Reactions of Singlet Oxygen and
N-Methyltriazolinediones with
,-Dimethylstyrene. Exceptional Syn
Selectivity in the Ene Products
Manolis Stratakis,*
,†,‡
Michael Orfanopoulos,
†
and
Christopher S. Foote*
,‡
Department of Chemistry, University of Crete,
71409 Iraklion, Greece, and Department of Chemistry and
Biochemistry, University of California,
Los Angeles, California 90095-1569
Received August 14, 1997
The ene reactions of singlet oxygen (
1
O
2
) and triazo-
linediones (RTAD, R ) methyl or phenyl, usually) with
alkenes are closely related mechanistically and exhibit
a fascinating variety of regio- and stereoselectivities. Both
reactions appear to proceed via intermediates; the singlet
oxygen reaction via a “perepoxide”
1
and the RTAD
reaction via an aziridinium imide (AI).
2
In the reaction
of
1
O
2
with trisubstituted alkenes
3
and enol ethers,
4
the
more reactive side of the olefin is the more substituted
one (“cis effect”), but there is very little Markovnikov
selectivity. These results have been rationalized
5
by
postulating an attractive interaction of singlet oxygen
with allylic hydrogens on the more substituted side of
the double bond. On the other hand, phenyl- and
methyltriazolinedione (PTAD and MTAD) exhibit strong
Markovnikov selectivity, giving products with the nitro-
gen exclusively on the less substituted carbon.
6
In the reaction of
1
O
2
and RTAD with cis-disubstituted
alkenes, the major ene products arise from allylic hydro-
gen abstraction next to the bulkiest group.
7
Also, gemi-
nal selectivity
8
with respect to a bulky alkyl substituent
at allylic or vinylic position is observed. These selectivi-
ties were rationalized in terms of nonbonded interactions
in the product-forming transition states.
9
Furthermore,
coordination of
1
O
2
to hydroxyl
10
and amino
11
groups, or
electronic repulsions with several other functionalities
12
in the allylic positions, can lead not only to highly threo
or erythro diastereoselective ene reactions but also can
control the regioselectivity.
13
In this paper, we report an unprecedentedly high “cis
effect” selectivity in the ene products from singlet oxygen
and MTAD addition to ,-dimethylstyrene (1). It was
reported
12
several years ago that sensitized photooxy-
genation of 1 in several solvents affords a variable
mixture of ene product (1b), benzaldehyde, and two
diastereomeric diendoperoxides 1d and 1e in 68/32 ratio;
diendoperoxides arise from initial [4 + 2] addition of
1
O
2
to 1, followed by a second addition of
1
O
2
to the newly
formed diene endoperoxide 1c, (Scheme 1).
To distinguish the syn/anti stereosectivity of the ene
products produced from the two geminal methyls, the
anti-methyl group was specifically labeled (>99% geo-
metrical purity) by a literature procedure.
15
The ene
adducts can be separated from the reaction mixture by
column chromatography using benzene as eluent. Ex-
amination of the syn/anti stereoselectivity of the ene
products of 2 in different solvents revealed that there is
a strong selectivity for attack on the methyl syn to the
phenyl group. The magnitude of this selectivity depends
on solvent polarity. On increasing the dielectric constant
of the solvent, a substantial increase in the amount of
hydrogen abstraction in the syn-methyl group occurs. For
instance, the ratio of syn/anti ene products increases by
a factor of 3.4 on going from CCl
4
to methanol (Table 1).
The intermolecular isotope effect upon competition of
1 with the deuterated olefin 3 in chloroform is negligible
(k
H
/k
D
)
total
) 1.00 ( 0.02), which means that formation
of perepoxide is irreversible, as in other trisubstituted
†
University of Crete.
‡
University of California.
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1315 J. Org. Chem. 1998, 63, 1315-1318
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Published on Web 01/22/1998