A novel synthesis of α- and β-morpholino enones by electron transfer sensitized photooxidation of 2-morpholinocyclopropanols

Article abstract of DOI:10.1039/a704024e

An electron transfer mechanism is proposed to account for the photooxidation of 2-morpholinocyclopropanols 1 to the amino enone derivatives 2 and 3 in the presence of 9,10-dicyanoanthracene or triphenylpyrylium tetrafluoroborate and triplet oxygen.

Full text of DOI:10.1039/a704024e

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A novel synthesis of a- and b-morpholino enones by electron transfer
sensitized photooxidation of 2-morpholinocyclopropanols
Wilfried Weigel* and Hans-Georg Henning
Department of Chemistry, Humboldt-University of Berlin, Hessische Str. 1-2, D-10115 Berlin, Germany
Table 1 Oxidation potentials and calculated DG values for ET from 1 to
An electron transfer mechanism is proposed to account for
the photooxidation of 2-morpholinocyclopropanols 1 to the
amino enone derivatives 2 and 3 in the presence of
9,10-dicyanoanthracene or triphenylpyrylium tetrafluoro-
borate and triplet oxygen.
1/3TPT* and 1DCA*
DG/kcal mol21
Compound E(D/D+)/Va,b
1TPT*c
3TPT*c
1DCA*d
Photoinduced electron transfer (ET) cis–trans isomerization
and oxidative ring opening of cyclopropanes have been the
subject of numerous investigations.1,2 Dioxolane derivatives
and, in some cases, hydroperoxides and chalcones are formed
by electron transfer photooxidation of aryl substituted cyclo-
propanes. Several mechanisms involving the superoxide anion
radical, a chain reaction with triplet oxygen, or reaction of
triplet oxygen with a 1,3-biradical formed by back electron
transfer to the cyclopropane cation radical have been dis-
cussed.3–5 Recently we reported that the irradiation of b-(N,N-
dialkylamino)propiophenones gives 2-aminocyclopropanols
that undergo oxidative ring opening to b-amino enones.6a Due
to the electron donor properties of amino groups, 2-morpholino-
1,2-diphenylcyclopropanol 1a and 2-morpholino-1,3-di-
phenylcyclopropanol 1b appeared to be excellent candidates for
electron transfer studies. They were synthesized by photo-
cyclization6 and used as model compounds to investigate the
possibility of oxidative ring opening in presence of the
photoexcited electron acceptors 9,10-dicyanoanthracene (DCA)
or triphenylpyrylium tetrafluoroborate (TPT).
1a
1b
1.44
1.37
225.11
226.72
213.11
214.72
212.27
213.88
a
b
Pt electrode/SCE, 0.1 m Et4NClO4 in MeCN. 2: E(D/D+) = 1.53 V.
c E(A2/A) = 20.29 V, E(1A*) = 65 kcal mol21, E(3A*) = 53 kcal mol21
(ref. 13). d E(A2/A) = 20.89 V, E(1A*) = 66 kcal mol21 (ref. 13).
1
from the cyclopropane derivatives to photoexcited TPT* or
1DCA* were estimated by application of the Rehm–Weller
equation [eqn. (1)].8 The Coulombic term (e2/ea) was neglected
DG = E(D/D+) 2 E(A2/A) 2 E(A*) 2 e2/ea
(1)
due to the lack of charge separation in case of TPT and the small
estimated value of 0.06 eV9 in MeCN for DCA as photo-
3
sensitizer. Involvement of TPT* in photoinduced ET proc-
esses, especially at low donor concentrations (ca. 1024 m), has
been reported and cannot be ruled out in the case of 1.10,11
Fluorescence quenching experiments of 1TPT* by 1a and 1b
(0.4 3 1023–6 x 1023 m) were performed in aerated CH2Cl2
solutions.§ The fluorescence was quenched at almost diffusion
controlled rates (1a: kq = 2.1 3 1010 m21 s21; 1b: kq = 2.0 3
1010 m21 s21), calculated from the slopes of the Stern–Volmer
plots (1a: kqt = 61 m21; 1b: kqt = 58 m21) and a singlet
lifetime of TPT of 2.9 ns.12 As expected, the formation of 2 in
the DCA-sensitized photolysis of 1a was completely quenched
by the addition of an equimolar amount of triethylamine, whose
oxidation potential [E(D/D+) = 0.76 V, SCE, MeCN]13 is lower
than that of 1a. The DCA anion radical was detected by EPR
measurements in the DCA-sensitized photoreaction of 1a and
1b in oxygen free MeCN.¶ No signals could be detected for the
cation radical of 1. The formation of the DCA anion radical was
also observed by DCA-sensitized photolysis of the b-amino
enone 2.
Irradiation (lirr > 395 nm) of aerated solutions of 1a (2 3
1024 m) in the presence of catalytic amounts (0.1 equiv.) of
DCA in MeCN or TPT in CH2Cl2 gave the b-morpholino-
b-phenylvinyl phenyl ketone 2 in 36 (tirr = 0.5 min) and 41%
(tirr = 5.2 min) yield, respectively. Photolysis of a mixture of 1b
and DCA or TPT under the same conditions gave the
a-morpholino chalcone 3 in 28 and 26% yield, respectively
(Scheme 1). Continuous irradiation leads to the decomposition
of 2 and 3. The reported yields are the maximum values
observed during the photolysis.† The formation of 2 and 3 was
confirmed by HPLC analysis with authentic reference com-
pounds.‡
The oxidation potentials E(D/D+) of 1a and 1b together with
the DG values for photoinduced ET are given in Table 1. The
free energy changes (DG) for the one-electron transfer process
The values of the oxidation potentials of 1 (Table 1) are lower
than those of the trans and cis isomers of 1,2-diphenyl-
cyclopropane, [E(D/D+) = 1.51 and 1.75 V].∑ Even though the
measured oxidation potentials of 1a,b are unexpectedly high
compared to those for tertiary amines [N-methylmorpholine:
E(D/D+) = 1.1 V, Ag/AgCl, MeCN]9 for reasons that are not
clear, they reflect the good electron donor ability of 1. The
negative DG values for single electron transfer from 1a and 1b
to 1/3TPT* and 1DCA*, the fluorescence quenching of 1TPT* at
a diffusion controlled rate and the detection of DCA2· by EPR
spectroscopy strongly suggest that the formation of the radical
cation of 1 by photoinduced ET is the primary process in the
O
Ph
Ph
N
HO
1
R2
2
O
R1
1a
2
TPT* or DCA*
3O2
–[H2O2]
Ph
3
N
O
Ph
1b
O
Ph
photooxidation of 1. The cation radical of 1 could undergo
reaction with triplet oxygen to give 1–O2 . Back ET gives 1–O2
or the ground state reactants. Hydroperoxides formed from
1–O2 by internal hydrogen transfer are assumed to be
intermediates which form 2 or 3 by elimination of hydrogen
peroxide. In contrast to TPT, the DCA-sensitized photooxida-
1a R1 = H, R2 = Ph
b R1 = Ph, R2 = H
N
+
·
O
3
Scheme 1
Chem. Commun., 1997
1893

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1 + TP+* / DCA* → 1+ • + TP• / DCA– •
presence of Methylene Blue as photosensitizer for singlet
oxygen.
In summary, the novel synthesis of a- and b-morpholino-
enones by DCA- or TPT-sensitized photooxidation of 2-mor-
pholinocyclopropanols described herein increases the synthetic
utility of the photochemical reactivity of cyclopropane deriva-
tives.
We thank Professor Dr H. Kurreck at the Free University of
Berlin for use of his EPR spectrometer. Helpful discussions
with Professor Dr W. Abraham at the Humboldt University of
Berlin are gratefully acknowledged.
+ •
1+ •
+
3O2 → 1–O2
1–O2+ • + TP• / DCA– • → 1–O2 + TP+ / DCA
DCA– •
+
3O2 → DCA + 3O2
– •
1+ •
+
3O2– • → 1–O2
1–O2 → 2 or 3 + H2O2
Scheme 2
tion could lead to the formation of a superoxide anion radical by
Footnotes and References
reaction of triplet oxygen with DCA2 and would provide a
·
* E-mail: weigel@chemie.fu-berlin.de
second pathway to generate 1–O2.10 A simplified mechanism
for photoinduced ET oxidation of 1 is summarized in Scheme
2.
† Consumption of 1 > 85%; 2 and 3 are formed in the E configuration,
assigned from lmax = 350 (2) and 282 nm (3); 2 and 3 were isolated by
column chromatography from irradiations in CH2Cl2 of 1a or 1b (4 3 1023
m) in the presence of TPT (4 3 1024 m) and identified by their NMR
spectra.
Possible pathways for the formation of 2 and 3 by reaction of
the cation radicals of 1a and 1b with oxygen are given in
Scheme 3. Obviously, the regioselectivity of ring opening is
determined by the position of the phenyl groups. C(1)–C(3) ring
cleavage of 1b excludes resonance stabilization of the radical
cation by the electron releasing morpholino group. However,
the almost bisected conformation of the C(3)-phenyl group and
the cyclopropane ring of 1b should allow a strong interaction
between their orbitals, in contrast to the morpholino group,
which is the better electron donor but is arranged in a
perpendicular fashion.6a**
‡ Reference compounds 2 and 3 were prepared according to literature
procedures (ref. 7).
§ [TPT] = 3.6 3 1025 m in CH2Cl2, excitation at 410 nm, fluorescence
intensity measured at 460 nm.
¶ Hyperfine coupling constants for DCA2 at 245 K generated by > 395 nm
·
irradiation of 1 (5 3 1023 m) and DCA (2 3 1023 m) in MeCN recorded on
a X Band Spectrometer Bruker ER 220D: 1a/DCA, 0.238, 0.132, 0.114 mT;
1b/DCA, 0.242, 0.125, 0.111 mT; cf. ref. (14).
∑ Oxidation potentials (Ag/AgNO3, MeCN) from ref. (1), 0.34 V added for
SCE as reference electrode.
** It should be noted that formation of 2 and 3 indicates the cleavage of the
respective longest cyclopropane bond of 1a, C(1)–C(2) = 1.54, C(1)–C(3)
= 1.51, C(2)–C(3) = 1.50 Å and of 1b, C(1)–C(3) = 1.52, C(1)–C(2) =
1.50, C(2)–C(3) = 1.49 Å, see X-ray structures of 1a and 1b in ref. 6(a).
†† Consumption of 1a < 10%; lirr = 405 nm by combination of a band pass
filter WG 305 and a metall interference filter UV-SKIF 405 nm (Carl Zeiss
Jena); actinometer potassium ferri oxalate (ref. 15).
High quantum yields for consumption of 1a in the presence of
TPT* (8 3 1025 m) in CH2Cl2 were found.†† The values show
considerable dependence on the concentration of the donor 1a
and amount to 11 ([1a] = 4.1 3 1024 m), 20 ([1a] = 6.0 x 1024
m) and 27 ([1a] = 1.6 3 1023 m). The high values indicate that
a chain reaction occurs with generation of 1a+ by hole transfer
·
+
·
from 1a–O2 to 1a. Quantum yields > 1 were reported for ET
sensitized oxygenations and ring opening of several cyclopro-
panol derivatives and small strained ring systems.3,16 An
alternative pathway for the photooxidation could involve singlet
oxygen generated by energy transfer from photoexcited TPT
and DCA. However, the cyclopropanol 1a was completely
recovered after photolysis (lirr > 395 nm) in MeCN in the
1 P. C. Wong and D. R. Arnold, Tetrahedron Lett., 1979, 23, 2101; S. B.
Karki, J. P. Dinnocenzo, S. Farid, J. L. Goodman, I. R. Gould and T. A.
Zona, J. Am. Chem. Soc., 1997, 119, 431.
2 T. Tamai, K. Mizuno, I. Hashida and Y. Otsuji, J. Org. Chem., 1992, 57,
5338 and references cited therein.
3 K. Mizuno, N. Kamiyama, N. Ichinose and Y. Otsuji, Tetrahedron,
1985, 41, 2207.
4 K. Gollnick and U. Paulmann, J. Org. Chem., 1990, 55, 5954; K.
Gollnick, X.-L. Xiao and U. Paulmann, J. Org. Chem., 1990, 55,
5945.
5 F. Algarra, M. V. Baldovi, H. Garcia, M. A. Miranda and J. Primo,
Tetrahedron, 1993, 47, 10897.
6 (a) W. Weigel, G. Reck, S. Schiller and H.-G. Henning, Tetrahedron
Lett., 1993, 34, 6737; (b) W. Weigel, S. Schiller and H.-G. Henning,
Tetrahedron, 1997, 53, 7855; (c) W. Weigel and P. J. Wagner, J. Am.
Chem. Soc., 1996, 118, 12 858.
7 N. H. Cromwell, J. Am. Chem. Soc., 1940, 62, 2897; F. Felluga, P. Nitta,
G. Pitacco and E. Valentin, J. Chem. Soc., Perkin Trans. 1, 1971,
1648.
NR2
HO
Ph
NR2
HO
+
+
•
•
Ph
1a+•
Ph
1b+•
Ph
+O2
+O2
NR2
H
HO
Ph
Ph
HO
Ph
+
+
H
OO• NR2
Ph •OO
8 D. Rehm and A. Weller, Ber. Bunsenges. Phys. Chem., 1969, 73,
834.
9 P. E. Correa, G. Hardy and D. P. Riley, J. Org. Chem., 1988, 53,
1695.
+ •
+ •
1a–O2
1b–O2
10 M. A. Miranda and H. Garcia, Chem. Rev., 1994, 94, 1063.
11 R. Akaba, H. Sakuragi and K. Tokumaru, Chem. Phys. Lett., 1990, 174,
80.
12 G. Haucke, P. Czerney and F. Cebulla, Ber. Bunsenges. Phys. Chem.,
1992, 96, 880.
•
•
1a–O2
1b–O2
~H•
~H•
NR2
13 G. J. Kavarnos and N. J. Turro, Chem. Rev., 1986, 86, 401.
14 E. Brunner, Ber. Bunsenges. Phys. Chem., 1968, 68, 468; A. P. Schaap,
K. A. Kaklika and L. Kaskar, J. Am. Chem. Soc., 1980, 102, 389.
15 H. J. Kuhn, S. E. Braslavsky and R. Schmidt, Pure Appl. Chem., 1989,
2, 187.
HO
Ph
Ph
HO
Ph
OOH NR2
–[H2O2]
Ph
OOH
–[H2O2]
16 K. Mizuno, N. Ichinose and Y. Otsuji, J. Org. Chem., 1992, 57, 1855;
K. Okada, K. Hisamitsu and T. Mukai, Tetrahedron Lett., 1981, 22,
1251.
2
3
NR2 = morpholino
Scheme 3
Received in Liverpool, UK, 9th June 1997; 7/04024E
1894
Chem. Commun., 1997