Photoreactions of β-aziridinylacrylonitrile. 1,3-Dipolar cycloadditions of photoinduced azomethine ylide

Article abstract of DOI:10.1039/b004850j

The photoinduced azomethine ylide A from the 3-(1-benzylaziridin-2-yl)prop-2-enenitrile 1 undergoes 1,3-dipolar cycloaddition with electron-deficient olefins to give the head-to-head adducts selectively and efficiently. The Royal Society of Chemistry 2000

Full text of DOI:10.1039/b004850j

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Photoreactions of ꢀ-aziridinylacrylonitrile. 1,3-Dipolar
cycloadditions of photoinduced azomethine ylide
Keitaro Ishii,* Yukio Shimada, Shigeo Sugiyama and Masahiro Noji
1
Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose-shi, Tokyo 204-8588, Japan
Received (in Cambridge, UK) 19th June 2000, Accepted 10th August 2000
Published on the Web 23rd August 2000
a
The photoinduced azomethine ylide A from the 3-(1-benz-
ylaziridin-2-yl)prop-2-enenitrile 1 undergoes 1,3-dipolar
cycloaddition with electron-deficient olefins to give the
head-to-head adducts selectively and efficiently.
Table 1 Photoreactions of nitrile 1 with olefins
Conversion
(%)
b
1
Olefin
Products and yields (%)‡
The 1,3-dipolar cycloaddition of azomethine ylides with olefins
E
Z
E
Z
Z
Z
Z
Z
Acrylonitrile
Acrylonitrile
100
100
87
(E)-4a (52) and (E)-4b (26)
(Z)-4a (52) and (Z)-4b (15)
(E)-5a (37) and (E)-5b (25)
(Z)-5a (38) and (Z)-5b (48)
6a (23) [21] and 6b (49) [13]
7 (39)
is an important and useful strategy for the construction of the
1
Methyl acrylate
Methyl acrylate
tert-Butyl acrylate
Pent-2-enone
N-Phenylmaleimide
Methyl propiolate
pyrrolidine system. The azomethine ylides used for 1,3-dipolar
98
90 [86]
cycloaddition have been generated mainly by desilylation of
c
2
N-(silylmethyl)amine derivatives or by heating or irradiation
91
84 [81]
66
3,4
of the aziridines, most of which bear an adjacent electron
withdrawing or phenyl group.
8 (39) [42]
9 (49)
We are investigating the photochemical reactions of α,β-
a
Ϫ3
5–8
A 0.060 mmol cm solution of 1 in acetonitrile with 10 equiv. of
b c
unsaturated γ,δ-epoxy nitriles systematically. These studies
olefin was irradiated at RT. Isolated yield. Values in square brackets
are yields of thermal reactions in refluxing xylene.
have revealed that the epoxy nitriles generate the carbonyl
5
ylides more efficiently than the corresponding epoxy enones. In
previous reports, we showed the usefulness of the carbonyl
7
ylides in the syntheses of spiroacetal derivatives8 and in 1,3-
propiolate) were studied. The results are summarized in Table 1.
The photoreactions of the nitrile 1 and other electron-deficient
olefins, such as dimethyl fumarate and dimethyl acetylenedi-
carboxylate, gave only dimethyl maleate and a complex mixture,
respectively. On the other hand, the reactions of 1 and non-
activated olefins (bicyclo[2.2.1]hept-2-ene and cyclohexene) or
electron-rich olefins (ethyl vinyl ether) afforded no cycloadducts
of these dipolarophiles, and gave only the dimer 3.
dipolar cycloadditions with electron-rich olefins. On the basis
of these studies, we became interested in extending our epoxy
nitrile photochemistry to the aziridine-containing compound 1.
9
The nitrile 1† was prepared from the aldehyde 2 in
7
(
5% yield (E:Z = 44:31) by the Horner–Emmons reaction
Scheme 1). The nitriles (E)- and (Z)-1 were easily separated
with silica gel column chromatography.
Scheme 1 Reagents and conditions: i, (EtO) P(O)CH CN, NaH, THF,
2
2
0
ЊC; ii, λ > 280 nm, acetone, RT; iii, λ = 254 nm, acetonitrile, RT.
On triplet sensitization, the nitrile (Z)-1 in acetone (λ > 280
nm) selectively undergoes (E/Z)-isomerization of the side
chain leading to (E)-1 (64%‡). Direct irradiation of (Z)-1 in
acetonitrile (λ = 254 nm) gave two head-to-head dimers 3A†
(
14%‡) and 3B† (32%‡) (Scheme 1), which are probably
formed by 1,3-dipolar cycloaddition of azomethine ylide A
generated photochemically from (Z)-1] and the ground state
of (Z)-1.
Since the photolysis of the nitrile 1 had given the cyclo-
The structures of the cycloadducts 3–9† were deduced on the
basis of their spectral data. The molecular ion peak in the mass
spectrum (MS) indicates the 1:1 adducts of the azomethine
ylide A and the olefin. The regio- and stereochemistries of 3A
and 3B were determined from the H–H and C–H COSY and
the phase-sensitive NOESY spectra. In particular, the cross-
[
adducts 3 in moderate yield, the cycloadditions of A and
electron-deficient olefins (acrylonitrile, methyl acrylate, tert-
butyl acrylate, pent-2-enone, N-phenylmaleimide and methyl
peaks between H-2Ј and H-3Ј, H-3Ј and H-4Ј, H-4Ј and H -5Ј
a
and H -5Ј and H-2Ј in the NOESY spectra (Fig. 1) show that
a
3
022
J. Chem. Soc., Perkin Trans. 1, 2000, 3022–3024
This journal is © The Royal Society of Chemistry 2000
DOI: 10.1039/b004850j

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and gave the same adducts 6a (21%‡) and 6b (13%‡) and 8
42%‡) as yielded by the photoreactions, respectively. The
(
results may suggest that the ring cleavage of the aziridine 1
proceeds photochemically or thermally and the cycloaddition
occurs thermally.
The regiochemistry of the adducts could not be clearly
10
explained by frontier-MO theory. In order to clarify the
reaction mechanism, further work with unsymmetrically sub-
stituted dipolarophiles and 3Ј-alkyl substituted aziridine is
currently in progress.
Fig. 1 Phase-sensitive NOESY.
Experimental
Typical procedure for the photochemical reaction of (Z)-1 and
acrylonitrile
A solution of (Z)-1 (50.6 mg, 0.271 mmol) and acrylonitrile
3
(
144 mg, 2.71 mmol) in acetonitrile (4.5 cm ) was irradiated
with a low-pressure mercury lamp (60 W) through a quartz
filter (100% conversion) under argon for 7 h at RT. After
removal of the solvent, chromatography (eluting with hexane–
ethyl acetate, 7:3) of the residue yielded (Z)-4a† (33.3 mg,
5
2%‡) and (Z)-4b† (9.7 mg, 15%‡).
Acknowledgements
The authors wish to thank the staff of the Analysis Center of
Meiji Pharmaceutical University for performing the elemental
analysis and for measurements of 500 MHz NMR spectra
(
Miss S. Yoshioka) and mass spectra (Miss T. Koseki). We are
Fig. 2
also grateful to Mr Y. Furukawa for X-ray structure analysis in
Sankyo Co., Ltd. This work was partially supported by the
Science Research Promotion Fund from the Promotion and
Mutual Aid Corporation for Private Schools of Japan.
1
Table 2 Chemical shift of H-C(3Ј) in the H NMR spectrum for 3–6
Adduct
δ
Adduct
δ
a
a
3
A
3.46 dd
3B
3.36 dd
Notes and references
(
(
(
(
E)-4a a
Z)-4aa
E)-5a
3.18–3.25 m
3.29 ddd
3.20–3.28 m
3.29–3.37 m
3.18–3.24 m
(E)-4b a
(Z)-4b
(E)-5b
(Z)-5b
2.82 ddd
2.85 ddd
2.81 ddd
2.83 ddd
2.74 ddd
1
13
†
All new compounds were isolated and exhibited IR, H NMR,
C
NMR and mass spectra that were consistent with the assigned struc-
tures, and gave satisfactory elemental analyses and/or high-resolution
a
Z)-5a
a
a
6
a
6b
mass spectra. Selected NMR data in CDCl for 3A, 3B, (Z)-4a, (Z)-4b
and 9 are representative (J values in Hz). 3A: δ 1.48 (1H, d, J 6.1), 1.68
(1H, d, J 3.4), 1.85–1.89 (1H, m), 2.11–2.18 (1H, m), 3.46 (1H, dd, J 8
and 6.1), 3.75 (1H, dd, J 9.2 and 6.1), 5.59 (1H, dd, J 11.0 and 0.6) and
3
a
The stereochemistry was also determined from the phase-sensitive
NOESY spectrum.
H
6
.65 (1H, dd, J 11.0 and 9.2); δ 33.4 (t), 38.8 (d), 40.0 (d), 43.1 (d), 54.4
C
the configurations at C(2Ј), C(3Ј) and C(4Ј) in the pyrrolidine
ring are all cis. Therefore the dimers 3A and 3B are epimeric at
C(2Љ). Further evidence for the structure of 3B was provided
by an X-ray structure analysis§ (Fig. 2).
(t) and 65.3 (d). 3B: δH 1.65 (1H, d, J 6.1), 1.75 (1H, d, J 3.4), 1.84–1.89
(1H, m), 1.96–2.02 (1H, m), 3.36 (1H, dd, J 8.5 and 7.0), 3.72 (1H, dd,
J 9 and 7.0), 5.53 (1H, dd, J 11.0 and 0.6) and 6.59 (1H, dd, J 11.0 and
9
.2); δ 33.9 (t), 37.5 (d), 40.5 (d), 42.5 (d), 56.0 (t) and 65.0 (d). (Z)-4a:
C
δH 3.29 (1H, ddd, J 8.8, 7.3 and 5.5), 3.68 (1H, dd, J 9.2 and 7.3), 5.59
1H, dd, J 11.0 and 0.6) and 6.61 (1H, dd, J 11.0 and 9.2); δC 28.5 (t),
The regio- and stereochemistries of (Z)-4a were determined
from its H–H and C–H COSY, phase-sensitive NOESY (Fig. 1)
and HMBC spectra. In the HMBC spectrum of (Z)-4a, the
(
3
6
3.3 (d), 51.8 (t) and 64.9 (d). (Z)-4b: δH 2.85 (1H, ddd, J 10.1, 8.9 and
.7), 3.75 (1H, dd, J 9.5 and 8.9), 5.56 (1H, d, J 11.0) and 6.28 (1H, dd,
3
crosspeaks between H-3 and C(3Ј) ( J), between H-2Ј and
J 11.0 and 9.5); δ 27.8 (t), 33.6 (d), 52.1 (t) and 68.3 (d). 9: δ 4.82–4.87
(1H, m), 5.39 (1H, dd, J 10.7 and 0.6), 6.37 (1H, dd, J 10.7 and 9.2) and
6.89 (1H, q, J 2.1); δ 59.0 (t), 68.8 (d), 133.5 (s) and 141.8 (d).
‡ Yields for compounds throughout the rest of the paper are based on
C
H
3
2
C-C(3Ј) ( J) and between H-2Ј and C(3Ј) ( J) are observed.
The structures of (Z)-4b, (E)-5a, (Z)-5a, 6a, 6b, 7 and 8 were
determined from their phase-sensitive NOESY (Fig. 1) spectra.
The structures of the other adducts (E)-4a, (E)-4b, (E)-5b and
C
converted starting material.
§
Crystal data: C H N , M = 368.48, monoclinic, a = 18.906(2),
24 24 4
3
(
Z)-5b were deduced from a comparison of the chemical shift
of H-C(3Ј) with that for 3A, 3B, (Z)-4a, (Z)-4b, (E)-5a, (Z)-5a,
a and 6b, which are summarized in Table 2. The regio-
b = 5.616(6), c = 20.119(2) Å, V = 2115(2) Å , T = 298 K, space group
P2 /n, Z = 4, µ(Cu-Kα) = 5.42 cm , 4418 reflections measured, 4284
Ϫ1
1
6
unique (Rint = 0.039), the final wR was 0.066 (observed data). CCDC
reference number 207/462. See http://www.rsc.org/suppdata/p1/b0/
b004850j/ for crystallographic files in .cif format.
chemistry of 9 was deduced from the crosspeaks between
H-C(4Ј) and H -C(5Ј) in its phase-sensitive NOESY spectrum.
2
The 1,3-dipolar cycloaddition of an azomethine ylide
(
derived from an aziridine bearing an ester function) and
1 For a review, see: W. J. Lown, in 1.3-Dipolar Cycloaddition Chem-
istry, ed. A. Padwa, Wiley, New York, 1984, vol. 1.
2 A. Hosomi, Y. Sakata and H. Sakurai, Chem. Lett., 1984, 1117;
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the electron-withdrawing group is located at the C(4Ј) position
in the pyrrolidine. We observed the opposite regiochemistry
4
1
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that the cycloadditions may occur via the excited state of A or
the electron-deficient olefin.
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acrylate or N-phenylmaleimide was heated in refluxing xylene
1
3
1
Chim. Acta, 1988, 71, 404; P. Garner, P. B. Cox, J. T. Anderson,
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5
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J. Chem. Soc., Perkin Trans. 1, 2000, 3022–3024