[2 + 2] Photocycloadditions and photorearrangements of 2- alkenylcarboxamido-2-cycloalken-1-ones

Article abstract of DOI:10.1016/S0040-4020(00)00366-5

While intermolecular photocycloaddition of alkenes with 2- carboxamidocyclo-2-pent-1-enones was not an efficient process, photolysis of 2-alkenylcarboxamido-2-cycloalken-1-ones led regio- and stereospecifically to a faster [2 + 2] intramolecular reaction and therefore to the corresponding cyclobutanes. However, photorearrangements involving three different intramolecular H-abstraction processes, compete with the observed cycloaddition. To explain the results, we propose that different deactivation pathways are available to the excited state, depending on the conformers present in the starting material. (C) 2000 Elsevier Science Ltd.

Full text of DOI:10.1016/S0040-4020(00)00366-5

TETRAHEDRON
Pergamon
Tetrahedron 56 (2000) 4479±4489
[212] Photocycloadditions and Photorearrangements of
2-Alkenylcarboxamido-2-cycloalken-1-ones
,²
Catherine Meyer, Olivier Piva, and Jean-Pierre Pete
*
*
   Â
Laboratoire des Reactions Selectives et Applications Associe au CNRS, UMR 6519, Universite de Reims,
Champagne-Ardenne, BP 1039, 51687 Reims cedex 2, France
Received 3 September 1999; accepted 26 April 2000
AbstractÐWhile intermolecular photocycloaddition of alkenes with 2-carboxamidocyclo-2-pent-1-enones was not an ef®cient process,
photolysis of 2-alkenylcarboxamido-2-cycloalken-1-ones led regio- and stereospeci®cally to a faster [212] intramolecular reaction and
therefore to the corresponding cyclobutanes. However, photorearrangements involving three different intramolecular H-abstraction
processes, compete with the observed cycloaddition. To explain the results, we propose that different deactivation pathways are available
to the excited state, depending on the conformers present in the starting material. q 2000 Elsevier Science Ltd. All rights reserved.
During recent years, [212] photocycloadditions have been
widely used for the synthesis of polycyclic molecules and
applied to natural product synthesis.1 The mechanism of the
reaction of cyclic enones with alkenes involves addition of
the excited enone triplet to ground-state alkene via 1,4-bi-
radicals. These intermediates can either close to the corre-
sponding cyclobutanes or revert to the starting materials.2
With disymmetric alkenes, complex mixtures of regio- and
stereoisomers may result, while control of the regio-
selectivity could be expected for intramolecular photocyclo-
additions.3
competition between photocycloaddition and intramolec-
ular H-abstraction (Fig. 1).9,10
b-Ketoamides 2 were prepared by dehydrogenation of N,N-
dialkyl-2-oxo-cycloalkanecarboxamides 1 using a mixture of
cupric acetate and lead tetraacetate11 (Scheme 1, Table 1).
This procedure was not successful for the synthesis of
b-ketoamides 7, which possess an unsaturated nitrogen
substituent. The reaction sequence starting from b-ketoester
312,13 is presented in Scheme 2. The unsaturated ketoacid 6
served as common intermediate, while the alkenylamino
group was introduced in the ®nal reaction step. Ketoamides
7 were obtained in satisfactory yields (Table 2). It should be
noted that compounds, differently substituted at nitrogen,
exist as rotameric mixtures around the amide bond.
Recently, we reported intramolecular photocycloadditions
of unsaturated esters of 3-carboxy-2-cyclohexen-1-ones
with high regio and syn/anti stereocontrol.4 Facial selec-
tivity was ®nally achieved when a removable chiral tether
group was placed between the enone and the alkenyl
moiety.5 In continuation in our interest for the study of
stereoselective [212] photocycloadditions, introduction of
functional groups at C-2 appears highly attractive. While
2-alkenyl-,6 2-alkenyloxy-7 and 2-[N-acyl-N-(2-propenyl)-
amino]cyclohex-2-enones8 have been already considered,
little attention has been paid to the photoreactivity of
N-alkyl-N-alkenylamido-2-cycloalken-1-ones. We, there-
fore, carried out a study on conjugated cycloalkenones bear-
ing a carbamido group (general structures 2 and 7) at C-2 in
order to determine the factors affecting selectivity and
We examined ®rst the photocycloaddition of 2a with cyclo-
pentene (70 equiv.) at 366 nm in acetonitrile. After 96 h,
photocycloadduct 8a (14%) and the rearranged compound
9a (20%) were isolated and identi®ed (74% conversion of
2a). Compound 8a was characterized by a molecular ion at
m/zˆ249 in the mass spectrum, as well as by the disappear-
ance of the sp2-C-atoms and the appearance of tertiary
carbons at 40.0, 44.6 and 45.2 ppm, and a quaternary carbon
at 59.0 ppm (cyclobutane) in the 13C NMR spectrum. The
Keywords: photocycloaddition; amides; cyclopentenones; cyclohexenones;
lactams.
* Corresponding authors. Fax: 133-4-72-44-81-36;
e-mail: piva@copssg.univ-lyon1.fr
Present address: Laboratoire de Chimie Organique, Photochimie et
²
Á
Synthese, UMR CNRS 5622, Universite Claude Bernard-Lyon I, 43, Bd
du 11 novembre 1918, 69622, Villeurbanne cedex, France.
Â
Fig. 1.
0040±4020/00/$ - see front matter q 2000 Elsevier Science Ltd. All rights reserved.
PII: S0040-4020(00)00366-5

4480
C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
Scheme 1.
Table 1. Preparation of unsaturated amides 2
usually the major photoreaction products albeit in low
yields. Polar material was not characterised.
1
N
R1
Et
R2
Et
Yield (%)
2
Yield (%)
Cyclohexenones 2d±2f did not give rise to photocyclo-
adducts and only very small amounts of rearranged
compounds 9d, 10e, and 9f were detected.
a
b
c
d
e
f
1
1
1
2
2
2
65
66
29
22
94
94
a
b
c
d
e
f
74
43
38
34
30
24
±(CH2)5±
±(CH2)5±
i-Pr
i-Pr
i-Pr
i-Pr
Next, the photoreactivity of N-alkenyl 2-carboxamido-2-
cyclopenten-1-ones 7 was examined. Irradiation of 7a at
366 nm in acetonitrile gave formation of 11a (41%) and
12a (14%). The structure of 11a was derived from dis-
appearance of one allyl group and of the conjugated double
bond, as well as from the presence of a quaternary carbon at
61 ppm and two tertiary carbons at 31.4 and 50.9 ppm
(cyclobutane). Analogous photocycloadducts arose from
irradiation of 7b±7d (Scheme 4, Table 4).
±(CH2)2±O±(CH2)2±
absence of a ketone group in 9a and 13C NMR signals of two
sp2-C-atoms and a signal at 86.5 ppm, attributed to a tertiary
carbon vicinal to a nitrogen and an oxygen atom, are
indicative of an oxazinone structure.
The photoreactivity of 2b±2e was then examined in the
presence of cyclopentene and the results are summarised
in Scheme 3 and Table 3.
The stereochemistry of compound 11a was determined by
nOe experiments as indicated in Scheme 4. The relative
stereochemistry thus established was accepted for 11b±
11d based on comparable NMR data. Dioxenones 12a and
12b (minor reaction products) resulted from rearrangements
as described for 2. Structures 9 and 12 were established
from relevant NMR spectra (Table 5).
In all enones, cycloaddition was inef®cient and very long
irradiation times, independent of the nature of the solvent
were required. Rearranged compounds 9 and 10 were
Table 2. Preparation of unsaturated ketoamides 7
7
m
R
Yielda (%)
The reaction appeared more ef®cient in toluene.
Cycloadduct 11a was isolated in 71% yield while the use
of acetonitrile delivered the same compound in lower yield.
Interestingly, b-lactam 13c rather than 12c was isolated
from irradiation of 7c (Rˆtert-Bu). Finally, the
ef®ciency of the process was really affected by the
length of the chain; 14f was the sole product isolated
from the irradiation of 7f (nˆ4). A similar adduct 17
a
b
c
d
e
f
1
1
1
2
3
4
Allyl
Me
tert-Bu
Me
Me
61
44
70
64
51
92
Me
a Yield based on consumption of 4.
Scheme 2.

C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
4481
Scheme 3.
Table 3. Irradiation of amides 2 with cyclopentene
Starting material
R1
R2
R3
R4
R5
Irradiation time (h)
Conv. (%)
8a (%)
9 (%)
10 (%)
2a
2b
2c
2d
2e
2f
Et
i-Pr
±(CH2)5±
Et
i-Pr
±(CH2)5±
Et
i-Pr
Et
i-Pr
±(CH2)4±
Et
±
Me
Me
H
Me
H
H
±
96
40
122
240
104
220
74
14
(a)
31
±
±
±
20
±
15
26
±
100
100
100
100
100
2
Et
i-Pr
Me
±
±
12
±
±(CH2)4±
H
8
1
a 8b (20%), which could be detected in the reaction mixture from the H NMR spectra, could not be isolated in a pure form.
and compound 16 were obtained from oxoamide 15 for
which no unsaturated chain were ®xed on the nitrogen atom
(Scheme 5).
tions of a d-hydrogen by the excited carbonyl group is
expected to lead to a biradical intermediate such as Bir1.
Cyclization of the methylene radical site will occur either on
the ketyl site to give 16 or at C-3 of the starting cyclo-
pentenone to produce 17 under its enolized form. The
high yield of the bicyclic alcohol 16 is in agreement with
previous reports on d-H abstraction processes, especially
It appears that intramolecular hydrogen abstraction
followed by cyclisation of the corresponding biradical inter-
mediates give rise to formation of 14, 16 and 17. Abstrac-
Scheme 4.
Table 4. Irradiation of amides 7
Starting compound
N
R
Conversion (%)
11 (%)a
12 (%)a
13 (%)a
14 (%)a
7a
7b
7c
7d
7e
7f
1
1
1
2
3
4
Allyl
Me
tert-Bu
Me
Me
100 85b
100
100
100
100
71 41b
36
50
9 14b
4
±
±
±
12
±
±
±
±
30
±
58
26
46
28
39
±
c
c
Me
100
a Yields of isolated compounds.
b Reaction in acetonitrile.
c Not detected.

4482
C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
Table 5. NMR data of compounds 9 and 12
Product
H2 (ppm)
C2 ppm)
C4 (ppm)
C5 (ppm)
C6 (ppm)
9a
9b
9c
9d
12a
12b
5.39, q, Jˆ6.0 Hz
±
5.08, dd, Jˆ9.5, 4.2 Hz
5.26, q, Jˆ6.0 Hz
5.58, d, Jˆ6.1 Hz
5.52, d, Jˆ6.5 Hz
86.5
95.0
88.1
83.8
88.9
91.1
167.4
164.6
168.6
163.8
165.3
165.1
109.2
108.5
108.7
107.1
108.4
108.3
162.6
162.8
165.4
160.8
153.2
158.4
Scheme 5.
important for ortho alkoxy acetophenones,14 b-alkoxy-15
and b-alkylamino-ketones.16 However, another pathway
has to be considered to explain the formation of 14 and
the surprising hydrogen abstraction from the N-methyl
group even in the presence of N-allyl substituents as in
7b, 7d. A direct b-H abstraction from the methyl group
by C-2 of the excited enone and cyclization of Bir2 might
also produce 14. In order to test which of (a) or (b) pathway
was really followed by the excited enone in the formation of
14, we carried out the reaction in CH3OD (Scheme 6). If an
enol intermediate was involved as in path (b), incorporation
of a deuterium atom would be expected. When 7b was
irradiated in CH3OD, until complete disappearance of the
starting material, the crude reaction mixture was next
examined in 13C NMR, without any puri®cation. No incor-
poration of deuterium could be detected in 14. Although the
hydrogen atom situated between the keto- and amido-
groups is expected to be very acidic, no exchange of this
proton of 15 could be detected, in the conditions used for the
NMR analysis.
competition between addition and rearrangement
processes might be steered by the conformational
equilibrium. Cycloadduct 11 and rearranged products
12±14 are expected to result from conformers A±C
respectively, as indicated in Scheme 7.
In order to know if the product distribution during the irra-
diation of 7b was determined by the relative stability of the
These results seem to exclude an enolic intermediate in the
process. The preference for an hydrogen abstraction from
the N-methyl rather than from the N-allyl group was unex-
pected but might indicate that an electron transfer precedes
hydrogen migration, with formation of a radical cation as
intermediate. An important increase of acidity is expected
for the C±H bonds close to nitrogen radical cations, and
migration of the less hindered methyl hydrogen atom
would be prefered.17
Depending on the nature of the substituents present on the
nitrogen atom, several rearranged products involving
various intramolecular hydrogen abstraction processes
were observed. The competition between d-H abstraction
by the excited carbonyl, g-H abstraction by the b-carbon
and b-H abstraction by the a-carbon of the excited enone, is
possible if various conformers of the starting enone are
simultaneously present in the excited state. The population
of conformers depends on the relative size and the
nature of the substituents on the nitrogen and the
Scheme 6.

C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
4483
Scheme 7.
1
products, the relative energy of 11b, 12b and 14b was
computed.18 The intramolecular [212] photocycloadduct
11b was found to be more stable than 12b and 14b. PM3
calculations were also performed to verify if the conformers
A±E were available from 7b. They indicate that confor-
mation E, having the two carbonyl groups in a coplanar
and head-to-head arrangement, is highly energetic and
avoided. All possible conformers appeared to be non planar
and very low energy differences were calculated for confor-
mers A±C. The great proximity between the N-methyl
chloride over calcium hydride. H and 13C NMR spectra
were recorded on a Bruker AC 250 spectrometer in chloro-
form, using tetramethylsilane as internal standard. Chemical
shifts are expressed in ppm. IR spectra were recorded on a
IR Mirdac spectrometer. Elemental analyses were
performed on a CHN 2400 Perkin±Elmer apparatus.
Mass spectra were recorded at the Faculty of Pharmacy,
University of Reims on a JEOL D300 spectrometer at
70 eV.
Ê
hydrogens and C-2 in conformer C (2.5 A) favours a b-H
abstraction by the a-carbon of the excited enone. The
Preparation of amides 1
Ê
distance (2.9 A) of allylic hydrogens and C-3 in conformer
A makes possible a g-H abstraction by C-3.19 Cyclization of
the delocalized biradical can produce either the dioxenones
or the b-lactam compound.
General procedure: To a solution of methyl 2-oxocyclo-
pentane carboxylate (2.00 g, 14.1 mmol) or ethyl 2-oxo-
cyclohexane carboxylate (2.40 g, 14.1 mmol) in toluene
(30 ml) were added DMAP (0.516 mg, 4.2 mmol) and the
amine (28.2 mmol). The mixture was heated to re¯ux for
50±84 h. After removal of toluene by distillation under
atmospheric pressure, oxoamides 1 were puri®ed by
¯ash-chromatography on silica (EtOAc/Petroleum ether:
40/60).
In conclusion, we have reported that irradiation of unsatu-
rated oxoamides afforded the expected [212] photoadducts
but also the formation of isomers which resulted from
competitive H-abstraction leading to spiranic b-lactams,
oxazinones and/or azadiquinane derivatives.
N,N-Diethyl-2-oxocyclopentanecarboxamide: 1a20 65%.
1H NMR: 1.08 (3H, t, Jˆ7.2 Hz), 1.15 (3H, t, Jˆ7.2 Hz),
1.72±1.89 (1H, m), 2.07±2.35 (4H, m), 2.38±2.50 (1H, m),
3.17±3.64 (5H, m). 13C NMR: 12.9 (CH3), 14.4 (CH3), 21.0
(CH2), 27.6 (CH2), 38.4 (CH2), 40.4 (CH2), 42.1 (CH2), 51.5
(CH), 168.1 (CvO), 214.6 (CvO). MS: 184 (M1z11, 14),
183 (M1z, 26), 128 (56), 72 (85), 58 (100). IR: 2970, 1745,
Experimental
General
Solvents were distilled according to standard procedures
before use under an argon atmosphere: THF, toluene and
diethylether over sodium/benzophenone, methylene
1635, 1450, 1100 cm21
.

4484
C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
Piperidyl-2-oxocyclopentanecarboxamide: 1b21 66%. H
NMR: 1.43±1.59 (6H, m), 1.74±1.85 (1H, m), 2.01±2.02
(4H, m), 2.31±2.46 (1H, m), 3.30±3.61 (5H, m). 13C NMR:
20.7 (CH2), 24.3 (CH2), 25.3 (CH2), 26.3 (CH2), 27.2 (CH2),
38.2 (CH2), 42.9 (CH2), 47.0 (CH2), 51.3 (CH), 166.5
(CvO), 214.1 (CvO). MS: 196 (M1z11, 48), 195 (M1,
20), 140 (38), 84 (100). IR: 2950, 2860, 1745, 1630, 1440,
1255, 1130, 1015 cm21. Elemental analysis: Calcd for
C11H17NO2: C 67.66, H 8.78, N 7.17. Found: C 67.37, H
9.11, N 6.98.
2 mmol) was added. The reaction mixture was stirred over-
night at rt. After ®ltration on ¯orisil and concentration under
vacuo, the unsaturated amides 2 were puri®ed by ¯ash-
chromatography on silica (EtOAc/petroleum ether: 80/20).
1
N,N-Diethyl-2-oxocyclopent-2-enecarboxamide: 2a 74%.
1H NMR: 1.02 (3H, t, Jˆ7.2 Hz), 1.08 (3H, t, Jˆ7.2 Hz),
2.36±2.40 (2H, m), 2.61±2.66 (2H, m), 3.08 (2H, q, Jˆ
7.2 Hz), 3.36 (2H, q, Jˆ7.2 Hz), 7.66 (1H, t, Jˆ2.8 Hz). 13C
NMR: 12.6 (CH3), 14.0 (CH3), 27.0 (CH2), 34.2 (CH2), 38.7
(CH2), 42.6 (CH2), 143.6 (CIV), 161.9 (CH), 164.1 (CvO),
204.6 (CvO). MS: 182 (M1z11, 17), 181 (M1z, 12), 109 (44),
N,N-Diisopropyl-2-oxocyclopentanecarboxamide: 1c 29%.
1H NMR: 1.15 (3H, t, Jˆ6.7 Hz), 1.26 (3H, d, Jˆ6.7 Hz),
1.32 (6H, d, Jˆ6.7 Hz), 1.73±2.28 (5H, m), 2.35±2.50 (1H,
m), 3.35 (1H, t, Jˆ8.4 Hz), 3.49 (1H, hept, Jˆ6.7 Hz), 4.10
(1H, hept, Jˆ6.7 Hz). 13C NMR: 14.0 (CH3), 20.3 (CH3),
21.0 (2CH3), 21.1 (CH2), 27.6 (CH2), 38.5 (CH2), 45.9 (CH),
48.8 (CH), 53.0 (CH), 167.5 (CvO), 214.6 (CvO). MS:
212 (M1z11, 48), 211 (M1z, 4), 100 (26), 86 (100). IR: 2970,
1745, 1630, 1440, 1340, 1210, 1140, 1040 cm21. Elemental
analysis: Calcd for C12H21NO2: C 68.21, H 10.02, N 6.63.
Found: C 68.45, H 10.42, N 6.83.
72 (100). IR: 3485, 2975, 1620, 1440, 1285, 1035 cm21
.
Piperidyl-2-oxocyclopent-2-enecarboxamide: 2b 43%. 1H
NMR: 1.46±1.55 (6H, m), 2.38±2.42 (2H, m), 2.63±2.68
(2H, m), 3.14 (2H, t, Jˆ5.2 Hz), 3.54 (2H, t, Jˆ5.2 Hz),
7.74 (1H, t, Jˆ2.7 Hz). 13C NMR: 24.1 (CH2), 25.2 (CH2),
26.2 (CH2), 27.1 (CH2), 34.3 (CH2), 42.4 (CH2), 47.9 (CH2),
143.3 (CIV), 160.7 (CH), 163.3 (CvO), 204.5 (CvO). MS:
194 (M1z11, 3), 193 (M1z, 12), 84 (100). IR: 2945, 1710,
1630, 1445, 1235, 1210, 1030 cm21
.
N,N-Diisopropyl-2-oxocyclohexanecarboxamide: 1d 22%.
1H NMR (d6-DMSO): 1.12 (3H, d, Jˆ6.7 Hz), 1.13 (3H, d,
Jˆ6.7 Hz), 1.34 (3H, d, Jˆ6.7 Hz), 1.39 (3H, d, Jˆ6.7 Hz),
1.50±2.37 (7H, m), 2.46±2.50 (1H, m), 3.34±3.44 (2H, m),
3.72 (1H, hept, Jˆ6.7 Hz). 13C NMR: 20.4 (CH3), 20.6
(CH3), 20.7 (CH3), 21.0 (CH3), 23.5 (CH2), 27.2 (CH2),
30.6 (CH2), 41.9 (CH2), 45.9 (CH), 48.7 (CH), 55.7 (CH),
168.1 (CvO), 207.9 (CvO). MS: 226 (M1z11, 4), 225
(M1z, 31), 182 (67), 100 (100), 86 (100), 58 (90). IR:
2960, 2875, 1705, 1630, 1450, 1350, 1320, 1210,
1050 cm21. Elemental analysis: Calcd for C13H23NO2: C
69.30, H 10.29, N 6.22. Found: C 69.25, H 10.55, N 6.10.
N,N-Diisopropyl-2-oxocyclopent-2-enecarboxamide: 2c
1
38%. H NMR: 1.10 (6H, d, Jˆ6.8 Hz), 1.41 (6H, d, Jˆ
6.8 Hz), 2.41 (2H, m), 2.66 (2H, m), 3.40 (1H, hept, Jˆ
6.8 Hz), 3.57 (1H, hept, Jˆ6.8 Hz), 7.63 (1H, t, Jˆ
2.7 Hz). 13C NMR: 20.2 (CH3), 20.2 (CH3), 20.6 (CH3),
20.6 (CH3), 27.0 (CH2), 34.2 (CH2), 45.7 (CH), 51.0 (CH),
145.1 (CIV), 160.8 (CH), 164.1 (CvO), 204.9(CvO). MS:
210 (M1z11, 9), 209 (M1z, 10), 166 (62), 109 (100), 100
(89), 86 (100). IR: 1710, 1620, 1450, 1050 cm21
.
N,N-Diisopropyl-2-oxocyclohex-2-enecarboxamide: 2d
1
34%. H NMR: 1.13 (6H, d, Jˆ6.8 Hz), 1.45 (6H, d, Jˆ
6.8 Hz), 2.00±2.10 (2H, m), 2.39±2.50 (4H, m), 3.42 (1H,
hept, Jˆ6.8 Hz), 3.62 (1H, hept, Jˆ6.8 Hz), 6.93 (1H, t,
Jˆ4.2 Hz). 13C NMR: 20.4 (CH3), 20.5 (CH3), 22.4 (CH2),
25.4 (CH2), 38.0 (CH2), 45.6 (CH), 51.0 (CH), 140.5 (CIV),
146.2 (CH), 166.7 (CvO), 195.7 (CvO). MS: 224 (M1z11,
4), 223 (M1z, 6), 123 (100), 100 (58). HMRS: Calcd for
C13H21NO2: 223.1567. Found: 223.1572. IR: 3690, 3610,
2975, 1670, 1445, 1370, 1215, 1020 cm21. UV(CH2Cl2)
1227ˆ5000, 1252ˆ2300, 1366ˆ27. Elemental analysis:
Calcd for C13H21NO2: C 69.92, H 9.48, N 6.27. Found: C
69.19, H 8.10, N 5.81.
Piperidyl-2-oxocyclohexanecarboxamide: 1e22 94%.
1H-NMR: 1.34±2.32 (13H, m), 2.40±2.59 (1H, m), 3.15±
3.19 (2H, m), 3.41±3.57 (3H, m). 13C NMR: 23.3 (CH2),
24.2 (CH2), 25.3 (CH2), 26.0 (CH2), 26.9 (CH2), 30.2 (CH2),
41.6 (CH2), 42.6 (CH2), 46.6 (CH2), 53.9 (CH), 167.5
(CvO), 207.3 (CvO). MS: 210 (M1z11, 8), 209 (M1z,
5), 140 (22), 84 (100). IR: 3390, 2945, 2860, 1705, 1640,
1445, 1345, 1190 cm21. Elemental analysis: Calcd for
C12H19NO2: C 68.87, H 9.15, N 6.69. Found: C 69.08, H
9.35, N 6.74.
1
1
Piperidyl-2-oxocyclohex-2-enecarboxamide: 2e 30%. H
Morpholyl-2-oxocyclohexanecarboxamide: 1f23 94%. H
NMR: 1.64±1.87 (2H, m), 1.95±2.39 (5H, m), 2.48±2.58
(1H, m), 3.29±3.33 (2H, m), 3.43±3.69 (6H, m), 3.77±3.85
(1H, m). 13C NMR: 23.5 (CH2), 26.9 (CH2), 25.3 (CH2),
30.0 (CH2), 41.8 (CH2), 42.1 (CH2), 46.1 (CH2), 53.1
(CH), 66.4 (CH2), 167.9 (CvO), 207.1 (CvO). MS: 212
(M1z11, 10), 211 (M1z, 5), 86 (100). IR: 3390, 2970, 2940,
1705, 1630, 1450, 1430, 1110 cm21. Elemental analysis:
Calcd for C11H17NO3: C 62.54, H 8.11, N 6.63. Found: C
62.39, H 8.33, N 6.59.
NMR: 1.46±1.60 (6H, m), 1.89±2.05 (2H, m), 2.36±2.46
(4H, m), 3.52±3.57 (2H, m), 7.00 (1H, t, Jˆ4.0 Hz). 13C
NMR: 22.2 (CH2), 24.2 (CH2), 25.2 (CH2), 25.4 (CH2), 26.0
(CH2), 37.8 (CH2), 42.3 (CH2), 48.0 (CH2), 138.6 (CIV),
148.5 (CH), 165.6 (CvO), 195.3 (CvO). MS: 208
(M1z11, 32), 207 (M1z, 28), 179 (16), 84 (100). HMRS:
Calcd for C12H17NO2: 207.1255. Found: 207.1259. IR:
3690, 3020, 2945, 1680, 1470, 1445, 1210 cm21
.
UV(CH2Cl2) 1228ˆ5100, 1305ˆ2500, 1366ˆ27.
Morpholyl-2-oxocyclohex-2-enecarboxamide: 2f 24%. 1H
NMR: 2.01±2.09 (4H, m), 2.44±2.50 (4H, m), 3.21 (2H, t,
Jˆ4.8 Hz), 3.61 (2H, t, Jˆ4.8 Hz), 3.65±3.69 (2H, m), 7.12
(1H, t, Jˆ4.0 Hz). 13C NMR: 22.2 (CH2), 25.6 (CH2), 37.8
(CH2), 42.0 (CH2), 47.3 (CH2), 66.6 (2CH2), 138.0 (CIV),
Preparation of unsaturated amides 2
General procedure: To a solution of amide 1 (2 mmol) in
benzene (23 ml) was added cupric acetate (0.182 g,
1 mmol). After 30 min at rt, lead tetraacetate (0.886 g,

C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
4485
150.2 (CH), 165.8 (CvO), 195.3 (CvO). MS: 210 (M1z11,
37), 209 (M1z, 84), 181 (49), 123 (100). HMRS: Calcd for
C11H15NO3: 209.1048. Found: 209.1052.
concentrated. Amides 7 were puri®ed by ¯ash chroma-
tography on silica. (EtOAc/hexane: 50/50).
N,N-Bisallyl-(3,3-dimethyl-5-oxo-1-cyclopentene)-carb-
oxamide: 7a Obtained as an oil in 61%. 1H NMR: 1.20 (6H,
s), 2.31 (2H, s), 3.77 (2H, d, Jˆ5.6 Hz), 4.06 (2H, d,
Jˆ5.6 Hz), 5.09±5.26 (4H, m), 5.66 (2H, m), 7.50 (1H, s).
13C NMR: 27.5 (2CH3), 39.8 (C), 46.6 (CH2), 50.0 (CH2),
50.2 (CH2), 117.4 (CH2), 117.5 (CH2), 132.2 (CH), 133.2
(CH), 139.8 (CIV), 164.5 (OCN), 170.8 (CH), 203.9 (CvO).
IR: 2960, 1715, 1645, 1625, 1415, 1305 cm21. MS m/z: 234
(70, M1z11), 233 (M1z, 85), 192 (82), 137 (87), 96 (83), 69
(100). HRMS: Calcd for C14H19NO2: 233.1411. Found:
233.1416. UV (CH2Cl2): 1229ˆ5800, 1366ˆ10.
Preparation of amides 7
4,4-Dimethyl-2-methoxycarbonyl-2-phenylselanylcyclo-
pentan-1-one: 4 To a solution of 4,4-dimethyl-2-methoxy-
carbonyl-cyclopentan-1-one 324 (4.05 g, 23.8 mmol) in
methylene chloride (15 ml) was added at 08C, pyridine
(2.3 ml, 28.6 mmol). After 5 min, a solution of phenyl-
selenyl bromide (6.74 g, 28.6 mmol) in methylene chloride
(5 ml) was added dropwise. After complete transformation
(TLC), the reaction mixture was quenched with a saturated
aqueous solution of ammonium chloride (10 ml) and
extracted twice with ethyl acetate (20 ml). The organic
layer was washed with water and dried over MgSO4. After
concentration, the product was puri®ed by ¯ash-chroma-
tography on silica (EtOAc/hexane: 10/90) giving 4 as an
N-Allyl-N-methyl-(3,3-dimethyl-5-oxo-cyclopentene)-
carboxamide: 7b Obtained as an oil in 44% (2 rotamers)
50/50 at RT. 1H NMR: Rotamer 1: 1.27 (6H, s), 2.38 (2H, s),
2.85 (3H, s), 3.77 (2H, dt, Jˆ5.7, 1.5 Hz), 5.13±5.32 (2H,
m), 5.68±5.88 (1H, m), 7.50 (1H, s). Rotamer 2: 1.30 (6H,
s), 2.39 (2H, s), 2.98 (3H, s), 4.08 (2H, dt, Jˆ6.1, 1.5 Hz),
5.13±5.32 (2H, m), 5.68±5.88 (1H, m), 7.58 (1H, s). 13C
NMR: Rotamer 1: 27.3 (2CH3), 32.1 (CH3), 39.6 (C), 49.1
(CH2), 49.9 (CH2), 117.2 (CH2), 131.8 (CH), 139.4 (C),
164.0 (NCO), 170.7 (CH), 203.6 (CvO). Rotamer 2: 27.3
(2CH3), 35.3 (CH3), 39.6 (C), 49.8 (CH2), 52.9 (CH2), 117.4
(CH2), 132.7 (CH), 139.9 (C), 164.4 (NCO), 171.6 (CH),
203.9 (CvO). IR: 2960, 2930, 1710, 1625, 1485, 1465,
1400, 1305 cm21. MS m/z: 208 (100, M1z11), 207 (M1.,
45), 192 (7), 137 (23), 110 (15), 70 (100). HRMS: Calcd for
C12H19NO2: 207.1255. Found: 207.1259. UV (CH2Cl2):
1230ˆ6300, 1327ˆ300, 1366ˆ80.
1
oil (5.54 g). 72%. H NMR: 1.00 (3H, s); 1.12 (3H, s);
2.03 (1HAB, JABˆ14.5 Hz); 2.20 (2H, s); 3.68 (3H, s); 2.61
(1HAB, Jˆ14.5 Hz); 7.30±7.47 (3H, m); 7.60±7.68 (2H, m).
13C NMR: 28.6 (CH3); 29.2 (CH3); 33.9 (C); 47.6 (CH2);
52.1 (CH2); 52.8 (OCH3); 56.8 (C); 127.0 (C); 128.7 (CH);
129.5 (CH); 137.4 (C); 170.0 (CO2); 208.8 (CvO). MS: 326
(M111, 100); 211(47); 183 (62); 157 (100); 137 (43); 83
(72), 77 (90). IR: 2955; 1720; 1440; 1250 cm21
.
3,3-Dimethyl-5-oxo-1-cyclopentene-1-carboxylic
acid
methyl ester: 5 To a solution of 4 (5.54 g, 17.0 mmol) in
methylene chloride (10 ml) was added (by small amounts)
at 08C, m-CPBA (6.76 g, 3.2 mmol). After 3 h, water (4 ml)
was added and the mixture was extracted with methylene
chloride. The organic layers were washed with brine and
dried over MgSO4. Removal of the solvent gave 5, which
N-Allyl-N-t-butyl-(3,3-dimethyl-5-oxo-cyclopentene)-carb-
oxamide: 7c Obtained in 70% from 6 as a mixture of 2
rotamers (4/96). H NMR: Rotamer 1: 1.22 (6H, s), 1.49
1
1
was used without puri®cation. H NMR: 1.28 (6H, s); 2.43
(9H, s), 2.32 (2H, s), 3.84±3.87 (2H, m), 5.09±5.17 (2H,
m), 5.76 (1H, ddt, Jˆ16.8, 10.7, 4.9 Hz), 7.33 (1H, s). Rota-
mer 2: 1.22 (6H, s), 1.49 (9H, s), 2.32 (2H, s), 3.84±3.87
(2H, m), 5.09±5.17 (2H, m), 5.76 (1H, ddt, Jˆ16.8±10.7±
4.9 Hz), 7.47 (1H, s). 13C NMR: 27.6 (2CH3), 28.5 (CH3),
39.6 (C), 48.5 (CH2), 50.0 (CH2), 57.7 (C), 115.9 (CH2),
136.5 (CH), 142.0 (C), 165.9 (NCO), 168.2 (CH), 204.5
(CvO). IR: 2965, 2930, 1870, 1720, 1640, 1610,
(2H, s); 3.83 (3H, s); 8.14 (1H, s). 13C NMR: 27.4 (2CH3);
39.0 (C); 51.2 (CH2); 52.0 (OCH3); 162.4 (CIV); 170.4
(CO2); 180.3 (CH); 202.6 (CvO).
3,3-Dimethyl-5-oxo-1-cyclopentene carboxylic acid: 6
Methyl ester 5 (3.06 g, 17 mmol) was added to an aqueous
0.5 M NaOH solution (110 ml) and the mixture was stirred
overnight at rt. After extraction with methylene chloride and
acidi®cation to pH 2, the acid was extracted with methylene
chloride. The organic layers were dried over MgSO4,
®ltered and concentrated under vacuo. Acid 6 (2.01 g) was
1450, 1395, 1375, 1365, 1295, 1225, 1200, 925 cm21
.
MS m/z: 250 (4, M1z11), 249 (17, M1z), 234 (11), 192
(42), 137 (100), 69 (79). HRMS: Calcd for C15H23NO2:
249.1723. Found: 249.1729. Elemental analysis: Calcd
for C15H23NO2: C, 72.25, H, 9.30, N, 5.62. Found: C,
71.71, H, 9.40, N, 5.76. UV (CH2Cl2): 1270ˆ370, 1366ˆ9.
1
used without further puri®cation. H NMR: 1.34 (6H, s);
2.57 (2H, s); 8.41 (1H, s). 13C NMR: 27.0 (2CH3); 40.0
(C); 50.3 (CH2); 161.9(CIV); 170.0 (CO2H); 183.5 (CH);
208.5 (CvO).
N-But-3-enyl-N-methyl-(3,3-dimethyl-5-oxo-cyclopentene)-
carboxamide: 7d Obtained in 64% as an oil (mixture of 2
rotamers). H NMR: Rotamer 1: 1.27 (6H, s), 2.23±2.39
1
Synthesis of N-alkenyl-N-alkyl-oxocarboxamides 7
(2H, s), 2.36 (2H, s), 2.87 (3H, s), 3.22 (2H, t, Jˆ7.2 Hz),
5.01±5.04 (2H, m), 5.64 (1H, ddt, Jˆ17.2, 10.3 and 6.9 Hz),
7.48 (1H, s). Rotamer 2: 1.27 (6H, s), 2.23±2.39 (2H, m),
2.36 (2H, s), 2.99 (3H, s), 3.51 (2H, t, Jˆ7.2 Hz), 5.01±5.14
(2H, m), 5.82 (1H, ddt, Jˆ17.0, 10.1 and 6.9 Hz), 7.51 (1H,
s). 13C NMR: Rotamer 1: 27.1 (2CH3), 30.9 (CH2), 31.9
(CH3), 39.3 (CIV), 46.0 (CH2), 49.5 (CH2), 116.1 (CH2),
133.6 (CH), 139.5 (CIV), 163.5 (CvO), 170.5 (CH), 203.2
(CvO). Rotamer 2: 27.1 (2CH3), 32.1 (CH2), 35.7 (CH3),
General procedure: To a solution of 6 (2.75 g, 17.8 mmol)
in methylene chloride (13 ml) were added DMAP (0.110 g,
0.9 mmol) and the amine (19.6 mmol). After cooling to 08C,
dicyclohexylcarbodiimide (3.86 g, 18.7 mmol) dissolved in
the same solvent was added dropwise. After 10 min, the
cooling bath was removed, the solution was allowed to
warm up to rt and was stirred overnight. After ®ltration
and washing of the urea with DCM, the solution was

4486
C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
39.3 (CIV), 46.0 (CH2), 49.5 (CH2), 116.8 (CH2), 134.5
(CH), 139.8 (CIV), 164.0 (CvO), 170.8 (CH), 203.5
(CvO). IR: 2960, 2930, 1710, 1625, 1485, 1435, 1405,
1305 cm21. MS m/z: 222 (M1z11, 24), 221(M1z, 23), 180
(15), 137 (33), 83 (100), 69 (38). HRMS: Calcd for
C13H19NO2: 221.1411. Found: 221.1416. UV (CH2Cl2):
1229ˆ5700, 1366ˆ7.
cyclopentene (1.5 ml, 16 mmol) in acetonitrile (15 ml) was
deoxygenated under argon during 15 min and irradiated at
366 nm until consumption of the starting material. After
concentration, the crude mixture was puri®ed by preparative
TLC (EtOAc/hexane: 80/20).
1-(N,N-Diethyl)-10-oxotricyclo[5.3.0.02.6]decanecarbox-
amide: 8a Viscous oil, 14%. 1H NMR: 1.15 (3H, t,
Jˆ6.8 Hz), 1.26 (3H, t, Jˆ6.8 Hz), 1.38±1.87 (6H, m),
1.90±1.96 (1H, m), 2.10±2.26 (1H, m), 2.46±2.58 (1H,
m), 2.52 and 2.85 (AB, JABˆ6.5 Hz, 2H), 2.75±2.91 (1H,
N-Methyl-N-pent-4-enyl-(3,3-dimethyl-5-oxo-cyclopen-
tene)-carboxamide: 7e Obtained in 51% as an oil (mixture
of 2 rotamers). 1H NMR: Rotamer 1: 1.28 (6H, s), 1.58±1.75
(2H, m), 1.94±2.02 (2H, m), 2.37 (2H, s), 2.88 (3H, s), 3.15
(2H, t, Jˆ7.6 Hz), 4.96±5.08 (2H, m), 5.72 (1H, ddt,
Jˆ16.8, 10.3, 6.9 Hz), 7.47 (1H, s). Rotamer 2: 1.28 (6H,
s), 1.58±1.75 (2H, m), 2.07±2.15 (2H, m), 2.37 (2H, s), 2.99
(3H, s), 3.45 (2H, t, Jˆ7.4 Hz), 4.96±5.08 (2H, m), 5.84
(1H, ddt, Jˆ16.8, 10.3, 6.5 Hz), 7.54 (1H, s). 13C NMR:
Rotamer 1: 26.1 (CH2), 27.7 (2CH3), 30.5 (CH2), 32.4
(CH3), 39.9 (C), 46.7 (CH2), 50.1 (CH2), 114.9 (CH2),
137.1 (CH), 140.2 (CIV), 164.5 (CvO), 170.9 (CH), 204.0
(CvO). Rotamer 2: 27.3 (CH2), 27.7 (2CH3), 30.7 (CH2),
36.1 (CH3), 39.9 (C), 50.1 (CH2), 50.2 (CH2), 115.6 (CH2),
137.8 (CH), 140.3 (CIV), 164.5 (CvO), 171.7 (CH), 204.2
(CvO). IR: 2960, 2920, 2860, 1720, 1645, 1455, 1405,
1395, 1305 cm21. MS m/z: 236 (7, M1z11), 235(10, M1.),
220 (14, M1z±CH3), 166 (16), 151 (15), 137 (100), 98 (74),
69 (94). HRMS: Calcd for C14H21NO2: 235.1567. Found:
235.1572. UV (CH2Cl2): 1270ˆ150, 1366ˆ12.
m), 3.11 (1H, t, Jˆ6.1 Hz), 3.33 and 3.66 (AB, JAB
ˆ
11.2 Hz, 1H, q, Jˆ6.8 Hz and 1H, q, Jˆ6.8 Hz), 3.34 and
3.67 (AB, JABˆ15.4 Hz, 1H, q, Jˆ6.8 Hz and 1H, q,
Jˆ6.8 Hz). 13C NMR: 12.5 (CH3), 13.9 (CH3), 24.9 (CH2),
25.7 (CH2), 29.3 (CH2), 32.6 (CH2), 37.8 (CH2), 38.8 (CH2),
40.0 (CH), 42.2 (CH2), 44.6 (CH), 45.2 (CH), 59.0 (C),
166.9 (C), 217.2 (C). MS m/z: 250 (9, M1z11), 249(4,
M1z), 182 (100), 149 (18), 108 (32), 72 (93). HRMS:
Calcd for C15H23NO2: 249.1723. Found: 249.1729.
1-Piperidinyl-10-oxotricyclo[5.3.0.02.6]decanecarboxamide:
8c 31%. 13C NMR: 24.4 (CH2), 25.0 (CH2), 25.6 (CH2), 25.7
(CH2), 26.2 (CH2), 29.4 (CH2), 32.4 (CH2), 37.6 (CH2), 39.9
(CH), 43.2 (CH2), 44.7 (CH), 45.1 (CH), 47.5 (CH2), 59.0
(C), 166.1 (NCO), 217.2 (CvO). MS m/z: 262 (M1z11, 3),
261 (M1z, 11), 194 (100), 149 (13), 109 (28).
3-Ethyl-4-methyl-2-oxo-5-oxa-3-azabicyclo[3.4]non-1-ene:
1
N-Hex-5-enyl-N-methyl-(3,3-dimethyl-5-oxo-cyclopen-
tene)-carboxamide: 7f Obtained as an oil in 92%. 1H NMR:
Rotamer 1: 1.28 (6H, s), 1.42±1.62 (4H, m), 2.37 (2H, s),
2.86 (3H, s), 3.14 (2H, t, Jˆ7.4 Hz), 4.95±5.06 (2H, m),
5.67±5.89 (1H, m), 7.48 (1H, s). Rotamer 2: 1.28 (6H, s),
1.42±1.62 (4H, m), 2.38 (2H, s), 2.99 (3H, s), 3.45 (2H, t,
Jˆ7.2 Hz), 4.95±5.06 (2H, m), 5.67±5.89 (1H, m), 7.54
(1H, s). 13C NMR: Rotamer 1: 25.6 (CH2), 27.6 (2CH3),
32.3 (CH3), 33.0 (CH2), 39.7 (C), 46.8 (CH2), 50.0 (CH2),
50.4 (CH2), 114.5 (CH2), 137.7 (CH), 140.2 (C), 164.3
(NCO), 170.8 (CH), 203.8 (CvO). Rotamer 2: 26.1
(CH2), 27.6 (2CH3), 33.2 (CH2), 35.9 (CH3), 39.7 (C),
46.8 (CH2), 50.1 (CH2), 50.4 (CH2), 114.9 (CH2), 138.3
(CH), 140.5 (C), 164.3 (NCO), 171.4 (CH), 204.0 (CvO).
IR: 2935, 1720, 1645, 1455, 1405, 1305 cm21 MS m/z: 250
(13, M1z11), 249(18, M1z), 234 (20), 166 (20), 137 (100),
112 (63), 69 (79). HRMS: Calcd for C15H23NO2: 249.1723.
Found: 249.1729. UV (CH2Cl2): 1270ˆ180, 1366ˆ5.
9a 20%. H NMR: 1.14 (3H, t, Jˆ7.1 Hz), 1.58 (3H, d,
Jˆ5.8 Hz), 1.89±2.03 (2H, m), 2.43±2.59 (4H, m), 3.19
and 3.68 (AB, JABˆ13.9 Hz, 1H, q, Jˆ7.1 Hz and 1H, q,
Jˆ7.1 Hz), 5.39 (1H, q, Jˆ2.8 Hz). 13C NMR: 14.2 (CH3),
18.2 (CH3), 19.8 (CH2), 25.9 (CH2), 31.1 (CH2), 36.7 (CH2),
86.5 (CH), 109.2 (CIV), 162.6 (C±O), 167.4 (NCyO). IR:
1660, 1630, 1430 cm21. MS m/z: 182 (12, M1z11), 181(18,
M1z), 110 (50), 56 (100). HRMS: Calc for C10H15NO2:
181.1099. Found: 181.1103.
2-Oxo-9-oxa-3-azatricyclo[8.3.0.0.3,8]tridec-1-ene: 9c 15%.
1H NMR: 1.10±2.20 (8H, m), 2.40±2.70 (5H, m), 4.20±4.30
(1H, m), 5.08 (1H, dd, Jˆ9.5 and 4.2 Hz). 13C NMR: 19.8
(CH2), 21.3 (CH2), 23.5 (CH2), 26.0 (CH2), 30.8 (CH2), 31.2
(CH2), 88.1 (CH), 108.7 (CIV), 165.4 (C±O), 168.6 (CvO).
IR: 2930, 1660, 1635, 1440, 1430, 1210 cm21
.
3-Ethyl-4-methyl-2-oxo-5-oxa-3-azabicyclo[4.4]dec-1-ene:
9d Oil, 26%. 1H NMR: 1.15 (3H, t, Jˆ7.1 Hz), 1.55 (3H, d,
Jˆ6.0 Hz), 1.61±1.70 (4H, m), 2.11±2.15 (2H, m), 2.26±
2.29 (2H, m), 3.19 (1H, d, JABˆ14.1 Hz), 3.68 (1H, d,
JABˆ14.1 Hz), 5.26 (1H, q, Jˆ6.0 Hz). 13C NMR: 14.0
(CH3), 18.1 (CH3), 21.4 (CH2), 22.0 (CH2), 22.1 (CH2),
27.2 (CH2), 36.9 (CH2), 83.8 (CH), 107.1 (CIV), 160.8 (C±
O), 163.7 (NCvO). IR: 3000, 2935, 1665, 1630, 1480,
1430, 1210 cm21. MS m/z: 196 (M1z11, 23), 195 (M1z,
41), 180 (37), 125 (40), 56 (100).
N-t-Butyl-N-methyl,-(3,3-dimethyl-5-oxo-cyclopentene)-
carboxamide: 15 Obtained in 76% (one rotamer). 1H NMR:
1.27 (9H, s), 1.47 (6H, s), 2.36 (3H, s), 7.52 (1H, s). 13C
NMR: 27.7 (2CH3), 27.9 (3CH3), 33.8 (CH3), 39.5 (C), 49.1
(CH2), 57.0 (C), 142.7 (C), 165.2 (NCO), 171.2 (CH), 203.9
(CO). IR: 2960, 1705, 1625, 1385 cm21. MS m/z: 224 (5,
M1z11), 223 (19, M1z), 208 (51), 168 (13), 137 (100), 110
(10), 69 (88). HRMS: Calcd for C15H23NO2: 249.1723.
Found: 249.1729. Elemental analysis: Calcd for
C13H21NO2: C 69.92, H 9.48, N 6.27. Found: C 69.56, H
9.65, N 6.31. UV (CH2Cl2): 1269ˆ430, 1366ˆ6.
3,3-Dimethyl-2-isopropyl-1,5-dioxo-2-azaspiro[3.4]octane:
10b Oil, 2%. 1H NMR: 1.24±1.46 (12H, m); 1.50±2.45 (6H,
m); 3.49±3.68 (1H, m). 13C NMR: 19.8 (CH2), 21.8 (2CH3);
21.9 (CH3); 25.1 (CH3); 27.8 (CH2); 38.9 (CH2); 44.3
(CH);61.8 (CIV); 71.3 (CIV); 165.8 (CvO); 213.4 (CvO).
Intermolecular photocycloadditions
IR: 1745, 1720, 1215 cm21
.
General procedure: A solution of amides 2 (0.25 mmol) and

C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
4487
3,3-Dimethyl-2-isopropyl-1,5-dioxo-2-azaspiro[3.5]no-
nane: 10e 12%. 1H NMR: 1.32 (3H, d, Jˆ6.9 Hz); 1.34 (3H,
d, Jˆ6.9 Hz); 1.37 (3H, s); 1.45 (3H, s); 1.47±2.24 (7H, m);
2.60±2.70 (1H, m); 3.50 (1H, hept, Jˆ6.9 Hz). 13C NMR:
21.9 (2CH3); 22.3 (CH2); 22.4 (CH3); 23.5 (CH3); 26.5
(CH2); 29.8 (CH2); 42.4 (CH2); 43.8 (CH); 62.6 (C); 71.9
(C); 166.0 (CvO); 207.4 (CvO). IR: 3020, 1745, 1700,
1335, 1220 cm21. MS m/z: 224 (M1z11, 7), 208 (17), 138
(100), 123 (61), 110 (49), 95 (59), 67 (64).
3,10,10-Trimethyl-2.12-dioxo-3-azatricyclo[7.3.0.01.5
]
1
dodecane: 11e 39%. H NMR: 1.07 (3H, s), 1.08 (3H, s),
1.26±1.41 (1H, m), 1.54±1.91 (4H, m), 2.08±2.26 (2H, m),
2.09 (1H, dd, JABˆ16.9 Hz, Jˆ1.2 Hz),), 2.76 (1H, dd,
JABˆ16.9 Hz, Jˆ1.2 Hz), 2.91±3.03 (2H, m), 2.99 (3H, s),
3.81±3.94 (1H, m). 13C NMR: 22.1 (CH3), 22.7 (CH2), 24.2
(CH3), 27.6 (CH2), 29.2 (CH3), 34.6 (CH2), 36.4 (CIV), 36.6
(CH2), 46.5 (CH), 48.1 (CH2), 50.6 (CH), 63.9 (CIV), 169.0
(CvO), 214.0 (CvO). IR: 2935, 1730, 1630, 1455, 1265,
1140 cm21. MS m/z: 236 (M1z11, 6), 235 (M1z, 27), 220
(32), 207 (31), 192 (30), 152 (100). Elemental analysis calcd
for C14H21NO2: C 71.46, H 9.00, N 5.95. Found: C 71.46, H
9.30, N 6.08.
Intramolecular [212] photocycloaddition
A solution of ketoamides 7 (0.84 mmol) in toluene (24 ml)
previously deoxygenated under argon was irradiated at
366 nm until complete consumption of starting material
(16±18 h). The solvent was removed by concentration and
the crude mixture was puri®ed by preparative TLC (EtOAc/
hexane: 60/40).
3-Allyl-8,8-dimethyl-2-oxo-4-vinyl-5-oxa-3-azabicyclo[3,4]-
non-1-ene: 12a Oil, 9%. H NMR: 1.14 (3H, s), 1.15 (3H,
1
s), 2.10±2.45 (4H, m), 3.52 (1H, ddt, JABˆ16.0 Hz, Jˆ6.6
and 1.2 Hz), 4.51±4.52 (1H, ddt, JABˆ16.0 Hz, Jˆ4.7 and
1.7 Hz), 5.14±5.25 (2H, m), 5.31±5.44 (2H, m), 5.58 (1H, d,
Jˆ6.1 Hz), 6.04 (1H, ddd, Jˆ17.5, 9.9 and 6.1 Hz). 13C
NMR: 29.9 (CH3), 30.1 (CH3), 36.6 (CIV), 41.1 (CH2),
44.6 (CH2), 46.2 (CH2), 88.9 (CIV), 108.4 (CIV), 117.3
(CH2), 120.5 (CH2), 131.5 (CH), 133.4 (CH), 153.2 (C-O),
165.3 (CvO). IR: 2955, 2930, 2870, 1670, 1455,
1415 cm21. UV (CH2Cl2): 1229ˆ5500, 1263ˆ2700, 1366ˆ8.
MS m/z: 234 (M1z11, 5), 233 (M1z, 28), 218 (9), 205 (13),
192 (10), 149 (100), 138 (37), 123 (34). HRMS: Calcd for
C14H19NO2: 233.1411. Found: 233.1416.
3-Allyl-8.8-dimethyl-2.10-dioxo-3-azatricyclo[5.3.0.01.5
decane: 11a Solid, 71%. H NMR: 1.07 (3H, s), 1.12 (3H,
s), 2.04 (1H, ddd, JABˆ13.2 Hz, Jˆ4.0 Hz and 9.2 Hz), 2.18
]
1
(1H, dd, JABˆ17.0 Hz, Jˆ1.0 Hz), 2.49 (1H, ddd, JAB
13.2 Hz, Jˆ6.2 Hz and 8.4 Hz), 2.64 (1H, dd, JAB
ˆ
ˆ
17.0 Hz, Jˆ1.0 Hz), 2.69±2.80 (2H, m), 3.32 (1H, dd,
JABˆ10.0 Hz, Jˆ3.8 Hz) 3.65 (1H, dd, JABˆ10.0 Hz,
Jˆ9.8 Hz), 3.84 (1H, ddt, JABˆ15.2 Hz, Jˆ6.2 Hz and
1.3 Hz), 4.02 (1H, ddt, JABˆ15.2 Hz, Jˆ6.0 Hz and
1.3 Hz), 5.18±5.26 (2H, m), 5.76 (1H, ddt, Jˆ17.4 Hz,
9.8 Hz and 6.1 Hz). 13C NMR: 22.4 (CH3), 26.6 (CH2),
28.1 (CH3), 31.4 (CH), 36.9 (CIV), 45.4 (CH2), 50.9 (CH),
51.1 (CH2), 53.2 (CH2), 61.0 (CIV), 171.0 (CvO), 212.8
(CvO). IR: 2960, 1745, 1680, 1445 cm21. MS m/z: 234
(M1z11, 12), 233 (M1z, 60), 164 (100), 137 (20), 69 (73).
Elemental analysis calcd for C14H19NO2: C 72.07, H 8.21, N
6.00. Found: C 72.26, H 8.22, N 6.06.
3,10,10-Trimethyl-2-oxo-4-vinyl-5-oxa-3-azabicyclo[3,4]-
non-1-ene: 12b Oil, 4%. H NMR: 1.14 (3H, s), 1.15 (3H,
1
s), 2.29±2.37 (4H, m), 2.90 (3H, s), 5.38±5.45 (2H, m), 5.52
(1H, d, Jˆ6.4 Hz), 6.04 (1H, ddd, Jˆ16.8, 10.5 and 6.4 Hz).
13C NMR: 29.7 (CH3), 29.9 (CH3), 30.0 (CH3), 36.3 (CIV),
41.1 (CH2), 46.2 (CH2), 91.1 (CH), 108.3 (CIV), 120.7
(CH2), 131.4 (CH), 158.4 (C±O), 165.1 (CIV). IR: 2955,
2935, 1740, 1670, 1470, 1445, 1410 cm21. MS m/z: 208
(M1z11, 24), 207 (M1z, 17), 156 (29), 138 (64), 123 (95),
95 (60), 83 (57). HRMS: Calcd for C12H17NO2: 207.1255.
Found: 207.1259.
3,8,8-Trimethyl-2.10-dioxo-3-azatricyclo[5.3.0.01.5] decane:
11b Oil, 36%. 1H NMR: 1.05 (3H, s), 1.11 (3H, s), 2.04 and
2.48 (AB, JABˆ13.2 Hz, 1H, dd, Jˆ9.2, 4.0 Hz and 1H, dd,
Jˆ8.4, 6.3 Hz), 2.16 and 2.64 (AB, JABˆ17.2 Hz, 2H),
2.68±2.83 (2H, m), 2.88 (3H, s), 3.34 and 3.69 (AB,
JABˆ9.9 Hz, 1H, Jˆ4.0 Hz and 1H, d, Jˆ9.7 Hz). 13C
NMR: 22.4 (CH3), 26.6 (CH2), 28.1 (CH3), 29.8 (CH3), 31.4
(CH), 36.9 (C), 50.7 (CH), 51.0 (CH2), 55.9 (CH2), 60.7 (C),
171.2 (C), 213.1 (C). IR: 2945, 1740, 1680, 1505, 1405, 1330,
1265, 1155. MS m/z: 208 (30, M1z11), 207 (100, M1z), 192
(57), 178 (19), 164 (52), 139 (50), 124 (69), 70 (100).
HRMS: Calcd for C12H17NO2: 207.1255. Found: 207.1259.
2-t-Butyl-7,7-dimethyl-1,5-dioxo-3-vinyl-2-azaspiro[3.4]-
octane: 13c Oil, 11%. 1H NMR: 1.00 (3H, s), 1.18 (3H, s),
1.33 (9H, s), 1.99±2.20 (2H, m), 2.03 (1H, d, JABˆ13.5 Hz),
2.36 (1H, d, JABˆ13.5 Hz), 3.92 (1H, d, Jˆ9.9 Hz), 5.22
(1H, dd, Jˆ9.9 and 1.3 Hz), 5.30 (1H, dd, Jˆ17.2 and
1.3 Hz), 6.18 (1H, ddd, Jˆ17.2, 9.9 and 9.9 Hz). 13C
NMR: 28.2 (CH3), 28.3 (2CH3), 28.5 (CH3), 28.6 (CH3),
34.5 (CIV), 44.5 (CH2), 54.4 (CH2), 55.0 (CIV), 65.5 (CH),
69.6 (CIV), 119.8 (CH2), 136.0 (CH), 165.9 (CvO), 212.2
(CvO). IR: 2960, 1725, 1680, 1465, 1390, 1370, 1270,
3-t-Butyl-8.8-dimethyl-2.10-dioxo-3-azatricyclo[5.3.0.01.5]
decane: 11c Solid, 50%. H NMR: 1.05 (3H, s), 1.10 (3H,
1255, 1145 cm21
.
1
s), 1.43 (9H, s), 2.00 and 2.44 (AB, JABˆ13.2 Hz, 1H, dd,
Jˆ8.9±3.8 Hz and 1H, dd, Jˆ8.2±6.3 Hz), 2.14 and 2.61
(AB, JABˆ17.2 Hz, 1H, d, Jˆ1.1 Hz and 1H), 3.9 Hz and
1H, d, Jˆ9.7 Hz). 13C NMR: 22.3 (CH3), 26.5 (CH2), 27.4
(3CH3), 27.9 (CH3), 30.4 (CH), 36.6 (C), 50.7 (CH), 51.0
(CH2), 52.2 (CH2), 54.3 (C), 62.1 (C), 171.6 (C), 214.0 (C).
IR: 2960, 1745, 1665, 1465, 1405, 1290, 1230 cm21. MS
m/z: 250 (7, M1z11), 249 (35, M1z), 234 (100), 206 (55),
137 (16). HRMS: Calcd for C15H23NO2: 249.1723. Found:
249.1729.
3-Allyl-6,6-dimethyl-2,8-dioxo-3-azabicyclo[3.3.0] octane:
14b Oil. Yield 30%. H NMR: 1.08 (3H, s), 1.10 (3H, s),
1
2.18 (1H, d, JABˆ17.7 Hz), 2.21 (1H, d, JABˆ17.7 Hz), 2.77
(1H, ddd, Jˆ8.9, 8.9 and 5.8 Hz), 3.28 (1H, d, Jˆ8.9 Hz),
3.26±3.48 (2H, m), 3.78±3.94 (2H, m), 5.14±5.21 (2H, m),
5.68 (1H, ddt, Jˆ16.6, 10.5 and 6.3 Hz). 13C NMR: 232.9
(CH3), 29.4 (CH3), 36.8 (CIV), 44.4 (CH), 45.5 (CH2), 46.5
(CH2), 51.4 (CH2), 56.6 (CH), 118.6 (CH2), 131.8 (CH),
167.1 (CvO), 208.6 (CvO). IR: 2960, 1755, 1680, 1645,
1465, 1440, 1415, 1270 cm21. MS m/z: 208 (M1z11, 47),

4488
C. Meyer et al. / Tetrahedron 56 (2000) 4479±4489
207 (M1z, 50), 123 (84), 85 (100). HRMS: Calcd for
C12H17NO2: 207.1255. Found: 207.1259.
ddd, Jˆ8.9, 8.9 and 5.3 Hz), 3.21 (1H, d, Jˆ9.0 Hz), 3.40
(1H, dd, JABˆ10.6 Hz and Jˆ5.3 Hz), 3.58 (1H, dd,
JABˆ10.6 Hz and Jˆ8.8 Hz). 13C NMR: 22.7 (CH3), 27.2
(2CH3), 29.0 (CH3), 36.7 (CIV), 43.2 (CH), 45.2 (CH2), 51.4
(CH2), 54.2 (CIV), 57.7 (CH), 167.2 (CvO), 208.9 (CvO).
IR: 2960, 1745, 1665, 1405, 1290, 1130. MS m/z: 224
(M1z11, 7), 223 (M1z, 42), 208 (100), 180 (28), 168 (42),
151 (9). HRMS: Calcd for C13H21NO2: 223.1567. Found:
223.1572.
3-(4-Butenyl)-6,6-dimethyl-2,8-dioxo-3-azabicyclo[3.3.0]
octane: 14c Oil. Yield 58%. H NMR: 1.12 (3H, s), 1.11
1
(3H, s), 2.10±2.41 (4H, m), 2.80 (1H, ddd, Jˆ8.9, 8.9 and
5.8 Hz), 3.26 (1H, d, Jˆ8.9 Hz), 3.32 (2H, t, Jˆ6.5 Hz),
3.38±3.53 (2H, m), 5.01±5.11 (2H, m), 5.75 (1H, ddt,
Jˆ17.2, 10.3 and 6.8 Hz). 13C NMR: 23.0 (CH3), 29.4
(CH3), 31.6 (CH2), 36.7 (CIV), 41.8 (CH2), 44.5 (CH),
47.1 (CH2), 51.2 (CH2), 56.7 (CH), 117.0 (CH2), 139.4
(CH), 167.4 (CzO), 208.6 (CzO). IR: 2955, 2930, 1755,
1685, 1640, 1435, 1275 cm21. MS m/z: 222 (M1z11, 7),
221 (M1z, 20), 180 (84), 85 (100). HRMS: Calcd for
C13H19NO2: 221.1411. Found: 221.1416.
Acknowledgements
Prof. James Bouquant is greatly acknowledged for having
performed the PM3 and ab initio calculations on 7b and the
corresponding photoproducts. C. M. warmly thanks
M.E.N.R.T. for ®nancial support.
6,6-Dimethyl-2,8-dioxo-3-(4-pentenyl)-3-azabicyclo[3.3.0]
octane: 14e Oil. Yield 26%. H NMR: 1.09 (6H, s), 1.58
1
(2H, quint, Jˆ7.5 Hz), 2.00 (2H, dd, Jˆ14.1 and 6.9 Hz),
2.14 (1H, d, JABˆ17.5 Hz), 2.22 (1H, d, JABˆ17.5 Hz), 2.78
(1H, ddd, Jˆ9.1, 9.1 and 5.6 Hz), 3.22±3.29 (3H, m), 3.32
References
(1H, dd, JABˆ10.4 Hz and Jˆ5.6 Hz), 3.46 (1H, dd, JAB
ˆ
1. (a) Cossy, J.; Carrupt, P. A.; Vogel, P. In The Chemistry of
Double-Bonded Functional Groups; Patai, S., Ed. Wiley: New
York, NY, USA, 1989; pp 1369±1565. (b) Becker, D.; Haddad,
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10.4 Hz and Jˆ9.1 Hz), 4.92±5.02 (2H, m), 5.75 (1H, ddt,
Jˆ17.2, 10.3 and 6.5 Hz). 13C NMR: 22.8 (CH3), 26.1
(CH2), 29.2 (CH3), 30.7 (CH2), 36.6 (CIV), 42.2 (CH2),
44.3 (CH), 46.8 (CH2), 51.3 (CH2), 56.5 (CH), 115.0
(CH2), 137.1 (CH), 167.2 (CvO), 208.6 (CvO). IR: 2960,
2920, 1755, 1680, 1440, 1275 cm21. MS m/z: 236 (M1z11,
22), 235 (M1z, 29), 180 (86), 124 (28), 97 (64), 83 (66).
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6,6-Dimethyl-2,8-dioxo3-(5-hexenyl)-3-azabicyclo[3.3.0]
octane: 14f Oil. Yield 46%. H NMR: 1.13 (6H, s), 1.30±
1
5. Faure, S.; Piva-Le Blanc, S.; Piva, O.; Pete, J. P. Tetrahedron
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1.59 (4H, m), 2.07 (2H, dd, Jˆ14.0 and 7.3 Hz), 2.19 (1H, d,
JABˆ17.4 Hz), 2.23 (1H, d, JABˆ17.4 Hz), 2.79 (1H, ddd,
Jˆ9.1, 9.1 and 5.6 Hz), 3.23±3.30 (2H, m), 3.28 (1H, d,
Jˆ9.1 Hz), 3.34 (1H, dd, JABˆ10.4 Hz and Jˆ5.6 Hz), 3.48
(1H, dd, JABˆ10.4 Hz and Jˆ9.1 Hz), 4.94±5.05 (2H, m),
5.77 (1H, ddt, Jˆ17.1, 10.4 and 6.7 Hz). 13C NMR: 22.7
(CH3), 25.7 (CH2), 26.1 (CH2), 29.2 (CH3), 32.8 (CH2),
36.5 (CIV), 42.4 (CH2), 44.2 (CH), 46.7 (CH2), 51.2 (CH2),
56.4 (CH), 114.5 (CH2), 137.9 (CH), 167.0 (CvO), 208.5
(CvO). IR: 2930, 1755, 1685, 1640, 1435, 1370, 1270 cm21.
MS m/z: 250 (M1z11, 18), 249 (M1z, 45), 234 (15), 208
(100), 180 (92), 168 (67), 124 (38), 111 (30), 96 (70).
HRMS: Calcd for C15H23NO2: 249.1723. Found: 249.1729.
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3-t-Butyl-7,7-dimethyl-2-oxo-3-azabicyclo[3.3]oct-1-en-
5-ol: 16 Oil, 50%. 1H NMR: 1.09 (3H, s), 1.15 (3H, s), 1.33
(3H, s), 1.39 (3H, s), 1.80 (1H, d, JABˆ13.3 Hz), 2.04 (1H,
1H, JABˆ13.3 Hz), 3.15 (1H, s), 3.32 (1H, dd, Jˆ10.2 and
0.5 Hz), 3.58 (1H, dd, Jˆ10.2 and 0.5 Hz), 6.18 (1H, s). 13C
NMR: 27.2 (CH3), 27.3 (2CH3), 28.1 (CH3), 28.6 (CH3),
36.6 (CIV), 50.3 (CIV), 52.1 (CH2), 58.8 (CH2), 81.1 (CIV),
142.5 (CH), 142.8 (CH), 164.7 (CvO). IR: 3270, 2955,
2935, 1745, 1675, 1645, 1465, 1455, 1360. UV (CH2Cl2)
1270ˆ490. MS m/z: 224 (M1z11, 7), 223 (M1z, 33), 208
(100), 180 (17), 168 (19), 137 (26). HRMS: Calcd for
C13H21NO2: 223.1567. Found: 223.1572.
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(1H, d, JABˆ17.4 Hz), 2.22 (1H, d, JABˆ17.4 Hz), 2.66 (1H,

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