Establishing cleavage conditions for an anthracene chiral auxiliary using a photochemical retro Diels-Alder reaction

Article abstract of DOI:10.1016/S0040-4039(02)02255-4

Photochemical Diels-Alder additions of chiral 9-anthranyl ethanol derivatives have been conducted giving rise to addition adducts in reasonable yield and excellent diastereoselectivity. Thermal and photochemical retro Diels-Alder additions have also been

Full text of DOI:10.1016/S0040-4039(02)02255-4

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TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 9097–9100
Establishing cleavage conditions for an anthracene chiral
auxiliary using a photochemical retro Diels–Alder reaction
J. C. Christian Atherton and Simon Jones*
Department of Chemistry, University of Newcastle upon Tyne, Bedson Building, Newcastle upon Tyne NE1 7RU, UK
Received 24 July 2002; revised 1 October 2002; accepted 11 October 2002
Abstract—Photochemical Diels–Alder additions of chiral 9-anthranyl ethanol derivatives have been conducted giving rise to
addition adducts in reasonable yield and excellent diastereoselectivity. Thermal and photochemical retro Diels–Alder additions
have also been achieved providing a facile cleavage method for use of this compound as a new chiral auxiliary. © 2002 Elsevier
Science Ltd. All rights reserved.
(Scheme 1). Identical results were obtained when the
reaction was carried out using a 2W phosphorescent
light source with a peak emission at 254 nm.
Recent studies from this laboratory and from others
have described the potential use of 9-substituted chiral
anthracene derivatives as a new class of chiral auxil-
iary.1 These differ from those currently used by making
use of an alkene to effect the addition process. Studies
to-date have involved the synthesis of these compounds
and have investigated the diastereoselectivity of the
addition process. However, the issue still remains of
developing a route that would facilitate the cleavage of
the masked alkene from the anthracene addition
adduct. One of the most common methods for this
process is the use of flash vacuum pyrolysis (FVP),2 but
given the potential value of the auxiliary and the spe-
cialist equipment needed to perform this reaction we
were interested in developing an easier, cleaner process.
Although the diastereoselective addition reaction may
be performed using a catalyst or by heating, we were
also interested in expanding previous work on the
photochemistry of the addition reaction. From the out-
set of this work, anthracene was attractive as a poten-
tial auxiliary as theoretically both addition and cleavage
steps could be carried out using different wavelengths
of UV light. Herein we describe our studies on the
photochemical additions of 9-methoxyethylanthracene
and attempts to facilitate efficient cleavage of the
alkene–anthracene addition adduct.
In the present work a more powerful 125 W medium
pressure mercury lamp was employed in a classical
immersion well reactor. This would allow the introduc-
tion of filter solutions that would enable us to effec-
tively ‘tune’ the wavelength of light emitted from the
lamp. Reactions were carried out in triplicate by illumi-
nation of a 0.1 mM solution of the ether 1 in degassed
acetonitrile for 1 h. Either cooling water or a cooled
filter solution was passed through the reactor to main-
tain the temperature of the reaction solution close to
30°C, thus suppressing any unwanted thermal addition
reaction. In addition to water, three other filter solu-
tions were used with different absorption spectra (Fig.
1) that would allow illumination at different wave-
lengths of light. Since the ether 1 and the addition
adduct 2 have very different absorption spectra (Fig. 2),
it was hoped that selective illumination would only
promote the forward (or reverse) reaction. In particular
NiSO4-containing solutions should inhibit absorption
at the 320–400 nm band of the auxiliary 1.
In previous work, thermal cycloaddition of the auxil-
iary 1 with maleic anhydride or N-methylmaleimide led
to exclusive formation of a single diastereoisomer e.g. 2
Keywords: Diels–Alder; retro Diels–Alder; diastereoselective cycload-
dition.
* Corresponding author. Tel.: 0191 222 7128; fax: 0191 222 6929;
e-mail: s.jones@ncl.ac.uk
Scheme 1. Photochemical addition of maleic anhydride to
ether 1. Reagents and conditions: (i) maleic anhydride, solvent,
hw as text.
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02255-4

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J. C. C. Atherton, S. Jones / Tetrahedron Letters 43 (2002) 9097–9100
cleavage step for our auxiliary. In the first instance, this
was attempted by heating the addition adduct 2 at
reflux in mesitylene. After 1 h, only a trace (4%) of
auxiliary 1 was recovered indicating that although the
reaction appeared to be reversible, thermal cleavage
was not viable.
At this temperature the equilibrium for this reaction
probably favours formation of product, which corre-
lates with our previous studies of the thermal Diels–
Alder additions of anthracene derivatives such as 1.1c
However, in these studies we had observed an apparent
increase in the rate of the Diels–Alder addition with
N-methylmaleimide as dienophile. If the Diels–Alder/
retro Diels–Alder was indeed proceeding via an equi-
librium process, heating the cycloadduct 2 in the
presence of N-methylmaleimide should lead to prefer-
ential formation of the addition product 4 (Scheme 2).
In practice, after heating anhydride 2 for 1 h in reflux-
ing mesitylene with 1 equiv. of N-methylmaleimide,
23% of the desired imide 4 was formed. This encourag-
ing result led us to consider a similar process under
photochemical conditions and photolysis of an acetoni-
trile solution of the cycloadduct 2 and N-methyl-
maleimide gave the desired product 4 with good
conversion (57%) after 1 h. Dimer 3 formation was
observed once again. Use of filter solutions offered no
real advantage in this reaction (Table 2).
Figure 1. UV spectra of filter solutions used in this study.
Although photochemical exchange appeared feasible,
photochemical cleavage would be a more desirable
process. To our delight, photolysis of an acetonitrile
solution of the adduct 2 with water cooling for 1 h led
to recovered auxiliary 1 (64%) along with dimer 3 (20%)
Figure 2. UV spectra of ether 1 and adduct 2.
Table 1. Photochemical additions of methyl ether 1 and
maleic anhydride
The results obtained from the photochemical additions
are presented below (Table 1). Although increased
quantities of product compared to the thermal reaction
were observed with no loss of diastereoselectivity, small
quantities (10%) of another component, identified as
the dimer 3, were also observed.3 The dimer was pre-
sumed to be the trans isomer, based on steric arguments
and literature precedent for this type of dimerization
process.4 Unfortunately, reproducible results could not
be obtained from these reactions, which in conjunction
with the formation of the unwanted dimer 3, made the
photochemical addition process somewhat limited in
the development of our chiral auxiliary at this point.
Coolant/filter solution
% Diels–Alder
adduct 2
% Dimer 3
Water
20
62
36
5
22
11
NiSO4 (0.2 M)
CoSO4 (0.3 M)
34
26
42
10
10
9
49
25
10
16
13
6
NiSO4 (1 M) and CoSO4
(1 M in 5% H2SO4) (1:1 v/v)
42
35
43
11
11
5
We next turned our attention to the retro Diels–Alder
reaction since this reaction would need to be carried
out in an efficient manner to be useful as the ultimate

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J. C. C. Atherton, S. Jones / Tetrahedron Letters 43 (2002) 9097–9100
9099
Scheme 3. Recycling of dimer 3. Reagents and conditions: (i)
either hw, CH3CN, 1 h (93%) or mesitylene, 1 h, D (99%).
Scheme 2. Thermal and photochemical exchange reactions.
Table 2. Photochemical exchange reactions
Coolant/filter solution
% Diels–Alder
adduct 4
% Dimer 3
Water
NiSO4 (0.2 M)
CoSO4 (0.3 M)
NiSO4 (1 M) and CoSO4 (1
M in 5% H2SO4) (1:1 v/v)
57
55
45
50
9
13
10
6
Scheme 4.
and maleic anhydride which equates to near quantita-
tive cleavage when the dimer is taken into account. At
first, dimer formation appeared to be a drawback of
this reaction, however, we were able to demonstrate
that this can act as a ‘masked’ auxiliary and itself be
recycled. Thus, photolysis of an acetonitrile solution of
the isolated dimer 3 for 1 h gave near quantitative
conversion to the auxiliary 1, as did heating in boiling
mesitylene for 1 h (Scheme 3).
Acknowledgements
We would like to thank EPSRC and Thomas Swan and
Co. Ltd. for financial support (J.C.C.A.).
References
1. (a) Jones, S.; Atherton, J. C. C. Tetrahedron: Asymmetry
2001, 12, 1117–1119; (b) Atherton, J. C. C.; Jones, S.
Tetrahedron Lett. 2001, 42, 8239–8241; (c) Atherton, J. C.
C.; Jones, S. J. Chem. Soc., Perkin Trans. 1 2002, 2166–
2173; (d) Sanyal, A.; Snyder, J. K. Org. Lett. 2000, 2,
2527–2530.
This method appears general for anhydride type addi-
tion products and alcohol 5 (R=H; X=O) was cleaved
to give dimer 6 (R=H) and monomer 7 (R=H)5 in 40
and 12% conversion, respectively, after 1 h (Scheme 4).
The somewhat reduced conversion again supports the
hypothesis that the addition adduct 5 (R=H; X=O) is
more thermodynamically stable than ether 2. With
maleimide products (R=H, Me; X=NMe) extensive
decomposition was observed. These compounds should
have a slow retro-Diels–Alder reaction compared to the
anhydrides due to their increased stability and in this
case illumination gives rise to another reaction path-
way, ultimately leading to adduct decomposition.
2. (a) Kaupp, G. Liebigs Ann. Chem. 1977, 254–275; (b)
Lasne, M.-C.; Ripoll, J.-L. Synthesis 1985, 121–143.
3. Selected data for compound 3 (accurate MS or CHN
analysis could not be obtained due to decomposition to
the monomeric compound upon heating or ionisation); mp
219–221°C; lH (300 MHz; CDCl3) 7.56 (2H, m, ArCH),
7.00 (2H, m, ArCH), 6.86–6.62 (12H, m, ArCH), 4.53
(2H, s, CHCHC-O), 4.43 (2H, m, CHC-O), 3.75 (6H, s,
OCH3) and 1.44 (6H, d, J 6.2, CH3); lC (125 MHz;
CDCl3) 144.7 (ArC), 144.5 (ArC), 144.2 (ArC), 144.1
(ArC), 143.4 (ArC), 142.3 (ArC), 141.7 (ArC), 128.9
(ArCH), 128.5 (ArCH), 128.5 (ArCH), 128.2 (ArCH),
127.9 (ArCH), 127.6 (ArCH), 125.4 (ArCH), 125.1
(ArCH), 125.0 (ArCH), 124.9 (ArCH), 124.9 (ArCH),
124.6 (ArCH), 124.5 (ArCH), 124.2 (ArCH), 82.2 (CCH),
60.9 (CHC), 58.8 (CH3CH), 58.2 (OCH3) and 15.9 (CH3).
m/z (CI+) 236 (15%, C17H16O+), 221 (10), 205 (100,
C16H13+). All other compounds in this study have been
described previously.
In conclusion we have investigated the photochemical
Diels–Alder and thermal and photochemical retro
Diels–Alder reactions of chiral 9-anthracylethanol
derivatives. The latter provides a clean and efficient
method for the cleavage of anhydride substrates from
the addition adduct. Having now established both addi-
tion and cleavage conditions for our anthracene auxil-
iary, further work will focus on the asymmetric
reactions that may be possible with these compounds.

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J. C. C. Atherton, S. Jones / Tetrahedron Letters 43 (2002) 9097–9100
4. Bouas-Laurent, H.; Castellan, A.; Desvergne, J.-P.;
Lapouyade, R. Chem. Soc. Rev. 2000, 29, 43–55.
5. Selected data for compound 6 (R=H; accurate MS or
CHN analysis could not be obtained due to decomposition
to the monomeric compound upon heating or ionisation;
13C was not possible due to limited solubility in DMSO);
mp 232–234°C; lH (300 MHz; DMSO) 7.73 (2H, m,
ArCH), 7.03 (2H, m, ArCH), 6.87–6.65 (12H, m, ArCH),
5.92 (2H, t, J 4.5, O-H), 5.01 (2H, m, CHC-O), 4.83
(2H, s, CHCHC-O) and 1.39 (6H, d, J 6.2, CH3); m/z
(CI+) 233 (15%), 222 (100, C16H14O+), 205 (96, C16H13+),
179 (83).