times were necessary under identical conditions for 1 in
comparison with methyl tiglate.15 Further methylation com-
pensated this effect, and to our surprise, many of these
substrates did show an initial mode selective and regioselec-
tive ene reaction with singlet oxygen that was followed by a
[4 þ 2]-cycloaddition, i.e. a singlet oxygen ene/[4 þ 2]-domino
process.16 As a typical example, the 1,3-diene ester E,E-417 was
prepared and reacted with singlet oxygen in nonpolar deuter-
ated solvents (taking advantage of the solvent deuterium
isotope effect)18 with meso-tetraphenylporphyrin (TPP) as a
sensitizer. After a short reaction time, the allylic hydroperoxide
5 was observed as the sole product (Scheme 3). In the NMR
spectrum of the crude reaction solution, only trace amounts
of an endoperoxide were detected and no traces of the
regioisomeric allylic hydroperoxide. Thus, the ene process
dominates the singlet oxygen reactivity by far and the
γ-hydrogen transfer is largely preferred. The influence of
the cis-effect on the reactivity of E,E-4 was investigated by
comparison with the E,Z-4 isomer that was available from
methyl angelate by a three-step process. A slight reactivity
decrease was detected for E,Z-4 (kE,E/kE,Z = 2.5, for cis/
trans-2-butene kc/kt = 4ꢀ5)19 due to the cis-effect, however,
with no apparent change in regioselectivity. The allylic hydro-
peroxide 5 is highly sensitive and decomposes already during
chromatographic purification. In order to establish the purity
and structure, we treated 5with substoichiometric amounts of
titanium(IV) isopropoxylate20 and isolated the epoxy alcohol
6 as a separable mixture of two diastereoisomers.
Scheme 1. Regioselectivity Pattern in Ene Reactions with 1O2
The photooxygenation of this substrate 113 resulted in the
allylic hydroperoxide 2; however, also large amounts of the
endoperoxide 3 were formed (Scheme 2). This competition
shows a solvent dependence in agreement with nonfunc-
tionalized 1,3-dienes, e.g. the well-studied 2,5-dimethyl-2,4-
hexadiene.14 Aprotic solvents favor the formation of the
endoperoxide 3, and protic solvents, the ene product 2. In
contrast to the purely methylated reference substrate, no
dioxetanes were formed from the electronically deactivated
substrate 1.
Scheme 2. Photooxygenation of 1
Scheme 3. Regioselective Ene Reaction of E,E-4 and
E,Z-4 with 1O2
The overall reactivity of 1 is strongly reduced in compar-
ison to the tiglate derivatives A; i.e., 5-fold longer irradiation
(13) Piers, E.; Jung, G. L.; Ruediger, E. H. Can. J. Chem. 1987, 65,
670.
(14) Gollnick, K.; Griesbeck, A. G. Tetrahedron 1984, 40, 3225.
(15) Griesbeck, A. G.; de Kiff, A.; Vollmer, M.; Kleczka, M.; Goldfuss,
B.; Leven, M., unpublished results.
Under the same photooxygenation reaction conditions,
the initially formed product 5 did add another equivalent
(16) Other domino processes with singlet oxygen and cyclic sub-
ꢀ
strates (1,4-cyclohexadienes and tetrahydronaphthalenes): Kurbanoglu,
N. I.; C-elik, M.; Kilic, H.; Alp, C.; S-ahin, E.; Balci, M. Tetrahedron 2010,
(17) Moinuddin, A. M.; Mortensen, M. S.; O’Doherty, G. A. J. Org.
Chem. 2006, 71, 7741.
€
66, 3485. Linker, T.; Frohlich, L. Angew. Chem., Int. Ed. 1994, 33, 1971.
Salamci, E.; Secen, H.; Suetbeyaz, Y.; Balci, M. J. Org. Chem. 1997, 62,
2453. Gueltekin, M. S.; Celik, M.; Turkut, E.; Tanyeli, C.; Balci, M.
Tetrahedron: Asymmetry 2004, 15, 453. Yardimci, S. D.; Kaya, N.; Balci,
€
(18) Griesbeck, A. G.; Schlundt, V.; Neudorfl, J. M. RSC Adv. 2013,
DOI:10.1039/c3ra40555a.
(19) Wilkinson, F.; Helman, W. P.; Ross, A. B. J. Phys. Chem. Ref.
Data Rep. 1995, 24, 663.
(20) Adam, W.; Braun, M.; Griesbeck, A. G.; Lucchini, V.; Staab, E.;
Will, B. J. Am. Chem. Soc. 1989, 111, 203.
€
M. Tetrahedron 2006, 62, 10633. Linker, T.; Frohlich, L. J. Am. Chem.
Soc. 1995, 117, 2694. Linker, T.; Kruger, T.; Hess, W.; Hilt, G.
ARKIVOC 2007, 8, 85. Kishali, N.; Sahin, E.; Kara, Y. Org. Lett.
2006, 8, 1791.
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Org. Lett., Vol. 15, No. 9, 2013