N-cyclopropylimine-1-pyrroline rearrangement. A novel photochemical reaction

Article abstract of DOI:10.1021/ol016847x

matrix presented A novel aza-(vinylcyclopropane-cyclopentene) photochemical rearrangement is reported. 1-Pyrrolines are easily synthesized in good yields from N-cyclopropylimines. Hydrogen, alkyl, and aryl groups can be placed anywhere within the system, and the reaction proceeds regiospecifically.

Full text of DOI:10.1021/ol016847x

ORGANIC
LETTERS
2001
Vol. 3, No. 25
4087-4089
N-Cyclopropylimine-1-pyrroline
Rearrangement. A Novel Photochemical
Reaction
Pedro J. Campos,* Alberto Soldevilla, Diego Sampedro, and
Miguel A. Rodr´ıguez*
Departamento de Qu´ımica, UniVersidad de La Rioja, Grupo de S´ıntesis Qu´ımica de La
Rioja, Unidad Asociada al C.S.I.C., Madre de Dios, 51, E-26006 Logron˜o, Spain
pedro.campos@dq.unirioja.es
Received October 3, 2001
ABSTRACT
A novel aza-(vinylcyclopropane-cyclopentene) photochemical rearrangement is reported. 1-Pyrrolines are easily synthesized in good yields
from N-cyclopropylimines. Hydrogen, alkyl, and aryl groups can be placed anywhere within the system, and the reaction proceeds regiospecifically.
During the study of the photochemical behavior of group
VI Fischer-type imine-carbene complexes to yield 2H-
pyrroles and 1-pyrrolines,1 we detected different product
distributions depending on the irradiation times (Scheme 1).
membered ring. Moreover, we have not found any thermal
example in the literature.
The rearrangement of vinylcyclopropane was first reported
by Neuretier in 1959.2 Since then, it has found a wide
application in organic synthesis3 as a result of its potentially
limitless permutations. Any of the five atoms in the vinyl-
cyclopropyl system may be replaced with almost any other
atom (Si, P, S, O, etc.), and the formation of five-membered
rings still takes place. Despite its synthetic utility, the use
of N in the system has been limited mainly to vinylaziridines4
and the effects of heteroatom substitution on the rearrange-
ments of C-cyclopropylmethyleneamines.5 We report here
a brand new reactivity involving the photochemically driven
rearrangement of N-cyclopropylimines to 1-pyrrolines. The
1-pyrroline ring system is found in natural products, espe-
cially hydroporphyrins,6 and constitutes an adequate substrate
for the synthesis of pyrroles.7 Besides, much attention is still
being paid to the synthesis of 1-pyrroline derivatives.8
Scheme 1
Irradiation until total consumption of carbene complexes
yielded the 1-pyrroline 2. However, with shorter irradiation
times, the N-cyclopropylimine 3 was isolated as well. When
we irradiated the N-cyclopropylimine 3, we detected the
corresponding 1-pyrroline 2. As far as we know, this is the
first example of a photochemically induced aza-(vinyl-
cyclopropane-cyclopentene) rearrangement where a nitrogen
atom is placed in the R position in relation to the three-
(2) Neuretier, N. P. J. Org. Chem. 1959, 24, 2044.
(3) For different reviews see: (a) Baldwin, J. E. J. Comput. Chem. 1998,
19, 222. (b) Wong, H. N. C.; Hon, M.-Y.; Tse, C.-W.; Yip, Y.-C.; Tanko,
J.; Hudlicky´, T. Chem. ReV. 1989, 89, 165. (c) Hudlicky´, T.; Kutchan, T.
M.; Naqvi, S. M. Org. React. 1985, 33, 247. (d) Hudlicky´, T.; Reed, J. W.
In ComprehensiVe Organic Synthesis; Trost, B. M., Fleming, I., Eds.;
Pergamon: Oxford, 1991; Vol. 5, p 899.
(4) Schultz, A. G.; Dittami, J. P.; Myong, S. O.; Sha, C.-K. J. Am. Chem.
Soc. 1983, 105, 3273.
(5) Wasserman, H. H.; Dion, R. P. Tetrahedon Lett. 1983, 24, 3409.
(6) Montforts, F.-P.; Gerlach, B.; Ho¨per, F. Chem. ReV. 1994, 94, 327
and references therein.
(1) Campos, P. J.; Sampedro, D.; Rodr´ıguez, M. A. Organometallics
2000, 19, 3082.
10.1021/ol016847x CCC: $20.00 © 2001 American Chemical Society
Published on Web 11/16/2001

To survey the synthetic applicability of this new reaction,
we first synthesized a set of N-cyclopropylimines with
different substitution patterns. Table 1 shows the results
obtained.
Table 2. Formation of 1-Pyrrolines 5
pyrroline R1 R2 R3 R4
t (h)a yield (%)
5a
5b
5c
5d
5e
5f
5g
5h
5i
H
H
H
H
H
H
Ph
Ph
Ph
Ph
H
H
H
Ph
H
Ph
6
6
5
5
5
4
0.75
0.75
0.5
5
70
65
80
65b,c
60b,d
85b
70
e
80
50b
Me Ph
Ph Ph
H
Table 1. N-Cyclopropylimines 4 Synthesized
Ph
Ph Me Ph
Ph Ph Ph
H
H
H
H
H
Ph
Me Ph
Ph Ph
H
imine
R1
R2
R3
R4
yield (%)
4a
4b
4c
4d
4e
4f
4g
4h
4i
H
H
H
H
H
H
Ph
Ph
Ph
Ph
H
H
H
Ph
Ph
Ph
H
H
H
H
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
Ph
98
90
94
96
95
90
98
72
90
94
5j
trans-CHdCHPh
Me
Ph
H
Me
Ph
H
Me
Ph
H
a Time for 1 mmol of imine 4 in 50 mL. b Pyrex filtered. c Pyrrole 6d
was isolated. d Mixture of two stereoisomers in a 1:3 ratio. e Only decom-
position products were detected.
propyl substituents, hydrogen and phenyl groups were placed
in positions 1 and 2 with no significant effect on the overall
reaction. Corresponding 1-pyrrolines 5 could be synthesized
easily in moderate to good yields. As an exception, 1-pyr-
roline 5d detected in the reaction crude12 was readily oxidized
during the workup and only the pyrrole 6d could be isolated
(Scheme 3).
4j
H
trans-CHdCHPh
All of these compounds were synthesized by a condensa-
tion reaction between the corresponding amines9 and car-
bonylic compounds.10 The anti-isomer was the only product
detected for the imines derived from aldehydes. This was
confirmed by NOE experiments for compound 4a. For
acetophenone imines 4b, 4e, and 4h the two isomers were
Scheme 3
1
detected by H NMR (1:10).
Next, we irradiated11 the N-cyclopropylimines 4 using a
Pyrex glass with the imines that showed an absorption above
the 290 nm limit in the UVA spectrum. The results are given
in Scheme 2 and Table 2.
For the 2-substituted imines 4d-f, two different regio-
isomers could be formed. In every case analyzed, the
regiochemistry of the rearrangement was directed by the
phenyl group in position 2. Therefore, only one of the two
possible regioisomers was obtained, and thus the reaction
became completely regiospecific.
Scheme 2
To ensure the photochemical nature of these reactions, we
refluxed several imines 4 in toluene for 3 days. The imines
were recovered unchanged with the exception of imines 4g
and 4h, where some decomposition was observed, but the
1
formation of 1-pyrroline was not detected by H NMR in
any case.
As shown in Table 2, no limitations were detected
regarding the position or nature of the substituents, as both
alkyl and aryl groups and hydrogen can be used without
significant influence on the product distribution. The sub-
stituents of the imine moiety can be easily modified in the
synthesis of the N-cyclopropylimines. Aryl and alkyl groups
and hydrogen were successfully used. Regarding the cyclo-
(10) An equimolecular solution of the corresponding amine and carbonyl
compound was refluxed in toluene for 1-2 days, with occasional addition
of molecular sieves. Once the reaction was finished (monitored by TLC),
it was filtered and the solvent was removed under vacuum. Most of the
imines were then ready to use. Compounds 4c, 4f, and 4i can be purified
by column chromatography in silica gel (hexane/ether 1:1). Alternatively,
an excess of amine (3-5 equiv) and lower temperatures (ca. 80 °C) must
be used for cyclopropylamine derivatives (R1 ) R2 ) H).
(11) One millimole of imines 4 in 50 mL of dry deoxygenated hexane
was irradiated (through Pyrex glass when indicated in Table 2) in a quartz
reactor with a medium-pressure 400-W mercury lamp. When no more imine
was detected by TLC, the solution was filtered through Celite, and the
solvent was evaporated. Corresponding 1-pyrrolines 5 could be purified by
distillation or column chromatography (silica gel, hexane/ether 8:2).
(12) Two different isomers were detected in the reaction crude by 1H
NMR in a 5:1 ratio. The major product was assigned as the cis isomer on
the basis of the coupling constants (PhCH-CHPh cis J ) 6 Hz, trans J )
8 Hz).
(7) Tehrani, K. A.; Borremans, D.; De Kimpe, N. Tetrahedron 1999,
55, 4133 and references therein.
(8) (a) Gagosz, F.; Zard, S. Z. Synlett 1999, 1978. (b) Duncan, D.;
Livinghouse, T. Organometallics 1999, 18, 4421. (c) Boivin, J.; Schiano,
A.-M.; Zard, S. Z.; Zhang, H. Tetrahedron Lett. 1999, 40, 4531.
(9) For the preparation of 1-phenylcyclopropylamine (imines 4g-j) by
a modified Curtius reaction, see: Kaiser, C.; Weinstock, J. Org. Synth. 1971,
51, 48. trans-2-Phenylcyclopropylamine (imines 4d-f) and cyclopropy-
lamine (imines 4a-c) are commercially available as a hydrochloride and
free amine, respectively.
4088
Org. Lett., Vol. 3, No. 25, 2001

All of the compounds herein described have been fully
characterized on the basis of their spectral data (IR, 1H and
13C NMR, MS-ES(+) and GC-MS).
(ACPI2000/02) and the Universidad de La Rioja (API-01/
B07) for their financial support. A.S. thanks the Ministerio
de Educacio´n, Cultura y Deporte for his fellowship.
Further investigation to explore the synthetic utility and
to gain a mechanistic insight into this new reaction is
currently underway in our group.
Supporting Information Available: Characterization
data for new compounds and representative UVA spectra
for compounds 4. This material is available free of charge
via the Internet at http://pubs.acs.org.
Acknowledgment. We thank the Spanish DGICYT
(PB97-0589), the Comunidad Auto´noma de La Rioja
OL016847X
Org. Lett., Vol. 3, No. 25, 2001
4089