ORGANIC
LETTERS
2011
Vol. 13, No. 24
6556–6559
Electronic-State Switching Strategy in the
Photochemical Synthesis of Indanones
from o-Methyl Phenacyl Epoxides
†
Peter Stacko, Tomas Solomek,* and Petr Klan*
,†,‡
,†,‡
ꢀ
ꢀ
ꢁꢀ
ꢁ
Department of Chemistry, Faculty of Science, Masaryk University, Kamenice 5/A8, 625
00 Brno, Czech Republic, and Research Centre for Toxic Compounds in the Environment,
Faculty of Science, Masaryk University, Kamenice 3, 625 00 Brno, Czech Republic
tom.solomek@gmail.com, klan@sci.muni.cz
Received October 26, 2011
ABSTRACT
An electronic excited-state switching strategy has been utilized to control the selectivity of a key photochemical step in the total synthesis
3
of indanorine. The excited-state character of 4,5-dimethoxy-2-methylphenacyl epoxide was changed from an unfavorable π,π* state to a
3
productive n,π* state by a temporary structural modification, resulting in a relatively efficient and high-yielding formation of an indanone
derivative. The corresponding structural modification was selected on the basis of quantum chemical calculations prior to the synthesis.
In the past decades, several strategies have been dev-
eloped to efficiently control the chemo- or regioselec-
tivity of organic reactions. In photochemical reactions,
selectivity remains to be a challenging task in targeted
synthesis.1 Complicating features of excited state reac-
tions, such as close-lying electronic states, conical intersec-
tions, or small reaction barriers, hamper the predictability
of photochemical reactions. For example, the chemical
reactivity of two close-lying triplet electronic states of
phenyl ketones, the relative energies of which are strongly
influenced by substitution on the aromatic ring or by the
solvent, is known to differ markedly.2 Hence, classical free
energy relationships often fail to predict excited state
behavior.2c,d,3
The order of the triplet energy levels is decisive for
reactions involving an excited-state hydrogen-atom
transfer step, such as the photoenolization of substituted
o-methylphenyl ketones 1 (Scheme 1).1,2e,2f,4 Hydroxy-
o-quinodimethane intermediates (o-xylylenols, 2) thereby
photogenerated have been used in the synthesis of various
pharmaceutically relevant compounds possessing an inda-
none core (3, in red; Scheme 1), such as donepezil
hydrochloride5 or pterosines,6 from 1 when good leaving
groups (X = LG) were present in an appropriate position.
These reactive intermediates can also be trapped in situ in a
† Department of Chemistry.
‡ Research Centre for Toxic Compounds in the Environment.
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2595–2607. (b) Pelliccioli, A. P.; Klan, P.; Zabadal, M.; Wirz, J. J. Am.
Chem. Soc. 2001, 123, 7931–7932. (c) Sammes, P. G. Tetrahedron 1976,
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2004, 69, 7582–7591. (b) Wessig, P.; Teubner, J. Synlett 2006, 1543–1546.
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Chem., Int. Ed. 2001, 40, 3675–3678. (c) Nicolaou, K. C.; Gray, D. L. F.;
Tae, J. S. J. Am. Chem. Soc. 2004, 126, 613–627.
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1973, 95, 5604–5614. (d) Wagner, P. J.; Siebert, E. J. J. Am. Chem. Soc.
1981, 103, 7329–7335. (e) Wagner, P. J.; Klan, P. In CRC Handbook of
Organic Photochemistry and Photobiology, 2nd ed.; Horspool, W. M.,
Lenci, F., Eds.; CRC Press LLC: Boca Raton, FL, 2003; Chapter 52, pp 1ꢀ31.
(f) Solomek, T.; Stacko, P.; Veetil, A. T.; Pospisil, T.; Klan, P. J. Org.
Chem. 2010, 75, 7300–7309. (g) Sebej, P.; Lim, B. H.; Park, B. S.; Givens,
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r
10.1021/ol202892r
Published on Web 11/17/2011
2011 American Chemical Society