Photoinduced transformation of α,β-epoxyketones to β-hydroxyketones by Hantzsch 1,4-dihydropyridine

Article abstract of DOI:10.1016/S0040-4039(02)02426-7

Irradiation (λ >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic α,β-epoxyketones in acetonitrile selectively breaks the Cα-O bond of the epoxides giving the corresponding β-hydroxyketones in excellent yields.

Full text of DOI:10.1016/S0040-4039(02)02426-7

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9687–9689
Photoinduced transformation of a,b-epoxyketones to
b-hydroxyketones by Hantzsch 1,4-dihydropyridine
Jun Zhang, Mei-Zhong Jin, Wei Zhang, Li Yang and Zhong-Li Liu*
National Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou, Gansu 730000, China
Received 31 July 2002; revised 7 October 2002; accepted 18 October 2002
Abstract—Irradiation (u >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic a,b-epoxyketones in acetonitrile selectively
breaks the CaꢀO bond of the epoxides giving the corresponding b-hydroxyketones in excellent yields. © 2002 Elsevier Science
Ltd. All rights reserved.
The selective transformation of a,b-epoxyketones to
b-hydroxyketones has long been a subject of interest in
synthetic organic chemistry1 since it allows not only
formation of acyclic b-hydroxyketones, but also of a
variety of cyclic b-hydroxyketones which are key inter-
mediates in the construction of numerous natural prod-
ucts. Diverse reducing reagents, such as samarium
diiodide,1a aluminium amalgam,1b lithium,1c sodium
hydrogen telluride1d and benzenselenolate,1e have been
used to achieve this transformation. Recent work
includes the use of lithium naphthalenide2 and
titanocene chloride3 to induce the reaction. In addition,
photochemical approaches have been developed in the
last decade by exciting a,b-epoxyketones in the pres-
ence of tributyltin hydride,4 triethylamine5 and 1,3-
Hantzsch 1,4-dihydropyridine (HDHP), a well-known
model compound of co-enzyme NADH, has been
extensively studied from both a mechanistic and syn-
thetic points of view.7 In our research program on
photoinduced electron transfer reactions8 we found that
photoexcited HDHP was a very good electron and
hydrogen donor that could reduce carbon tetra-
chloride.8a In this reaction HDHP was oxidized to the
corresponding pyridine derivative by sequential transfer
of an electron, a proton and a hydrogen atom. There-
fore, photoexcited HDPH should also be able to induce
reductive cleavage of a,b-epoxyketones. We report
herein a selective CaꢀO cleavage reaction of aromatic
a,b-epoxyketones by photoexcited HDHP that pro-
duces the corresponding b-hydroxyketones in excellent
yields.
dimethyl-2-phenyl-benzimidazoline
(DMPBI).6
However, photoexictation of a ketone inevitably brings
about side reactions, hence lowering the yield of the
expected b-hydroxyketones.4–6 Since two electrons and
two protons are required for converting a,b-epoxyke-
tones to b-hydroxyketones it is expected that photoexci-
tation of electron donors which could afford two
electrons and two protons (or their equivalent) would
also accomplish the transformation, offering an alterna-
tive photochemical approach.
A solution of a,b-epoxyketones 1 (1 mmol) and HDHP
(1 mmol) in 10 mL of anhydrous acetonitrile was
irradiated with a 500 W high pressure mercury lamp in
a Pyrex bottle (u >300 nm) under an argon atmosphere
at ambient temperature. The reaction was monitored by
thin layer chromatography and the solvent was
removed under reduced pressure after the reaction was
Scheme 1.
Keywords: photoinduced electron transfer; a,b-epoxyketone; b-hydroxyketone; Hantzsch ester.
* Corresponding author. Tel.: +86-931-891-1186; fax: +86-931-8625657; e-mail: liuzl@lzu.edu.cn
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02426-7

9688
J. Zhang et al. / Tetrahedron Letters 43 (2002) 9687–9689
Table 1. Photochemical reactions between 1 and HDHP
Substrate
R1
R2
Ered (V versus SCE)
DG (kJ/mol)
t (h)
Conversions (%)
Yieldsa (%)
1ab
1bb
1cb
1db
1eb
1f
1g
1h
1i
1j
Ph
Ph
Ph
Ph
Ph
4-Cl-C6H4
4-MeO-C6H4
−1.704a
−1.735a
−1.735a
−1.765a
−81.0
−78.1
−78.1
−75.2
1
1
1.5
1.5
1
1
1
1.5
1.5
1.5
1.5
100
100
95
100
100
100
100
98
2a (92)
2b (94)
2c (88)
2d (91)
2e (92)
2f (91)
2g (93)
2h (92)
2i (90)
2j (95)
2k (0)
i-Pr
Me
Ph
i-Pr
Ph
i-Pr
Ph
Ph
Ph
4-Cl-C6H4
4-Cl-C6H4
4-MeO-C6H4
4-MeO-C6H4
4-CN-C6H4
Me
−1.60c
−90.6
−85.5
−1.864a
98
100
33
−1.394a
−2.405b
−110.9
−13.5
1k
r\
a Isolated yields.
b Reaction conducted in the presence of 1 mmol of anhydrous Mg(ClO4)2.
c Estimated from the Hammett plot based on the reduction potentials of 1a, 1h and 1k.
complete. The products were easily isolated by silica gel
column chromatography and identified by 1H NMR
and mass spectroscopy as b-hydroxyketones 2 and the
pyridine derivative 39 (Scheme 1). The results are sum-
marized in Table 1.
It was found that although compounds 1a–e showed no
reaction under the experimental conditions, addition of
anhydrous magnesium perchlorate (1 mmol) to the
reaction system made the reaction proceed smoothly.
Compounds 1f–j reacted in the absence of Mg(ClO4)2,
while 1k gave no b-hydroxyketone even in the presence
of Mg(ClO4)2, but did give decomposition products. All
of these compounds showed no reaction with HDHP
and Mg(ClO4)2 in the dark even at 60°C for 3 h. Since
the wavelength of the incident light was longer than 300
nm only HDHP (umax=360 nm) was excited. Therefore,
a photoinduced electron transfer mechanism can be
proposed, as shown in Scheme 2. In Scheme 2, photoin-
duced electron transfer between the excited HDHP and
the aryl epoxy ketone 1 produces the radical cation of
HDHP and the radical anion of 1. It is well-known that
the bond dissociation energy (BDE) of radical ions are
much lower than their parent molecules,10 hence radical
ions undergo facile bond cleavage.8a,c Maslak and co-
workers11 have termed the unimolecular fragmentation
of radical ions as mesolytic cleavage and demonstrated
the acceleration of bond cleavage due to mesolytic
processes. In the present reaction the anionic mesolysis
selectively breaks the CaꢀO bond of the epoxide, form-
Scheme 2.
ing the enolate alkoxy radical 4, and the cationic mesol-
ysis of HDHP+ exudes a proton, forming the HDHP
calculated using the Rehm–Weller equation,12 taking
the oxidation potential of HDHP as 0.72 V (versus
SCE)7b and the excitation energy of 3.2 eV, as deter-
mined from the fluorescence spectrum.13 Some reduc-
tion potentials of 14a,5 are also listed in Table 1. It can
be seen from Table 1 that the reduction potentials of
the aryl epoxy ketones are in the range of −1.3ꢀ−1.9 V
which makes their electron transfer with HDHP highly
exothermic (DG=−70ꢀ−110 kJ mol−1) giving a ther-
modynamically feasible reaction, while the DG for the
alkyl ketone 1k is a very small negative value (−13.5 kJ
mol−1) making the reaction difficult to occur. The sub-
radical 5. Protonation of the enolate 4 and hydrogen
abstraction from 5 gives the final products 2 and 3. It is
clear that aromatization of HDHP also affords a driv-
ing force for the reaction.
Our results suggest that this reaction is controlled by
both thermodynamic and kinetic factors. All the aryl
ketones (1a–j) gave excellent yields of 2, while the alkyl
ketone 1k did not react. This is understandable in view
of the thermodynamics of the photoinduced electron
transfer process between 1 and HDHP. The free energy
change, DG, of the reactions, as listed in Table 1, can be

J. Zhang et al. / Tetrahedron Letters 43 (2002) 9687–9689
9689
stituent R2 on the epoxy side exerts a small effect on the
reduction potential and the reactivity.
E.; Ishiyama, K.; Kato, T.; Horaguchi, T.; Shimizu, T. J.
Org. Chem. 1992, 57, 5352–5359.
5. (a) Hasegawa, E.; Ishiyama, K.; Horaguchi, T.; Shimizu,
T. J. Org. Chem. 1991, 56, 1631–1635; (b) Cossy, J.;
Bouzide, A.; Ibhi, S.; Aclinou, P. Tetrahedron 1991, 47,
7775–7782.
6. (a) Hasegawa, E.; Kato, T.; Kitazume, T.; Yanagi, K.;
Hasegawa, K.; Horaguchi, T. Tetrahedron Lett. 1996, 37,
7079–7082; (b) Hasegawa, E.; Yoneoka, A.; Suzuki, K.;
Kato, T.; Kitazume, T.; Yanagi, K. Tetrahedron 1999, 55,
12957–12968.
7. (a) Yasui, S.; Ohno, A. Bioorg. Chem. 1986, 14, 70–96;
(b) Fukuzumi, S.; Tanaka, T. In Photoinduced Electron
Transfer, Part C; Fox, M. A.; Chanon, M., Eds.;
Elsevier: Amsterdam, 1988; p. 578; (c) Fukuzumi, S.;
Suenobu, T.; Kawamura, S.; Ishida, A.; Mikami, K.
Chem. Commun. 1997, 291–292.
It is worth noting that although the reactions of 1a–e
are thermodynamically feasible they did not react in the
absence of magnesium perchlorate. This suggests that
kinetic factors may also contribute to the reaction.
Metal ion-catalyzed reduction of carbonyl compounds
by HDHP and other NADH model molecules has been
extensively studied previously.7 It was suggested that
magnesium ions coordinate to carbonyls and may lower
the activation energy of the initial single electron trans-
fer step, hence catalyzing the electron transfer
process.7b
In conclusion, this work affords a new, facile approach
for the selective transformation of a,b-epoxy aryl
ketones to the corresponding b-hydroxy ketones with
high yields and using long wavelength irradiation. The
crucial difference of this approach from the photo-
chemical cleavage of a,b-epoxy ketones reported pre-
viously4–6 is excitation of the electron and proton donor
(HDHP) rather than excitation of the a,b-epoxy
ketone. In the latter case, side reactions from the
excited triplet ketones were observed, making the reac-
tion less clean and not as efficient as the present one.
Extension of this approach to a,b-epoxy alkyl ketones
and other photochemical reduction reactions is under-
way in this laboratory.
8. (a) Jin, M. Z.; Yang, L.; Wu, L. M.; Liu, Y. C.; Liu, Z.
L. Chem. Commun. 1998, 2451–2452; (b) Jin, M. Z.;
Zhang, D.; Yang, L.; Liu, Y. C.; Liu, Z. L. Tetrahedron
Lett. 2000, 41, 7357–7360; (c) Zhang, W.; Shao, X.;
Yang, L.; Liu, Z. L.; Chow, Y. L. J. Chem. Soc., Perkin
Trans. 2 2002, 1029–1032; (d) Zhang, W.; Yang, L.; Wu,
L. M.; Liu, Y. C.; Liu, Z. L. J. Chem. Soc., Perkin Trans.
2 1998, 1189–1193; (e) Yang, L.; Zhang, M. X.; Liu, Y.
C.; Liu, Z. L.; Chow, Y. L. Chem. Commun. 1995,
1055–1061.
1
9. Spectral data for some typical products. 2a: H NMR (80
MHz, CDCl3/TMS), l (ppm) 3.39 (d, J=6.0 Hz, 2H,
CH2), 5.37 (t, J=6.0 Hz, 1H, CH), 7.30–8.01 (m, 10H,
2×PhH), MS (m/z, %) 226 (M+, 12), 208 (M+−18, 27), 105
Acknowledgements
1
(M+−121, 100); 2d: H NMR (80 MHz, CDCl3/TMS), l
(ppm) 1.02 (d, J=5.7 Hz, 6H, 2×CH3), 1.83 (m, 1H, CH),
3.09 (d, J=5.6 Hz, 2H, CH2), 4.01 (m, 1H, CH), 7.35–
8.04 (m, 5H, PhH), MS (m/z, %) 192 (M+, 2), 174
We thank the National Natural Science Foundation of
China (Grant Nos. 29972018 and QT Program
29802005) for financial support.
1
(M+−18, 32), 105 (M+−87, 100); 2e: H NMR (80 MHz,
CDCl3/TMS), l (ppm) 1.27 (d, J=6.5 Hz, 3H, CH3),
3.07 (d, J=5.9 Hz, 2H, CH2), 3.40 (s, 1H, OH), 4.46 (m,
1H, CH), 7.33–7.96 (m, 5H, PhH), MS (m/z, %) 164 (M+,
References
1
4), 146 (M+−18, 13), 105 (M+−59, 100); 3: H NMR (80
1. (a) Molander, G. A.; Hahn, G. J. Org. Chem. 1986, 51,
2596–2599; (b) Miranda Moreno, M. J. S.; Sae Melo, M.
L.; Campos Neves, A. S. Tetrahedron Lett. 1993, 34,
353–356; (c) McChesney, J. D.; Thompson, T. N. J. Org.
Chem. 1985, 50, 3473–3481; (d) Osuka, A.; Taka-Oka,
K.; Suzuki, H. Chem. Lett. 1984, 271–272; (e) Miyashita,
M.; Hoshino, M.; Suzuki, T.; Yoshikoshi, A. Tetrahedron
Lett. 1987, 28, 4293–4296; (f) Engman, L.; Stern, D. J.
Org. Chem. 1994, 59, 5179–5183.
MHz, CDCl3/TMS), l (ppm) 1.42 (t, J=7.1 Hz, 6H,
2×CH3), 2.87 (s, 6H, 2×CH3), 4.41 (q, J=7.1 Hz, 4H,
2×CH2), 7.60 (s, 1H, ArH); MS (m/z, %) 252 (M+, 100).
10. Mella, M.; Fagnoni, M.; Freccero, M.; Fasani, E.; Albini,
A. Chem. Soc. Rev. 1998, 27, 81–89.
11. Maslak, P.; Narvaez, J. N. Angew. Chem., Int. Ed. Engl.
1990, 29, 283–285.
12. (a) Rehm, D.; Weller, A. Isr. J. Chem. 1970, 8, 259–271;
(b) DG=23.06 (ED/D −E /A−E0,0 −0.06) kcal/mol in
’
’
−
+
2. Jankowiska, R.; Mhehe, G. L.; Liu, H. J. Chem. Com-
A
MeCN.
mun. 1999, 1581–1582.
13. The fluorescence spectrum of HDHP was determined in
acetonitrile giving the absorption and emission maximum
at 360 and 430 nm, respectively, corresponding to the E0,0
of 3.2 eV.
3. Hardouin, C.; Chevallier, F.; Rousseau, B.; Doris, E. J.
Org. Chem. 2001, 66, 1046–1048.
4. (a) Hasegawa, E.; Ishiyama, K.; Horaguchi, T.; Shimizu,
T. Tetrahedron Lett. 1991, 32, 2029–2032; (b) Hasegawa,