Photochemical release of aldehydes from α-acetoxy nitroveratryl ethers

Article abstract of DOI:10.1021/ol051280w

(Chemical Equation Presented) Photolabile aldehyde-releasing precursors (α-acetoxy ethers) were prepared by reduction of the corresponding esters with DIBAL and quenching the intermediate aluminum hemiacetal with acetic anhydride. These species smoothly released aldehydes upon irradiation with UV light at 350 nm. Using this method, not only simple model aliphatic aldehydes were liberated but also specimens relevant for the flavor and fragrance industry (methional, phenylacetaldehyde, and (R)-citronellal).

Full text of DOI:10.1021/ol051280w

ORGANIC
LETTERS
2005
Vol. 7, No. 16
3545-3547
Photochemical Release of Aldehydes
from -Acetoxy Nitroveratryl Ethers
r
Jaime Lage Robles and Christian G. Bochet*
Department of Chemistry, UniVersity of Fribourg, Chemin du Muse´e 9,
CH-1700 Fribourg, Switzerland
christian.bochet@unifr.ch
Received June 1, 2005
ABSTRACT
Photolabile aldehyde-releasing precursors (r-acetoxy ethers) were prepared by reduction of the corresponding esters with DIBAL and quenching
the intermediate aluminum hemiacetal with acetic anhydride. These species smoothly released aldehydes upon irradiation with UV light at 350
nm. Using this method, not only simple model aliphatic aldehydes were liberated but also specimens relevant for the flavor and fragrance
industry (methional, phenylacetaldehyde, and (R)-citronellal).
Slow and controlled release of substances is of great interest
in many applications. Chemical,1 enzymatic,2 and photo-
chemical3 liberation of various caged organic molecules have
been achieved in the past decade. In the particular case of
the fragrance industry, the slow photorelease of odorant
aldehyde has been studied on many instances (e.g., by
Norrish type II fragmentation).4 The very recent report by
Banerjee et al. on the photochemical liberation of ketones
from enol ethers prompted us to disclose our progress in
this field.5
photolabile bis(o-nitrophenyl)ethane-1,2-diol,6 a symmetrical
version of the glycol developed by Gravel et al.7 On the other
hand, when stability in solution is not a central issue,
R-acetoxy ethers could represent an attractive substitute to
regular acetals, because their liberation is significantly less
sensitive to the reaction medium (e.g., pH, water content)
and for their inherently simpler structure.
2-Nitroveratrol 1 was acylated with acid chlorides 2a-h
in excellent yields using standard conditions (RCOCl, NEt3)
in dichloromethane to give the esters 3a-i. In one case, a
carboxylic acid was used (citronellic acid 2i) in combination
with a classical DCC-mediated esterification. The R-acetoxy
Aldehydes and ketones are traditionally protected as acetals
and ketals. The latter species offer good chemical resistance
with respect to various conditions (basic, oxidizing, reducing,
etc.), and we have exploited this feature introducing the
Scheme 1. Preparation of R-Acetoxy Ethers
(1) (a) de Saint-Laumer, J. Y.; Fre´rot, E.; Herrmann, A. HelV. Chim.
Acta 2005, 86, 2871-2899. (b) Enggist, P.; Rochat, S.; Herrmann, A. J.
Chem. Soc., Perkin Trans. 2 2001, 438-440.
(2) Ikemoto, T.; Okabe, B. I.; Mimura, K.; Kitahara, T. FlaVour
Fragrance J. 2002, 17, 452-455.
(3) (a) Pika, J.; Konosonoks, A.; Robinson, R. M.; Singh, P. N. D.;
Gudmundsdo´ttir, A. D. J. Org. Chem. 2003, 68, 1964-1972. (b) Blankespoor,
R. L.; DeVries, T.; Hansen, E.; Kallemeyn, J. M.; Klooster, A. M.; Mulder,
J. A.; Smart, R. P.; Vander Griend, D. A. J. Org. Chem. 2002, 67, 2677-
2681. (c) Brinson, R. G.; Jones, P. B. Org. Lett. 2004, 6, 3767-3770. (d)
For a review, see: Bochet, C. G. J. Chem. Soc., Perkin Trans. 1 2002,
125-142.
(4) (a) Herrmann, A. Spectrum 2004, 17 (2), 10-13; 19. (b) Levrant,
B.; Herrmann, A. Photochem. Photobiol. Sci. 2002, 1, 907-919. (c) Rochat,
S.; Minardi, C.; de Saint-Laumer, J. Y.; Herrmann, A. HelV. Chim. Acta
2000, 83, 1645-1671.
(5) Yong, P. K.; Banerjee, A. Org. Lett. 2005, 7, 2485-2487.
10.1021/ol051280w CCC: $30.25
© 2005 American Chemical Society
Published on Web 07/13/2005

ethers 4a-i were then prepared by the procedure developed
by Rychnovsky8 and Rovis:9 very slow addition of a solution
of DIBAL in hexane at -78 °C was followed by the
sequential addition of pyridine, DMAP in CH2Cl2, and finally
acetic anhydride, while maintaining a careful control of
temperature (Scheme 1, Table 1). The R-acetoxy ethers
Scheme 3. Photolysis of R-Acetoxy Ethers
Table 1. Preparation of Photolabile R-Acetoxy Ethers
entry
2
R
estera
ethera
1
2
3
4
5
6
7
8
9
2a Me
2b Et
2c Pr
2d n-C4H9
2e n-C5H11
3a (89%) 4a (80%)
3b (94%) 4b (81%)
3c (96%)
4c (70%)
3d (96%) 4d (65%)
3e (94%)
3f (74%)
4e (66%)
4f (72%)
2f
n-C11H23
2g CH2Ph
2h (CH2)2SMe
3g (89%) 4g (90%)
3h (89%) 4h (77%)
2i
CH2CH(Me)(CH2)2CdMe2 3i (48%)b 4i (71%)
a Isolated yield. b DCC-mediated esterification with (R)-citronellic acid
released, without traces of products other than the usual
aromatic residues typical to the 2-nitroveratrol derivatives
photolysis and acetic acid (Scheme 3, Table 2). Similar
results were obtained even when oxygen was not strictly
excluded, an important observation for potential applications
in photosensitive materials.
2i.
showed a reasonable stability both in solution and as a wax.
Purification by flash chromatography did not lead to
significant degradation.
On the other hand, this protocol was not possible with
cation-stabilizing substitutents (R ) vinyl, phenyl), presum-
ably because of the spontaneous ionization of the final
R-acetoxy ether. To study the thermal stability of these
species, we submitted 4c to thermolysis at 200 °C for 4 h.
The corresponding enol ether 5 was cleanly obtained (51%)
by elimination of acetic acid, as a 3:2 Z/E isomeric mixture
(Scheme 2). The latter underwent the same type of photolysis
Table 2. Photochemical Liberation of Aldehydes 6a-i
reaction
entry ether
R
time (h) aldehydea
1
2
3
4
5
6
7
8
9
4a
4b
4c
4d
4e
4f
4g
4h
4i
Me
Et
Pr
n-C4H9
n-C5H11
n-C11H23
CH2Ph
(CH2)2SMe
3
4
4
3
4
3
4
4
3
6a (58%)
6b (79%)
6c (70%)
6d (74%)
6e (57%)
6f (69%)
6g (62%)
6h (53%)
6i (73%)
Scheme 2. Preparation of Enol Ethers from R-Acetoxy Ethers
CH2CH(Me)(CH2)2CdMe2
a Yield determined by 1H NMR, using an internal standard. The
photolyses were carried out in nondegassed acetonitrile at 350 nm.
as its parent R-acetoxy ether, i.e., releasing the aldehyde but
avoiding the concomitant release of smelly acetic acid. This
simple elimination reaction represent an interesting strategy
to access photosensitive enol ethers, complementary to the
one developed by Banerjee et al.5
Solutions of 4a-i in acetonitrile were exposed to UV light
in a Rayonet apparatus equipped with 16 RPR3500 lamps
(λmax 350 nm). Not unexpectedly, aldehydes were smoothly
As the purpose of this work is not a preparative method
to generate aldehydes, they were not systematically isolated,
but the very large chromatographic retention factor differ-
ences between the aldehyde and the side products make
purification very easy. The aldehydes were, however,
unambiguously characterized spectroscopically by compari-
son with pure samples prepared separately.10 Noteworthy,
aldehydes with specific odors were released, such as the
sulfure-containing methional 6h (potato), phenylacetaldehyde
6g (fruity, honey-like), and (R)-citronellal 6i (citrus green).
In summary, we were able to prepare photosensitive
R-acetoxy ethers, which could release aldehydes upon
exposure to UV light. While not representing a preparative
(6) Blanc, A.; Bochet, C. G. J. Org. Chem. 2003, 68, 1138-1141.
(7) Gravel, D.; Murray, S.; Ladouceur, G. J. Chem. Soc., Chem. Commun.
1985, 1828-1829.
(8) (a) Kopecky, D. J.; Rychnovsky, S. D. J. Org. Chem. 2000, 65, 191-
198. (b) Kopecky, D. J.; Rychnovsky, S. D. Org. Synth. 2003, 80, 177-
183.
(9) (a) Zhang, Y.; Rovis, T. Tetrahedron 2003, 59, 8979-8987. (b)
Zhang, Y.; Rovis, T. Org. Lett. 2004, 6, 1877-1879.
(10) All of the aldehydes 6a-i are commercially available.
Org. Lett., Vol. 7, No. 16, 2005
3546

method, this strategy is attractive in the perspective of smart
materials, which respond chemically to external stimuli.3b
Resin-bound photolabile linkers have been developed and
used.3d,11 Our progress in this direction will be reported in
due course.
the Swiss National Science Foundation is gratefully aknowl-
edged.
Supporting Information Available: Detailed experi-
mental procedures and spectral information for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
Acknowledgment. We thank Professors Rychnovsky and
Rovis for their valuable advise. The generous support from
(11) Kessler, M.; Glatthar, R.; Giese, B.; Bochet, C. G. Org. Lett. 2003,
5, 1179-1181.
OL051280W
Org. Lett., Vol. 7, No. 16, 2005
3547