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Competition of Endoperoxide and Hydroperoxide Formation in the Reaction of Singlet Oxygen with Cyclic Conjugated Dienes.

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[3] a) J . Furukawa, S. Okuda, K. Saito, S . 1. Hatanaka, Phytochemistry 24
(1985) 593; b) R. J. Nash, E. A. Bell, J. M. Williams, ibid. 24 (1985)
141 a) H. Paulsen, I. Sangster, K. Heyns, Chem. Ber. 100 (1967) 802; b) H.
Paulsen, K. Todt, Adu. Carbohydr. Chern. 23 (1968) 115; c) G. Kinast, M.
Schedel, Angew. Chem. 93 (1981) 199; Angew. Chem. Int. Ed. Engl. 20
(1981) 805; d ) A. Vasella, R. Voeffray, Helu. Chim. Acfa 65 (1982) 1134; e)
G . Legler, E. Julich, Carbohydr. Res. 128 (1984) 61; f) R. C. Bernotas, B.
Ganem, Tetrahedron Lett. 26 (1985) 1123; g) G. W. J. Fleet, L. E. Fellows,
D W. Smith, Tetrahedron 43 (1987) 979; h) S . Inouye, T. Tsuruoka, T. Ito,
T. Nidda, ibzd. 23 (1968) 2125.
[5] H . lida, N. Yamazaki, C. Kibayashi, J. Org. Chem. 82 (1987) 3337.
[6] G. W. J. Fleet, S . J. Nicholas, P. W. Smith, S. V. Evans, L. E. Fellows, R.
J. Nash. Tetrahedron Lett. 26 (1985) 3127.
[7] F. Effenberger, A. Straub, Tetrahedron Lett. 28 (1987) 1641, and references cited therein.
[XI a) A. Mocali, D. Aldinucci, F. Paoletti, Curbohydr. Res. 143 (1985) 288; b)
M. Kapuscinski, F. P. Franke, I. Flanigan, J. K. MacLeod, J. F. Williams,
ibrd. 140 (1985) 69; c) J. Bolte, C. Demuynck, H. Samaki, Tetrahedron
Lerr 28 (1987) 5525.
Competition of Endoperoxide and Hydroperoxide
Formation in the Reaction of Singlet Oxygen
with Cyclic, Conjugated Dienes**
Two facts emerge therefrom: First, hydroperooxides are
formed to a considerable extent; that is, [4+21 cycloaddition and ene reaction compete. Second, the cis-trans ratio
(based o n the position of the peroxide function to the isopropyl group) is constant for both the endoperoxides as
well as the diastereomeric hydroperoxides; it is 3 :2 .
The latter finding suggests the existence of a common
intermediate for endo- and hydroperoxides. Monroe[31has
postulated this for the reaction of '0, with acyclic dienes;
for cyclic dienes, however, he proposed a concerted [4+ 21
cycloaddition exclusively, since only endoperoxide formation was observed.
Fig. I . Conformations la and l b of (R)-(-)-a-phellandrene 1
By Rudolf Matusch.* and Gerhard Schmidt
Singlet oxygen ( loz)usually reacts with cyclic, conjugated dienes in the sense of a [4+2] cycloaddition to give
endoperoxides, whereas non-conjugated olefins with allylic hydrogen atoms undergo a double-bond shift with
formation of hydroperoxides. In the following we show
that both reactions can occur, and that a common intermediate can be formulated in the case of cyclic, conjugated
In the search for biologically active plant constituents
we isolated the two endoperoxides 2 and 3 as active components which are accessible synthetically by reaction of
'0, with (R)-(- )-a-phellandrene l1'Iand were previously
considered t o be the sole products of this reaction. To our
surprise, however, not only the peroxides 2 and 3 are
formed but also all theoretically possible hydroperoxides
4, 5 , 6, 7, and 8, together with the aromatization product
p-cymol 9.1z1Scheme 1 shows the distribution of all products after a preparative HPLC separation (data in wt-%).
26 90
2.9 "lo
Scheme 1
[*] Prof. Dr. R. Matusch, Dr. G. Schmidt
lnstitut fur Pharmazeutische Chemie der Universitat
Marbacher Weg 6, D-3550 Marburg (FRG)
Lecture at the Annual Conference of the Deutsche Pharmazeutische Gesellschaft in Miinster, September 10, 1987.
Angew. Chem. Int. Ed. Engl. 27 (1988) No. 5
Dreiding models show that a-phellandrene 1 can assume two conformations (Fig. 1). At room temperature a
considerable amount of 1 is present in the conformation
In a concerted [4+2] cycloaddition with attack of '0,
from above, steric interactions of the isopropyl group with
the dienophile should be considerable for l a and negligible for l b . On the other hand, both conformers are equally
likely to react with '02from below. In summary, therefore,
more trans-endoperoxide 3 should result. The observed
higher proportion of the cis-endoperoxide 2 thus contradicts an endoperoxide formation by concerted [4 21 cycloaddition.
Especially interesting concerning the hydroperoxides is
the preferred cis-conformation of 6 compared to 7.Since
the abstracted H atom here comes from a methyl group, a
cis-trans ratio of 1 : 1 would be expected, irrespective of the
conformation,[51if the '02does not preferably approach
from above.
How then does this cis-directing effect come about? The
point is that '0, preferably abstracts axial allylic H atoms
in an ene reaction, whereas equatorial allylic H-atoms remain undisturbed.@]
Regarding the cis sides of l a and l b in respect to the
formation of 4 and 5, H-3B being the only proton that
could react in an ene reaction has the unreactive equatorial
position in the case of l a and, additionally, the isopropyl
group disfavors abstraction because of unfavorable steric
interactions. In contrast this H-30 is axial in the conformer
l b . Exactly the opposite holds true on the trans side for
H-3a: in l a it is axial, and in l b it is equatorial. We therefore presumed that the cis products are mainly formed
from the conformer l b and the trans products mainly from
the conformer l a . To substantiate our assumption we carried out the reaction at - 50°C. Since conformer l a is the
energetically less fav~rable;~''the amount of trans products should decrease further. As expected the cis-trans ratio increases from 3 :2 to 4 :2, both in the case of the endoas well as the hydroperoxides.
According to the above observations the mechanism of
the ene reaction must first be considered. In the recent literature['] a loose complex 10 is proposed in which '02interacts with the olefinic C atoms and with the allylic H
atoms to be abstracted. If, as in the present case, both
endo- as well as hydroperoxides are formed from a diene,
0 VCH Verlagsgesellschaji mbH, 0-6940 Weinheim. 1988
0870-0833/88/0508-0717 $ 02.50/0
7 17
the interactions of the second 0 atom with the allylic H
atom and with the second double bond must compete with
each other, as indicated in 11.
observed in the reaction of '02with a-terpinene 12. Here
too the endoperoxide, namely ascaridol 13, was thought to
be the only reaction product.@]And, once again, on closer
examination we found the racemic hydroperoxides (8, 14,
15) depicted quantitatively in Scheme 3.
Received: January 28, 1988:
revised: February 29, 1988 [Z 2593 IE]
German version: Angew. Chem. 100 (1988) 729
The relative strengths of these interactions and thus the
electronic and steric factors now decide whether route a
(ene reaction) or route b ([4 + 21-cycloaddition) will dominate (Scheme 2). If 11 is used as a model for the two conformers l a and l b , then not only are interactions of the
second 0-atom with the axial H-3 and with the second
double bond possible but also interactions with an H atom
of the methyl group (Fig. 2; lc and Id).
Fig. 2. Postulated intermediates l c and Id for the interactions of l a and Ib,
respectively, with singlet oxygen.
This, however, provides an explanation for the cis-trans
ratio of the hydroperoxides 6 and 7. Since a complex in
which the second oxygen atom can undergo three interactions is obviously more favorable than a complex with a
lower number of interactions, the respective axial H-3 and
thus the conformer equilibrium l a * l b also directs the
formation of 6 and 7. Finally, enantiomerically pure 8 is
formed by '0,-attack at the other double bond and abstraction of H-4.
Synthesis of Optically Active Phosphanes
via Sharpless Epoxidation""
By Henri Brunner* and Adolf Sicheneder
Optically active phosphanes are the most useful ligands
in enantioselective catalysis with transition metal comp l e x e ~ . ' ~Methods
for preparing such phosphanes involve
either a resolution step or the transformation of a chiral
precursor from the chiral
In the present paper we
describe a new synthesis of optically active phosphanes
making use of the high optical inductions accessible in the
Sharpless epoxidation of allyl a l ~ o h o l s . ~Using
~ - ~ ~ this
methodology, achiral allyl alcohols can be converted in a
few steps, via epoxy alcohols and their proper derivatization (Scheme I), into optically active diphosphanes capable of forming five-membered and six-membered chelate
The ally1 alcohols l a and l b were transformed into the
epoxy alcohols 2a (yield 55%; 93%ee) and 2b (yield 75%;
> 95% ee) as described by Sharpless et aI.['~*]The primary
alcohol groups of 2a and 2b were easily tosylated without
affecting the epoxide ring to give 3a and 3b. Subsequent
reaction with LiPPhz introduced two PPhz substituents,
one by tosylate replacement and the other by epoxide ringopening.
0.5 ?a
Scheme 3
The competition between cycloaddition and ene reaction in the case of cyclic, conjugated dienes can also be
7 18
G. 0. Schenck, K. Ziegler, Nafurwissenschaften32 (1944) 157.
For the generation of singlet oxygen we used a sodium vapor lamp as
light source, Bengal rose as sensitizer, and methanol as solvent. The reaction time at room temperature was 40 min. To rule out a radical reaction,
the radical inhibitor 2,6-terr-butyl-p-cresol was added. The same product
pattern was obtained when using other sensitizers (tetraphenylporphyrin,
methylene blue) and other solvents (dichloromethane, isopropyl alcohol).
Also no oxidative changes were observed after 40 minutes' treatment with
'O1. Separation of the reaction mixture was accomplished by preparative
HPLC (25 x 250 mm column; Li-Chrosorb Si 60, 5 pm, n-pentane/diethyl
ether 9 : 1). The amounts of the products (wt-%) in Schemes I and 3 are
based on the total amount of fractions eluted; the remaining 2.5%
(Scheme 1) and 0.3% (Scheme 3) lie in the interstitial fractions. All the
products gave correct analytical data.
B. M. Monroe, J . Am. Chem. SOC.103 (1981) 7253.
a) W. Burgstahler, H. Ziffer, U. Weiss, J. Am. Chem. Sor. 83 (1961) 4660;
b) A. Moscowitz, E. Charney, U. Weiss, H. Ziffer, rbid. 83 (1961) 4661; c)
H. Ziffer, E. Charney, U. Weiss, ;bid. 84 (1962) 2961.
K Gollnick, H. J. Kuhn in H. H. Wassermann, R. W. Murray (Eds.):
Singler Oxygen, Academic Press, New York 1979, p. 326.
R. W. Denny, A. Nickon, Org. React. 20 (1973) 133.
a) I. R. Hurst, G. B. Schuster, J . Am. Chem. Sor. 104 (1982) 6854; b) M.
Hotokka, 8. Roos, P. Siegbahn, ibid. 105 (1983) 5263; c) K. Yamaguchi, I.
Saito, K. N. Houk, Tetrahedron Letr. 22 (1981) 749; d) K. N. Houk, J. C.
Williams, P. A. Mitchell, K. Yamaguchi, J . Am. Chem Sac. 103 (1981)
a) G. 0. Schenck, K. Ziegler, DRP 752437 (July 22, 1941); b) see [5], p.
0 VCH Verlagsgesellsrhaft mbH, 0-6940 Weinheim. 1988
[*] Prof. Dr. H. Brunner. DiplLChem. A. Sicheneder
Fakultat fur Chemie und Pharmazie der Unrversitat
Universitatsstr. 31, D-8400 Regensburg (FRG)
[**I Enantioselective Catalysis, Part 42. This work was supported by the
Deutsche Forschungsgemeinschaft, the Fonds der Chemischen Industrie, and BASF AG, Ludwigshafen.-Part 41: [I].
0S70-0833/88/050S-0718 $ 02.50/0
Angew. Chem. Int. Ed. Engl. 27 (1988) No. 5
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cyclic, reaction, diener, hydroperoxide, formation, endoperoxide, conjugate, single, competition, oxygen
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