5-hydrogen shift. From a mechanistic point of view the
ene reaction can be concerted,1 or can proceed stepwise,
involving a diradical intermediate.2 Ene reactions can
be Lewis acid catalyzed, and in these cases the reactions
occur under mild conditions through either a concerted
or a stepwise zwitterionic mechanism.3 Asymmetric
catalytic ene reactions using the modified binaphthol-
derived aluminum reagent4 as well as binaphthol-derived
titanium catalysts5 have also been reported.
We report herein a thermal reaction involving N-
unsaturated alkyl â-carboxamido enamines in which the
enamine is the hetero-ene component, with the aim of
obtaining substituted spirolactams under relatively mild
thermal conditions (80-150 °C).10
Resu lts a n d Discu ssion
Ene reactions can be divided into “carba-ene” reactions,
in which the enophile is an alkene substituted with
electron-withdrawing groups, and “hetero-ene” reactions,
in which hetero-enophiles including carbonyl and thio-
carbonyl compounds, imines, nitro compounds, azo com-
pounds, and dioxygen are employed.1 In contrast, there
appear to be very few hetero-ene reactions involving
Tertiary and secondary â-carboxamido enamines of
type I and II have been prepared in quantitative yields
from the corresponding â-keto amides of type A.11
X Abstract published in Advance ACS Abstracts, September 1, 1997.
(1) (a) Carruthers, W. In Cycloaddition Reactions in Organic
Synthesis; Pergamon Press: Oxford, 1990; p 241. (b) Snider, B. B. Ene
Reactions With Alkenes as Enophiles and Oppolzer, W. Metallo-ene
Reactions in Comprehensive Organic Synthesis; Trost, B. M., Fleming,
I., Eds.; Pergamon Press: Oxford, 1991; Vol. 5, Chapters 1.1 and 1.2.
(2) (a) Hoffmann, H. M. R. Angew. Chem., Int. Ed. Engl. 1969, 8,
556-577. (b) Oppolzer, W.; Snieckus, V. Angew. Chem., Int. Ed. Engl.
1978, 17, 476-486. (c) Stephenson, L. M.; Orfanopoulos, M. J . Org.
Chem. 1981, 46, 2200-2201. (d) Nahm, S. H.; Cheng, H. N. J . Org.
Chem. 1986, 51, 5093-5100.
(6) (a) Brocard, J .; Moinet, G.; Conia, J . M. Bull. Soc. Chim. Fr. 1972,
1711-1717. (b) Mandville, G.; Leyendecker, F.; Conia, J . M. Bull. Soc.
Chim. Fr. 1973, 963-971. (c) Leyendecker, K.; Drouin, J .; Conia, J .
M. Tetrahedron Lett. 1974, 2931-2934. (d) Conia, J . M.; Le Perchec,
P. Synthesis 1975, 1-19. (e) Bortolussi, M.; Bloch, R.; Conia, J . M.
Bull. Soc. Chim. Fr. 1975, 2727-2730. (f) Conia, J . M.; Lange, G. L.
J . Org. Chem. 1978, 43, 564-567.
(7) Marson, C. M.; Giles, P. R. J . Org. Chem. 1995, 60, 8067-8073.
(8) (a) Arnold, R. T.; Showell, J . S. J . Am. Chem. Soc. 1957, 79, 419-
422. (b) Koerner Von Gustorf, E. H. Tetrahedron Lett. 1968, 4693-
4694. (c) Chan, B. L.; Taylor, D. R. J . Chem. Soc., Perkin Trans. 1
1977, 1463-1468. (d) Laporterie, A.; Dubac, J .; Manuel, G.; Deleris,
G. Tetrahedron 1978, 2669-2673.
(3) (a) Snider, B. B. Acc. Chem. Res. 1980, 13, 426-432. (b) Snider,
B. B.; Ron, E. J . Am. Chem. Soc. 1985, 107, 8160-8164.
(4) (a) Maruoka, K.; Hoshino, Y.; Shirasaka, T.; Yamamoto, H.
Tetrahedron Lett. 1988, 29, 3967-3970. (b) Whitesell, J . K. Acc. Chem.
Res. 1985, 18, 280-284. (c) Whitesell, J . K.; Bhattacharya, A.;
Buchanan, C. C.; Chen, H. H.; Deyo, D.; J ames, D.; Liu, C.-L.; Minton,
M. A. Tetrahedron 1986, 42, 2993-3001.
(5) (a) Mikami, K.; Terada, M.; Nakai, T. J . Am. Chem. Soc. 1989,
111, 1940-1941. (b) Mikami, K.; Terada, M.; Nakai, T. Chem. Express
1989, 4, 589-592. (c) Mikami, K.; Terada, M.; Nakai, T. J . Am. Chem.
Soc. 1990, 112, 3949-3954.
S0022-3263(97)00257-0 CCC: $14.00 © 1997 American Chemical Society

Intramolecular Ene Reactions
J . Org. Chem., Vol. 62, No. 21, 1997 7107
Ta ble 1. Th er m ocycliza tion of Ter tia r y â-Ca r boxa m id o
Sch em e 1. Hyd r olysis of En a m in es
En a m in es
Ta ble 2. Ch em ica l Sh ifts (p p m ) of th e Meth yl Gr ou p in
En a m in o Sp ir ola cta m s a n d Th eir Cor r esp on d in g Keto
Sp ir ola cta m s
enamino
keto
spirolactams
a
b
spirolactams
a
b
14
19
15
17
18
0.91
0.92
0.90
0.97
0.98
0.82
0.85
0.75
0.67
0.91
29
1.02
1.09
30
33
34
1.01
0.99
0.98
1.05
1.09
1.15
Racemic and chiral nonracemic keto spirolactams 29,
30, and 33 were obtained by the hydrolysis of the
corresponding enamino spirolactams 14/19, 15, and 17
(Table 1, Scheme 1) and imino spirolactams 22, 23, and
25 (vide infra, Table 3) and by the hydrolysis of the
corresponding chiral imino spirolactams 26, 27, and 28
(vide infra, Table 4). Racemic compounds 34 were
similarly obtained from compounds 18 (Scheme 1).
The relative and absolute configuration of keto spiro-
lactams (-)-29a and (+)-29a was established by X-ray
diffraction (vide infra). Thus, only the (Z)-isomer was
obtained and by analogy the same configuration can be
assigned to compounds (-)-30a /(+)-30a and (-)-33a /(+)-
33a . The 1H NMR spectra of the major racemic com-
pounds 29a , 30a , and 33a are identical to those of the
corresponding chiral compounds; thus their relative
configuration can be also established, as well as the
relative configurations of the parent enamino spiro-
lactams 14a /19a , 15a , 17a , and imino spirolactams 22,
23, and 25. By analogy, the same relative configuration
can be attributed to the major isomers 18a and 34a
(Scheme 1).
The thermolysis of neat tertiary â-carboxamido en-
amines I was achieved by heating at 150 °C for 5 h, while
the acetylenic compound 3 was heated neat at 80 °C for
1 h. The results are reported in Table 1.
The enamino spirolactams arising from the thermolysis
of compounds 1-6 were isolated in good to excellent
yields (65-95%) and with good diastereoselectivity (78/
22 to 90/10). When enamine 1 was heated at high
temperature (230 °C), the yield increased to 95% and the
diastereoselectivity remained unchanged. The thermoly-
sis of the enamine derived from piperidine (compound
6) gave poorer results (yield and diastereoselectivity)
than the corresponding enamine derived from pyrrolidine
(compound 1). Furthermore, when the thermolyses of
â-carboxamido enamines 1, 2, 4, 5, and 6 were performed
in xylene heated at reflux (c ) 10-2 M), and the ther-
molysis of 3 was carried out in benzene heated at reflux,
the corresponding enamino spirolactams were isolated
in the same yield (and diastereoselectivity) as when they
were thermolyzed neat. We point out that the formation
of the enamino spirolactams could not be catalyzed by
Lewis acids such as Me2AlCl or Et2AlCl.3a
1
In the case of the major stereoisomers a , the H NMR
spectra show doublets for the methyl group at slightly
lower field than the corresponding ones in the minor
stereoisomers b (Table 2).
The mixture of compounds 17a and 17b has been
quenched with methyl vinyl ketone in benzene to produce
the Michael adduct 20 as a mixture of isomers in 53%
yield. It is worth noting that enamine 20 is remarkably
(9) Montevecchi, P. C.; Navacchia, M. L. J . Org. Chem. 1995, 60,
6455-6459.
(10) Cossy, J .; Bouzide, A. Tetrahedron Lett. 1992, 33, 2505-2508.
(11) (a) Cossy, J .; Belotti, D.; Thellend, A.; Pete, J . P. Synthesis 1988,
720-723. (b) Cossy, J .; Thellend, A. Synthesis 1989, 753-755.

7108 J . Org. Chem., Vol. 62, No. 21, 1997
Cossy et al.
Ta ble 4. Th er m olysis of Non r a cem ic Secon d a r y
Ta ble 3. Th er m olysis of Secon d a r y â-Ca r boxa m id o
En a m in es
â-Ca r boxa m id o En a m in es a n d Hyd r olysis of th e Im in o
Sp ir ola cta m s
stable to silica gel purification. Its hydrolysis was carried
out by using aqueous acetic acid in THF heated at reflux.
When secondary â-carboxamido enamines 7-10 were
thermolyzed at 150 °C (neat) for 5 h, the corresponding
imino spirolactams were obtained in good to excellent
yields (76-95%) and with total diastereoselectivity. Only
the (Z)-stereoisomer (vide supra) was obtained (Table 3).
Because the thermolysis of â-carboxamido enamines
afforded only one diastereoisomer, we took advantage of
this stereoselectivity to achieve the synthesis of non-
racemic imino spirolactams by using a nonracemic amino
moiety.
The condensation of â-keto amides with (R)-phenyl-
ethylamine led to the corresponding nonracemic second-
ary â-carboxamido enamines which were thermolyzed at
150 °C (neat) for 5 h. The results are summarized in
Table 4.
Hydrolysis of the imino spirolactams (-)-26a ′, (+)-
26a ′′, (-)-27a ′, (-)-27a ′′, (+)-28a ′, and (-)-28a ′′ (CH3-
CO2H, H2O) gave quantitatively the corresponding non-
racemic keto spirolactams (-)-29a , (+)-29a , (-)-30a , (+)-
30a , (-)-33a , and (+)-33a (Table 4).
Neither spectral analysis of the keto spirolactams nor
HPLC analysis showed the presence of any other isomer.
The RD values of isomers a and b, measured in ethanol,
confirmed that these compounds were enantiomers. In
these reactions the diasteroselectivity is thus higher than
99:1 and the enantiomeric excesses were 50-54%. The
enamino and imino spirolactams are most probably
formed from an ene reaction.
The thermolyses of 11, 12, and 13 each produced two
diastereoisomers: (-)-26a ′, (+)-26a ′′ (77/23), (-)-27a ′,
(-)-27a ′′ (75/25), and (+)-28a ′, (-)-28a ′′ (76/24), respec-
tively, in good yields (77-95%). The diastereoisomers
were separated by flash chromatography on silica gel.
The absolute and relative configurations of compounds
(-)-26a ′ and (+)-26a ′′ were established by X-ray diffrac-
tion (Figure 1).12
The cyclization of the tertiary â-carboxamido enamines
arises from a carba-ene reaction. The diastereoselectivity
of the reaction varies from 78/22 to 90/10, and the
compound where the methyl group and the enamine
group have a cis-relationship with respect to the C(4)-
C(5) bond of the lactam ring is the major isomer. This
latter compound is probably generated from an exo
transition state where overlap of the π system can take
place without any steric constraint. The minor isomer
results from an endo transition state. In this transition
state, the system is strained and steric interactions exist
between Hb and Hd (Figure 2).
(12) The author has deposited atomic coordinates for this structure
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K.

Intramolecular Ene Reactions
J . Org. Chem., Vol. 62, No. 21, 1997 7109
from â-carboxamido enamines. In the case of secondary
carboxamido enamines, the diastereoselectivity is higher
than 99:1. If chiral nonracemic analogs are used, 50-
54% enantiomeric excesses can be achieved in the final
products.
Exp er im en ta l Section
F igu r e 1. Structures of compounds (-)-26a ′ and (+)-26a ′′
determined by X-ray diffraction.
Gen er a l. All experiments were run under an Ar atmo-
sphere. 1H NMR and 13C NMR spectra were obtained at 300
and 75 MHz, respectively. IR spectra were recorded in CDCl3.
Mass spectra were run on a Hewlett-Packard instrument (EI
mode at 70 eV). Microanalysis, HRMS, and X-ray diffraction
were performed at Paris VI University. Flash chromatography
was accomplished with petroleum ether (PE) and ethyl acetate
on Merck silica gel 0.043-0.063 mm. Analytical thin layer
chromatography (TLC) was performed on Merck silica gel 60
F254
. Acetonitrile, toluene, and amines were distilled from
CaH2.
Syn th esis of â-En a m in o Ca r boxa m id es. To a solution
of â-keto amide11 (10 mmol) in toluene (25 mL) was added the
amine [pyrrolidine and piperidine (30 mmol), primary amines
(13 mmol)]. After 12 h at reflux in a Dean-Stark apparatus,
the solvent was evaporated under reduced pressure. The
tertiary enamino carboxamides 1-6 were purified by distil-
lation (0.1 mmHg), and the secondary enaminocarboxamides
7-13 were purified by flash chromatography. Yields of
â-carboxamido enamines were quantitative.
N ,N -D ia lly l-2-p y r r o lid in o c y c lo p e n t -1-e n e c a r b o x -
a m id e (1): yellow oil; yield 98%; IR 1660, 1625, 1480, 1450
cm-1; 1H NMR (C6H6) δ 1.70-1.90 (m, 6H), 2.53-2.65 (m, 4H),
3.17-3.25 (m, 4H), 3.07-3.25 (m, 4H), 3.86-4.05 (m, 4H),
5.08-5.27 (m, 4H), 5.69-5.85 (m, 2H); 13C NMR (C6D6) δ 22.9
(t), 26.1 (2t), 35.4 (t), 35.8 (2t), 38.8 (t), 50.2 (2t), 99.2 (s), 117.1
(2t), 135.6 (2d), 149.2 (s), 171.3 (s); MS m/z 260 (M+, 20), 219
(15), 191 (10), 176 (10), 164 (100), 137 (50), 136 (80), 111 (60);
HRMS m/z (M+) calcd for C16H24N2O 260.1888, found 260.1881.
N-Allyl-N-m eth yl-2-p yr r olid in ocyclop en t-1-en eca r box-
a m id e (2): yellow oil; yield 96%; IR 1655, 1630, 1480, 1450
cm-1; 1H NMR (C6D6) δ 1.30-1.46 (m, 4H), 1.62-1.72 (m, 2H),
2.25 (m, 2H), 2.68 (m, 2H), 2.80 (s, 3H); 3.80 (s, 3H), 2.90 (m,
4H), 3.65-4.00 (m, 2H), 4.95-5.05 (m, 2H), 5.60-5.80 (m, 1H);
13C NMR (C6D6) δ 22.8 (t), 26.1 (2t), 35.4 (t), 35.54 (t), 39.2
(q), 50.0 (2t), 50.2 (t), 99.4 (s), 116.9 (t), 135.5 (d), 148.6 (s),
171.4 (s); MS m/z 234 (M+, 20), 164 (100), 136 (68), 118 (18),
111 (52); HRMS m/z (M+) calcd for C14H22N2O 234.1732, found
234.1729.
F igu r e 2. Endo and exo transition states.
In the case of secondary â-carboxamido enamines, the
ene adduct has the imine group and the methyl group
also in a cis-relationship with respect to the C(4)-C(5)
bond of the lactam ring. The spiroannulation process
described here can be explained a priori in terms of an
aza-ene reaction involving the abstraction of HN by the
allylic chain or in terms of a carba-ene reaction involving
the abstraction of Hc at the R′ position by the allylic chain
(Figure 3).
In order to prove which pathway occurs, we tried to
replace HN by a deuterium atom in compound 7. Unfor-
tunately, selective deuteriation was not possible because
the protons at the allylic position of the enamine were
also exchanged in an imine-enamine equilibrium (Scheme
2).
Sch em e 2. Deu ter ia tion of th e En a m in e 7
N -Me t h yl-N -p r op a r gyl-4,4-d im e t h yl-2-p yr r olid in o-
cyclop en t-1-en eca r boxa m id e (3): yellow oil; yield 98%; IR
According to the transition states, the aza-ene reaction
can produce only the cis-isomer. This process will not
allow the formation of the trans-isomer because overlap
with the π-system is impossible. If the carba-ene reaction
took place, the cis-adduct should be the major product
and should be accompanied by the trans-adduct. Accord-
ing to the transition states outlined above and the
experimental results obtained (only the cis-adduct is
formed), it appears that the aza-ene reaction is respon-
sible for the formation of the imino spirolactams from
secondary â-carboxamido enamines in analogy with the
imino-Michael reaction although through a different
geometry of the transition state.13
1
1650, 1625, 1450 cm-1; H NMR (C6D6) δ 1.08 (s, 6H), 1.38-
1.45 (m, 4H), 2.02 (m, 1H), 2.15 (m, 2H), 2.50 (s, 2H), 2.93 (s,
3H), 3.00-3.05 (m, 4H), 4.10 (s, 2H); 13C NMR (C6D6) δ 25.6
(2q), 25.5 (2t), 36.0 (q), 40.5 (s), 49.3 (t), 49.5 (t), 49.8 (2t), 53.2
(t), 71.8 (d), 80.2 (s), 96.6 (s), 148.2 (s), 170.5 (s); MS m/z 260
(M+, 20), 245 (100), 235 (25), 192 (60), 124 (22); HRMS m/z
(M+) calcd for C16H24N2O 260.1888, found 260.1892.
N ,N -D ia lly l-2-p y r r o lid in o c y c lo h e x -1-e n e c a r b o x -
a m id e (4): yellow oil; yield 98%; IR 1655, 1630, 1450 cm-1
;
1H NMR (C6D6) δ 130-1.60 (m, 8H), 1.85-2.20 (m, 4H), 2.80-
3.20 (m, 4H), 3.50-4.20 (m, 4H), 4.92-5.12 (m, 4H), 5.40-
5.80 (m, 2H); 13C NMR (C6D6) δ 23.6 (t), 24.0 (t), 25.9 (2t), 28.3
(2t), 29.3 (t), 48.5 (t), 49.6 (2t), 97.9 (s), 117.5 (2t), 134.8 (2d),
141.4 (s), 173.5 (s); MS m/z 274 (M+, 25), 233 (10), 205 (10),
178 (45), 150 (50), 124 (25), 96 (80), 56 (55), 41 (100). Anal.
Calcd for C17H26N2O: C, 74.41; H, 9.55; N, 10.21. Found: C,
74.47; H, 9.48; N, 10.15.
We have shown for the first time that enamines can
be involved in ene reactions without any electron-
withdrawing group present in the enophile and that these
reactions can produce enamino or imino spirolactams
N-Allyl-N-m eth yl-2-p yr r olid in ocycloh ex-1-en eca r box-
a m id e (5): yellow oil; yield 96%; IR 1655, 1630, 1480, 1450
cm-1; 1H NMR (C6D6) δ 1.20-1.63 (m, 8H), 2.00-2.52 (m, 4H),
2.48 (s, 3H), 2.60-3.10 (m, 4H), 3.75-4.15 (m, 2H), 4.80-5.10
(m, 2H), 5.50-5.82 (m, 1H); 13C NMR (C6D6) δ 23.6 (t), 24.1
(t), 25.6 (t), 26.0 (2t), 28.4 (t), 34.7 (q), 46.7 (t), 49.4 (2t), 102.5
(s), 117.2 (t), 134.2 (d), 141.1 (s), 174.7 (s); MS m/z 248 (M+,
30), 178 (68), 164 (22), 150 (63), 136 (20), 123 (22), 70 (100).
(13) (a) Sevin, A.; Tortajada, J .; Pfau, M. J . Org. Chem. 1986, 51,
2671-2675. (b) Sevin, A.; Masure, D.; Giessner-Prettre, C.; Pfau, M.
Helv. Chim. Acta 1990, 73, 552-573. (c) Pfau, M.; Tomas, A.; Lim, S.;
Revial, G. J . Org. Chem. 1995, 60, 1143-1147. (d) J abin, I.; Revial,
G.; Tomas, A.; Lemoine, P.; Pfau, M. Tetrahedron: Asymmetry 1995,
6, 1795-1812.

7110 J . Org. Chem., Vol. 62, No. 21, 1997
Cossy et al.
F igu r e 3. Transition states of the aza-ene and carba-ene reactions.
Anal. Calcd for C15H24N2O: C, 72.53; H, 9.74; N, 11.29.
Found: C, 72.59; H, 8.68; N, 11.35.
N ,N -Dia llyl-2-(b e n zyla m in o)cycloh e x-1-e n e ca r b ox-
a m id e (10): yellow oil; yield 90%; mixture of enamine/imine
(NMR ratio 50/50). Enamine-imine IR 3350, 1680, 1650,
1610, 1450 cm-1; enamine 1H NMR (CDCl3) δ 1.50-2.20 (m,
8H), 3.40-4.05 (m, 4H), 4.50 (s, 2H), 5.00-5.25 (m, 4H), 5.40
(s, 1H), 5.60-5.90 (m, 2H), 7.15-7.37 (m, 5H); 13C NMR
(CDCl3) δ 22.4 (t), 26.5 (t), 28.5 (t), 30.3 (t), 48.24(t), 53.8 (2t),
116.6 (2t), 126.8 (d), 127.6 (2d), 128.0 (2d), 133.1 (2d), 140.35
(s), 170.8 (s), 172.2 (s), 174.2 (s); imine 1H NMR (CDCl3) δ
1.50-2.20 (m, 8H), 2.80 (m, 1H), 3.40-4.05 (m, 4H), 4.20-
4.45 (m, 2H), 5.30-5.20 (m, 4H), 5.60-5.90 (m, 2H), 7.10-
7.40 (m, 5H); 13C NMR (CDCl3) δ 23.8 (t), 25.6 (t), 26.5 (t),
30.3 (t), 47.9 (t), 51.2 (d), 53.8 (2t), 117.1 (2t), 126.8 (d), 127.95
(2d), 128.4 (2d), 133.8 (2d), 145.3 (s), 169.5 (s), 172.2 (s);
enamine-imine MS m/z 310 (M+, 30), 214 (100). Anal. Calcd
for C20H26N2O: C, 77.38; H, 8.44; N, 9.02. Found: C, 77.29;
H, 8.51; N, 9.11.
N ,N -D ia lly l-2-p ip e r id in o c y c lo p e n t -1-e n e c a r b o x -
a m id e (6): yellow oil; yield 98%; IR 1660, 1630, 1460, 1420
cm-1; 1H NMR (C6D6) δ 1.40-1.60 (m, 4H), 1.70-1.92 (m, 2H),
2.10-2.52 (m, 6H), 2.70-3.40 (m, 4H), 3.60-4.00 (m, 4H),
5.10-5.25 (m, 4H), 5.60-5.80 (m, 2H); 13C NMR (C6D6) δ 20.0
(2t), 24.0 (t), 27.4 (t), 34.9 (t), 38.4 (2t), 49.1 (t), 48.1 (t), 49.6
(t), 102.4 (s), 116.2 (2t), 132.5 (2d), 147.6 (s), 168.8 (s); MS m/z
274 (M+, 20), 259 (10), 233 (20), 178 (100), 150 (85), 125 (62),
110 (15). Anal. Calcd for C17H26N2O: C, 74.41; H, 9.55; N,
10.21. Found: C, 74.48; H, 9.49; N, 10.25.
N,N-Dia llyl-2-(b en zyla m in o)cyclop en t -1-en eca r b ox-
a m id e (7): yellow oil; yield 95%; Rf 0.45 (PE/AcOEt 80/20);
IR 3250, 1680, 1600, 1550, 1460 cm-1 1H NMR (CDCl3) δ
;
1.60-1.67 (m, 2H), 2.38 (t, J ) 7.5 Hz, 2H), 2.58 (t, J ) 7.0
Hz, 2H), 3.85 (d, J ) 5.1 Hz, 4H), 4.28 (d, J ) 6.5 Hz, 2H),
5.00-5.10 (m, 4H), 5.50-5.80 (m, 2H), 7.10-7.30 (m, 5H), 8.50
(s, 1H); 13C NMR (CDCl3) δ 22.4 (t), 31.3 (t), 32.5 (t), 48.2 (t),
48.5 (2t), 116.1 (2t), 126.7 (2d), 126.9 (d), 128.4 (2d), 134.6 (2d),
139.6 (d), 164.5 (s), 171.2 (s), 178.2 (s); MS m/z 296 (M+, 30),
281 (25), 268 (19), 205 (35), 201 (40), 200 (100), 177 (30), 147
(40), 91 (80); HRMS m/z (M+) calcd for C19H24N2O 296.1888,
found 296.1893.
(-)-N,N-Dia llyl-2-[(1-p h en yleth yl)a m in o]cyclop en t-1-
en eca r boxa m id e [(-)-11]: yellow oil; yield 96%; Rf 0.40 (PE/
AcOEt 70/30); [R]22D ) -320 (c 5, ethanol); IR 3250, 1680, 1630,
1600, 1550, 1450 cm-1 1H NMR (CDCl3) δ 1.48 (d, J ) 6.6
;
Hz, 3H), 1.60-1.80 (m, 2H), 2.05-2.20 (m, 1H), 2.40-2.50 (m,
1H), 2.60 (t, J ) 6.8 Hz, 2H), 3.95 (d, J ) 4.9 Hz, 4H), 4.55 (q,
J ) 6.6 Hz, 1H), 5.10-5.20 (m, 4H), 5.25-5.40 (m, 2H), 7.15-
7.35 (m, 5H), 8.65 (m, 1H); 13C NMR (CDCl3) δ 23.2 (t), 25.8
(q), 32.4 (t), 33.1 (t), 49.1 (2t), 55.0 (d), 95.5 (s), 116.9 (2t), 126.3
(2d), 127.4 (d), 129.2 (2d), 135.5 (2d), 146.6 (s), 164.9 (s), 172.1
(s); MS m/z 310 (M+, 15), 214 (40), 205 (25), 186 (22), 152 (20),
124 (15), 110 (40), 105 (100). Anal. Calcd for C20H26N2O: C,
77.38; H, 8.44; N, 9.02. Found: C, 77.29; H, 8.49; N, 9.11.
N-Allyl-N-m eth yl-2-(ben zyla m in o)cyclop en t-1-en eca r -
boxa m id e (8): yellow oil; yield 90%; Rf 0.35 (PE/AcOEt 70/
30); IR 3300, 1680, 1650, 1550, 1480 cm-1; 1H NMR (CDCl3) δ
1.72-1.82 (m, 2H), 2.45 (t, J ) 7.0 Hz, 2H), 2.67 (t, J ) 7.0
Hz, 2H), 2.91 (s, 3H), 3.94 (dt, J ) 5.2 and 1.5 Hz, 2H), 4.38
(d, J ) 7.6 Hz, 2H), 5.15 (m, 2H), 5.80-5.90 (m, 1H), 7.20-
7.40 (m, 5H), 8.50 (s, 1H); 13C NMR (CDCl3) δ 22.5 (t), 31.4
(t), 32.8 (t), 34.7 (q), 48.4 (t), 51.5 (t), 95.1 (s), 116.2 (t), 127.0
(2d), 127.1 (d), 128.5 (2d), 134.6 (d), 139.8 (s), 164.1 (s), 171.8
(s); MS m/z 270 (M+, 10), 201 (14), 200 (53), 179 (17), 172 (21),
91 (100). Anal. Calcd for C17H22N2O: C, 75.52; H, 8.20; N,
10.36. Found: C, 75.67; H, 8.29; N, 10.25.
N-Met h yl-N-p r op a r gyl-2-(b en zyla m in o)cyclop en t -1-
en eca r boxa m id e (9): yellow oil; yield 92%; Rf 0.45 (PE/
AcOEt 80/20); IR 3300, 1675, 1650, 1555, 1470 cm-1; 1H NMR
(CDCl3) δ 1.80 (m, 2H), 2.20 (t, J ) 2.5 Hz, 1H), 2.45 (t, J )
2.5 Hz, 2H), 2.70 (t, J ) 6.8 Hz, 2H), 3.04 (s, 3H), 4.10 (d, J )
2.5 Hz, 2H), 3.37 (d, J ) 6.8 Hz, 2H), 7.20-7.35 (m, 5H), 8.55
(s, 1H); 13C NMR (CDCl3) δ 22.3 (t), 31.2 (t), 32.40 (t), 34.5 (q),
38.0 (t), 48.1 (t), 70.9 (s), 80.1 (d), 94.3 (s), 102.5 (s), 126.5 (2d),
126.5 (d), 128.2 (2d), 139.3 (s), 164.8 (s); MS m/z 268 (M+, 20),
240 (15), 214 (10), 177 (50), 149 (15), 120 (10), 91 (100), 79
(20). Anal. Calcd for C17H20N2O: C, 76.09; H, 7.51; N, 10.43.
Found: C, 76.12; H, 7.43; N, 10.49.
(-)-N-Allyl-N-m et h yl-2-[(1-p h en ylet h yl)a m in o]cyclo-
p en t-1-en eca r boxa m id e [(-)-12]: yellow oil; yield 95%; Rf
0.35 (PE/AcOEt 65/35); [R]22 ) -375 (c 2, ethanol); IR 3500,
D
1650, 1630, 1550 cm-1
;
1H NMR (CDCl3) δ 1.48 (d, J ) 6.9
Hz, 3H), 1.58-1.80 (m, 2H), 2.08-2.20 (m, 1H), 2.38-2.50 (m,
1H), 2.60 (t, J ) 6.8 Hz, 2H), 2.93 (s, 3H), 3.95 (d, J ) 5.2 Hz,
2H), 4.55 (q, J ) 7.0 Hz, 1H), 5.15 (m, 2H), 5.75-5.90 (m, 1H),
7.15-7.35 (m, 5H), 8.58 (d, J ) 7.6 Hz, 1H); 13C NMR (CDCl3)
δ 23.2 (t), 25.8 (q), 32.4 (t), 33.3 (t), 35.4 (q), 52.2 (t), 54.9 (d),
95.7 (s), 116.9 (t), 126.3 (2d), 127.4 (d), 129.2 (2d), 135.3 (d),
146.0 (s), 164.5 (s), 172.5 (s); MS m/z 284 (M+, 5), 214 (15),
213 (53), 184 (83), 156 (100). Anal. Calcd for C18H24N2O: C,
76.02; H, 8.50; N, 9.85. Found: C, 76.07; H, 8.62; N, 9.76.
(-)-N,N-Dia llyl-2-[(1-p h en ylet h yl)a m in o]cycloh ex-1-
en eca r boxa m id e [(-)-13]: yellow oil; yield 90%; Rf 0.40 (PE/
AcOEt 70/30); [R]22D ) -328 (c 5, ethanol); IR 3250, 1655, 1630,
1600, 1550, 1450 cm-1 1H NMR (CDCl3) δ 1.50 (d, J ) 6.6
;
Hz, 3H), 1.60-1.80 (m, 4H), 2.05-2.20 (m, 1H), 2.40-2.50 (m,

Intramolecular Ene Reactions
J . Org. Chem., Vol. 62, No. 21, 1997 7111
1H), 2.60 (t, J ) 6.8 Hz, 2H), 3.95 (d, J ) 4.9 Hz, 4H), 4.55 (q,
J ) 6.6 Hz, 1H), 5.10-5.20 (m, 4H), 5.25-5.40 (m, 2H), 7.15-
7.35 (m, 5H), 8.65 (m, 1H); 13C NMR (CDCl3) δ 22.2 (t), 25.8
(q), 32.5 (t), 33.1 (t), 34.5 (t), 49.1 (2t), 56.0 (d), 96.5 (s), 117.8
(2t), 126.3 (2d), 127.4 (d), 130.2 (2d), 134.5 (2d), 146.6 (s), 166.9
(s), 174.1 (s); MS m/z 324 (M+, 10), 309 (40), 228 (25), 200 (20),
166 (25), 138 (15), 119 (100). Anal. Calcd for C21H28N2O: C,
77.73; H, 8.69; N, 8.63. Found: C, 77.64; H, 8.49; N, 8.75.
Th er m olysis of En a m in es a n d Im in es. The enamines
and imines were thermolyzed neat at 150 or 80 °C under an
argon atmosphere. The spirolactams were purified by distil-
lation under reduced pressure (0.1 mmHg) or by flash chro-
matography. The mixture of diastereoisomers 14, 15, 17, 18,
and 19 could not be separated.
2-Allyl-4-m et h yl-6-p yr r olid in o-2-a za sp ir o[4.4]n on -6-
en -1-on e (14): yellow oil; yield 85%; IR 1680, 1610, 1490, 1430
cm-1; 1H NMR (C6D6) major isomer 14a δ 0.91 (d, J ) 7.0 Hz,
3H), 4.53 (t, J ) 3.0 Hz, 1H); minor isomer 14b δ 0.82 (d, J )
7.0 Hz, 3H), 4.48 (t, J ) 3.0 Hz, 1H); for both isomers δ 1.40-
1.50 (m, 4H), 1.50-1.62 (m, 1H), 1.98-2.07 (m, 1H), 2.20-
2.28 (m, 2H), 2.58 (t, J ) 9.0 Hz, 1H), 2.70-3.00 (m, 6H), 3.55
(dd, J ) 9.0 and 6.0 Hz, 1H), 4.00 (dd, J ) 9.0 and 6.0 Hz,
1H), 4.90-5.02 (m, 2H), 5.50-5.65 (m, 1H); 13C NMR (C6D6)
major isomer 14a δ 14.7 (q), 25.04 (2t), 28.3 (t), 38.6 (d), 39.0
(t), 45.9 (t), 49.6 (2t), 51.7 (t), 61.0 (s), 101.9 (d), 117.7 (t), 133.0
(d), 149.5 (s), 177.0 (s); minor isomer 14b δ 11.7 (q), 24.9 (2t),
29.1 (t), 35.5 (d), 39.0 (t), 45.2 (t), 48.7 (2t), 50.8 (t), 61.2 (s),
99.1 (d), 117.0 (t), 133.4 (d), 149.0 (s), 177.5 (s); MS m/z 260
(M+, 25), 245 (52), 231 (25), 217 (58), 190 (20), 164 (100), 152
(58), 136 (36), 108 (30), 97 (45). Anal. Calcd for C16H24N2O:
C, 73.80; H, 9.29; N, 10.76. Found: C, 73.87; H, 9.32; N, 10.75.
2,4-Dim eth yl-6-p yr r olid in o-2-a za sp ir o[4.4]n on -6-en -1-
on e (15): yellow oil; yield 76%; IR 1680, 1610, 1495 cm-1; 1H
NMR (C6D6) major isomer 15a δ 0.90 (d, J ) 7.0 Hz, 3H); minor
isomer 15b δ 0.75 (d, J ) 7.0 Hz, 3H); for both isomers δ 1.40-
1.50 (m, 4H), 1.50-1.60 (m, 1H), 1.95-2.05 (m, 1H), 2.20-
2.33 (m, 2H), 2.40-2.60 (m, 4H), 2.60-3.00 (m, 6H), 4.55 (t,
1H); 13C NMR (C6D6) major isomer 15a δ 14.5 (q), 25.1 (2t),
28.3 (t), 29.9 (t), 38.7 (q), 44.9 (d), 49.5 (2t), 54.3 (t), 60.7 (s),
102.1 (d), 149.5 (s), 177.3 (s); minor isomer 15b δ 15.4 (q), 24.5
(2t), 28.3 (t), 29.4 (t), 37.6 (q), 44.9 (d), 49.5 (t), 53.5 (t), 60.7
(s), 102.1 (d), 149.4 (s), 173.3 (s); MS m/z 234 (M+, 80), 219
(35), 191 (50), 181 (33), 164 (100), 136 (25), 126 (65), 108 (25),
91 (12). Anal. Calcd for C14H22N2O: C, 71.75; H, 9.46; N,
12.02. Found: C, 71.81; H, 9.37; N, 11.95.
isomers δ 1.20-1.70 (m, 8H), 1.80-2.00 (m, 1H), 2.00-2.20
(m, 2H), 2.40-3.00 (m, 6H), 2.52 (s, 3H), 5.00 (m, 1H); 13C NMR
(C6D6) major isomer 18a (C6D6) δ 15.8 (q), 18.7 (t), 24.0 (t),
24.6, (2t), 29.7 (t), 37.8 (t), 38.8 (d), 40.0 (t), 50.5 (2t), 55.1 (s),
108.5 (d), 144.5 (s), 177.7 (s); minor isomer 18b δ 13.0 (q), 21.4
(t), 24.0 (t), 25.0 (2t), 29.5 (t), 34.8 (q), 39.1 (d), 41.7 (t), 51.9
(2t), 53.8 (s), 109.2 (d), 144.5 (s), 177.7 (s); MS m/z 248 (M+,
50), 219 (20), 195 (30), 178 (55), 150 (30), 126 (40), 110 (100),
97 (50). Anal. Calcd for C15H24N2O: C, 72.54; H, 9.74; N,
11.28. Found: C, 74.51; H, 9.61; N, 11.21.
2,4-Dim et h yl-6-p ip er id in o-2-a za sp ir o[4.4]n on -6-en -1-
on e (19): yellow oil; yield 65%; IR 1680, 1610, 1495, 1400,
1260 cm-1; 1H NMR (C6D6) major isomer 19a (C6D6) δ 0.92 (d,
J ) 7.0 Hz, 3H); minor isomer 19b δ 0.85 (d, J ) 7.0 Hz, 3H);
for both isomers δ 1.40-1.55 (m, 4H), 1.55-2.07 (m, 2H), 2.20-
2.32 (m, 4H), 2.62 (t, J ) 9.0 Hz, 1H), 2.70-3.00 (m, 6H), 3.60
(dd, J ) 9.0 and 6.0 Hz, 2H), 4.10 (dd, J ) 9.0 and 6.0 Hz,
1H), 4.90-5.02 (m, 2H), 5.50-5.65 (m, 1H); 13C NMR (C6D6)
major isomer 19a δ 15.9 (q), 20.1 (t), 25.04 (2t), 27.3 (t), 37.6
(d), 38.9 (t), 46.9 (t), 50.6 (2t), 50.7 (t), 61.3 (s), 102.9 (d), 116.5
(t), 135.0 (d), 148.5 (s), 177.3 (s); minor isomer 19b δ 11.7 (q),
21.2 (t), 24.9 (2t), 30.1 (t), 36.5 (d), 40.0 (t), 44.2 (t), 48.9 (2t),
51.8 (t), 60.2 (s), 100.1 (d), 117.3 (t), 131.4 (d), 145.0 (s), 176.5
(s); MS m/z 274 (M+, 30), 233 (52), 219 (58), 191 (20), 130 (100),
83 (45). Anal. Calcd for C17H26N2O: C, 74.41; H, 9.54; N,
10.20. Found: C, 74.57; H, 9.32; N, 10.55.
2-Allyl-6-(ben zylim in o)-4-m eth yl-2-azaspir o[4.4]n on an -
1-on e (22): yellow oil; yield 81%; Rf 0.38 (PE/AcOEt 95/05);
IR 1680, 1610, 1480 cm-1; 1H NMR (CDCl3) δ 1.01 (d, J ) 6.8
Hz, 3H), 1.65-1.75 (m, 1H), 1.80-1.95 (m, 1H), 2.00-2.50 (m,
5H), 3.13 (dd, J ) 9.5 and 9.5 Hz, 1H), 3.38 (dd, J ) 9.5 and
9.5 Hz, 1H), 3.80 (m, 1H), 4.05 (m, 1H), 4.45 (d, J ) 6.5 Hz,
2H), 5.00-5.30 (m, 2H), 5.55-5.75 (m, 1H), 7.15-7.35 (m, 5H);
13C NMR (CDCl3) δ 12.2 (q), 22.4 (t), 30.5 (t), 33.9 (t), 39.2 (d),
45.3 (t), 51.5 (t), 57.1 (t), 60.1 (s), 117.0 (t), 126.1 (d), 127.5
(2d), 128.4 (2d), 132.6 (d), 140.3 (s), 176.6 (d), 178.9 (s); MS
m/z 296 (M+, 20), 281 (15), 203 (80), 201 (30), 200 (100), 147
(20), 91 (60). Anal. Calcd for C19H24N2O: C, 76.99; H, 8.16;
N, 9.45. Found: C, 77.10; H, 8.21; N, 9.39.
6-(Ben zylim in o)-2,4-d im eth yl-2-a za sp ir o[4.4]n on a n -1-
on e (23): yellow oil; yield 76%; Rf 0.38 (PE/AcOEt 70/30); IR
1680, 1480, 1420 cm-1 1H NMR (CDCl3) δ 0.98 (d, J ) 6.9
;
Hz, 3H), 1.62-2.50 (m, 7H), 2.84 (s, 3H), 2.80 (dd, J ) 9.4
and 4.2 Hz, 1H), 3.62 (dd, J ) 9.4 and 4.2 Hz, 1H), 4.45 (d, J
) 8.5 Hz, 2H), 7.25-7.35 (m, 5H); 13C NMR (CDCl3) δ 15.01
(q), 21.6 (t), 29.6 (t), 29.9 (q), 34.8 (t), 39.1 (d), 54.7 (t), 57.0
(t), 60.2 (s), 126.3 (d), 127.1 (2d), 128.5 (2d), 140.2 (s), 176.8
(s), 179.5 (s); MS m/z 270 (M+, 20), 600 (60), 179 (22), 170 (30),
91 (100). Anal. Calcd for C17H22N2O: C, 75.52; H, 8.20; N,
10.36. Found: C, 75.61; H, 8.27; N, 10.41.
2,8,8-T r im e t h y l-4-m e t h y le n e -6-p y r r o lid in o -2-a za -
sp ir o[4.4]n on -6-en -1-on e (16): yellow oil; yield 95%; IR 1690,
1660, 1625, 1490 cm-1; 1H NMR (C6D6) δ 1.25 (s, 3H), 1.42 (s,
3H), 1.47 (m, 4H), 1.85 (d, J ) 12.5 Hz, 1H), 2.40 (d, J ) 12.5
Hz, 1H), 2.57 (s, 3H), 2.85-2.95 (m, 4H), 3.35-3.60 (m, 2H),
4.45 (s, 1H), 4.70 (m, 1H), 5.20 (m, 1H); 13C NMR (C6D6) δ
25.6 (2q), 28.8 (t), 32.6 (2t), 42.1 (s), 48.1 (q), 49.5 (t), 49.8 (2t),
62.5 (s), 108.1 (d), 110.9 (t), 144.6 (s), 148.2 (s), 176.2 (s); MS
m/z 260 (M+, 22), 245 (100), 124 (50), 91 (12), 68 (30). Anal.
Calcd for C16H24N2O: C, 73.80; H, 9.29; N, 10.76. Found: C,
73.85; H, 9.22; N, 10.67.
6-(Be n zylim in o)-2-m e t h yl-4-m e t h yle n e -2-a za sp ir o-
[4.4]n on a n -1-on e (24): yellow oil; yield 77%; Rf 0.35 (PE/
1
AcOEt 70/30); IR 1660, 1490, 1455 cm-1; H NMR (CDCl3) δ
1.65-2.05 (m, 3H), 2.15-2.50 (m, 3H), 2.92 (s, 3H), 3.85 (dt, J
) 13.2 and 1.8 Hz, 1H), 4.17 (dt, J ) 13.2, 2.3 Hz, 1H), 4.48
(s, 2H), 4.97 (t, J ) 2.2 Hz, 1H), 5.07 (t, J ) 2.1 Hz, 1H), 7.10-
7.35 (m, 5H); 13C NMR (CDCl3) δ 22.4 (t), 28.8 (t), 29.4 (q),
34.4 (t), 53.7 (t), 56.9 (t), 60.7 (s), 106.5 (t), 126.2 (d), 126.7
(2d), 128.0 (2d), 139.8 (s), 147.0 (s), 175.1 (s), 181.2 (s). Anal.
Calcd for C17H20N2O: C, 76.08; H, 7.51; N, 10.44. Found: C,
76.19; H, 7.57; N, 10.51.
2-Allyl-4-m eth yl-6-p yr r olid in o-2-a za sp ir o[4.5]d ec-6-en -
1-on e (17): yellow oil; yield 92%; IR 1680, 1490, 1350 cm-1
;
1H NMR (C6D6) major isomer 17a (C6D6) δ 0.97 (d, J ) 7.0
Hz, 3H); minor isomer 17b δ 0.67 (d, J ) 7.0 Hz, 3H); for both
isomers δ 1.10-1.70 (m, 8H), 1.85-1.95 (m, 1H), 2.00-2.25
(m, 2H), 2.42-2.58 (m, 1H), 2.62-2.78 (m, 3H), 2.85-3.08 (m,
2H), 3.50-4.00 (m, 2H), 4.90-5.10 (m, 3H), 5.45-5.70 (m, 1H);
13C NMR (C6D6) major isomer 17a (C6D6) δ 16.0 (q), 18.7 (t),
24.4 (2t), 24.6 (t), 37.9 (t), 39.9 (d), 45.7 (t), 50.9 (2t), 52.3 (s),
52.5 (t), 109.2 (d), 117.5 (t), 133.2 (d), 144.7 (s), 177.5 (s); minor
isomer 17b δ 12.9 (q), 21.4 (t), 25.0 (2t), 25.5 (t), 34.8 (2t), 40.12
(d), 45.3 (t), 51.4 (t), 52.3 (s), 52.5 (t), 109.2 (d), 117.0 (t), 133.0
(d), 144.7 (s), 177.52 (s); MS m/z 274 (M+, 93), 259 (20), 245
(40), 231 (30), 221 (30), 178 (87), 162 (27), 150 (50), 123 (58),
97 (55), 41 (100). Anal. Calcd for C17H26N2O: C, 74.41; H,
9.55; N, 10.21. Found: C, 74.51; H, 9.61; N, 10.25.
2-Allyl-4-m eth yl-6-(ben zylim in o)-2-a za sp ir o[4.5]d eca n -
1-on e (25): yellow oil; yield 95%; Rf 0.30 (PE/AcOEt 70/30);
IR 1680, 1635, 1480 cm-1; 1H NMR (CDCl3) δ 1.02 (d, J ) 7.0
Hz, 3H), 1.50-2.40 (m, 9H), 2.93 (dd, J ) 9.3 and 9.3 Hz, 1H),
3.12 (dd, J ) 9.0 and 7.7 Hz, 1H), 3.75-4.00 (m, 2H), 4.50 (m,
2H), 5.10 (m, 2H), 5.60-5.70 (m, 1H), 7.25-7.35 (m, 5H); 13C
NMR (CDCl3) δ 15.4 (q), 21.17 (t), 24.0 (t), 28.6 (t), 35.5 (t),
41.3 (d), 45.6 (t), 51.5 (t), 53.7 (t), 57.3 (t), 117.3 (t), 126.2 (d),
127.9 (2d), 128.4 (2d), 133.0 (d), 140.9 (s), 170.3 (s), 177.5 (s);
MS m/z 310 (M+, 25), 295 (15), 281 (10), 219 (80), 214 (100),
106 (21), 91 (70). Anal. Calcd for C20H26N2O: C, 77.38; H,
8.44; N, 9.02. Found: C, 77.44; H, 8.43; N, 9.01.
2,4-Dim eth yl-6-p yr r olid in o-2-a za sp ir o[4.5]d ec-6-en -1-
on e (18): yellow oil; yield 85%; IR 1675, 1490, 1400 cm-1; 1H
NMR (C6D6) major isomer 18a (C6D6) δ 0.98 (d, J ) 7.0 Hz,
3H); minor isomer 18b δ 0.91 (d, J ) 7.0 Hz, 3H); for both
(-)-(4R ,5R )-2-Allyl-4-m e t h yl-6-[(R )-(1-p h e n yle t h yl)-
im in o]-2-a za sp ir o[4.4]n on a n -1-on e [(-)-26a ′]: white solid;
yield 69%; Rf 0.35 (PE/AcOEt 70/30); mp ) 58 °C; [R]22D ) -117

7112 J . Org. Chem., Vol. 62, No. 21, 1997
Cossy et al.
1
(c 5, ethanol); IR 1680, 1480, 1440 cm-1; H NMR (CDCl3) δ
1.20 (d, J ) 7.0 Hz, 3H), 1.35 (d, J ) 7.0 Hz, 3H), 1.48-1.80
(m, 4H), 1.85-2.00 (m, 1H), 2.00-2.15 (m, 1H), 2.20-2.35 (m,
2H), 2.70 (m, 1H), 3.05-3.12 (m, 2H), 3.82 (m, 1H), 4.05 (m,
1H), 4.77 (q, J ) 7.0 Hz, 1H), 5.05-5.25 (m, 2H), 5.67-5.83
(m, 1H), 7.15 (m, 1H), 7.25 (m, 4H); 13C NMR (CDCl3) δ 15.6
(q), 21.8 (t), 24.8 (t), 26.0 (q), 28.7 (t), 36.0 (t), 42.0 (d), 46.3
(t), 52.3 (t), 57.6 (s), 58.1 (d), 117.9 (t), 126.8 (d), 127.1 (2d),
128.8 (2d), 133.9 (d), 146.9 (s), 168.5 (s), 178.1 (s); MS m/z 324
(M+, 40), 309 (10), 228 (90), 219 (100), 124 (40), 105 (75). Anal.
Calcd for C21H28N2O: C, 77.43; H, 8.70; N, 8.63. Found: C,
77.44; H, 8.72; N, 8.70.
Hyd r olysis. To a solution of an imine or a mixture of
enamines a /b (0.5 mmol) in THF (5 mL) was added aqueous
acetic acid (50%, 0.5 mL). After 2 h at reflux, the reaction
mixture was extracted with ether (2 × 10 mL). The organic
phase was washed with water (5 mL) and dried over MgSO4.
The solvent was removed in vacuo, and the residue was
purified by flash chromatography. Ketones a and b arising
from enamines 14, 15, 17, and 19 could not be separated.
However, the 1H NMR spectra of the mixture of ketones 29a ,b,
30a ,b, and 33a ,b allowed one to distinguish, without any
ambiguity, the spectra of the major isomer a and the minor
isomer b.14
1.12 (d, J ) 6.8 Hz, 3H), 1.41 (d, J ) 6.6 Hz, 3H), 1.65-1.77
(m, 1H), 1.80-1.95 (m, 1H), 2.03-2.17 (m, 1H), 2.23-2.40 (m,
4H), 3.16 (dd, J ) 8.3 and 8.3 Hz, 1H), 3.52 (dd, J ) 10.0 and
8.8 Hz, 1H), 3.70 (ddt, J ) 15.6 Hz, 6.0 and 1.3 Hz, 1H), 4.18
(ddt, J ) 15.6, 4.9 and 1.5 Hz, 1H), 4.50 (q, J ) 6.6 Hz, 1H),
5.10 (m, 1H), 5.26 (m, 1H), 5.55-5.70 (m, 1H), 7.15-7.30 (m,
5H); 13C NMR (CDCl3) δ 12.0 (q), 22.72 (t), 24.9 (q), 29.9 (t),
33.6 (t), 39.2 (d), 45.6 (t), 51.8 (t), 59.2 (s), 61.9 (d), 117.2 (t),
126.3 (d), 126.4 (2d), 128.0 (2d), 132.9 (d), 145.6 (s), 176.4 (s),
176.7 (s); MS m/z 310 (M+, 17), 281 (41), 214 (100), 207 (80),
152 (34), 110 (49), 105 (94). Anal. Calcd for C20H26N2O: C,
77.38; H, 8.44; N, 9.02. Found: C, 77.42; H, 8.46; N, 9.02.
(+)-(4S ,5S )-2-Allyl-4-m e t h yl-6-[(R )-(1-p h e n yle t h yl)-
im in o]-2-a za sp ir o[4.4]n on a n -1-on e [(+)-26a ′′]: white solid;
yield 21%; Rf 0.30 (PE/AcOEt 70/30); mp ) 58 °C; [R]22D ) +34
(c 1.5, ethanol); IR 1680, 1480, 1440 cm-1; 1H NMR (CDCl3) δ
0.80 (d, J ) 6.8 Hz, 3H), 1.37 (d, J ) 6.6 Hz, 3H), 1.58-1.68
(m, 1H), 1.70-1.85 (m, 1H), 2.03-2.55 (m, 1H), 2.01-2.55 (m,
4H), 3.10 (dd, J ) 8.3 and 8.3 Hz, 1H), 3.45 (dd, J ) 10.0 and
8.8 Hz, 1H), 3.70 (ddt, J ) 15.7, 6.0 and 1.3 Hz, 1H), 4.22 (ddt,
J ) 15.7, 4.9 and 1.5 Hz, 1H), 4.40 (q, J ) 6.6 Hz, 1H), 5.18
(m, 1H), 5.42 (m, 1H), 5.73-5.87 (m, 1H), 7.15-7.30 (m, 5H);
13C NMR (CDCl3) δ 11.8 (q), 22.6 (t), 24.8 (q), 29.9 (t), 33.5 (t),
39.4 (d), 45.4 (t), 51.7 (t), 59.3 (s), 62.8 (d), 116.9 (t), 126.3 (d),
126.6 (2d), 128.1 (2d), 132.6 (d), 146.0 (s), 176.2 (s), 176.6 (s);
MS m/z 310 (M+, 17), 281 (41), 214 (100), 207 (80), 152 (34),
110 (49), 105 (94). Anal. Calcd for C20H26N2O: C, 77.38; H,
8.44; N, 9.02. Found: C, 77.44; H, 8.49; N, 9.07.
2-Allyl-4-m eth yl-2-a za sp ir o[4.4]n on a n e-1,6-d ion e (29)
[from 14a ,b, 19a ,b, 22, (-)-26a ′, (+)-26a ′′]. (()-29a , (-)-29a ,
and (+)-29a : yellow oils; Rf 0.35 (PE/AcOEt 70/30); IR 1740,
1690, 1480 cm-1; 1H NMR (CDCl3) δ 1.02 (d, J ) 7.0 Hz, 3H),
2.85 (dd, J ) 9.4 and 4.3 Hz, 1H), 3.69 (dd, J ) 9.4 and 8.2
Hz, 1H), 1.80-2.05 (m, 2H), 2.15-2.45 (m, 4H), 2.62 (m, 1H),
3.80-4.00 (m, 2H), 5.10-5.25 (m, 2H), 5.64-5.80 (m, 1H); 13
C
(-)-(4R,5R)-2,4-Dim eth yl-6-[(R)-(1-p h en yleth yl)im in o]-
2-a za sp ir o[4.4]n on a n -1-on e [(-)-27a ′]: white solid; yield
NMR (CDCl3) δ 15.5 (q), 19.3 (t), 27.9 (t), 32.9 (d), 37.6 (t),
45.1 (t), 51.9 (t), 61.9 (s), 117.6 (t), 131.9 (d), 173.1 (s); 216.5
(s); MS m/z 207 (M+, 37); 152 (100), 97 (30). Anal. Calcd for
C12H17NO2: C, 69.53; H, 8.26; N, 6.76. Found: C, 69.58; H,
58%; Rf 0.35 (PE/AcOEt 70/30); mp ) 60 °C; [R]22 ) -47 (c
D
2.5, ethanol); IR 1675, 1490, 1450, 1430 cm-1; 1H NMR (CDCl3)
δ 1.10 (d, J ) 6.9 Hz, 3H), 1.40 (d, J ) 7.0 Hz, 3H), 1.63-1.73
(m, 1H), 1.75-1.90 (m, 1H), 2.00-2.15 (m, 1H), 2.20-2.45 (m,
4H), 2.88 (s, 3H), 3.20 (dd, J ) 8.0 and 8.0 Hz, 1H), 3.42 (dd,
8.37; N, 6.82. (-)-29a : [R]22 ) -128 (c 2.5, ethanol). (+)-
D
29a : [R]22 ) +128 (c 2.5, ethanol). (()-29b: yellow oil; Rf
D
J ) 8.0 and 8.0 Hz, 1H), 4.45 (m, 1H), 7.12-7.36 (m, 5H); 13
C
0.35 (PE/AcOEt 70/30); IR 1740, 1690, 1480, 1430 cm-1
;
1H
NMR (CDCl3) δ 12.8 (q), 23.5 (t), 25.6 (q), 30.5 (q), 30.6 (t),
34.2 (t), 39.9 (d), 54.9 (s), 59.8 (t), 126.2 (d), 126.9 (d), 126.9
(2d), 128.8 (2d), 146.4 (s), 177.2 (s), 177.8 (s); MS m/z 284 (M+,
47), 214 (91), 180 (23), 165 (17), 126 (45), 110; (52), 105 (100).
Anal. Calcd for C18H24N2O: C, 76.02; H, 8.50; N, 9.85.
Found: C, 76.08; H, 8.55; N, 9.86.
NMR (CDCl3) δ 1.09 (d, J ) 7.0 Hz, 3H), 1.85-2.00 (m, 2H),
2.10-2.45 (m, 4H), 2.60 (m, 1H), 3.20-3.38 (m, 2H), 3.82-
4.00 (m, 2H), 5.20 (m, 2H), 5.67-5.80 (m, 1H); 13C NMR
(CDCl3) δ 12.3 (q), 20.1 (t), 32.3 (t), 38.3 (d), 39.6 (d), 45.2 (t),
51.2 (t), 62.0 (s), 117.4 (t), 131.9 (d), 173.1 (s), 216.5 (s); MS
m/z 207 (M+, 37), 152 (100), 97 (36). Anal. Calcd for
C12H17NO2: C, 69.53; H, 8.27; N, 6.76. Found: C, 69.53; H,
8.35; N, 6.80.
(-)-(4S,5S)-2,4-Dim eth yl-6-[(R)-(1-p h en yleth yl)im in o]-
2-a za sp ir o[4.4]n on a n -1-on e [(-)-27a ′′]: white solid; yield
19%; Rf 0.30 (PE/AcOEt 70/30); mp ) 112 °C; [R]22 ) -3.6 (c
D
2,4-Dim eth yl-2-azaspir o[4.4]n on an e-1,6-dion e (30) [from
15a ,b, 23, (-)-27a ′, (-)-27a ′′]. (()-30a , (-)-30a , and (+)-
30a : yellow oils; Rf 0.30 (PE/AcOEt 70/30); IR 1730, 1675,
1490, 1430 cm-1; 1H NMR (CDCl3) δ 1.01 (d, J ) 7.0 Hz, 3H),
1.84-2.06 (m, 2H), 2.10-2.42 (m, 4H), 2.52-2.62 (m, 1H), 2.85
(s, 3H), 3.30 (m, 2H); 13C NMR (CDCl3) δ 15.6 (q), 19.5 (t),
28.0 (t), 29.9 (q), 33.0 (d), 37.7 (t), 54.7 (t), 62.5 (s), 173.9 (s),
216.0 (s); MS m/z 181 (M+, 68), 140 (17), 126 (100), 111 (20),
98 (20). Anal. Calcd for C10H15NO2: C, 66.27; H, 8.34; N, 7.72.
1.5, ethanol); IR 1670, 1490 cm-1; 1H NMR (CDCl3) δ 0.83 (d,
J ) 6.8 Hz, 3H), 1.35 (d, J ) 7.0 Hz, 3H), 1.63-1.73 (m, 1H),
1.75-1.90 (m, 1H), 2.00-2.55 (m, 5H), 2.93 (s, 3H), 3.17 (dd,
J ) 8.0 and 8.0 Hz, 1H), 3.49 (dd, J ) 10.0 and 8.0 Hz, 1H),
4.40 (q, J ) 6.7 Hz, 1H), 7.12-7.36 (m, 5H); 13C NMR (CDCl3)
δ 12.8 (q), 23.4 (t), 25.5 (q), 30.6 (q), 30.8 (t), 34.4 (t), 40.2 (d),
54.9 (t), 60.0 (s), 63.4 (d), 127.1 (d), 127.4 (2d), 128.8 (2d), 146.9
(s), 177.0 (s), 177.9 (s); MS m/z 284 (M+, 74), 214 (91), 180
(23), 126 (45), 110 (52), 105 (100). Anal. Calcd for
C18H24N2O: C, 76.02; H, 8.51; N, 9.85. Found: C, 76.12; H,
8.60; N, 9.92.
Found: C, 66.37; H, 8.37; N, 7.71. (-)-30a : [R]22 ) -94 (c
D
1.7, ethanol). (+)-30a : [R]22 ) +94 (c 1.6, ethanol). (()-
D
30b: yellow oil; Rf 0.30 (PE/AcOEt 70/30); IR 1730, 1675, 1490,
1430, 1400 cm-1; 1H NMR (CDCl3) δ 1.05 (d, J ) 7.0 Hz, 3H),
1.90 (m, 2H), 2.10-2.40 (m, 4H), 2.55 (m, 1H), 2.87 (m, 3H),
3.20-3.30 (m, 2H); 13C NMR (CDCl3) δ 13.23 (q), 20.96 (t),
30.53 (q), 32.92 (t), 39.06 (d), 40.32 (t), 54.44 (t), 62.45 (s),
174.04 (s), 217.15 (s); MS m/z 181 (M+, 68), 126 (100), 111 (20),
98 (20), 71 (42). Anal. Calcd for C10H15NO2: C, 66.27; H, 8.34;
N, 7.72. Found: C, 66.35; H, 8.33; N, 7.69.
(+)-(4R ,5R )-2-Allyl-4-m e t h yl-6-[(R )-(1-p h e n yle t h yl)-
im in o]-2-a za sp ir o[4.5]d eca n -1-on e [(+)-28a ′]: white solid;
yield 72%; Rf 0.35 (PE/AcOEt 70/30); mp ) 57 °C; [R]22D ) +62
(c 1.5, ethanol); IR 1680, 1480, 1440 cm-1; 1H NMR (CDCl3) δ
0.85 (d, J ) 7.0 Hz, 3H), 1.41 (d, J ) 7.0 Hz, 3H), 1.50-2.00
(m, 6H), 2.12-2.38 (m, 2H), 2.80-2.88 (m, 1H), 2.98 (m, 1H),
3.10 (m, 1H), 3.75-3.85 (m, 1H), 4.06-4.15 (m, 1H), 4.70 (q,
J ) 7.0 Hz, 1H), 5.12-5.30 (m, 2H), 5.75-5.90 (m, 1H), 7.15-
7.25 (m, 5H); 13C NMR (CDCl3) δ 15.4 (q), 21.85 (t), 24.8 (t),
25.7 (q), 28.9 (t), 36.2 (t), 42.4 (d), 46.4 (t), 52.2 (t), 55.7 (s),
59.2 (d), 118.0 (t), 127.1 (d), 127.6 (2d), 128.8 (2d), 138.8 (d),
174.0 (s), 168.5 (s), 178.2 (s); MS m/z 324 (M+, 40), 309 (10),
228 (90), 219 (100), 124 (40), 105 (57). Anal. Calcd for
C21H28N2O: C, 77.73; H, 8.70; N, 8.63. Found: C, 77.49; H,
8.75; N, 8.67.
2,8,8-Tr im et h yl-4-m et h ylen e-2-a za sp ir o[4.4]n on a n e-
1,6-d ion e (31) [from 16]: yellow oil; Rf 0.33 (PE/AcOEt 60/
40); IR 1740, 1690, 1660, 1430, 1410 cm-1; 1H NMR (CDCl3) δ
1.15 (s, 3H), 1.25 (s, 3H), 1.90 (d, J ) 14.0 Hz, 1H), 2.35 (m,
1H), 2.55 (d, J ) 14.0 Hz, 1H), 2.95 (s, 3H), 3.85 (dt, J ) 13.5
and 2.0 Hz, 1H), 4.28 (dt, J ) 13.5 and 2.1 Hz, 1H), 5.10 (t, J
) 2.0 Hz, 1H), 5.17 (t, J ) 2.0 Hz, 1H); 13C NMR (CDCl3) δ
28.87 (q), 29.60 (q), 29.69 (q), 33.11 (t), 45.71 (t), 53.08 (t), 53.67
(s), 65.08 (s), 107.91 (t), 144.25 (s), 171.82 (s), 211.97 (s); MS
(-)-(4R ,5R )-2-Allyl-4-m e t h yl-6-[(R )-(1-p h e n yle t h yl)-
im in o]-2-a za sp ir o[4.5]d eca n -1-on e [(-)-28a ′′]: white solid;
yield 22.5%; Rf 0.30 (PE/AcOEt 70/30); mp ) 54 °C; [R]22
)
D
-99 (c 1.5, ethanol); IR 1680, 1645 cm-1; H NMR (CDCl3) δ
(14) Cossy, J .; Bouzide, A. Tetrahedron 1997, 53, 5775-5784.
1

Intramolecular Ene Reactions
J . Org. Chem., Vol. 62, No. 21, 1997 7113
m/e 207 (M+, 20), 125 (9), 124 (100), 107 (8), 81 (8), 77 (10).
Anal. Calcd for C12H17NO2: C, 69.53; H, 8.27; N, 6.76.
Found: C, 69.61; H, 8.42; N, 6.88.
Alk yla tion of th e En a m in o Sp ir ola cta m 17. A solution
of compound 17 (0.27 g, 1 mmol) in benzene (5 mL) was added
dropwise to methyl vinyl ketone (0.14 g, 2 mmol), and the
reaction mixture was stirred at rt for 15 h. After evaporation
of the solvent, the residue was purified by flash chromatog-
raphy.
2-Met h yl-4-m et h ylen e-2-a za sp ir o[4.4]n on a n e-1,6-d i-
on e (32) [from 24]: yellow oil; Rf 0.55 (PE/AcOEt 20/80); IR
1
1740, 1680, 1650, 1485, 1425 cm-1; H NMR (CDCl3) δ 1.90-
2.15 (m, 2H), 2.25-2.45 (m, 2H), 2.60-2.70 (m, 2H), 2.95 (s,
3H), 3.85 (dt, J ) 13.5 and 1.8 Hz, 1H), 4.17 (dt, J ) 13.5 and
2.5 Hz, 1H), 5.03 (t, J ) 2.0 Hz, 1H), 5.11 (t, J ) 2.0 Hz, 1H);
13C NMR (CDCl3) δ 20.20 (t), 29.66 (q), 32.87 (t), 37.90 (t), 53.56
(t), 63.30 (s), 108.01 (t), 143.96 (s), 172.05 (s), 213.95 (s); MS
m/e 179 (M+, 40), 150 (24), 138 (20), 124 (100), 87 (59), 85 (91).
Anal. Calcd for C10H13NO2: C, 67.01; H, 7.31; N, 17.85.
Found: C, 67.05; H, 7.35; N, 17.82.
2-Allyl-4-m et h yl-7-(3-oxob u t yl)-6-p yr r olid in o-2-a za -
sp ir o[4.5]d ec-6-en -1-on e (20): yellow oil; yield 53%; Rf 0.25
(PE/AcOEt 70/30); IR 1710, 1685, 1675, 1640, 1475, 1440, 1410,
1350, 1260, 1160 cm-1 1H NMR (CDCl3) δ 1.11 (d, J ) 7.0
;
Hz, 3H), 1.45-1.80 (m, 8H), 1.90-2.40 (m, 6H), 2.16 (s, 3H),
2.50-2.60 (m, 2H), 2.90-3.05 (m, 4H), 3.20-3.25 (m, 1H), 3.90
(m, 2H), 5.12-5.25 (m, 2H), 5.62-5.80 (m, 1H); 13C NMR
(CDCl3) δ 15.6 (q), 18.4 (t), 25.8 (2t), 26.1 (t), 28.9 (t), 29.8 (q),
35.9 (t), 40.5 (d), 41.9 (t), 45.7 (t), 52.4 (t), 52.7 (2t), 54.4 (s),
117.6 (t), 132.8 (d), 135.3 (s), 139.72 (s), 178.2 (s), 208.3 (s);
MS m/z 344 (M+, 37), 326 (7), 301 (67), 287 (100), 273 (35),
190 (20), 160 (11). Anal. Calcd for C21H32N2O2: C, 73.22; H,
9.36; N, 8.13. Found: C, 73.31; H, 9.44; N, 8.22.
Hyd r olysis of En a m in o La cta m 20. To a solution of
compound 20 (0.17 g, 0.5 mmol) in THF (5 mL) was added
aqueous acetic acid (50%) (0.5 mL). After 2 h at reflux, the
reaction mixture was extracted with ether (2 × 10 mL). The
organic phase was washed with water (5 mL), dried over
MgSO4, and filtered. The solvent was removed in vacuo, and
the residue was purified by flash chromatography, yielding
dione 21 as an isomeric mixture.
2-Allyl-4-m eth yl-2-a za sp ir o[4.5]d eca n e-1,6-d ion e (33)
[from 17a ,b, 25, (+)-28a ′, (-)-28a ′′]. (()-33a , (+)-33a , (-)-
33a : yellow oils; Rf 0.35 (PE/AcOEt 70/30); IR 1700, 1675,
1495, 1455 cm-1; 1H NMR (CDCl3) δ 1.09 (d, J ) 7.0 Hz, 3H),
1.54-1.92 (m, 4H), 2.00-2.28 (m, 4H), 2.40-2.60 (m, 1H),
3.00-3.27 (m, 2H), 3.70-3.93 (m, 2H), 4.98-5.25 (m, 2H),
5.52-5.78 (m, 1H); 13C NMR (CDCl3) δ 13.8 (q), 20.9 (t), 24.3
(t), 34.23 (t), 39.2 (d), 41.5 (t), 45.2 (t), 51.3 (t), 61.6 (s), 117.4
(t), 131.9 (d), 173.5 (s), 208.6 (s); MS m/z 221 (M+, 37), 193
(25), 165 (30), 152 (100), 97 (30). Anal. Calcd for C13H19NO2:
C, 70.55; H, 8.65; N, 6.33. Found: C, 70.49; H, 8.72; N, 6.29.
(-)-33a : [R]22 ) -33 (c 3.5, ethanol). (+)-33a : [R]22 ) +34
D
D
(c 3.5, ethanol). (()-33b: Rf 0.35 (PE/AcOEt 70/30); IR 1700,
1675, 1495, 1455 cm-1 1H NMR (CDCl3) δ 0.99 (d, J ) 7.0
;
2-Allyl-4-m eth yl-7-(3-oxobu tyl)-2-a za sp ir o[4.5]d eca n e-
1,6-d ion e (21): yellow oil; yield 67%; Rf 0.22 (PE/AcOEt 70/
Hz, 3H), 1.63-1.79 (m, 3H), 1.95-2.14 (m, 2H), 2.17-2.30 (m,
1H), 2.38-2.50 (m, 1H), 2.83 (dd, J ) 9.5 and 7.0 Hz, 1H),
2.96-3.10 (m, 2H), 3.35 (dd, J ) 9.5 and 7.0 Hz, 1H), 3.83-
3.93 (m, 2H), 5.13-5.21 (m, 2H), 5.63-5.87 (m, 1H); 13C NMR
(CDCl3) δ 13.4 (q), 20.6 (t), 26.76 (t), 30.2 (t), 31.5 (d), 40.3 (t),
45.3 (t), 50.4 (t), 61.5 (t), 117.8 (t), 132.0 (d), 172.4 (s), 200.3
(s); MS m/z 221 (M+, 37), 193 (25), 165 (30), 152 (100), 97 (30).
Anal. Calcd for C13H19NO2: C, 70.55; H, 8.65; N, 6.33.
Found: C, 70.50; H, 8.80; N, 6.39.
1
30); IR 1710, 1680, 1640, 1480 cm-1; H NMR (CDCl3) δ 1.05
(d, J ) 7.0 Hz, 3H), 1.50-2.80 (m, 7H), 2.13 (s, 3H), 2.23-
2.41 (m, 3H), 2.52 (t, J ) 7.0 Hz, 2H), 2.90 (dd, J ) 9.5 and
7.5 Hz, 1H), 3.30 (dd, J ) 9.5 and 7.4 Hz, 1H), 3.80-4.00 (m,
2H), 5.15-5.30 (m, 2H), 5.65-5.85 (m, 1H); 13C NMR (CDCl3)
δ 15.8 (q), 20.9 (t), 23.7 (t), 29.7 (q), 30.8 (t), 34.2 (t), 38.6 (d),
40.8 (t), 45.4 (t), 49.2 (d), 51.2 (t), 62.1 (s), 117.8 (t), 132.3 (d),
174.0 (s), 208.7 (s), 209.8 (s); MS m/z 291 (M+, 25), 273 (40),
234 (90), 221 (35), 206 (25), 195 (100), 152 (90), 137 (20), 97
(50), 82 (40). Anal. Calcd for C17H25NO3: C, 70.07; H, 8.64;
N, 4.80. Found: C, 70.12; H, 8.59; N, 4.75.
2,4-Dim eth yl-2-a za sp ir o[4.5]d eca n e-1,6-d ion e (34) (hy-
drolysis of 18a ,b, followed by flash chromatography separa-
tion). 34a : yellow oil; Rf 0.29 (PE/AcOEt 70/30); IR 1700, 1675,
1490 cm-1; 1H NMR (CDCl3) δ 1.15 (d, J ) 7.0 Hz, 3H), 1.62-
1.98 (m, 4H), 2.08-2.33 (m, 4H), 2.50-2.65 (m, 1H), 2.85 (s,
3H), 3.33 (dd, J ) 6.9 and 6.9 Hz, 1H), 3.62 (dd, J ) 6.9 and
1.2 Hz, 1H); 13C NMR (CDCl3) δ 14.0 (q), 21.0 (t), 24.5 (t), 29.8
(q), 34.4 (t), 39.4 (d), 41.7 (t), 54.0 (t), 61.5 (s), 173.9 (s), 209.0
(s); MS m/z 195 (M+, 50), 167 (14), 152 (16), 71 (100). Anal.
Calcd. for C11H17NO2: C, 67.66; H, 8.77; N, 7.17. Found: C,
67.72; H, 8.83; N, 7.27. 34b: Rf 0.55 (PE/AcOEt); IR 1700,
X-r a y Deter m in a tion . X-ray data were collected at 18 °C
on an Enraf-Nonius CAD-4F diffractometer with Mo KR
radiation (graphite monochromator). Computations were
performed by using CRYSTALS adapted to a Micro Vax II.
The structures were solved by direct methods using the
SHELX-86 program and subsequent Fourier maps.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
1, 2, 3 and 7, ORTEP drawings for (-)-26a ′ and (+)-26a ′′, and
details of the data acquisition (17 pages). This material is
contained in libraries on microfiche, immediately follows this
article in the microfilm version of the journal, and can be
ordered from the ACS; see any current masthead page for
ordering information.
1
1675, 1490, 1430, cm-1; H NMR (CDCl3) δ 0.98 (d, J ) 7.0
Hz, 3H), 1.60-1.75 (m, 3H), 1.90-2.30 (m, 4H), 2.35-2.42 (m,
1H), 2.83 (s, 3H), 2.90-3.10 (m, 2H), 3.30 (m, 1H); 13C NMR
(CDCl3) δ 13.6 (q), 20.7 (t), 26.8 (t), 29.6 (d), 29.9 (t), 31.6 (q),
40.4 (t), 53.3 (t), 61.3 (s), 172.8 (s), 208.5 (s); MS m/z 195 (M+,
50), 181 (8), 167 (14), 152 (16), 139 (24), 126 (35), 110 (10), 71
(100). Anal. Calcd. for C11H17NO2: C, 67.66; H, 8.77; N, 7.17.
Found: C, 67.78; H, 8.65; N, 7.11.
J O970257O