Photoreactions of β-aziridinylacrylonitriles and acrylates with alkenes: Formation of head-to-head adducts and application to the preparation of pyrrolizidine alkaloid

Article abstract of DOI:10.1016/j.tet.2004.09.031

The photochemical C,C-bond cleavage of N-benzyl β- aziridinylacrylonitrile 1 and acrylate 2 and the subsequent [3+2] cycloaddition with electron-deficient alkenes afforded head-to-head adducts selectively and efficiently. Irradiation of N-phenyl aziridine 3 with acrylonitrile gave adducts, but photoreaction of N-benzoyl aziridine 4 and thermal reactions of 3 and 4 with alkenes yielded C(γ),N-cleaved products instead of cycloadducts. N-trityl aziridine 5 also reacted with electron-deficient alkenes, affording 2,3-cis-pyrrolidine derivatives exclusively. A formal synthesis of a pyrrolizidine alkaloid, isoretronecanol (27), starting from 5 was achieved in a convenient manner.

Full text of DOI:10.1016/j.tet.2004.09.031

Tetrahedron 60 (2004) 10887–10898
Photoreactions of b-aziridinylacrylonitriles and acrylates with
alkenes: formation of head-to-head adducts and application to the
preparation of pyrrolizidine alkaloid
*
Keitaro Ishii, Takuya Sone, Yukio Shimada, Takahide Shigeyama, Masahiro Noji
and Shigeo Sugiyama
Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
Received 3 July 2004; revised 10 September 2004; accepted 13 September 2004
Available online 1 October 2004
Abstract—The photochemical C,C-bond cleavage of N-benzyl b-aziridinylacrylonitrile 1 and acrylate 2 and the subsequent [3C2]
cycloaddition with electron-deficient alkenes afforded head-to-head adducts selectively and efficiently. Irradiation of N-phenyl aziridine 3
with acrylonitrile gave adducts, but photoreaction of N-benzoyl aziridine 4 and thermal reactions of 3 and 4 with alkenes yielded C(g),N-
cleaved products instead of cycloadducts. N-trityl aziridine 5 also reacted with electron-deficient alkenes, affording 2,3-cis-pyrrolidine
derivatives exclusively. A formal synthesis of a pyrrolizidine alkaloid, isoretronecanol (27), starting from 5 was achieved in a convenient
manner.
q 2004 Elsevier Ltd. All rights reserved.
1. Introduction
The 1,3-dipolar cycloaddition of azomethine ylides with
alkenes is an important and useful strategy for the
construction of nitrogen-containing five-membered hetero-
cycles.1 One of the method for the generation of azomethine
ylide is the heating or irradiation of aziridines, most of
Scheme 1.
which bear an adjacent electron-withdrawing or phenyl
group.2 However, mild and efficient methods for the C,C-
bond cleavage of aziridines have not been widely studied.
and subsequent cycloaddition reactions, leading to head-to-
head adducts selectively and efficiently (Scheme 1).4 In this
paper, we describe the details of the reactions of nitrile 1,
We have investigated photochemical reactions of a,b-
unsaturated g,d-epoxy nitriles systematically.3 These
studies have revealed that carbonyl ylides photochemically
generated from epoxy nitriles undergo 1,3-diporlar cyclo-
addition with electron-rich alkenes to afford tetrahydro-
furans.3d On the basis of these studies, we became interested
in extending the photochemistry of epoxy nitriles to that of
b-aziridinylacrylonitrile.
the photochemical behavior of b-aziridinylacrylate 2, and
the effects of N-substituents in the aziridine ring [N-phenyl,
N-benzoyl and N-trityl aziridines 3–5 (Fig. 1)] on the
cycloaddition with alkenes. Furthermore, we describe that
using the cycloadducts 5, the formal preparation of a
pyrrolizidine alkaloid, isoretronecanol (27),5 was achieved
conveniently.
As part of these studies, we reported in a previous letter that
direct irradiation or heating of b-aziridinylacrylonitrile 1
with electron-deficient alkenes causes the ring-opening of 1
Keywords: Aziridine; Photolysis; [3C2] Cycloaddition; Pyrrolidine;
Pyrrolizidine.
* Corresponding author. Tel./fax: C81 424958783;
e-mail: ishiikei@my-pharm.ac.jp
Figure 1.
0040–4020/$ - see front matter q 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2004.09.031

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K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
2. Results and discussion
(E)-4 was prepared in 58% yield by the detritylation and
benzoylation of (E)-5 (Scheme 2).
The N-benzylnitrile 1 and ester 2 were prepared from
aldehyde 66 with diethyl cyanomethylphosphonate and
diethyl ethoxycarbonylmethylphosphonate in 75% yield
(E/ZZ44:31) and 75% yield (E/ZZ68:7), respectively.
N-phenyl ester (E)-3 and N-trityl ester (E)-5 were
synthesized from the corresponding alcohol 77 and aldehyde
8,8 respectively, as shown in Scheme 2. N-Benzoyl ester
Direct irradiation of a solution of (Z)-1 in acetonitrile with a
low-pressure mercury lamp in a quartz test tube at rt
(conversion 83%) afforded dimers 9A (32%9) and 9B (14%)
(Scheme 3). On triplet sensitization, the nitrile (Z)-1 in
acetone with a high-pressure mercury lamp in a Pyrex test
tube at rt (conversion 58%) selectively underwent (E/Z)-
isomerization of the side chain leading to (E)-1 (64%9)
(Scheme 3).
Since the photolysis of nitrile 1 had given cycloadducts 9 in
moderate yield, the reactions of 1 and electron-deficient
alkenes or an alkyne were studied. The results are
summarized in Table 1 and Figure 2. No significant
differences in reactivity between (E)- and (Z)-1 were
observed (entries 1–4).
Scheme 2. Reagents and conditions: (i) (EtO)2 P(O)CH2CN, NaH, THF,
0 8C; (ii) (EtO)2 P(O)CH2CO2Et, NaH, THF, 0 8C; (iii) oxalyl chloride,
DMSO, CH2Cl2, K78 8C; (iv) (EtO)2P(O)CH2CO2Et, NaH, CH2Cl2, 0 8C;
(v) TFA, MeOH, CHCl3; (vi) (PhCO)2O, NEt3, CHCl3.
Scheme 3. Reagents and conditions: (i) lZ254 nm, acetonitrile, rt; (ii) lO
280 nm, acetone, rt.
Figure 2.
Table 1. Photochemical and thermal reactions of aziridine 1 with alkenes or an alkynea
Entry
(E)/(Z)-1
Alkene or alkyne
Reaction time (h)
Conversion (%)
Products and
yields (%)9,b
1
2
3
4
5
(E)
(Z)
(E)
(Z)
(Z)
Acrylonitrile
6
100
100
87
(E)-10a (52)
and (E)-10b (26)
(Z)-10a (52)
and (Z)-10b (15)
(E)-11a (37)
and (E)-11b (25)
(Z)-11a (38)
and (Z)-11b (48)
12a (23) [21]
and 12b (49) [13]
13 (39)
Acrylonitrile
7
Methyl acrylate
Methyl acrylate
tert-Butyl acrylate
2
4
98
2 [3]c
90 [86]
6
7
8
(Z)
(Z)
(Z)
2-Cyclopentenone
N-Phenylmaleimide
Methyl propiolate
2.5
2 [2]
0.75
91
84 [81]
66
14 (39) [42]
15 (49)
a A 0.060 mol LK1 solution of 1 in acetonitrile with 10 equiv of alkene or alkyne was irradiated at rt.
b Isolated yield.
c Values in square brackets are yields of thermal reactions of 1 with 10 equiv of alkene in refluxing xylene.

K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
10889
The reactions 1 and mono-substituted alkenes selectively
afforded 3-substituted pyrrolidines in moderate yields (62–
86%9) (entries 1–5). The photoreactions of nitrile 1 and
dimethyl fumarate or dimethyl acetylenedicarboxylate gave
only dimethyl maleate and a complex mixture, respectively.
On the other hand, the reactions of 1 and non-activated
(bicyclo[2.2.1]hept-2-ene and cyclohexene) or electron-rich
alkenes (ethyl vinyl ether) gave only dimers 9 instead of the
adducts with alkenes.
The thermal 1,3-dipolar cycloaddition of an azomethine
ylide derived from an aziridine bearing an ester function and
electron-deficient alkenes normally affords products posses-
sing the electron-withdrawing group (EWG) at the C(4)
position in the pyrrolidine (Fig. 3).2b However, the position
of the EWG in our cycloadducts was at C(3). In order to
investigate the mechanism of the cycloaddition step
between electron-deficient alkenes and ring-cleaved inter-
mediate A (Fig. 3), thermal reactions of 1 and alkenes were
performed. A solution of (Z)-1 with tert-butyl acrylate or
N-phenylmaleimide was heated in refluxing xylene and
gave the same adducts 12 (a 21% and b 13%9) and 14
(42%9) as yielded by the photoreactions, respectively. The
results may suggest that the C,C-bond cleavage of aziridine
1 proceeds photochemically or thermally and the cyclo-
addition occurs thermally.
Figure 3.
We next investigated ethyl b-aziridinylacrylate 2 possessing
an ester group, which is easily transformed to other
functional groups. Direct irradiation of a solution of (E)-2
in acetonitrile with a low-pressure mercury lamp in a quartz
test tube at rt (conversion 98%) afforded dimers 16A (19%9)
and 16B (7%9) (Fig. 4).
On triplet sensitization, ester (E)-2 in acetone with a high-
pressure mercury lamp in a Pyrex test tube at rt (conversion
84%) selectively underwent (E/Z)-isomerization of the side
chain leading to (Z)-2 (25%9).
Since the photochemical behavior of ester 2 was similar to
that of nitrile 1, the reactions of 2 and acrylonitrile were
studied (Table 2, Fig. 4).
The structures of the cycloadducts 9–15 were deduced
mainly on the basis of their spectral data and were discussed
in the previous communication.4 Particularly, in the 1H
NMR spectra of the N-benzyl pyrrolidines 9–12, the signals
due to H-(30) for 2,3-cis-pyrrolidines appear in a lower field
(d 3.18–3.46) than those of 2,3-trans-pyrrolidines (d 2.74–
2.85) (Table 3).
The molecular ion peak in the mass spectrum (MS) of 17
indicates the 1:1 adducts of 2 and acrylonitrile. The regio-
and stereochemistries of 17a and 17b were determined by
the H–H and C–H COSY spectra. In particular, the
configurations at the 20,30-positions of 17a and 17b
were deduced from a comparison of the chemical shifts
Figure 4.
Table 2. Photochemical reactions of aziridines 2–5 with alkenesa
Entry
Aziridine
Alkene
Reaction time (h)
Conversion (%)
Products and yields
(%)9,b
1
2
3
4
5
(E)-2
(E)-3
(E)-4
(E)-5
(E)-5
Acrylonitrile
Acrylonitrile
Acrylonitrile
Acrylonitrile
Methyl acrylate
3
2
5
1.3
4
100
52
74
40
17a (42) and 17b (21)
18a (10) and 18b (6)
20 (30)
22 (43)
23 (61)
57
a A 0.060 mol LK1 solution of 2–5 in acetonitrile with 10 equiv of alkene was irradiated at rt.
b Isolated yield.

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K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
Table 3. The chemical shift of H–C(30) in the 1H NMR spectra for 9–12, 16
and 17
The structures of 18a and 18b were deduced from the
chemical shifts for H–(C30) in the 1H NMR spectra in
comparison with those of the adducts shown in Table 3; the
signal (d 3.28) for 18a appears in a lower field than that for
18b (d 3.06–3.11). Furthermore, in the phase-sensitive
NOESY spectrum of 18a the crosspeak between H-20 and
H-30 was observed. The structure of 19 was determined on
the basis of its spectral data. In particular, the molecular ion
cis-Adduct
d
trans-Adduct
d
(E)-10a
(Z)-10aa
(E)-11aa
(Z)-11aa
12aa
3.18–3.25 m
3.29 ddd
3.20–3.28 m
3.29–3.37 m
3.18–3.24 m
3.16–3.21 m
(E)-10b
(Z)-10ba
(E)-11b
(Z)-11b
12ba
2.82 ddd
2.85 ddd
2.81 ddd
2.83 ddd
2.74 ddd
2.84 ddd
17a
9Aa
17b
1
peak in MS indicates that 19 is an isomer of 3, and the H
3.46 dd
3.36 dd
16Aa
16B
2.49 dd
2.62 dd
NMR spectrum shows the signals due to four aromatic
protons, two isolated alkenic protons and amino moiety (see
Section 4).
9Ba
a The stereochemistry was also determined by phase-sensitive NOESY
spectrum.
An acetonitrile solution of 4 and acrylonitrile was irradiated
with a low-pressure mercury lamp in a quartz test tube
affording the C(g),N-bond-cleaved product 20 (Table 2,
Fig. 4). The thermal reaction of (E)-4 and tert-butyl acrylate
in refluxing xylene yielded no adducts but a mixture of
C(g),N-bond-cleaved compounds (mainly isomers of 20)
and pyridine derivative 21 (4%9) (Fig. 4).12
(d 3.16–3.21 for 17a and d 2.84 for 17b) with those of the
compounds described in Table 3.
The molecular ion peak in the mass spectrum (MS) of 16A
and 16B shows that they are the dimers of 2. The regio-
and stereochemistries of 16A and 16B were determined
from the H–H and C–H COSY spectra and from a
comparison of the spectral data with those of 9A and 9B.
The structure of 20 was deduced from the spectral data (see
Section 4). The structure of 21 was determined by a
comparison of the spectral data with those of reference 12.
The N-benzoyl substituent indicated a tendency to cleave
the C(g),N-bond on thermal and photochemical reactions.
1
In particular, in the H NMR spectrum, the 20,30-trans
configuration in the pyrrolidine ring was0 deduced from a
comparison of the chemical shifts at the 3 -position of 16A
(d 2.49) and 16B (d 2.62) with the data described in Table 3.
Furthermore, in 0the NOESY spectrum of 16A, the cross-
peaks showed 2 ,30-trans and 30,40-trans configurations in
the pyrrolidine ring (Fig. 5). However, the stereochemistries
at C(200) for 16A and 16B could not be determined.
In order to improve the stereoselectivity at the 2,3-position
of the pyrrolidine ring on the cycloaddition, we chose trityl
group, which is more bulky than benzyl group, as the N-
substituent of aziridine. Acetonitrile solutions of N-trityl
aziridine 5 with acrylonitrile and methyl acrylate were
irradiated with a low-pressure mercury lamp in quartz test
tubes affording the adducts 22 and 23, respectively (Table 2,
Fig. 4).
The regio- and stereochemistries of 22 and 23 were
determined by the H–H COSY and the phase-sensitive
NOESY0spectra. In particular, the 0crosspeaks between0H-20
and H-3 , between H-30 and Ha-4 and between Ha-4 and
Ha-50 are observed in the NOESY spectra of 23 (Fig. 5).
Figure 5. Phase-sensitive NOESY for 16A and 23.
As the photochemical reactions of N-benzyl aziridines 1 and
2 with electron-deficient alkenes afforded the cycloadducts
in moderate yields, the effects of other N-substituents in the
aziridine ring on the cycloaddition were studied. Aziridines
substituted with phenyl or benzoyl groups, which possess
stronger electron-withdrawing characteristics than the
benzyl group, were supposed to react with electron-rich or
non-activated alkenes.2b
In the case of the reaction of 0N-trityl aziridine 5, the relative
configuration between C(2 ) and C(30) in the isolated
adducts was absolutely cis. In the transition state B for the
formation of 22 and 23, both the acrylate moiety of the
aziridine-ring-cleaved intermediate and the substituent R of
alkenes were presumably orientated on the opposite side of
the trityl group because of the steric hindrance (Fig. 4).
Irradiation of a solution of (E)-3 and acrylonitrile in
acetonitrile with a low-pressure mercury lamp in a quartz
test tube afforded the adducts 18a and 18b (Table 2, Fig. 4).
The yields of adducts from 3 were reduced in comparison
with those from the N-benzyl aziridine 2. Aziridine (E)-3
also did not react with electron-rich alkene (ethyl vinyl
ether) photochemically giving a complex mixture. On the
other hand, the thermal reaction of (E)-3 and 3,4-dihydro-
2H-pyran in refluxing xylene yielded no adducts but
underwent an electrocyclic reaction leading to benzazepine
19 (Fig. 4). This type of rearrangement is also observed by
thermal reaction10 or treatment with silica gel11 of 1-phenyl-
2-vinylaziridines.
Since the photolysis of N-trityl aziridine 5 and methyl
acrylate gave 2,3-cis-pyrrolidine 23 in moderate yield, we
were interested in the synthesis of a pyrrolizidine alkaloid,
isoretronecanol (27), using the stereochemistry of 23.
Hydrogenolysis of the side chain in 23 over Pd/C gave no
reduced product. After detritylation of 23 with trifluoroa-
cetic acid, reduction of the double bond in 24 over Pd/C
proceeded successfully, affording propionate 25 (64%).
Cyclization of 25 in toluene gave pyrrolizidine 265 in 87%
yield, which can be transformed by authentic methods5 into
27 (Scheme 4).
To clarify the chemical behavior and the utility of

K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
10891
Scheme 4. Reagents and conditions: (i) TFA, rt; (ii) 10% Pd/C, H2 (1 bar), AcOEt; (iii) toluene, 110 8C.
b-aziridinylacrylates, further work with 2,3-disubstituted
aziridines and the synthetic application of the cycloadducts
is currently in progress.
dry THF (40 mL) was added dropwise, and stirring was
continued for 1.5 h at 0 8C. Ice/water was added to the
mixture, and the organic phase was extracted with diethyl
ether. The ethereal extract was washed with brine, dried
with MgSO4, and concentrated in vacuo, giving a residue
that was subjected to flash column chromatography
[hexane–ethyl acetate (9:1)] to afford (E)-1 (3.30 g, 44%)
and (Z)-1 (2.34 g, 31%).
3. Summary
In conclusion, the photoreactions of N-benzyl b-aziridinyl-
acrylonitrile 1 and acrylate 2 with electron-deficient alkenes
afforded novel head-to-head adducts selectively and effi-
ciently. Aziridines 3 and 4, possessing the N-conjugated
substituent had a tendency to cleave the C(g),N-bond.
N-trityl aziridine 5 also reacted with electron-deficient
alkenes, yielding 2,3-cis-pyrrolidine derivatives selectively.
A formal synthesis of a pyrrolizidine alkaloid, isoretro-
necanol (27), starting from the pyrrolidine 23 was achieved
in a convenient manner.
Compound (E)-1. Bp 130 8C at 0.35 mm Hg; IR (film):
1
2300 cmK1 0(C^N); H NMR (AL4): d 1.84 (d, 1H, JZ
6.4 Hz, H-3 ), 1.92 (d, 1H, JZ3.2 Hz, H-30), 2.09–2.14 (m,
1H, H-20), 3.47, 3.58 (each d, 2H, JZ13.6 Hz, CH2Ph), 5.59
(dd, 1H, JZ16.4, 0.8 Hz, H-2), 6.55 (dd, 1H, JZ16.4,
6.8 Hz, H-3), 7.26–7.42 (m, 5H, Ph); 13C NMR (AL4): d
37.7 (t, C-30), 39.0 (d, C-20), 64.0 (t, CH2Ph), 99.8 (d, C-2),
117.1 (s, C-1), 127.2, 127.6 128.3 (3d, 5 C in Ph), 137.9 (s, C
in Ph), 153.9 (d, C-3); EI-MS m/z 184 (MC, 19%), 104 (4),
91 (100), 77 (3), 65 (10), 51 (3), 39 (7). Anal. Calcd for
C12H12N2: C, 78.23; H, 6.57; N, 15.20%. Found: C, 78.01;
H, 6.72; N, 14.85%.
4. Experimental
4.1. General
Compound (Z)-1. An oil; IR (CHCl3): 2220 cmK1 (C^N);
1H NMR (AL4): d 1.94 (d, 1H, JZ6.4 Hz,0 H-30), 2.02 (d,
1H, JZ3.6 Hz, H-30), 2.56–2.62 (m, 1H, 2 -H), 3.46, 3.66
(each d, 2H, JZ13.2 Hz, CH2Ph), 5.39 (dd, 1H, JZ10.8,
0.8 Hz, H-2), 6.10 (dd, 1H, JZ16.4, 9.3 Hz, H-3), 7.26–7.42
Melting points and boiling points are uncorrected. Melting
points were measured with a Yanaco MP-3 apparatus and
boiling points were measured with a Bu¨chi Kugel Rohr
GKR-50 apparatus. UV spectra were recorded on a Hitachi
124 spectrometer and IR spectra on a Hitachi 215
spectrometer. NMR spectra were obtained with a JEOL
JNM-AL300 (300 MHz; AL3), a JEOL JNM-AL400
(400 MHz; AL4) or JEOL JNM-LA500 (500 MHz; LA)
spectrometers in CDCl3 using tetramethylsilane as an
internal standard. Mass spectra (MS) and high-resolution
MS (HRMS) were taken on a JEOL JMS-700 spectrometer.
Column chromatography was performed with Merck silica
gel 60 (230–400 mesh) and Chromatorex NH (Fuji Silysia
Chemical LTD.), and preparative TLC with Wakogel B-5F.
13
(m, 05H, Ph); C NMR (AL4): d 36.1 (t, C-30), 39.0 (d,
C-2 ), 64.1 (t, CH2Ph), 99.7 (d, C-2), 115.6 (s, C-1), 127.2,
127.8, 128.3 (3d, 5C in Ph), 137.8 (s, C in Ph), 154.2 (d,
C-3); EI-MS m/z 184 (MC, 15%), 104 (4), 91 (100), 77 (3),
65 (9), 51 (3), 39 (6); HRMS calcd for C12H12N2: 184.1000.
Found: 184.1004.
4.2.2. Ethyl (E)-3-(1-benzylaziridin-2-yl)acrylate (E)-2
and ethyl (Z)-3-(1-benzylaziridin-2-yl)acrylate (Z)-2. By
analogy with the synthesis of 1, aldehyde 6 (6.79 g,
42.1 mmol) was treated with NaH (1.52 g, 63.2 mmol)
and diethyl ethoxycarbonylmethylphosphonate (14.2 g,
63.2 mmol) in dry THF at 0 8C, and the resulting mixture
was stirred for 1 h at 0 8C. Flash column chromatography
[hexane–ethyl acetate (9:1)] of the reaction mixture afforded
esters (E)-2 (6.61 g, 68%) and (Z)-2 (680 mg, 7%).
An Eikosha 60 W low-pressure mercury lamp and a Riko
400 W high-pressure mercury lamp were used for
irradiation. The photolysis solutions were purged with
argon both before and during irradiation.
4.2. Preparations of aziridines
Compound (E)-2. An oil; IR (film): 1710 cmK1 (C]O); 1H
NMR (AL4): d 1.27 (t, 3H, JZ6.9 Hz, CH3), 1.84 (d, 1H,
JZ6.6 Hz, H-30), 1.95 (d, 1H, JZ3.0 Hz, H-30), 2.09–2.17
(m, 1H, H-20), 3.51, 3.54 (each d, 2H, JZ13.5 Hz, CH2Ph),
4.18 (q, 2H, JZ6.9 Hz, OCH2), 6.05 (d, 1H, JZ15.8 Hz,
H-2), 6.69 (dd, 1H, JZ15.8, 7.9 Hz, H-3), 7.24–7.34 (m,
4.2.1. (E)-3-(1-Benzylaziridin-2-yl)acrylonitrile (E)-1
and (Z)-3-(1-benzylaziridin-2-yl)acrylonitrile (Z)-1. To
a suspension of NaH [1.48 g, 61.8 mmol; prepared from a
NaH dispersion (60%, 2.47 g) by washing it twice with
hexane (30 mL)] in dry THF (125 mL) was added dropwise
a solution of diethyl cyanomethylphosphonate (10.9 g,
61.8 mmol) in dry THF (125 mL) at 0 8C. After the mixture
had been stirred for 10 min at 0 8C, a solution of
N-benzylaziridinecarbaldehyde 66 (6.64 g, 41.2 mmol) in
13
5H, Ph); C NMR (AL4): d 14.3 (q, CH3), 36.8 (t, C-30),
39.3 (d, C-20), 60.3, 64.3 (2t, OCH2, CH2Ph), 121.8 (d, C-2),
127.0, 127.6, 128.2 (3d, 5C in Ph), 138.3 (s, C in Ph), 147.8
(d, C-3), 165.8 (s, C-1); EI-MS m/z 231 (MC, 2%), 186 (9),

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K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
158 (98), 140 (36), 112 (47), 96 (19), 91 (100), 83 (27);
HRMS calcd for C14H17NO2: 231.1259. Found: 231.1259.
1.2 Hz, Ph);013C NMR (AL4): d 14.4 (q, CH3), 30.8 (t, C-30),
33.2 (d, C-2 ), 60.3 (t, OCH2), 74.4 (s, CPh3) 121.9 (d, C-2),
127.2, 127.4, 129.0 (3d, 15C in Ph), 143.8 (s, 3C in Ph),
149.0 (d, C-3), 166.0 (s, C-1); EI-MS m/z 383 (MC, 0.1%),
257 (4), 243 (100), 228 (8), 215 (4), 180 (3), 165 (52), 154
(2), 115 (2), 91 (3), 77 (4). Anal. Calcd for C26H25NO2: C,
81.43; H, 6.57; N, 3.65%. Found: C, 81.30; H, 6.50; N,
3.59%.
Compound (Z)-2. An oil; IR (film): 1705 cmK1 (C]O); 1H
NMR (AL4): d 1.30 (t, 3H, JZ7.1 Hz, CH3), 1.87 (d, 1H,
JZ6.6 Hz, H-30), 1.92 (d, 1H, JZ3.2 Hz, H-30), 3.43, 3.65
(each d, 2H, JZ13.4 Hz, CH2Ph), 3.43–3.48 (m, 1H, H-20),
4.20 (q, 2H, JZ7.1 Hz, OCH2), 5.80 (dd, 1H, JZ11.5,
8.5 Hz, H-3), 5.86 (d, 1H, JZ11.5 Hz, H-2), 7.24–7.34 (m,
13
5H, Ph); C NMR (AL4): d 14.4 (q, CH3), 36.1 (t, C-30),
4.2.5. Ethyl (E)-3-(1-benzoylaziridin-2-yl)acrylate (E)-4.
To a solution of 5 (897 mg, 2.34 mmol) in CHCl3 (2.3 mL)
and MeOH (1.8 mL) was added dropwise trifluoroacetic
acid (3.5 mL) at 0 8C. After the mixture had been stirred for
30 min at 0 8C, water was added to the mixture, and the
organic phase was extracted with CHCl3. The organic
extract was washed with sat. aqueous NaHCO3 solution and
brine, dried with Na2SO4, and concentrated in vacuo. To a
solution of the residue (236 mg) in CHCl3 (3 mL) was added
triethylamine (0.47 mL) and then benzoic anhydride
(378 mg, 1.67 mmol) at 0 8C. After the mixture had been
stirred for 2 h at 0 8C, water was added to the mixture, the
organic phase was extracted with CHCl3. The extract was
subjected to the same workup as used for the synthesis of 1.
The residue was subjected to flash column chromatography
[hexane–ethyl acetate (3:1)] to yield ester (E)-4 (334 mg,
58% from 5). A colorless oil; IR (film): 1710 cmK1 (C]O);
1H NMR (AL4): d 1.31 (t, 3H, JZ7.2 Hz, CH3), 2.43 (d, 1H,
JZ3.2 Hz, H-30), 2.85 (d, 1H, JZ5.6 Hz, H-30), 3.11–3.17
(m, 1H, H-20), 4.22 (q, 2H, JZ7.2 Hz, OCH2), 6.21 (d, 1H,
JZ16.0 Hz, H-2), 6.74 (dd, 1H, JZ16.0, 8.0 Hz, H-3) 7.45
(t, 2H, JZ7.6 Hz, Ph), 7.54–7.59 (m, 1H, Ph), 7.99 (d, 2H,
JZ7.6 Hz, Ph); 13C NMR (AL4): d 14.3 (q, CH3), 33.6 (t,
C-30), 38.0 (d, C-20), 60.7 (t, OCH2), 124.4 (d, C-2), 128.4,
129.0, 132.9 (3d, 5C in Ph), 132.3 (s, C in Ph), 144.0 (d,
C-3), 165.3 (s, C-1), 177.9 (s, NC]O); EI-MS m/z 245
(MC, 7%), 200 (2), 140 (3), 117 (20), 105 (100), 95 (2), 77
(22), 51 (3); HRMS calcd for C14H15NO3: 245.1052. Found:
245.1053.
37.4 (d, C-20), 60.7, 64.2 (2t, OCH2, CH2Ph), 120.9 (d, C-2),
126.9, 127.8, 128.2 (3d, 5C in Ph), 138.5 (s, C in Ph), 149.7
(d, C-3), 166.2 (s, C-1); EI-MS m/z 231 (MC, 3%), 186 (6),
158 (90), 140 (31), 112 (38), 96 (18), 91 (100), 83 (28);
HRMS calcd for C14H17NO2: 231.1259. Found: 231.1250.
4.2.3. Ethyl (E)-3-(1-phenylaziridin-2-yl)acrylate 3. To a
solution of oxalyl chloride (410 mg, 3.2 mmol) in dry
CH2Cl2 (7.0 mL) was added dropwise a solution of DMSO
(440 mg, 5.6 mmol) in dry CH2Cl2 (7.0 mL) at K70 8C.
After the mixture had been stirred for 20 min at K70 8C, a
solution of alcohol 77 (404 mg, 2.8 mmol) in dry CH2Cl2
(5.0 mL) was added dropwise, and stirring was continued
for 15 min at K70 8C. Triethylamine (1.9 mL, 14 mmol)
was added slowly to the reaction mixture, which was stirred
for 10 min at K70 8C, warmed to 0 8C and further stirred for
2 h. Water was added to the mixture, and the organic phase
was extracted with CH2Cl2. The organic extract was washed
with brine, dried with MgSO4, and concentrated in vacuo,
giving a aldehyde that was used for the next step without
further purification. By analogy with the synthesis of 1, the
aldehyde (1.03 g, 7.0 mmol) was treated with NaH (202 mg,
8.4 mmol) and diethyl ethoxycarbonylmethylphosphonate
(1.88 g, 8.4 mmol) in dry CH2Cl2 at 0 8C, and the resulting
mixture was stirred for 10 min at 0 8C. Flash column
chromatography [hexane–ethyl acetate (3:1)] of the reaction
mixture afforded ester (E)-3 (679 mg, 45%). An oil; IR
1
(film): 1710 cmK1 (C]O); H NMR (AL3):0d 1.29 (t, 3H,
JZ7.2 Hz, CH3), 2.35 (d, 1H, JZ3.3 Hz, H-3 ), 2.42 (d, 1H,
JZ6.3 Hz, H-30), 2.70–2.77 (m, 1H, H-20), 4.21 (q, 2H, JZ
7.2 Hz, OCH2), 6.19 (d, 1H, JZ15.6 Hz, H-2), 6.78 (dd, 1H,
JZ15.6 Hz, 7.8, H-3), 6.95–7.05, 7.21–7.29 (m, 5H, Ph);
13C NMR (AL4): d 14.3 (q, CH3), 35.9 (t, C-30), 39.6 (d,
C-20), 60.4 (t, OCH2), 120.3, 122.7, 128.8 (3d, 5C in Ph),
122.5 (d, C-2), 146.7 (d, C-3), 152.9 (s, C in Ph), 165.6 (s,
C-1); EI-MS m/z 217 (MC, 16%), 172 (6), 144 (100), 112
(13), 104 (13), 91 (6), 84 (14), 77 (20), 51 (5); HRMS calcd
for C15H15NO2: 217.1103. Found: 217.1104.
4.3. Irradiation of acrylonitrile 1
4.3.1. (2Z,20RS,30RS,40SR,200SR)-3-[1-Benzyl-4-(1-benzyl-
aziridin-2-yl)-3-cyanopyrrolidin-2-yl]acrylonitrile 9A
and (2Z,20RS,30RS,40SR,200RS)-3-[1-Benzyl-4-(1-benzyl-
aziridin-2-yl)-3-cyanopyrrolidin-2-yl]acrylonitrile 9B.
A solution of (Z)-1 (733 mg, 3.98 mmol) in acetonitrile
(66 mL) was irradiated with a low-pressure mercury lamp in
a quartz test tube (conversion 83%) for 6.5 h at rt. After
removal of the solvent, flash column chromatography
[hexane–ethyl acetate (7:3)] of the residue afforded dimers
9A (197 mg, 32%) and 9B (83.8 mg, 14%).9
4.2.4. Ethyl (E)-3-(1-tritylaziridin-2-yl)acrylate (E)-5.
By analogy with the synthesis of 1, aldehyde 88 (4.0 g,
12.8 mmol) was treated with NaH (460 mg, 19 mmol) and
diethyl
ethoxycarbonylmethylphosphonate
(4.3 g,
Compound 9A. Colorless crystals, mp 113–114 8C (hexane/
1
19 mmol) in dry CH2Cl2 at 0 8C, and the resulting mixture
was stirred for 10 min at 0 8C. Flash column chromatog-
raphy [hexane–ethyl acetate (9:1)] of the reaction mixture
afforded ester (E)-5 (4.26 g, 87%). Colorless crystals; mp
82–83 8C (hexane–ethyl acetate); IR (CHCl3): 1710 cmK1
ethyl acetate); IR (CHCl3): 2240, 2230 cmK1 (C^N); H
NMR (LA): d 1.65 (d, 1H, JZ6.1 Hz, H-300), 1.75 (d, 1H,
JZ3.4 Hz, H-300), 1.84–1.89 (m, 1H, H-200), 1.96–2.02 (m,
1H, H-40), 2.45 (dd, 1H, JZ10.1, 7.9 Hz, H-50), 2.73 (dd,
1H, JZ100.01, 4.3 Hz, H-50), 3.31, 3.50 (each d, 2H, JZ
12.8 Hz, 1 -CH2Ph), 3.36 (dd, 1H, JZ8.5, 7.0 Hz, H-30),
3.40, 3.69 (each d, 2H, JZ13.4 Hz, 10-CH2Ph), 3.72 (dd,
1H, JZ9, 7.0 Hz, H-20), 5.53 (dd, 1H, JZ11.0, 0.6 Hz,
H-2), 6.59 (dd, 1H, JZ11.0, 9.2 Hz, H-3), 7.16–7.33 (m,
1
(C]O); H NMR (AL4): d 1.29 (t, 3H, JZ7.3 Hz, CH3),
1.48 (d, 1H, JZ6.4 Hz, H-30), 1.80–1.85 (m, 1H, H-20), 1.92
(d, 1H, JZ2.4 Hz, H-30), 4.20 (q, 2H, JZ7.3 Hz, OCH2),
6.04 (d, 1H, JZ15.6 Hz, H-2), 6.94 (dd, 1H, JZ15.6,
8.0 Hz, H-3), 7.18–7.45 (m, 9H, Ph), 7.47 (d, 6H, JZ
13
10H, Ph); C NMR (LA): d 33.9 (t, C-300), 37.5 (d, C-30),

K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
10893
40.5 (d, C-200), 42.5 00(d, C-40), 56.0 (t, C-50), 57.1 (t,
10-CH2Ph), 64.5 (t, 1 -CH2Ph), 65.0 (d, C-20), 103.6 (d,
C-2), 114.9, 116.9 (2s, C-1, CN), 127.3, 127.4, 128.29,
128.31, 128.4, 128.5 (6d, 10C in Ph), 137.4, 138.6 (2s, 2C in
Ph), 151.9 (d, C-3); EI-MS m/z 368 (MC, 0.9%), 277 (4),
261 (12), 210 (23), 158 (8), 120 (27), 91 (100), 65 (5). Anal.
Calcd for C24H24N4: C, 78.23; H, 6.57; N, 15.20%. Found:
C, 78.17; H, 6.63; N, 15.10%.
2H, H2-40), 2.47–2.55 (m with q character, 1H, JZ9 Hz,
H-50), 2.82 (ddd, 1H, JZ10.3, 7.7, 5.9 Hz, H-30), 3.08 (dd0d,
1H, JZ9.5, 8, 2.9 Hz, H-50), 3.32 (t, 1H, JZ7.7 Hz, H-2 ),
3.37, 3.86 (each d, 2H, JZ12.8 Hz, 10-CH2Ph), 5.77 (dd,
1H, JZ16.1, 0.7 Hz, H-2), 6.58 (dd, 1H, JZ16.1, 7.7 Hz,
H-3), 7.23–7.38 (m, 5H, Ph); 13C NMR (A0L4): d 27.8 (t,
C-40), 34.0 (d, C-30), 52.0 (t, C-50), 57.9 (t, 1 -CH2Ph), 69.6
(d, C-20), 103.5 (d, C-2), 116.0, 119.8 (2s, C-1, CN), 127.5,
128.3, 128.4 (3d, 5C in Ph), 137.0 (s, C in Ph), 151.9 (d,
C-3); EI-MS m/z 237 (MC, 27%), 197 (6), 184 (16), 160 (6),
146 (10), 91 (100), 65 (9); HRMS calcd for C15H15N3:
237.1266. Found: 237.1270.
Compound 9B. Colorless crystals, mp 58–60 8C (hexane/
1
ethyl acetate); IR (CHCl3): 2260, 2240 cmK1 (C^N); H
NMR (LA): d 1.48 (d, 1H, JZ6.1 Hz, H-300), 1.68 (d, 1H,
JZ3.4 Hz, H-300), 1.85–1.89 (m, 1H, H-200), 2.11–2.18 (m,
1H, H-40), 2.49 (dd, 1H, JZ10, 9.2 Hz, H-50), 2.98 (ddd,
1H, JZ10, 5.2, 4.9 Hz, H-50), 3.07, 4.03 (each d, 2H, JZ
13.4 Hz, 100-CH2Ph), 3.40, 3.83 (each d, 2H, JZ13.4 Hz,
10-CH2Ph), 3.46 (dd, 1H, JZ8, 6.1 Hz, H-30), 3.75 (dd, 1H,
JZ9.2, 6.1 Hz, H-20), 5.59 (dd, 1H, JZ11.0, 0.6 Hz, H-2),
6.65 (dd, 1H, JZ11.0, 9.2 Hz, H-3), 7.25–7.33 (m, 10H,
Ph); 13C NMR (LA): d 33.4 (t, C-300), 38.8 (d, C-30), 40.0 (d,
C-200), 43.1 (d, C-40), 54.4 (t, C-50), 57.3 (t, 10-CH2Ph), 64.2
(t, 100-CH2Ph), 65.3 (d, C-20), 104.0 (d, C-2), 114.8, 117.4
(2s, C-1, CN), 127.1, 127.5, 128.1, 128.38, 128.43, 128.44
(6d, 10C in Ph), 137.5, 138.6 (2s, 2C in Ph), 151.9 (d, C-3);
EI-MS m/z 368 (MC, 0.8%), 277 (4), 261 (15), 210 (31), 158
(6), 120 (31), 91 (100), 65 (5); HRMS calcd for C24H24N4:
368.2001. Found: 368.2007.
4.4.3. (2Z,20RS,30RS)-3-(1-Benzyl-3-cyanopyrrolidin-2-
yl)acrylonitrile (Z)-10a. Colorless crystals; mp 105–
106 8C (hexane–ethyl acetate); IR (CHCl3): 2230,
1
2210 cmK1 (C^N); H NMR (LA): d 2.16–2.24, 2.25–
2.30 (each m, 2H, H2-40), 2.31–2.36, 3.12–3.16 (each m, 2H,
H2-50), 3.29 (ddd, 1H, JZ8.8, 7.3, 5.5 Hz, H-30), 3.43, 3.83
(each d, 2H, JZ13.4 Hz, 10-CH2Ph), 3.68 (dd, 1H, JZ9.2,
7.3 Hz, H-20), 5.59 (dd, 1H, JZ11.0, 0.6 Hz, H-2), 6.61 (dd,
1H, JZ11.0, 9.2 Hz, H-3), 7.24–7.36 (5H, m, Ph);013C NMR
(LA): d 28.5 (t, C-40), 33.3 (d, C-30), 51.8 (t, C-5 ), 57.4 (t,
10-CH2Ph), 64.9 (d, C-20), 103.8 (d, C-2), 114.9, 119.3 (2s,
C-1, CN), 127.5, 128.4, 128.6 (3d, 5C in Ph), 137.5 (s, C in
Ph), 151.9 (d, C-3); EI-MS m/z 237 (MC, 35%), 197 (5), 184
(20), 160 (7), 146 (10), 91 (100), 65 (9). Anal. Calcd for
C15H15N3: C, 75.92; H, 6.37; N, 17.71%. Found: C, 75.71;
H, 6.48; N, 17.61%.
4.3.2. Triplet sensitization of 1. A solution of (Z)-1
(794 mg, 4.31 mmol) in acetone (80 mL) was irradiated
with a high-pressure mercury lamp in a Pyrex test tube
(conversion 58%) for 20 h at rt. After removal of the
solvent, flash column chromatography [hexane–ethyl acet-
ate (7:3)] of the residue afforded (E)-1 (295 mg, 64%9).
4.4.4. (2Z,20RS,30SR)-3-(1-Benzyl-3-cyanopyrrolidin-2-
yl)acrylonitrile (Z)-10b. A colorless oil; IR (CHCl3):
1
2260, 2240 cmK1 (C^N); H NMR (LA): d 2.12–2.19,
2.26–2.35 (each m, 2H, H2-40), 2.48–2.55 (m with q
character, 1H, JZ9 Hz, H-50), 2.85 (ddd, 1H, JZ10.1,
8.9, 6.7 Hz, H-30), 3.05–3.10 (m with td character, 01H, JZ9,
3 Hz, H-50), 3.44, 3.83 (each d, 2H, JZ12.8 Hz, 1 -CH2Ph),
3.75 (dd, 1H, JZ9.5, 8.9 Hz, H-20), 5.56 (d, 1H, JZ
11.0 Hz, H-2), 6.28 (dd, 1H, JZ11.0, 9.5 Hz, H-3), 7.25–
7.33 (m, 5H, Ph);013C NMR (LA): d 27.8 (t, C-40), 033.6 (d,
C-30), 52.1 (t, C-5 ), 57.8 (t, 10-CH2Ph), 68.3 (d, C-2 ), 104.2
(d, C-2), 114.7, 119.5 (2s, C-1, CN), 127.6, 128.4, 128.7 (3d,
5C in Ph), 137.5 (s, C in Ph), 151.2 (d, C-3); EI-MS m/z 237
(MC, 35%), 197 (7), 184 (17), 160 (8), 146 (14), 91 (100),
65 (10); HRMS calcd for C15H15N3: 237.1266. Found:
237.1270.
4.4. General procedure for the irradiation of
acrylonitrile 1 with various alkenes
A 0.060 mol LK1 solution of (E)- or (Z)-1 in dry acetonitrile
with 10 equiv of alkene was irradiated with a low-pressure
mercury lamp in a quartz test tube at 0 8C. After removal of
the solvent, flash column chromatography afforded the
adducts. The results are summarized in Table 1.
4.4.1. (2E,20RS,30RS)-3-(1-Benzyl-3-cyanopyrrolidin-2-
yl)acrylonitrile (E)-10a. An oil; IR (CHCl3): 2240 cmK1
1
(C^N); H NMR (AL4): d 2.04–2.20, 2.21–2.30 (each m,
2H, H2-40), 2.37–2.43 (m with td character, 1H, JZ9.5,
7 Hz, H-50), 3.13 (0ddd, 1H, JZ9.5, 7.0, 2.9 Hz, H-50), 3.18–
3.25 (m, 1H, H-3 ), 3.34–3.39 (m, 1H, overlapped with d
at d 3.36, H-20), 3.36, 3.86 (each d, 2H, JZ13.6 Hz,
10-CH2Ph), 5.77 (dd, 1H, JZ16.1, 1.1 Hz, H-2), 6.78 (dd,
1H, JZ16.1, 7.3 Hz, 0H-3), 7.24–7.38 (m, 5H, Ph); 013C NMR
(AL4): d 28.5 (t, C-4 ), 33.4 (d, C-30), 51.6 (t, C-5 ), 57.5 (t,
10-CH2Ph), 65.5 (d, C-20), 103.7 (d, C-2), 116.2, 118.8 (2s,
C-1, CN), 127.2, 128.17, 128.20 (3d, 5C in Ph), 137.1 (s, C
in Ph), 151.1 (d, C-3); EI-MS m/z 237 (MC, 30%), 197 (6),
184 (17), 160 (5), 146 (8), 91 (100), 65 (9); HRMS calcd for
C15H15N3: 237.1266. Found: 237.1271.
4.4.5. Methyl (2RS,3RS)-1-benzyl-2-[(E)-2-cyanovinyl]-
pyrrolidine-3-carboxylate (E)-11a. An oil; IR (CHCl3):
2210 (C^N), 1725 cmK1 (C]O); 1H NMR (AL4): d 1.95–
2.14, 2.15–2.26 (each m, 2H, H2-4), 2.40–2.47 (m with td
character, 1H, JZ9.5, 6 Hz, H-5), 3.04–3.10 (m with ddd
character, 1H, JZ9, 7.5, 2 Hz, H-5), 3.20–3.28 (m with q
character, 1H, JZ9 Hz, H-3), 3.41, 3.80 (each d, 2H, JZ
13.2 Hz, 1-CH2Ph), 3.51 (ddd, 1H, JZ9.2, 7.0, 1.1 Hz,
H-2), 3.68 (s, 3H, OCH3), 5.53 (dd, 1H, JZ16.1, 1.1 Hz,
H-20), 6.78 (dd, 1H, JZ16.1, 7.0 Hz, H-10), 7.24–7.35 (m,
5H, Ph); 13C NMR (AL3): d 26.7 (t, C-4), 48.1 (d, C-3), 52.0
(q, OCH3), 52.4 (t, C-5), 58.1 (t, 1-CH2Ph), 66.0 (d, C-2),
101.6 (d, C-20), 116.9 (s, CN), 127.2, 128.3, 128.4 (3d, 5C in
Ph), 137.9 (s, C in Ph), 152.8 (d, C-10), 171.8 (s, CO2);
EI-MS m/z 270 (MC, 18%), 230 (15), 211 (22), 179 (51), 91
4.4.2. (2E,20RS,30SR)-3-(1-Benzyl-3-cyanopyrrolidin-2-
yl)acrylonitrile (E)-10b. An oil; IR (CHCl3): 2220 cmK1
(C^N); H NMR (AL4): d 2.07–2.16, 2.20–2.30 (each m,
1

10894
K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
(100), 65 (11); HRMS calcd for C16H18N2O2: 270.1368.
Found: 270.1371.
JZ9.5 Hz, 2-H), 5.34 (dd, 1H, JZ11.0, 0.9 Hz, H-20), 6.45
(dd, 1H, JZ11.0, 10 Hz, H-10), 7.22–7.31 (m, 5H, Ph); 13C
NMR (LA): d 27.0 (t, C-4), 28.1 (q, CMe3), 48.5 (d, C-3),
52.4 (t, C-5), 57.7 (t, 1-CH2Ph), 65.2 (d, C-2), 81.1 (s,
CMe3), 100.7 (d, C-20), 115.5 (s, CN), 127.2, 128.3, 128.7
(3d, 5C in Ph), 138.4 (s, C in Ph), 153.7 (d, C-10), 171.2 (s,
CO2); EI-MS m/z 312 (MC, 11%), 255 (21), 239 (17), 221
(19), 211 (11), 184 (9), 165 (37), 133 (14), 91 (100), 41 (9);
HRMS calcd for C19H24N2O2: 312.1838. Found: 312.1834.
4.4.6. Methyl (2RS,3SR)-1-benzyl-2-[(E)-2-cyanovinyl]-
pyrrolidine-3-carboxylate (E)-11b. An oil; IR (CHCl3):
2210 (C^N), 1725 cmK1 (C]O); 1H NMR (AL4): d 2.01–
2.14 (m, 2H, H2-4), 2.34–2.42 (m with q character, 1H, JZ
9 Hz, H-5), 2.81 (ddd, 1H, JZ9.9, 7.7, 5.5 Hz, H-3), 2.98–
3.03 (m with ddd character, 1H, JZ9.5, 7.3, 2.9 Hz, H-5),
3.30, 3.85 (each d, 2H, JZ12.8 Hz, 1-CH2Ph), 3.34–3.39 (m
with t character, 1H, JZ7 Hz, 2-H), 3.72 (s, 3H, OCH3),
5.69 (dd, 1H, JZ16.3, 1.1 Hz, H-20), 6.70 (dd, 1H, JZ16.3,
7.2 Hz, H-10), 7.24–7.35 (m, 5H, Ph); 13C NMR (AL4): d
27.2 (t, C-4), 49.2 (d, C-3), 52.2 (q, OCH3), 52.7 (t, C-5),
58.5 (t, 1-CH2Ph), 68.6 (d, C-2), 101.3 (d, C-20), 116.9 (s,
CN), 127.2, 128.3, 128.5 (3d, 5C in Ph), 138.1 (s, C in Ph),
155.0 (d, C-10), 173.5 (s, CO2); EI-MS m/z 270 (MC, 17%),
230 (27), 211 (26), 179 (75), 91 (100), 65 (11); HRMS calcd
for C16H18N2O2: 270.1368. Found: 270.1364.
4.4.10. tert-Butyl (2RS,3SR)-1-benzyl-2-[(Z)-2-cyano-
vinyl]pyrrolidine-3-carboxylate 12b. Colorless needles;
mp 78–79 8C (hexane/ethyl acetate); IR (CHCl3): 2230
(C^N), 1725 cmK1 (C]O); 1H NMR (LA): d 1.48 (s, 9H,
CMe3), 1.99–2.08, 2.12–2.18 (each m, 2H, H2-4), 2.37–2.43
(m with q character, 1H, JZ9 Hz, H-5), 2.74 (ddd, 1H, JZ
10.3, 8, 5 Hz, H-3), 2.97–3.02 (m with ddd character, 1H,
JZ9, 8, 2 Hz, H-5), 3.38, 3.82 (each d, 2H, JZ13.1 Hz,
1-CH2Ph), 3.57–3.61 (m with dd character, 1H, JZ9, 8 Hz,
H-2), 5.40 (dd, 1H, JZ11.0, 0.6 Hz, H-20), 6.37 (dd, 1H,
JZ11.0, 9.5 Hz, H-10), 7.21–7.31 (m, 5H, Ph); 13C NMR
(LA): d 26.6 (t, C-4), 27.9 (q, CMe3), 50.2 (d, C-3), 53.2 (t,
C-5), 58.3 (t, 1-CH2Ph), 68.3 (d, C-2), 81.4 (s, CMe3), 101.6
(d, C-20), 115.6 (s, CN), 127.2, 128.2, 128.7 (3d, 5C in Ph),
138.5 (s, C in Ph), 154.9 (d, C-10), 172.0 (s, CO2); EI-MS
m/z 312 (MC, 4%), 255 (39), 239 (15), 216 (10), 165 (48),
91 (100), 41 (6). Anal. Calcd for C19H24N2O2: C, 73.05; H,
7.74; N, 8.97%. Found: C, 73.14; H, 7.81; N, 8.92%.
4.4.7. Methyl (2RS,3RS)-1-benzyl-2-[(Z)-2-cyanovinyl]-
pyrrolidine-3-carboxylate (Z)-11a. An oil; bp 160 8C at
0.40 mm Hg; IR (CHCl3): 2220 (C^N) and 1730 cmK1
1
(C]O); H NMR (AL4): d 2.01–2.09, 2.23–2.89 (each m,
2H, H2-4), 2.45 (dt, 1H, JZ9.5, 7.0 Hz, H-5), 3.04–3.09 (m,
1H, H-5), 3.29–3.37 (m with q character, 1H, JZ9 Hz, H-3),
3.54, 3.76 (each d, 2H, JZ13.2 Hz, 1-CH2Ph), 3.66 (s, 3H,
OCH3), 3.86–3.91 (m with dd character, 1H, JZ9.5, 9.2 Hz,
H-2), 5.35 (dd, 1H, JZ11.0, 0.7 Hz, H-20), 6.42 (dd, 1H,
JZ11.0, 9.5 Hz, H-10), 7.29–7.31 (5H, m, Ph); 13C NMR
(AL3): d 27.1 (t, C-4), 47.7 (d, C-3), 51.8 (q, OCH3), 52.4 (t,
C-5), 57.7 (t, 1-CH2Ph), 65.2 (d, C-2), 101.0 (d, C-20), 115.3
(s, CN), 127.2, 128.2, 128.7 (3d, 5C in Ph), 138.1 (s, C in
Ph), 153.3 (d, C-10), 172.6 (s, CO2); EI-MS m/z 270 (MC,
33%), 230 (16), 211 (24), 184 (15), 179 (62), 91 (100), 65
(8). Anal. Calcd for C16H18N2O2: C, 71.09; H, 6.71; N,
10.36%. Found: C, 70.94; H, 6.70; N, 10.30%.
4.4.11. (2Z,10RS,20RS,50SR)-3-(3-Benzyl-8-oxo-3-azabi-
cyclo[3.3.0]oct-2-yl)acrylonitrile 13. Colorless crystals;
mp 91–92 8C (hexane/ethyl acetate); IR (CHCl3): 2220
(C^N), 1730 cmK1 (C]O); 1H NMR (AL4): d 1.80–1.89,
2.03–2.14 (each m, 2H, H2-60), 2.21–2.30 (m with dddd
character, 1H, JZ18, 8, 5, 1 Hz, H-70), 2.35–2.46 (m, 1H,
H-70), 2.54 (dd, 1H, JZ9.8, 8 Hz, H-40), 2.78–2.83 (m with t
character, 1H, JZ8 Hz, H-10), 2.89 (dd, 1H, JZ9.8, 1.4 Hz,
H-40), 2.900–2.98 (m, 1H, H-50), 3.17, 3.79 (each d, 2H, JZ
13.8 Hz, 3 -CH2Ph), 3.68 (dd, 1H, JZ9.8, 7.3 Hz, H-20),
5.51 (dd, 1H, JZ11.0, 0.7 Hz, H-2), 6.46 (dd, 1H, JZ11.0,
9.8 Hz, H-30), 7.22–7.32 (50H, m, Ph); 13C NMR (AL3):0 d
28.3 (t, C-6 ), 38.0 (d, C-5 ), 39.4 (t, C-70), 55.2 (d, C-1 ),
57.9, 61.0 (2t, C-40, 1-CH2Ph), 68.3 (d, C-20), 102.1 (d,
C-2), 115.3 (s, C-1), 127.0, 128.1, 128.2 (3d, 5C in Ph),
138.2 (s, C in Ph), 153.0 (d, C-3), 217.9 (s, C-80); EI-MS m/z
266 (MC, 33%), 226 (5), 210 (20), 184 (13), 175 (16), 91
(100), 65 (9). Anal. Calcd for C17H18N2O: C, 76.66; H,
6.81; N, 10.52%. Found: C, 76.71; H, 6.86; N, 10.46%.
4.4.8. Methyl (2RS,3SR)-1-benzyl-2-[(Z)-2-cyanovinyl]-
pyrrolidine-3-carboxylate (Z)-11b. Colorless crystals; mp
45–48 8C; IR (CHCl3): 2220 (C^N), 1730 cmK1 (C]O);
1H NMR (AL4): d 2.05–2.23 (m, 2H, H2-4), 2.37–2.45 (m,
1H, H-5), 2.83 (ddd, 1H, JZ10.6, 8.4, 5.5 Hz, H-3), 3.00–
3.05 (m with ddd character, 1H, JZ9.5, 8.1, 2 Hz, H-5),
3.40, 3.80 (each d, 2H, JZ13.2 Hz, 1-CH2Ph), 3.61–3.67 (m
with t character, 1H, JZ9 Hz, H-2), 3.75 (s, 3H, OCH3),
5.42 (dd, 1H, JZ11.0, 0.7 Hz, H-20), 6.38 (dd, 1H, JZ11.0,
9.2 Hz, H-10), 7.25–7.32 (m, 5H, Ph); 13C NMR (AL4): d
26.8 (t, C-4), 49.0 (d, C-3), 52.3 (q, OCH3), 53.1 (t, C-5),
58.4 (t, 1-CH2Ph), 68.3 (d, C-2), 101.8 (d, C-20), 115.2 (s,
CN), 127.1, 128.1, 128.6 (3d, 5C in Ph), 138.2 (s, C in Ph),
154.3 (d, C-10), 173.0 (s, CO2); EI-MS m/z 270 (MC, 23%),
230 (34), 211 (29), 179 (100), 91 (82), 65 (9); HRMS calcd
for C16H28N2O2: 270.1368. Found: 270.1367.
4.4.12. (2Z,10RS,20RS,50SR)-3-(3-Benzyl-6,8-dioxo-7-
phenyl-3,7-diazabicyclo[3.3.0]oct-2-yl)acrylonitrile 14.
Colorless crystals; mp 49–51 8C; IR (CHCl3): 2230
1
(C^N), 1720 cmK1 (C]O); H NMR (LA): d 2.56 (dd,
1H, JZ10.1, 7.9 Hz, H-40), 3.33, 3.83 (each d, 2H, JZ
13.4 Hz, 30-CH2Ph), 3.36 (td, 1H, JZ7.9, 0.6 Hz, H-50),
3.47 (d, 1H, JZ10.1 Hz, H-40), 3.54 0(t, 1H, JZ7.9 Hz,
H-10), 3.79 (dd, 1H, JZ9.8, 7.9 Hz, H-2 ), 5.59 (dd, 1H, JZ
11.0, 0.6 Hz, H-2), 6.45 (dd, 1H, JZ11.0, 9.8 Hz, H-3),
7.20–7.23, 7.24–7.32, 7.39–7.43, 7.47–7.51 (4m, 10H, Ph);
13C0 NMR (LA):0 d 43.4 (d, C-50), 48.8 0(d, C-10), 55.9 (t,
C-4 ), 56.8 (t, 3 -CH2Ph), 66.4 (d, C-2 ), 103.5 (d, C-2),
115.2 (s, C-1), 126.3, 127.6, 128.4, 128.5, 128.8, 129.2 (6d,
10C in Ph), 131.7, 136.8 (2s, 2C in Ph), 151.1 (d, C-3),
4.4.9. tert-Butyl (2RS,3RS)-1-benzyl-2-[(Z)-2-cyanovi-
nyl]pyrrolidine-3-carboxylate 12a. Colorless crystals;
mp 54–55 8C; IR (CHCl3): 2230 (C^N), 1725 cmK1
1
(C]O); H NMR (LA): d 1.42 (s, 9H, CMe3), 1.96–2.03,
2.16–2.26 (each m, 2H, H2-4), 2.46 (dt, 1H, JZ9.2, 7.0 Hz,
H-5), 3.02 (ddd, 1H, JZ9.2, 8, 2 Hz, H-5), 3.18–3.24 (m
with q character, 1H, JZ9 Hz, H-3), 3.55, 3.75 (each d, 2H,
JZ13.4 Hz, 1-CH2Ph), 3.88–3.92 (m with t character, 1H,

K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
10895
174.4, 177.4 (2s, C-60, C-80); EI-MS m/z 357 (MC, 55%),
317 (21), 266 (21), 184 (19), 119 (8), 91 (100), 65 (8);
HRMS calcd for C22H19N3O2: 357.1477. Found: 357.1479.
1.99–2.05 (m, 1H, H-40), 2.40 (dd, 1H, JZ9.8, 7.9 Hz,
H-50), 2.62 (dd, 1H, JZ8.5, 5.8 Hz, H-30), 2.73 (dd, 1H, JZ
9.8, 2.7 Hz, H-50), 3.16, 3.86 (each d, 2H, JZ13.4 Hz,
100-CH2Ph), 3.19, 3.50 (each d, 2H, JZ12.8 Hz, 10-CH2Ph),
3.34 (m with t character, 1H, JZ8 Hz, H-20), 4.11, 4.20
(2q, 4H, JZ7.0 Hz, 2OCH2), 6.05 (dd, 1H, JZ15.6, 0.6 Hz,
H-2), 6.87 (dd, 1H, JZ15.6, 7.9 Hz, H-3), 7.15–7.31 (m,
10H, 20P0 h); 13C NMR (LA): d 14.17, 14.23 (2q, 2CH3), 33.0
(t, C-3 ), 43.5 (d, 0C0 -200), 44.5 (d, C-40), 53.5 (d, C-30), 57.0
(t, C-50), 57.8 (t, 1 -CH2Ph), 60.4, 60.8 (2t, 2OCH2), 64.7 (t,
10-CH2Ph), 68.5 (d, C-20), 123.5 (d, C-2), 127.0, 127.1,
128.2, 128.3, 128.5 (5d, 10C in Ph), 138.6, 138.9 (2s, 2C in
Ph), 148.2 (d, C-3), 166.2, 172.9 (2s, C-1, 30-CO2); EI-MS
m/z 462 (MC, 2%), 417 (12), 342 (100), 282 (20), 233 (23),
120 (6), 91 (77); HRMS calcd for C28H34N2O4: 462.2518.
Found: 462.2516.
4.4.13. Methyl (Z)-1-benzyl-2-(2-cyanovinyl)-3-pyrro-
line-3-carboxylate 15. An oil; bp 160 8C at 0.20 mm Hg;
1
IR (CHCl3): 2230 (C^N), 1720 cmK1 (C]O); H NMR
(LA): d 3.50 (ddd, 1H, JZ17, 5, 2 Hz, H-5), 3.74 (s, 3H,
OCH3), 3.74, 3.97 (each d, 2H, JZ13.4 Hz, 1-CH2Ph), 3.87
(ddd, 1H, JZ17, 5.5, 2 Hz, H-5), 04.82–4.87 (m, 1H, 2-H),
5.39 (dd, 1H, JZ10.7, 0.6 Hz, H-2 ), 6.37 (dd, 1H, JZ10.7,
9.2 Hz, H-10), 6.89 (q, 1H, JZ2.1 Hz, H-4), 7.23–7.33 (m,
5H, Ph); 13C NMR (LA): d 51.7 (q, OCH3), 57.5 (t, 1-
CH2Ph), 59.0 (t, C-5), 68.8 (d, C-2), 100.7 (d, C-20), 115.7
(s, CN), 127.3, 128.4, 128.6 (3d, 5C in Ph), 133.5 (s, C-3),
138.3 (s, C in Ph), 141.8 (d, C-4), 153.2 (d, C-10), 163.0 (s,
CO2); EI-MS m/z 268 (MC, 8%), 216 (17), 177 (15), 91
(100), 65 (14); HRMS calcd for C16H16N2O2: 268.1212.
Found: 268.1218.
4.6.2. Triplet sensitization of 2. By analogy with the
photolysis of 1, a solution of (E)-2 (424 mg, 1.83 mmol) in
acetone (31 mL) was irradiated with a high-pressure
mercury lamp in a Pyrex test tube (conversion 84%) for
11.5 h at rt. After removal of the solvent, flash column
chromatography [hexane–ethyl acetate (3:2)] of the residue
afforded (Z)-2 (67 mg, 25%9).
4.5. Thermal reactions of nitrile 1 with alkenes
By analogy with the photoreactions of (Z)-1,
a
0.060 mol LK1 solution of (Z)-1 in xylene with 10 equiv
of tert-butyl acrylate or N-phenylmaleimide was heated
under reflux. Flash column chromatography afforded the
adducts. The results are summarized in Table 1.
4.6.3. Ethyl (2E,20RS,30RS)-3-(1-benzyl-3-cyanopyrroli-
din-2-yl)acrylate 17a and ethyl (2E,20RS,30SR)-3-(1-
benzyl-3-cyanopyrrolidin-2-yl)acrylate 17b. By analogy
with the photoreactions of 1, a 0.060 mol LK1 solution of
(E)-2 in dry acetonitrile with 10 equiv of acrylonitrile was
irradiated. Preparative TLC [hexane–ethyl acetate (3:1)]
afforded the adducts. The results are summarized in Table 2.
4.6. Irradiation of ethyl acrylate 2
4.6.1. Ethyl (2E,20RS,30SR,40SR)-3-[1-benzyl-4-(1-benzyl-
aziridin-2-yl)-3-ethoxycarbonylpyrrolidin-2-yl]acrylate
16A and ethyl (2E,20RS,30SR,40SR)-3-[1-benzyl-4-(1-ben-
zylaziridin-2-yl)-3-ethoxycarbonylpyrrolidin-2-yl]acryl-
ate 16B. By analogy with the photolysis of 1, a solution of
(E)-2 (51.8 mg, 0.223 mmol) in acetonitrile was irradiated
(conversion 98%) for 2 h at rt. Preparative TLC [hexane–
ethyl acetate–diethylamine (9:1:0.5)] of the reaction
mixture afforded dimers 16A (9.8 mg, 19%9) and 16B
(3.3 mg, 7%9).
Compound 17a. An oil; bp 180 8C at 0.20 mm Hg
(decomp.); IR (CHCl3): 2250 (C^N), 1715 cmK1
1
(C]O); H NMR (LA): d 1.31 (t, 3H, JZ7.0 Hz, CH3),
2.13–2.27 (m, 2H, H2-40), 2.28–2.34 (m with dt character,
1H, JZ9, 8 Hz, H-50), 3.07–3.12 (m with ddd character, 1H,
JZ9, 8, 3 Hz, H-50), 3.16–3.21 (m with ddd character, 1H,
JZ8.5, 7, 6.1 Hz, H-30), 3.27, 3.92 (each d, 2H, JZ13.1 Hz,
10-CH2Ph), 3.27–3.31 (m, 1H, H-20), 4.22 (q, 2H, JZ
7.0 Hz, OCH2), 6.14 (dd, 1H, JZ15.6, 0.9 Hz, H-2), 6.98
(dd, 1H, JZ15.6, 8.2 Hz, H-3), 7.22–7.330(m, 5H, Ph); 130C
NMR (LA): d 14.2 (q, CH3), 28.4 (t, C-4 ), 33.7 (d, C-3 ),
51.3 (t, C-50), 57.1 (t, 10-CH2Ph), 60.7 (t, OCH2), 65.8 (d,
C-20), 119.6 (s, CN), 126.2 (d, C-2), 127.3, 128.3, 128.5 (3d,
5C in Ph), 137.9 (s, C in Ph), 144.0 (d, C-3), 165.3 (s, C-1);
EI-MS m/z 284 (MC, 10%), 255 (11), 239 (10), 211 (35),
193 (68), 158 (38), 140 (14), 112 (19), 91 (100); HRMS
calcd for C17H20N2O2: 284.1525. Found: 284.1529.
Compound 16A. An oil; IR (CHCl3): 1720 cmK1 (C]O);
1H NMR (LA): d 1.22, 1.31 (2t, 6H, JZ7.0 Hz, 2CH3), 1.36
(d, 1H, JZ6.1 Hz, H-300), 1.63–1.67 (m, 2H, H-200, H-3000),
2.16–2.22 (m, 1H, H-40), 2.38 (dd,01H, JZ9.7, 8 Hz, H-5 ),
2.49 (dd, 1H, JZ8.2, 5.2 Hz, H-3 ), 2.77 (dd, 1H, JZ9.7,
2.4 Hz, H-50), 3.14, 3.88 (each d, 2H, JZ13.1 Hz, 100-
CH2Ph), 3.23, 3.56 (each d, 2H, JZ12.8 Hz, 10-CH2Ph),
3.25 (m, 1H, H-20), 4.21, 4.22 (2q, 4H, JZ7.0 Hz, 2OCH2),
6.00 (dd, 1H, JZ15.6, 0.6 Hz, H-2), 6.80 (dd, 1H, JZ15.6,
7.9 Hz, H-3), 7.22–7.33 (m, 10H,002Ph); 13C NMR (LA): d
14.2, 14.3 (2q, 2CH3), 33.2 (t, C-3 ), 42.8 (d, C-200), 43.5 (d,
C-40), 54.2 (d, C-30), 55.6 (t, C-50), 58.0 (t, 100-CH2Ph), 60.4,
60.8 (2t, 2OCH2), 64.7 (t, 10-CH2Ph), 69.0 (d, C-20), 123.2
(d, C-2), 127.0, 127.1, 128.26, 128.34, 128.5 (5d, 10C in
Ph), 138.7, 139.2 (2s, 2C in Ph), 148.2 (d, C-3), 166.2, 173.3
(2s, C-1, 30-CO2); EI-MS m/z 462 (MC, 2%), 417 (6), 342
(41), 282 (17), 233 (17), 120 (7), 91 (100); HRMS calcd for
C28H34N2O4: 462.2518. Found: 462.2527.
Compound 17b. An oil; IR (CHCl3): 2240 (C^N),
1
1715 cmK1 (C]O); H NMR (LA): d 1.31 (t, 3H, JZ
7.0 Hz, CH3), 2.05–2.12, 2.26–2.30 (2m, 2H, H2-40), 2.38–
2.44 (m with q character, 1H, JZ9 Hz, H-50), 2.84 (ddd,
1H, JZ10.7, 8.2, 6.4 Hz, H-30), 3.03 (ddd, 1H, JZ9.5,
8.2, 2.7 Hz, H-50), 3.25, 3.93 (each d, 2H, JZ12.8 Hz,
10-CH2Ph), 3.27 (t, 1H, JZ8.2 Hz, 20-H), 4.22 (q, 2H, JZ
7.0 Hz, OCH2), 6.20 (dd, 1H, JZ15.9, 0.6 Hz, H-2), 6.79
(dd, 1H, JZ15.9, 8.2 Hz, H-3), 7.23–7.330(m, 5H, Ph); 130C
NMR (LA): d 14.2 (q, CH3), 27.7 (t, C-4 ), 33.8 (d, C-3 ),
51.8 (t, C-50), 57.6 (t, 10-CH2Ph), 60.7 (t, OCH2), 69.5 (d,
C-20), 120.5 (s, CN), 125.6 (d, C-2), 127.4, 128.4, 128.6 (3d,
Compound 16B. An oil; IR (CHCl3): 1730 cmK1 (C]O);
1H NMR (LA): d 1.22, 1.30 (2t, 6H, JZ7.0 Hz, 2CH3), 1.44
(d, 1H, JZ6.4 Hz, H-300), 1.68–1.73 (m, 2H, H-200, H-300),

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K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
5C in Ph), 137.7 (s, C in Ph), 145.1 (d, C-3), 165.5 (s, C-1);
EI-MS m/z 284 (MC, 5%), 255 (11), 239 (15), 211 (25), 193
(67), 158 (27), 140 (12), 112 (15), 91 (100); HRMS calcd for
C17H20N2O2: 284.1525. Found: 284.1523.
JZ7.2 Hz, OCH2), 4.42–4.44 (m with d character, 1H, JZ
7.2 Hz, H-5), 5.61–5.66 (m, 1H, H-3), 5.97–6.04 (m, 1H,
H-4), 6.87 (dd, 1H, JZ7.6, 1 Hz, H-9), 6.96 (td, 1H, JZ7.6,
1.2 Hz, H-7), 7.04 (dd, 1H, JZ7.6, 1.6 Hz, H-6), 7.16 (td,
2H, JZ7.6, 1.6 Hz, H-8); 13C NMR (AL4): d 14.3 (q, CH3),
48.4 (t, C-2), 49.2 (d, C-5), 61.0 (t, OCH2), 121.8 (d, C-9),
122.5 (d, C-7), 124.3 (d, C-4), 128.1 (d, C-8), 128.6 (d, C-6),
129.1 (d, C-3), 134.3 (s, C-5a), 147.9 (s, C-9a), 172.5 (s,
5-CO); EI-MS m/z 217 (MC, 28%), 188 (3), 172 (5), 144
(100), 127 (4), 115 (7), 72 (2); HRMS calcd for C13H15NO2:
217.1103. Found: 217.1099.
4.7. Reaction of N-phenylaziridine (E)-3
4.7.1. Ethyl (2E,20RS,30RS)-3-(3-cyano-1-phenylpyrroli-
din-2-yl)acrylate 18a and ethyl (2E,20RS,30SR)-3-(3-
cyano-1-phenylpyrrolidin-2-yl)acrylate 18b. By analogy
with the photoreactions of (Z)-1, a 0.060 mol LK1 solution
of (E)-3 in dry acetonitrile with 10 equiv of acrylonitrile was
irradiated. Preparative TLC [SiO2; hexane–ethyl acetate
(3:1)] afforded the adducts. The results are summarized in
Table 2.
4.8. Reaction of N-benzoylaziridine (E)-4
4.8.1. Ethyl (2E,4E)-5-benzamido-2,4-pentadienoate 20.
By analogy with the photoreactions of 1, a solution of (E)-4
(124 mg, 0.51 mmol) in dry acetonitrile (8.5 mL) with
10 equiv of acrylonitrile (270 mg, 5.1 mmol) was irradiated
for 5 h at rt (conversion 74%). After removal of the solvent,
preparative TLC [hexane–ethyl acetate (3:1)] of the residue
afforded dienoate 20 (27.9 mg, 30%9). Colorless plates; mp
124–127 8C (hexane/ethyl acetate); IR (CHCl3): 1690 cmK1
Compound 18a. An oil; IR (CHCl3): 2240 (C^N),
1
1720 cmK1 (C]O); H NMR (AL3): d 1.28 (t, 3H, JZ
7.2 Hz, CH3), 2.26–2.41, 2.44–2.53 (2m, 2H, H2-40), 3.28
(ddd, 1H, JZ12.0, 7.8, 6.3 Hz, H-30), 3.34–3.43 (m with td
character, 1H, JZ9, 7 Hz, H-50), 3.60–3.67 (m with td
character, 1H, JZ9, 2 Hz, H-50), 4.19 (q, 2H, JZ7.2 Hz,
OCH2), 4.55–4.60 (m, 1H, H-20), 6.00 (dd, 1H, JZ15.6,
1.5 Hz, H-2), 6.51–6.54 (m with d character, 2H, JZ7.9 Hz,
1
(C]O); H NMR (AL4): d 1.27 (t, 3H, JZ7.2 Hz, CH3),
4.19 (q, 2H, JZ7.2 Hz, OCH2), 5.74 (d, 1H, JZ15.2 Hz,
H-2), 6.09 (dd, 1H, JZ14.0, 11.6 Hz, H-4), 7.31 (dd, 1H,
JZ15.2, 11.6 Hz, H-3), 7.45 (t, 2H, JZ7.2 Hz, H-30, H-5),
7.49–7.54 (m with d character, 1H, JZ14.0 Hz, H-2), 7.56
(t, 1H, JZ7.2 Hz, H-40), 7.86 (d, 2H, JZ7.2 Hz, H-20,
H-60), 8.78 (br d, 1H, JZ11 Hz, NH); 13C NMR (AL4): d
14.3 (q, CH3), 60.2 (t, OCH2), 111.3, 111.8 (2d, C-2, C-4),
127.3, 128.5 (2d, 4C in Ph), 132.5, 133.2 (2d, C-5, C in Ph),
132.8 (s, C in Ph), 143.4 (d, C-3), 164.7, 167.2 (2s, C-1,
CONH); EI-MS m/z 245 (MC, 19%), 200 (4), 140 (7), 105
(100), 77 (26), 51 (4); HRMS calcd for C14H15NO3:
245.1052. Found: 245.1046.
00
H-2 , H-600), 6.75–6.80 (m with t character, 1H, JZ7.3 Hz,
00
H-4 ), 7.04 (dd, 1H, JZ15.6, 4.8 Hz, H-3), 7.21–7.26 (m,
2H,0H-300, H-500); 13C NMR (AL4): d 14.3 (q, CH3), 27.9 (t,
C-4 ), 33.1 (d, C-30), 47.0 (t, C-50), 59.9 (d, C-20), 60.8 (t,
OCH2), 112.1 (d, C-200, C-600), 117.5 (s, CN), 117.7 (d, C-
400), 125.3 (d, C-2), 129.2 (d, C-300, C-500), 142.4 (d, C-3),
145.4 (s, C-100), 165.1 (s, C-1); EI-MS m/z 270 (MC, 68%),
241 (70), 225 (34), 197 (50), 171 (18), 144 (100), 112 (16),
104 (11), 84 (13), 77 (24); HRMS calcd for C17H20N2O2:
270.1368. Found: 270.1371.
Compound 18b. An oil; IR (CHCl3): 2240 (C^N),
1
1720 cmK1 (C]O); H NMR (AL3)0: d 1.27 (t, 3H, JZ
4.8.2. Thermal reactions of (E)-4. A solution of (E)-4
(300 mg, 1.22 mmol) in xylene (20 mL) with 10 equiv of
tert-butyl acrylate (1.54 g, 12 mmol) was heated under
reflux for 3.5 h (conversion 83%). After removal of the
solvent, flash column chromatography [hexane–ethyl acet-
ate (6:1)] of the residue afforded pyridine 2112 (9.1 mg,
4%9) and a mixture of isomers of dienoate 20 (134 mg).
7.2 Hz, CH3), 2.32–2.39 (m, 2H, H2-4 ), 3.06–3.11 (m, 1H,
H-30), 3.57–3.72 (m, 2H, H2-50), 4.18 (q, 2H, JZ7.2 Hz,
OCH2), 4.58–4.62 (m, 1H, H-20), 5.99 (dd, 1H, JZ15.3,
1.7 Hz, H-2), 6.54–6.58 (m with d character, 2H, JZ9 Hz,
H-2 , H-600), 6.76–6.82 (m with t character, 1H, JZ7.3 Hz,
00
00
H-4 ), 6.86 (dd, 1H, JZ15.3, 4.8 Hz, H-3), 7.20–7.28 (m,
2H,0H-300, H-500); 13C NMR (AL4): d 14.3 (q, CH3), 27.8 (t,
C-4 ), 34.7 (d, C-30), 47.2 (t, C-50), 60.9 (t, OCH2), 63.3 (d,
C-20), 112.6 (d, C-200, C-600), 117.8 (d, C-400), 119.7 (s, CN),
124.0 (d, C-2), 129.2 (d, C-300, C-500), 144.3 (d, C-3), 145.6
(s, C-100), 165.4 (s, C-1); EI-MS m/z 270 (MC, 67%), 241
(72), 225 (32), 197 (53), 171 (24), 144 (100), 112 (15), 104
(12), 84 (13), 77 (28); HRMS calcd for C17H20N2O2:
270.1368. Found: 270.1365.
4.9. Reaction of N-trityl aziridine (E)-5
4.9.1. Ethyl (2E,20RS,30RS)-3-(3-cyano-1-tritylpyrroli-
din-2-yl)acrylate 22. By analogy with the photoreactions
of (Z)-1, a 0.060 mol LK1 solution of (E)-5 in dry
acetonitrile with 10 equiv of acrylonitrile was irradiated.
Preparative TLC [hexane–ethyl acetate (5:1)] afforded the
adduct 22. The results are summarized in Table 2. An oil; IR
(CHCl3): 2240 (C^N), 1710 cmK1 (C]O); 1H NMR
(AL4): d 1.27–1.34 (m, 1H, H-30) 1.36 (t, 03H, JZ7.2 Hz,
CH3), 1.62–1.70, 1.75–1.87 (2m, 2H, H2-4 ), 3.07 (td, 1H,
JZ13, 8.4 Hz, H-50), 3.48 (ddd, 1H, JZ13, 10.0, 4.0 Hz,
H-50), 4.19 (t, 1H, JZ6.4 Hz, H-20) 4.28 (q, 2H, JZ7.2 Hz,
OCH2), 6.34 (d, 1H, JZ15.6 Hz, H-2), 7.09 (dd, 1H, JZ
15.6, 6.4 Hz, H-3), 7.18–7.57 (m, 15H, Tr); 103C NMR
(AL4): d 14.4 (q, CH3), 29.1 (t, C-40), 31.3 (d, C-3 ), 48.3 (t,
C-50), 60.8 (t, OCH2), 63.0 (d, C-20), 78.0 (s, CPh3), 118.9
(s, CN), 123.7 (d, C-2), 126.6 (d, 3C in Ph), 127.9 (d, 6C in
Ph), 128.8 (d, 6C in Ph), 143.8 (s, 3C in Ph), 144.8 (d, C-3),
4.7.2. Ethyl 2,5-dihydro-1H-1-benzazepine-5-carboxyl-
ate 19. A solution of (E)-3 (100 mg, 0.46 mmol) in xylene
(7.6 mL) with 10 equiv of 3,4-dihydro-2H-pyrane (386 mg,
4.6 mmol) was heated under reflux for 1.5 h (conversion
98%). After removal of the solvent, preparative TLC
[hexane–ethyl acetate (3:1)] of the residue afforded
benzazepine 19 (41.2 mg, 42%9). An oil; IR (CHCl3):
3340 (N–H), 1720 cmK1 (C]O); 1H NMR (AL4): d 1.22 (t,
3H, JZ7.2 Hz, CH3), 3.30 (br s, 1H, NH), 3.66–3.73 (m
with ddd character, 1H, JZ17.2, 4.8, 2.8 Hz, H-2), 3.75–
3.82 (m with d character, 1H, JZ17.2 Hz, H-2), 4.19 (q, 2H,

K. Ishii et al. / Tetrahedron 60 (2004) 10887–10898
10897
165.8 (s, C-1); EI-MS m/z 436 (MC, 0.4%), 359 (1), 243
(100), 165 (2); HRMS calcd for C29H28N2O2: 436.2151.
Found: 436.2150.
NH-silica gel column chromatography [hexane–ethyl acet-
ate (1:5)] to afford 25 (11.7 mg, 64%).
1
An oil; IR (CHCl3): 3410 (N–H), 1720 cmK1 (C]O); H
4.9.2. Ethyl (2E,20RS,30RS)-3-(3-methoxycarbonyl-1-tri-
tylpyrrolidin-2-yl)acrylate 23. By analogy with the
photoreactions of (Z)-1, a solution of (E)-5 in dry
acetonitrile with 10 equiv of methyl acrylate was irradiated.
Preparative TLC [hexane–ethyl acetate (7:1)] afforded the
adduct 23. The results are summarized in Table 2. Colorless
crystals; mp 134–135 8C (hexane/ethyl acetate); IR
(CHCl3): 1720 (C]O), 1710 cmK1 (C]O); 1H NMR
(AL4): d 1.33 (t, 3H, JZ7.1 Hz, OCH2CH3), 1.34–1.40,
1.86–1.97 (2m, 2H, H2-40), 1.59 (dt, 1H, JZ10.5, 8.3 Hz,
H-30), 2.97–3.06, 3.41–3.49 (m, 2H, H2-50), 3.49 (s, 3H,
OCH3), 4.19–4.23 (m, 1H, overlapping with q at d 4.23,
H-20) 4.23 (q, 2H, JZ7.1 Hz, OCH2), 6.14 (d, 1H, JZ
15.6 Hz, H-2), 6.86 (dd, 1H, JZ15.6, 6.4 Hz, H-3), 7.12–
7.29 (m, 9H, Tr), 7.56 (d, 6H, JZ7.6 Hz, Tr); 13C NMR
(AL4): d 14.3 (q, OCH2CH3), 26.6 (t, C-40), 47.6 (d, C-30),
48.3 (t, C-50), 51.5 (q, OCH3), 60.4 (t, OCH2), 63.4 (d, C-20),
78.0 (s, CPh3), 122.1 (d, C-2), 126.3 (d, 3C in Ph), 127.7 (d,
6C in Ph), 129.0 (d, 6C in Ph), 144.2 (s, 3C in Ph), 146.6 (d,
C-3), 166.2 (s, C-1), 171.6 (s, CO2CH3); EI-MS m/z 469
(MC, 1%), 392 (3), 243 (100), 228 (4), 198 (2), 165 (23),
154 (2), 91 (2); HRMS calcd for C30H31NO4: 469.2253.
Found: 469.2252.
NMR (AL4): d 1.25 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.62–
1.85 (m, 3H, NH and H2-3), 1.93–2.10 (m, 2H, H2-40), 2.44–
2.50 (m, 2H, H2-2), 2.79–2.87 (m, 1H, H-50), 2.92–2.97 (m,
1H, H-30), 3.04–3.11 (m, 1H, H-20), 3.18–3.25 (m, 1H, H-
50), 3.68 (s, 3H, OCH3), 4.13 (q, 2H, JZ7.2 Hz, OCH2); 13C
NMR (AL4): d 14.4 (q, OCH2CH3), 26.4 (t, C-3), 30.3 (t,
C-40), 32.5 (t, C-2), 46.4 (t, C-50), 047.6 (d, C-30), 51.5 (q,
OCH3), 60.4 (t, OCH2), 63.0 (d, C-2 ), 173.0, 174.9 (2s, C-1,
CO2CH3); EI-MS m/z 229 (MC, 4%), 183 (34), 155 (29),
152 (24), 128 (100), 97 (76), 69 (26); HRMS calcd for
C11H19NO4: 229.1314. Found: 229.1314.
4.10.3. Methyl (4RS,5RS)-8-oxo-1-azabicyclo[3.3.0]oct-
4-ylcarboxylate 26.
A solution of 25 (14.6 mg,
0.065 mmol) in toluene (1.0 mL) was refluxed for 15.5 h.
The reaction mixture was concentrated in vacuo, giving a
residue that was subjected to flush column chromatography
[ethyl acetate] to afford 265 (10.3 mg, 87%).
1
An oil; IR (CHCl3): 1730 (C]O), 1695 cmK1 (C]O); H
NMR (AL4): d 1.69–1.78 (m, 1H, H-6), 2.16–2.43 (m, 4H,
H2-3, H-6, H-7), 2.61–2.70 (m, 1H, H-7), 3.02 (td, 1H, JZ
7.1, 3.4 Hz, H-4), 3.04–3.11 (m, 1H, H-2), 3.70 (s, 3H,
OCH3), 3.82 (td, 1H, JZ11.2, 7.6 Hz, H-2), 4.16 (q, 1H, JZ
7 Hz, H-5); 13C NMR (AL4): d 22.6 (t, C-6), 30.4 (t, C-3),
34.0 (t, C-7), 41.3 (t, C-2), 45.5 (d, C-4), 51.9 (q, OCH3),
63.2 (d, C-5), 172.6, 175.2 (2s, C-8, CO2CH3); EI-MS m/z
183 (MC, 37%), 183 (34), 155 (45), 152 (26), 97 (100), 69
(44); HRMS calcd for C9H13NO3: 183.0895. Found:
183.0892.
4.10. Application to the synthesis of (G)-isoretronecanol
27
4.10.1. Ethyl (2E,20RS,30RS)-3-(3-methoxycarbonylpyr-
rolidin-2-yl)acrylate 24. To a solution of 23 (430 mg,
0.86 mmol) in chloroform (0.7 mL) and methanol (0.7 mL)
was trifluoroacetic acid (1.3 mL) at rt. After being stirred for
1 h at rt, the reaction mixture was extracted with water (2!
3 mL). The aqueous phase was neutralized with aqueous
saturated NaHCO3 and extracted with chloroform (3!
5 mL). The organic phase was washed with brine, dried with
MgSO4, and concentrated in vacuo to yield 24 (168 mg,
83%).
Compound 26.5b 1H NMR (250 MHz): d 1.5–1.75 (m, 1H),
2.0–2.4 (m, 4H), 2.45–2.7 (m, 1H), 2.85–3.1 (m, 2H), 3.6 (s,
3H), 3.5–3.8 (m, 1H), 4.08 (q, 1H, JZ7 Hz); 13C NMR
(62.5 MHz): d 22.3, 30.2, 33.6, 41.0, 45.2, 51.8, 63.1, 172.9,
175.4.
An oil; IR (CHCl3): 3510 (N–H), 1710 cmK1 (C]O); H
1
Acknowledgements
NMR (AL4): d 1.28 (t, 3H, JZ7.2 Hz, OCH2CH3), 1.77
(brs, 1H, NH), 2.01–2.20 (m, 2H, H2-40), 2.91–2.99 (m with
ddd-character, 1H, JZ11, 8.3, 7.8 Hz, H-50), 3.11–3.17 (m,
1H, H-30), 3.29 (ddd, 1H, JZ11.2, 8.6, 04.4 Hz, H-50), 3.64
(s, 3H, OCH3), 3.87–3.92 (m, 1H, H-2 ) 4.19 (q, 2H, JZ
7.2 Hz, OCH2), 5.99 (dd, 1H, JZ15.6, 1.5 Hz, H-2), 6.89
(dd, 1H, JZ15.6, 6.3 Hz, H-3); 13C NMR (AL4): d 14.3 (q,
OCH2CH3), 29.3 (t, C-40), 46.3 (t, C-50), 48.5 (d, C-30), 51.7
(q, OCH3), 60.4 (t, OCH2), 62.8 (d, C-20), 122.3 (d, C-2),
144.5 (d, C-3), 165.7 (s, C-1), 173.4 (s, CO2CH3); EI-MS
m/z 227 (MC, 21%), 198 (100), 181 (40), 154 (41), 128 (38),
116 (80), 100 (48), 56 (42); HRMS calcd for C11H17NO4:
227.1158. Found: 227.1160.
This work was partially supported by the Grant-in-Aid for
Scientific Research (C) (No. 13672239) administered by
Japan Society for the Promotion of Science and by Bio
Venture Center of Meiji Pharmaceutical University. The
authors wish to thank the staff of the Analysis Center of
Meiji Pharmaceutical University for performing the
elemental analysis and measurements of LA-NMR
(HMBC and NOESY spectra) (Miss S. Kubota) and mass
spectra (Miss T. Koseki). We are also grateful to Mr. N. Goi
for his technical assistance.
4.10.2. Ethyl (20RS,30RS)-3-(3-methoxycarbonylpyrroli-
din-2-yl)propanate 25. A solution of 24 (18.1 mg,
0.08 mmol) in ethyl acetate (0.5 mL) with 10% Pd/C
(5.2 mg) under hydrogen was stirred for 21 h at rt. The
reaction mixture was filtered with celite, and the filtrate was
concentrated in vacuo, giving a residue that was subjected to
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