Intrazeolite photooxygenation of chiral alkenes. Control of facial selectivity by confinement and cation-π interactions

Article abstract of DOI:10.1016/j.tet.2006.07.102

Depending on the nature of the substituents on the stereogenic carbon atom, the ene reaction of singlet oxygen with several chiral alkenes by confinement within thionin-supported zeolite NaY, may exhibit significant changes on facial selectivity by comparison to their photooxygenation reaction in solution. It is proposed that, apart from the conformational consequences as a result of the alkene confinement within the zeolite cavities, a synergism between Na⁺-π interactions and singlet oxygen-Na⁺ interactions plays a significant role in the transition states of ene hydroperoxidation. Within NaY, the diastereoselectivity may significantly depend on the site selectivity, as probed through specific deuterium labelling of trisubstituted alkenes bearing a gem-dimethyl group. In certain cases, a remote stereogenic centre relative to the reacting double bond may induce enhanced diastereoselection and regioselectivity.

Full text of DOI:10.1016/j.tet.2006.07.102

Tetrahedron 62 (2006) 10623–10632
Intrazeolite photooxygenation of chiral alkenes. Control of
facial selectivity by confinement and cation–p interactions
*
Manolis Stratakis, Christos Raptis, Nikoletta Sofikiti, Constantinos Tsangarakis,
Giannis Kosmas, Ioannis-Panagiotis Zaravinos, Dimitris Kalaitzakis,
Dimitris Stavroulakis, Constantinos Baskakis and Aggeliki Stathoulopoulou
Department of Chemistry, University of Crete, Voutes, 71003 Iraklion, Greece
Received 27 April 2006; revised 5 July 2006; accepted 5 July 2006
Available online 7 September 2006
Abstract—Depending on the nature of the substituents on the stereogenic carbon atom, the ene reaction of singlet oxygen with several chiral
alkenes by confinement within thionin-supported zeolite NaY, may exhibit significant changes on facial selectivity by comparison to their
photooxygenation reaction in solution. It is proposed that, apart from the conformational consequences as a result of the alkene confinement
within the zeolite cavities, a synergism between Na+–p interactions and singlet oxygen–Na+ interactions plays a significant role in the
transition states of ene hydroperoxidation. Within NaY, the diastereoselectivity may significantly depend on the site selectivity, as probed
through specific deuterium labelling of trisubstituted alkenes bearing a gem-dimethyl group. In certain cases, a remote stereogenic centre
relative to the reacting double bond may induce enhanced diastereoselection and regioselectivity.
Ó 2006 Elsevier Ltd. All rights reserved.
1. Introduction
NaY supercages, and generated a novel photosensitizing sys-
tem capable of producing very efficiently O2 upon visible
1
Mechanistic studies and synthetic applications of singlet
oxygen (1O2) reactions with organic compounds, have at-
tracted the interest of organic chemists for the past 50 years.1
The singlet oxygen reactions are typically performed in a
homogeneous environment in which the dissolved photo-
sensitizing dye is vulnerable to decomposition. In recent
years, however, immobilizing the dyes on solid supports
has attracted considerable attention, as it contributes to the
green character of the oxidation process, while their stability
is considerably enhanced, as well.2 Apart from the practical
advantages of using solid materials as singlet oxygen gener-
ators, a large number of studies have been focused, on study-
ing the product selectivity of the 1O2 reactions by confining
the reacting substrates within supramolecular assemblies as
microreactors.3 Typical examples are zeolites with small
pores,4 Nafion membranes5 and surfactant vesicles.6 One
of the most practical and efficient systems, which has been
studied extensively for the past 10 years is thionin or methyl-
ene blue-supported zeolite NaY.7 In pioneering work, Li
and Ramamurthy8 confined through partial ion exchange
dyes, that are organic cations, in the interior of the zeolite
light irradiation. Pace and Clennan9 improved the efficiency
of methylene blue-supported NaY as a photosensitizing
system, by replacing the solvent hexane with perfluoro-
hexane. The fluorophobicity of the alkenes in perfluorohex-
ane allows their facile migration into the zeolite cavities.
Thus, the zeolite medium may be used for preparative scale
photooxygenation reactions, without significant changes
in product selectivity or loss of the reaction mass balance.
In the same study, the upper limit of the 1O2 lifetime within
NaY was extrapolated to be around 7.5 ms. More recently,
1
Ramamurthy and co-workers10 measured directly the O2
lifetime within NaY, and found to depend on the alumina
content of the zeolite lattice and the intrazeolite water
content.
From the early studies, it was clearly evident that a new trend
existed for the intrazeolite photooxygenation of trisubsti-
tuted alkenes. The reaction is regioselective with predomi-
nant or even exclusive formation of the secondary allylic
hydroperoxides.8,11 Moreover, in contrast to the reaction in
solution, enhanced reactivity of the less hindered allylic
hydrogens was found through specific labelling in the photo-
oxygenation of several gem-dimethyl trisubstituted alkenes
within NaY.12 Several models have been postulated to
explain the intrazeolite regioselectivity trends,1,7c however,
none of them is widely acceptable and each specific model
is rather considered as a working hypothesis. Yet, the
Keywords: Singlet oxygen; Hydroperoxides; Zeolites; Regioselectivity;
Diastereoselection; Cation–p interactions.
* Corresponding author. Tel.: +30 2810 545087; fax: +30 2810 545001;
e-mail: stratakis@chemistry.uoc.gr
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.07.102

10624
M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
CH3
CH3
CH3
CH3
CH3
CH3
majority of them consider a favourable electrostatic interac-
tion between the intrazeolite alkali metal cations and 1O2 in
the transition state of the ene hydroperoxidation reaction.
Apart from the changes in the regioselectivity for the case
of trisubstituted alkenes, it was reported that isobutenylar-
enes afford within NaY primarily the ene products relative
to the Diels–Alder cycloadducts, in a highly chemoselective
manner.13 This selectivity was attributed to the higher desta-
bilization of an open zwitterion (leading to the [4+2] prod-
ucts) relative to a perepoxide intermediate (leading to the
ene products) as a consequence of the strong Na+–arene
interactions. Generally, cation–p interactions seem to play
a major role in intrazeolite reactions14 and will be postulated
as one of the main driving forces to explain the changes of
the diastereoselection trends in the photooxygenation of the
chiral alkenes presented throughout this paper.
Me
Et
Ph
Ph
Ph
3
1
2
CH3
CH3
CH3
CH3
Me
Ph
n-Pr
Ph
CH3
5
4
CH3
CH3
CH3
CH3
CH3
Ph
6
7
Chart 1. Structures of the chiral alkenes 1–7 whose intrazeolite photooxy-
genation was examined.
2.2. Diastereoselectivity in the photooxygenation of
chiral alkenes bearing a stereogenic centre at the
a-position with respect to the double bond (1–4)
The study of the diastereoselection in the electrophilic addi-
1
tion of O2 to the p face of chiral alkenes is of primary
interest in organic synthesis.15 The confined environment of
zeolite and cation–p interactions as well, might be expected
to affect significantly the facial selectivity in the intrazeolite
photooxygenation of chiral alkenes. One general aspect
would be that blocking the less sterically hindered face of
a double bond through cation binding within the zeolite,
would leave the other face accessible to 1O2 attack. For ex-
ample, Na+–p interactions have been postulated to alter the
p facial photoreduction of some enone steroids confined
within NaY,16 relative to their reaction in a homogeneous en-
vironment. In addition, diastereoselection might be expected
even in cases where a stereogenic centre resides at a remote
position with respect to the reacting double bond. As a result
of ‘substrate-coiling’ within the zeolite cavities, a remote
chiral centre may be brought proximal to the reacting double
bond and thus affect the facial selectivity. Ramamurthy and
co-workers17 have elegantly shown this aspect in the photo-
chemical disrotatory electrocyclic reaction of a chiral tropo-
lone ether. Having in mind these possible contributing
parameters to the p facial selectivity of the intrazeolite reac-
tions, we focused our interest on the photooxygenation of
chiral alkenes bearing a stereogenic centre at the a- or at
more remote positions with respect to the reacting double
bond. In addition, specific labelling of the less hindered
methyl group for the majority of the gem-dimethyl trisubsti-
tuted alkenes studied herein was accomplished, to examine
the interplay of site selectivity on diastereoselection, as
abstraction of an allylic hydrogen atom from the two geminal
methyls occurs through the participation of two non-equili-
brating diastereomeric perepoxide type-intermediates,12c
which may induce a different degree of diastereoselection.
Among the chiral alkenes presented in Chart 1, the first four
(1–4) possess a stereogenic centre at the a-position with
respect to the reacting double bond. The distribution of the
ene products for the photooxygenation of 1–4 in solution
(dichloromethane, methylene blue as sensitizer, 0 ꢀC) is pre-
sented in Table 1. The erythro secondary allylic hydroperox-
ides were primarily formed relative to the threo isomers,
while the labile tertiary allylic hydroperoxides were formed
in up to 14% relative yield, depending on the nature of the
substituents R1 and R2. Analysis by NOE clearly revealed
that they have the Z configuration on the newly formed tri-
substituted double bond. It is surprising,18 from the first
point of view, that alkene 3 in which the two substituents on
the stereogenic carbon atom (phenyl and cyclohexyl) have
more or less similar steric demands, affording the highest
diastereomeric ratio among 1–4. It is obvious, therefore, that
for the phenyl-substituted alkenes 1–3, steric effects cannot
explain the stereochemical outcome. The possible reasons
will be analyzed below.
Apart from the photooxygenation of 1 for which the relative
configuration of the allylic hydroperoxides is known,20 the
Table 1. Photooxygenation of chiral alkenes 1–4 in solution
CH3
H3C
R1
1-4
R2
1O2 CH2Cl2
OOH
CH3
H2C
CH3
H2C
R1
H3C
R2
CH3
+
2. Results and discussion
+
R1
OOH
OOH
R2
R2
2.1. Synthesis of chiral alkenes
R1
tertiary (Z)
erythro
threo
The chiral alkenes (1–7) whose photooxygenation was stud-
ied are presented in Chart 1. The synthesis of 1–7 was
accomplished by Wittig coupling of isopropylidenetri-
phenylphosphorane with the corresponding aldehydes. The
necessary aldehydes for the synthesis of substrates 1 and 4
are commercially available, while the rest were prepared
according to trivial procedures described in Section 4.
Alkene
Tertiary (%)a erythro (%)a threo (%)a
R1¼Me, R2¼Ph (1)
R1¼Et, R2¼Ph (2)
6
10
72
70
71
62
22
20
15
38
R1¼Cyclohexyl, R2¼Ph (3) 14
R1¼Me, R2¼n-Pr (4)
—
a
Relative percentages.

M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
10625
δ-
ene products for the case of 2 and 3 were reduced in situ with
PPh3 and the resulting allylic alcohols were compared to
the diastereomeric alcohols produced from the reaction of
2-propenylmagnesium bromide with a-ethyl or cyclohexyl-
phenylacetaldehyde (Scheme 1). It is well known21 that the
addition of organolithium or Grignard reagents to a-alkyl
substituted phenylacetaldehydes is erythro diastereoselec-
tive. In our case, reaction of 2-propenylmagnesium bromide
with 2-phenylbutyraldehyde afforded the allylic alcohols
in a ratio erythro/threo¼4.6/1, while a-cyclohexylphenyl-
acetaldehyde gave a product ratio of erythro/threo¼1.4/1.
The predominant formation of the erythro allylic hydro-
peroxide in the photooxygenation of 4, was reasonably
assessed from the photooxygenation results of similar chiral
trisubstituted alkenes20 bearing alkyl substituents on the
stereogenic centre.
CH3
O
H2C
OOH
δ+
H3C
Ph
CH3
O
R
H
R
+
OOH
Ph
(Z)
Ph
R
erythro
H3C
CH3
TS1
δ-
O
δ+
CH3
H2C
O
H
R
R
OOH
Ph
Ph
H3C
CH3
threo
TS2
δ-
O
δ+
CH3
H2C
O
Ph
H
R
OOH
R
Ph
H3C
CH3
threo
TS3
MgBr
OH
Ph
Et
erythro, 82%
OH
Et
H3C
H2C
H3C
H2C
Et
CH3
Et2O
δ-
+
CHO
O
δ+
Ph
CH3
Ph
H2C
O
threo, 18%
Me
Pr
H
Me
OOH
MgBr
CH3
Pr
H3C
CH3
TS4
OH
Ph
OH
erythro
H3C
H2C
H3C
H2C
+
Scheme 2. Possible transition states for the photooxygenation of alkenes
1–4 in solution.
Et2O
CHO
Ph
Ph
threo, 43%
erythro, 57%
predominantly formed, and the ratio threo/erythro increases
withincreasing thebulkiness of the R group (for alkenes 1–3).
Scheme 1. Addition of 2-propenylmagnesium bromide to a-substituted
phenylacetaldehydes.
The predominant formation of the threo secondary allylic
hydroperoxides by zeolite confinement can be rationalized
as follows. Taking into account the strong electrostatic inter-
action23 of the phenyl ring to the Na+ within the NaY super-
cages, the alkene most likely adopts the conformation shown
The selective formation of the erythro stereoisomer in the
photooxygenation of 1–3 in solution can be explained con-
sidering preferential facial approach of O2 to the double
1
bond as shown in transition state TS1 of Scheme 2. The
phenyl group is placed to the opposite face of the double
bond with respect to the attacking singlet oxygen, due to
the unfavourable oxygen–arene electronic repulsions. In
addition, for TS1, the 1,3-allylic strain between the tertiary
allylic hydrogen atom and the more hindered allylic methyl
group is minimized. Abstraction of the suitably oriented
tertiary allylic hydrogen atom leads to the formation of the
minor (Z)-tertiary allylic hydroperoxides. Transition states
TS2 and TS3, which lead to the threo diastereomers are
expected to be less stable compared to TS1, due to the sub-
stantial 1,3-allylic strain between the R group and the prox-
imal allylic methyl for the case of TS2, or to unfavourable
oxygen–arene electronic repulsions for the case of TS3. By
increasing the bulkiness of the alkyl group (R) from methyl
to cyclohexyl, enhanced erythro diastereoselection is found
as reasonably expected (TS1 vs TS2). For alkene 4, the mod-
erate erythro selectivity arises through the more favourable
transition state TS4 in which the steric effects (methyl vs
n-propyl) and the minimum 1,3-allylic strain as well, dictate
the facial selectivity.
1
in Scheme 3. Preferential attack of O2 from the less hin-
dered top face gives the major threo secondary allylic hydro-
peroxides, while attack from the less accessible bottom face
gives the minor erythro diastereomers. As the bulkiness of
the R group increases, the energy difference between the
threo and erythro forming transition states increases as well,
in favour of the threo isomer. The participation of the threo-
forming transition state TS5 (Scheme 3), in which apart from
the cation–arene interaction, a favourable 1O2–Na+ interac-
tion operates cannot be excluded. In the case of alkene 4,
we postulate that preferential interaction of the Na+ with
the less hindered face of the double bond allows the threo-
forming transition state TS6 (Scheme 3) to predominate
Table 2. Photooxygenation of chiral alkenes 1–4 within zeolite NaY
CH3
CH3
H2C
R1
H2C
R1
CH3
H3C
R1
1O2
+
OOH
R2
erythro
OOH
NaY
1-4
R2
threo
R2
Photooxygenation of 1–422 by confinement within thionin-
supported zeolite NaY is highly regioselective, since only
the secondary allylic hydroperoxides were obtained, how-
ever, with an inverse diastereoselection trend, which is more
profound and even remarkable in the case of the cyclohexyl-
substituted alkene 3 (Table 2). The threo diastereomers were
Alkene
erythro (%)a
threo (%)a
R1¼Me, R2¼Ph (1)
R1¼Et, R2¼Ph (2)
46
23
9
54
77
91
53
R1¼Cyclohexyl, R2¼Ph (3)
R1¼Me, R2¼n-Pr (4)
47
a
Relative percentage.

10626
M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
slightly. Furthermore, for alkene 4, the change of the dia-
stereoselection trend on going from the reaction in solution
to the confined zeolite environment, is not as impressive as in
the case of 1–3. We postulate that since the electrostatic
interaction between 4 and an Na+ is not expected to be as
strong24 as with the phenyl-substituted alkenes 1–3, reaction
in which the more bulky cyclohexyl group has replaced
the methyl group on the stereogenic centre of 5. Photooxy-
genation of 7 in solution gave a mixture of tertiary and
secondary allylic hydroperoxides in a ratio 59/41, and a rela-
tively enhanced diastereomeric ratio for the case of the sec-
ondary allylic hydroperoxides (dr¼62/38, not specified).
While the reaction by zeolite confinement is 85% regioselec-
tive in favour of the formation of the secondary allylic
hydroperoxides, the diastereoselection was not enhanced, as
in the case of 5, but essentially slightly decreased to 57/43
(Scheme 4). We assume that the bulkiness of the cyclohexyl
ring may force 7 at NaY to adopt a conformation in which
the stereogenic centre may not become proximal to the react-
ing double bond, and thus, affect substantially the facial
selectivity. We next studied the photooxygenation of the
chiral alkene 6 (Scheme 4), which bears the same substitu-
ents on the stereogenic centre as alkene 5, however, situated
at the more remote g-position with respect to the double
bond. In solution, the expected regioselectivity trend was
found, while the diastereomeric ratio for the secondary
allylic hydroperoxides was negligible (by GC and 1H NMR).
Photooxygenation of 6 within NaY gave predominantly the
secondary allylic hydroperoxides (65% relative ratio), yet,
the diastereoselection, as for the reaction in solution, was
negligible. We would like to point out the significant dif-
ference in the regioselectivity on going from 5 to 7 within
NaY. The relative ratio of the tertiary allylic hydroperoxide
in the case of 5 is remarkably low (6%) and increases
to 35% for 7. Similar regioselectivity changes had been
reported by our group12c on studying the regioselectivity
in the photooxygenation of structurally analogous phenyl-
substituted alkenes and had been explained in terms of dif-
ferent substrate conformations within NaY which allow
methylene allylic hydrogen abstraction to occur with differ-
ent energetic consequences. From the above results we con-
clude that it is difficult to predict an enhancement of facial
selectivity for the case of alkenes bearing remote stereogenic
centres, since the relative bulkiness of the substituents in
the interior of the zeolite cage, may or may not provide suit-
able proximity of the pre-existing chirality to the reacting
double bond.
1
of O2 with non-Na+ bound alkene 4 conformers within
NaY25 may also occur.
1O2
top attack: threo
(more favorable)
H3C
H3C
H
Na
R
bottom attack: erythro
1O2
(less favorable)
Na
δ-
O
H2C
δ+
CH3
O
Ph
R
R
H
OOH
Ph
H3C
CH3
threo
TS5
Na
H2C
CH3
Me
R
Me
H
OOH
Pr
H3C
CH3
threo
TS6
preferential bottom
1O2
attack by 1O2
Scheme 3. Possible threo-forming transition states for the photooxygena-
tion of 1–4 within NaY.
2.3. Diastereoselectivity in the photooxygenation of
chiral alkenes bearing a stereogenic centre at a remote
position with respect to the double bond (5–7)
As we discussed earlier, due to the adsorption of the reactant
alkenes in the confined environment, increased diastereo-
selectivity might be expected in cases where a chiral centre
resides at a remote position with respect to the reacting
double bond, as a consequence of ‘substrate-coiling’ in the
limited space of zeolite cavities. To examine this interesting
aspect we performed the photooxygenation of alkenes 5,26
6, and 7, which possess a stereogenic centre at the b- or
g-position with respect to the double bond. Reaction of 5
with 1O2 in solution gave the expected ene product distribu-
tion (secondary vs tertiary allylic hydroperoxides¼47/53),
while for the secondary hydroperoxides a low diastereo-
meric ratio was found (w10% dr, not specified). By NaY con-
finement, however, the reaction is 94% regioselective in
favour of the secondary hydroperoxides (Scheme 4), and
the diastereomeric ratio enhances significantly (dr¼72/28).
We postulate that, upon interaction of the alkene with the
Na+ within the cages, the substrate folds, and the chirality
is ‘transferred’ close to the reaction centre (double bond).
HOO
1O2
CH2
CH3
CH3
OOH
Me
Ph
Me
Ph
5
+
CH3
CH2Cl2
53%
6%
47% (d.r.=55/45)
93% (d.r.=72/28)
1O2
NaY
H3C HOO
Ph
1O2
CH3
CH3
CH2
CH3
+
+
Ph
OOH
CH3
6
CH2Cl2
52%
35%
48% (d.r.~50/50)
65% (d.r.~50/50)
1O2
NaY
HOO
CH3
OOH
CH3
CH2
CH3
1O2
7
CH2Cl2
Ph
Ph
59%
15%
41% (d.r.=62/38)
1O2
85% (d.r.=57/43)
NaY
1
Consequently, the facial selectivity of O2 to the double
bond is significantly affected. For a further examination of
Scheme 4. Photooxygenation of chiral alkenes 5–7 in solution and within
zeolite NaY.
this enhanced diastereoselection, we prepared alkene 7,27

M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
10627
A dramatic change in regioselectivity and diastereoselection
was found in the photooxygenation of a-terpinyl acetate (8),
by zeolite confinement relative to reaction in solution
(Table 3), and exemplifies the role of the zeolite confinement
as a powerful medium to control product selectivity, even if
a stereogenic centre resides at a remote position with respect
to the reacting double bond. In contrast to the photooxygena-
tion of 8 in solution, which gives the expected ene product
distribution based on the already published results of similar
cycloalkenes such as limonene,29 the intrazeolite photooxy-
genation of 830 gave mainly one regioisomeric adduct (8d)
in >90% dr. It is worthy to emphasize here, the predominant
formation of a tertiary allylic hydroperoxide (8d), which
is unique for an intrazeolite reaction, since trisubstituted
alkenes afford within NaY primarily it is the secondary
allylic hydroperoxides.
substituted side of the double bond, we prepared stereoselec-
tively the deuterium labelled at the twin position chiral
alkenes 1d3–6d3. The synthesis was accomplished in >95%
purity for the (E)-isomer as shown in Scheme 6, applying
an already well known methodology.12c
COOMe
Ph3P
COOMe
CH3
H
R
LiAlD4/AlCl3
Et2O
CH3
O
R
CH2Cl2
1b-6b
1a-6a
CD2OMs
CD2OH
CH3
LiAlD4
Et2O
MsCl
CH2Cl2
CH3
R
R
R
1c-6c
1d-6d
CD3 twin methyl group
CH3
twix methyl group
1d3-6d3
Table 3. Photooxygenation of a-terpinyl acetate (8) in solution and within
NaY
Scheme 6. Synthesis of the chiral labelled alkenes 1d3–6d3.
CH2
HOO
CH2
CH3
HOO
+
HOO
Photooxygenation of 1d3–6d3 in solution (Table 4) afforded
the mixture of tertiary and secondary allylic hydroperoxides,
as shown in Table 1 and in Scheme 4 for their perprotio
analogues. For clarity purposes, since photooxygenation of
1d3–6d3 in solution is around 92–95% regioselective for
allylic hydrogen atom abstraction from the more substituted
side of the alkene (cis effect selectivity),32 we will analyze
below the diastereoselectivity arising only from the reaction
of the twix methyl group. We define H-threo or H-erythro as
the diastereomeric secondary allylic hydroperoxides result-
ing from allylic hydrogen atom abstraction from the twix
methyl group (CH3), and D-threo and D-erythro as the hydro-
peroxides resulting from allylic deuterium atom abstraction
from the labelled twin methyl group (CD3). The ratio of
secondary H-threo/H-erythro allylic hydroperoxides was
assessed by integration of the terminal olefinic hydrogen
atoms in the region of 5 ppm.
+
+
CH3
H3C
CH3
OAc
8c
H3C
CH3
H3C
CH3
OAc
8a
OAc
8b
1O2
H3C
CH3
OOH
CH3
HOO
+
HOO
H3C
CH3
OAc
+
8
H3C
CH3
OAc
8d
H3C
CH3
H3C
CH3
OAc
8e
OAc
8f
8a (%)a 8b (%)a 8c (%)a 8d (%)a 8e/8f (%)a
In solution
Within NaY
27
5
17
4
7
2
40
87
9
2
a
Relative percentage.
Table 4. Stereochemistry in the photooxygenation of 1d3–6d3 in solution
The enhanced regioselectivity/diastereoselectivity within
NaY can be explained considering a synergism of 1O2–Na+
and Na+–acetate interactions. Essentially, an Na+ bound to
the –OAc functionality directs singlet oxygen to abstract
a pseudoaxially oriented allylic hydrogen atom at the more
substituted side of the alkene (Scheme 5).
CD3
H3C
R1
1d3-6d3
R2
1O2
CH2Cl2
CD3
H3C
CD3
H2C
R1
H3C
R1
H2C
R1
CD2
CD2
+
Na
δ-
+
R1
+
O
OOD
OOH
OOD
OOH
δ+
O
H3C
AcO
H3C
R2
D-erythro
OOH
CH3
R2
H-erythro
R2
D-threo
R2
H-threo
AcO
H3C
H
CH3
8d
H3C
H
92-95%
5-8%
(relative ratio not determined)
Scheme 5. Transition state for the selective formation of the hydroperoxide
8d in the intrazeolite photooxygenation of a-terpinyl acetate.
Alkene
H-erythro/H-threo (%)
R1¼Me, R2¼Ph (1d3)
R1¼Et, R2¼Ph (2d3)
77/23
78/22
83/17
2.4. Interplay of regioselectivity and diastereoselectivity
in the photooxygenation of the chiral alkenes 1–6,
through specific methyl group labelling
R1¼Cyclohexyl, R2¼Ph (3d3)
R1¼Me, R2¼n-Pr (4d3)
62/38
5d3
6d3
55/45a
w50/50a
To determine the ratio of the threo/erythro stereoisomers
induced by abstraction of an allylic hydrogen atom either
from the more (twix CH3)31 or from the less (twin CH3)31
a
The relative configuration of the major and minor erythro or threo dia-
stereomers in the photooxygenation of 5d3 and 6d3 was not assessed.

10628
M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
The intrazeolite photooxygenation of 1d3–6d3 afforded the
mixture of tertiary and secondary allylic hydroperoxides,
with the latest being predominant or only products. For
discussion purposes we will emphasize only to the stereo-
chemical analysis of the secondary allylic hydroperoxides
(Table 5). Enhanced twin selectivity was found, in accor-
dance with the previously reported studies on other labelled
trisubstituted alkenes,7c and therefore, analysis of the dia-
stereoselectivity obtained from allylic hydrogen abstraction
either from the labelled twin (CD3) or from the twix methyl
group became possible.
The ratio of secondary H-threo/H-erythro allylic hydroper-
oxides was assessed by integration of the terminal olefinic
hydrogen atoms in the region of 5 ppm. On the other hand,
the ratio D-threo/D-erythro, formed by abstraction of an
allylic deuterium atom from the twin methyl group (CD3),
was assessed either by integration of the diastereotopic
allylic methyls, or extrapolated, taking into account the total
ratio of threo/erythro hydroperoxides and the ratio H-threo/
1
H-erythro, as well. The typical H NMR spectra, based on
which the H-threo/H-erythro and D-threo/D-erythro ratios
were calculated, for the photooxygenation of 3d3 in solution
and within NaY are shown in Figure 1.
Table 5. Stereochemistry in the photooxygenation of 1d3–6d3 within NaY
The intrazeolite results present in Table 5 indicate that for al-
kenes 1d3–4d3 the diastereoselection arisen from abstraction
of an allylic H or D atom (from the twix or the twin methyl
group, respectively), is more or less very similar. The only
significant change was found in the intrazeolite photo-
oxygenation of 5d3, where the diastereoselectivity depends
significantly on the orientation of singlet oxygen to form
the perepoxide intermediates, either towards the more or
towards the less substituted side of the double bond. Thus,
abstraction of a D atom from the twin methyl group proceeds
with moderate diastereoselection (18% dr), while H atom
abstraction from the twix methyl group proceeds with signif-
icantly higher facial selectivity (54% dr). The significant
dependence of diastereoselectivity on site selectivity, most
probably indicates that upon folding of the alkene within
NaY cages, the stereogenic centre is more proximal to the
more substituted side of the double bond, and therefore, con-
trol of the facial approach in the case of the twix-oriented
perepoxide intermediate is more profound.
CD3
H3C
R1
1d3-6d3
R2
1O2 NaY
H3C
R1
H3C
R1
CD3
CD3
H2C
R1
H2C
R1
CD2
CD2
+
+
+
OOD
OOD
OOH
OOH
R2
R2
R2
R2
D-threo
D-erythro
H-threo
H-erythro
twix abstraction
twin abstraction
H-erythro/ H-erythro/
twix (%) H-threo (%) H-threo (%)
Alkene
twin/
R1¼Me, R2¼Ph (1d3)
R1¼Et, R2¼Ph (2d3)
62/38
60/40
52/48
23/77
11/89
44/56
77/23a
44/56
22/78
08/92
R1¼Cyclohexyl, R2¼Ph (3d3) 55/45
R1¼Me, R2¼n-Pr (4d3)
52/48
30/70
50/50
5d3
6d3
58/42a
w50/50a
3. Conclusions
47/54 w50/50a
a
As a conclusion, we have shown that the confined environ-
ment of zeolite NaY may in certain cases remarkably alter
The relative configuration of the major and minor erythro or threo dia-
stereomers in the photooxygenation of 5d3 and 6d3 was not assessed.
(D)HOO
(D)HOO
CD3(CH3)
CD3(CH3)
+
Ph
CH2(CD2)
Ph
CH2(CD2)
c
a
a
d
b
d
c
a
c
b
c
a
5.00
4.95
4.90
(2)
4.85
4.80
5.05 5.00 4.95 4.90 4.85 4.80 4.75
(1)
Figure 1. Part of the crude 1H NMR spectrum in the region 4.7–5.1 ppm for the photooxygenation of 3d3 in solution (1) and within NaY (2). Abbreviations: (a)
terminal olefinic hydrogen (H-erythro); (b) allylic hydrogen on the carbon bearing the –OOH(D) functionality (H-erythro+D-erythro); (c) terminal olefinic
hydrogen (H-threo); (d) allylic hydrogen on the carbon bearing the –OOH(D) functionality (H-threo+D-threo).

M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
10629
the facial selectivity in the photooxygenation of some chiral
alkenes compared to their reaction in solution. It is postu-
lated that within zeolite, a synergism between cation–p
and singlet oxygen–cation interactions as well, are the main
driving forces for the facial selectivity changes. In certain
cases, enhanced regioselectivity and diastereoselection can
be induced by a remote stereogenic centre relative to the
reacting double bond, as a consequence of substrate confine-
ment within the limited space of a cavity. We believe that
the current results may provide a basis for the development
of models with predictive capability in order to tune the
behaviour of 1O2 reactions by zeolite confinement.
The reaction mixture was washed with saturated solution
of NaHCO3, the organic layer was dried and the solvent was
evaporated to yield after column chromatography (hexane/
ethyl acetate¼6/1) 0.62 g of 3-cyclohexyl-3-phenylpropan-
1
1-ol (70%). H NMR: 7.11–7.29 (m, 5H), 3.45 (m, 1H),
3.36 (m, 1H,), 3.36 (m, 1H), 0.75–2.10 (m, 13H).
4.2.4. 3-Cyclohexyl-3-phenylpropanal. The alcohol was
oxidized to the corresponding aldehyde (3-cyclohexyl-3-
phenylpropanal) in 75% isolated yield by PCC oxidation of
3-cyclohexyl-3-phenylpropan-1-ol in dry dichloromethane.
1H NMR: 9.70 (s, 1H), 7.13–7.29 (m, 5H), 2.97 (t, 1H,
J¼6.0 Hz), 2.78 (m, 2H), 0.82–1.81 (m, 11H).
4. Experimental
4.1. General
4.2.5. (1-Cyclohexyl-4-methylpent-3-enyl)benzene (7).
The aldehyde reacted with the ylide obtained from the reac-
tion of triphenylphosphoniumisopropyl iodide with n-BuLi
in dry THF, to obtain after column chromatography (hexane
as eluent) the desired alkene 7 in 59% isolated yield.
1H NMR: 7.09–7.27 (m, 5H), 4.94 (t, 1H, J¼7.0 Hz), 2.52
(m, 2H), 2.34 (m, 1H), 2.24 (m, 1H), 1.59 (s, 3H), 1.53 (s,
3H), 0.77–1.91 (m, 10H). 13C NMR: 144.5, 131.7, 128.7,
127.7, 125.6, 123.2, 52.4, 42.5, 31.5, 31.1, 30.7, 26.7,
25.7, 17.7.
Nuclear magnetic resonance spectra were obtained on a 300
and 500 MHz instruments. Isomeric purities were deter-
mined by 1H NMR and by GC analysis on a 60 m HP-5 cap-
illary column. All spectra reported herein were taken in
CDCl3. Since, in addition to the synthesis of 1–6, the stereo-
selectively labelled at the twin position analogous substrates
1d3–6d3 were prepared, we will describe below the synthesis
of the labelled alkenes only. The only chiral alkene, which
was not prepared in its labelled form was (1-cyclohexyl-
4-methylpent-3-enyl)benzene (7) and the details of its syn-
thesis are presented separately below.
4.3. Synthesis of the labelled chiral alkenes 1d3–6d3
4.3.1. Chiral aldehydes 1a–6a. The aldehydes 1a and 4a are
commercially available. The rest were prepared as follows.
Aldehyde 2a: it was prepared in 71% isolated yield by
oxidation of 2-phenyl-1-butanol with PCC in dichloro-
4.2. Synthesis of (1-cyclohexyl-4-methylpent-3-enyl)-
benzene (7)
1
methane. H NMR: 9.69 (br s, 1H), 7.20–7.47 (m, 5H),
3.43 (t, 1H, J¼7.0 Hz), 2.13 (m, 1H), 1.78 (m, 1H), 0.92
(t, 3H, J¼7.5 Hz). Aldehyde 3a: it was prepared in two steps
from reduction of a-cyclohexylphenylacetic acid with
LiAlH4, followed by PCC oxidation of the resulting alcohol
(60% yield, over two steps). 1H NMR: 9.71 (d, 1H,
J¼3.5 Hz), 7.18–7.38 (m, 5H), 3.25 (dd, 1H, J1¼9.5 Hz,
J2¼3.5 Hz), 2.12 (m, 1H), 0.80–1.86 (m, 10H). Aldehyde
6a: it was prepared in two steps as follows: 3-phenyl-1-
butanol was transformed to corresponding bromide in 96%
4.2.1. Methyl 3-cyclohexyl-3-hydroxy-3-phenylpropa-
noate. In a flame-dried flask were added 2-bromoacetate
(55 mmol), cyclohexylphenyl ketone (30 mmol), 2 g of acti-
vated Zn, and as a solvent was used a mixture of 100 mL dry
benzene and 50 mL of dry ether. The slurry was refluxed for
1 day and then it was poured into 100 mL 2 N H2SO4. After
extraction, the organic layer was dried and the solvent was
removed under vacuum to produce methyl 3-cyclohexyl-
3-hydroxy-3-phenylpropanoate in 75% yield as a white
solid. The starting material cyclohexylphenyl ketone, was
obtained in two steps by phenylmagnesium bromide addi-
tion to cyclohexanecarboxaldehyde, followed by oxidation
of the resulting alcohol with Jone’s reagent (70% yield
1
yield by reacting with the PPh3–Br2 complex. H NMR of
the bromide: 7.19–7.35 (m, 5H), 3.32 (m, 1H), 3.18 (m,
1H), 2.96 (m, 1H), 2.11 (q, 2H, J¼7.5 Hz), 1.29 (d, 3H,
J¼7.0 Hz). The bromide was transformed to the organo-
magnesium reagent in the presence of 1.4 mol equiv of
Mg turnings, and then the Grignard reagent reacted with
N-formylpiperidine33 at 0 ꢀC for 30 min. Acidic work up
(3 N HCl) and extraction of the crude reaction mixture
afforded the crude aldehyde 6a, which was purified by flash
column chromatography using hexane as eluent (56% iso-
1
over two steps). H NMR of the hydroxyl ester: 7.19–7.35
(m, 5H), 4.30 (br s, 1H), 3.49 (s, 3H), 3.02 (d, 1H,
J¼16 Hz), 2.84 (d, 1H, J¼16 Hz), 0.96–1.75 (m, 11H).
4.2.2. 1-Cyclohexyl-1-phenylpropane-1,3-diol. Themethyl
3-cyclohexyl-3-hydroxy-3-phenylpropanoate was reduced
into 95% yield by reacting for 8 h at ambient temperature
and under inert atmosphere, with 1 mol equiv of LiAlH4 in
dry ether. 1H NMR: 7.21–7.36 (m, 5H), 3.70 (m, 2H), 3.47
(t, 2H, J¼7.5 Hz), 0.86–1.97 (m, 11H).
1
lated yield). H NMR: 9.69 (t, 1H, J¼1.5 Hz), 7.16–7.33
(m, 5H), 2.72 (m, 2H), 2.32 (m, 2H), 1.90 (m, 2H), 1.29
(d, 3H, J¼7.0 Hz).
4.3.2. a,b-Unsaturated esters 1b–6b. In a one-necked flask
were placed 60 mL of dry CH2Cl2, and 40 mmol of the
stabilized ylide methyl(triphenylphosphoranylidene)propio-
nate and 25 mmol of the aldehydes 1a–6a. The solution was
refluxed until consumption of the aldehyde (normally 2–6 h
is necessary). For the case of the bulkiest aldehyde 6c, the
reaction time was 2 days. Most of the solvent was removed
by evaporation and then 50 mL of hexane were added. The
4.2.3. 3-Cyclohexyl-3-phenylpropan-1-ol. In a flame-dried
flask were placed 0.99 g of 1-cyclohexyl-1-phenylpropane-
1,3-diol (4 mmol) and 15 mL dry dichloromethane. At
0 ꢀC were added by syringe 10 mmol (1.5 mL) of BF3 ether-
ated and then 0.73 mL of triethylsilane.28 After 24 h the
reduction of the benzylic hydroxyl was complete by TLC.

10630
M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
solid residue was washed with hexane (4ꢁ50 mL), the
solvent was evaporated and the oily residue was chromato-
graphed or distilled at reduced pressure (for volatile deriva-
tive 4b). The a,b-unsaturated esters were isolated in 50–75%
yield and in >95% purity for the (E)-isomer. 1H NMR data:
compound 1b: 7.22–7.35 (m, 5H), 6.87 (d, 1H, J¼11.0 Hz),
3.77 (m, 1H), 3.72 (s, 3H), 1.91 (s, 3H), 1.39 (d, 3H,
J¼7.0 Hz). Compound 2b: 7.19–7.35 (m, 5H), 6.88 (d,
1H, J¼10.0 Hz), 3.73 (s, 3H), 3.50 (m, 1H), 1.90 (s, 3H),
1.78 (m, 2H), 0.88 (t, 3H, J¼7.5 Hz). Compound 3b:
7.16–7.31 (m, 5H), 6.97 (dd, 1H, J1¼10.5 Hz, J2¼1.5 Hz),
3.72 (s, 3H), 3.28 (t, 1H, J¼10.0 Hz), 1.86 (d, 3H,
J¼1.5 Hz), 0.80–1.85 (m, 11H). Compound 4b: 6.51 (d,
1H, J¼8.0 Hz), 3.72 (s, 3H), 2.50 (m, 1H), 1.83 (s, 3H),
1.25 (m, 4H), 0.97 (d, 3H, J¼7.0 Hz), 0.87 (t, 3H,
J¼7.0 Hz). Compound 5b: 7.19–7.32 (m, 5H), 6.73 (t, 1H,
J¼6.5 Hz), 3.71 (s, 3H), 2.87 (m, 1H), 2.44 (m, 2H), 1.77
(s, 3H), 1.28 (d, 3H, J¼6.5 Hz). Compound 6b: 7.19–7.34
(m, 5H), 6.76 (t, 1H, J¼7.0 Hz), 3.75 (s, 3H), 2.74 (m,
1H), 2.08 (m, 2H), 1.76 (m, 2H), 1.75 (s, 3H), 1.29 (d, 3H,
J¼7.0 Hz).
added dropwise at 0 ꢀC. The reaction mixture was stirred
overnight. After treatment with 2 mL of water and extraction
with ether, the resulting crude alkenes 1d3–6d3 were purified
by flash silica gel chromatography using hexane as eluent.
The geometric purity of the (E)-alkenes was >95% and
was estimated by comparison with the spectra of their corre-
sponding perprotio alkenes. 1H NMR of 1d3: 7.17–7.33 (m,
5H), 5.29 (dq, 1H, J1¼9.5 Hz, J2¼1.0 Hz), 3.67 (m, 1H),
1.69 (d, 3H, J¼1.0 Hz), 1.30 (t, 3H, J¼7.5 Hz); 13C NMR
of 1d3: 147.3, 130.4, 130.2, 128.3, 126.9, 125.7, 38.1, 25.1
(septet, JC–D¼19 Hz), 22.4, 17.9; MS, m/z¼163 (100%,
1
m/z¼148). H NMR of 2d3: 7.14–7.32 (m, 5H), 5.28 (dq,
1H, J1¼9.5 Hz, J2¼1.0 Hz), 3.36 (m, 1H), 1.57–1.76 (m,
2H), 1.67 (d, 3H, J¼1.0 Hz), 0.86 (t, 3H, J¼7.5 Hz); 13C
NMR of 2d3: 146.2, 131.2, 128.9, 128.3, 127.3, 125.7,
46.1, 30.1, 25.0 (septet, JC–D¼19 Hz), 18.0, 12.2; MS,
m/z¼177 (100%, m/z¼148); HRMS calcd for C13H15D3:
1
177.1597, found: 177.1597. H NMR of 3d3: 7.15–7.29
(m, 5H), 5.35 (dq, 1H, J1¼10.0 Hz, J2¼1.0 Hz), 3.14 (t,
1H, J¼10.0 Hz), 0.77–1.89 (m, 11H), 1.63 (d, 3H,
J¼1.0 Hz); 13C NMR of 3d3: 145.3, 131.3, 128.2, 127.9,
125.5, 51.16, 43.6, 31.5, 31.1, 26.6, 26.5, 26.4, 25.1 (septet,
JC–D¼19 Hz), 18.1; HRMS calcd for C17H21D3: 231.2066,
found: 231.2064. 1H NMR of 4d3: 4.90 (d, 1H, J¼9.0 Hz),
2.34 (m, 1H), 1.62 (s, 3H), 1.17–1.30 (m, 4H), 0.92 (d,
3H, J¼7.0 Hz), 0.89 (t, 3H, J¼7.0 Hz). 13C NMR of 4d3:
131.6, 129.3, 40.1, 32.1, 24.8 (septet, JC–D¼19 Hz), 21.2,
4.3.3. Allylic alcohols-d2, 1c–6c. In a flame-dried two-
necked flask were placed 12 mmol of LiAlD4 and 15 mL
of dry ether. The flask was cooled to 0 ꢀC and subsequently
4 mmol of anhydrous AlCl3 were added in portions. The re-
sulting slurry was stirred for an additional 20 min, followed
by the dropwise addition of the a,b-unsaturated ester 1b–6b
(15 mmol). The reaction mixture was stirred for 1–2 h and
then treated with 1 mL of water. After extraction with
diethyl ether, the deuterated allylic alcohols 1c–6c were iso-
1
20.5, 17.8, 14.2. H NMR of 5d3: 7.19–7.32 (m, 5H), 5.10
(t, 1H, J¼6.5 Hz), 2.72 (m, 1H), 2.25 (m, 2H), 1.56
1
(s, 3H), 1.24 (d, 3H, J¼7.0 Hz). H NMR of 6d3: 7.19–
7.33 (m, 5H), 5.12 (t, 1H, J¼7.0 Hz), 2.73 (m, 1H), 1.91
(m, 2H), 1.59–1.68 (m, 2H), 1.55 (s, 3H), 1.27 (d, 3H,
J¼7.0 Hz).
1
lated in 85–95% yield. H NMR: compound 1c: 7.18–7.34
(m, 5H), 5.58 (d, 1H, J¼9.5 Hz), 3.73 (m, 1H), 1.75 (s,
3H), 1.58 (br s, 1H), 1.29 (t, 3H, J¼7.0 Hz). Compound
2c: 7.17–7.36 (m, 5H), 5.57 (dd, 1H, J1¼9.5 Hz,
J2¼1.0 Hz), 3.41 (m, 1H), 1.73 (d, 3H, J¼1.0 Hz), 1.62–
1.78 (m, 2H), 1.49 (br s, 1H), 0.87 (t, 3H, J¼7.0 Hz). Com-
pound 3c: 7.15–7.30 (m, 5H), 5.63 (d, 1H, J¼9.5 Hz), 3.19
(t, 1H, J¼9.5 Hz), 1.87 (m, 1H), 1.69 (s, 3H), 0.78–1.74
(m, 10H). Compound 4c: 5.11 (d, 1H, J¼8.0 Hz), 2.37 (m,
1H), 1.66 (s, 3H), 1.54 (br s, 1H), 1.17–1.30 (m, 4H), 0.92
(d, 3H, J¼7.0 Hz), 0.87 (t, 3H, J¼7.0 Hz). Compound 5c:
7.18–7.32 (m, 5H), 5.37 (t, 1H, J¼7.5 Hz), 2.73 (m, 1H),
2.31 (m, 2H), 1.60 (s, 3H), 1.56 (br s, 1H), 1.25 (d, 3H,
J¼7.0 Hz). Compound 6c: 7.20–7.33 (m, 5H), 5.39 (t, 1H,
J¼7.0 Hz), 2.73 (m, 1H), 1.97 (m, 2H), 1.68 (m, 2H), 1.60
(s, 3H), 1.28 (d, 3H, J¼7.0 Hz), 1.29 (br s, 1H).
4.4. Photooxygenation of chiral alkenes 1–7 and their
labelled analogues
The photooxygenation of the alkenes in solution was accom-
plished by dissolving 10 mg of each alkene in a solution of
10ꢂ4 M methylene blue in dichloromethane (5 mL). The
solution was bubbled with oxygen gas and then irradiated
with a 300 W Xenon lamp until the alkene was consumed
(by TLC). The intrazeolite reactions were carried as follows.
In a test tube were added 1 g of freshly dried thionin-
supported zeolite NaY and 5 mL of dry hexane, which con-
tained 10 mL of pyridine. After 5 min, a hexane solution
(5 mL) containing each alkenes-d3 or their perprotio ana-
logues (10 mg) was added. The tube was immediately pho-
tolyzed at 0 ꢀC under a constant slow stream of oxygen
gas for 1–2 min, followed by immediate addition of 10 mL
of moistened tetrahydrofuran. The slurry was stirred for
3 h and then the solid was removed by filtration. The solvent
4.3.4. Mesylates of the allylic alcohols-d2, 1d–6d. The
allylic alcohols-d2, 1c–6c (10 mmol) were placed into a flask
charged with 30 mmol of dry triethylamine and 30 mL of
dry dichloromethane. Subsequently, 11 mmol of methane-
sulfonyl chloride were added dropwise at 0 ꢀC. After
25 min the reaction was complete (by TLC). The solids
were removed by filtration and the organic layer was washed
with 5% HCl (until pH was acidic), then with saturated solu-
tion of NaHCO3, and finally with 50 mL of brine. The allylic
mesylates do not persist and were used immediately in the
next step without purification.
1
was removed by rotary evaporation and the H NMR spec-
trum was taken directly on the crude reaction mixture. The
spectroscopic data for the ene allylic hydroperoxides
obtained from the photooxygenation of 1 have been reported
(see Ref. 19). Photooxygenation of 2 (or 2d3): tertiary hydro-
peroxide {7.10–7.35 (m, 5H), 5.56 (s, 1H), 2.31 (q, 2H,
J¼7.5 Hz), 1.16 (s, 6H), 0.98 (t, 3H, J¼7.5 Hz)}; erythro
secondary hydroperoxide {7.83 (br s, 1H), 7.10–7.35 (m,
5H), 4.89 (br s, 1H), 4.87 (br s, 1H), 4.51 (d, 1H,
J¼9.5 Hz), 2.60 (m, 1H), 2.12 (m, 1H), 1.57 (s, 3H),
1.62 (m, 1H), 0.73 (t, 3H, J¼7.0 Hz)}; threo secondary
4.3.5. Chiral alkenes-d3, 1d3–6d3. To a flame-dried flask
charged with 20 mL of dry ether were suspended 4 mmol
of LiAlD4. The crude mesylates 1d–6d (10 mmol) were

M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
10631
hydroperoxide {7.65 (br s, 1H), 7.10–7.35 (m, 5H), 5.11 (br s,
References and notes
1H), 5.06 (br s, 1H), 4.51 (d, 1H, J¼9.5 Hz), 2.58 (m, 1H),
1.78 (s, 3H), 1.64 (m, 1H), 1.52 (m, 1H), 0.71 (t, 3H,
J¼7.0 Hz)}. Photooxygenation of 3 (or 3d3): tertiary hydro-
peroxide {7.05–7.30 (m, 5H), 5.55 (s, 1H), 2.09 (br t, 1H,
J¼11.0 Hz), 1.12 (s, 6H), 0.80–1.85 (m, 10H)}; erythro sec-
ondary hydroperoxide {7.75 (br s, 1H), 7.05–7.30 (m, 5H),
4.94 (br s, 1H), 4.91 (br s, 1H), 4.83 (d, 1H, J¼10.5 Hz),
2.70 (dd, 1H, J1¼10.5 Hz, J2¼4.5 Hz), 1.61 (s, 3H), 0.80–
1.85 (m, 10H)}; threo secondary hydroperoxide {7.60
(br s, 1H), 7.05–7.30 (m, 5H), 4.99 (br s, 1H) 4.92 (br s,
1H), 4.88 (d, 1H, J¼7.5 Hz), 2.55 (t, 1H, J¼7.0 Hz), 1.68
(s, 3H), 0.80–1.85 (m, 10H)}. Photooxygenation of 4 (or
4d3): erythro secondary hydroperoxide (as alcohol obtained
after reduction with PPh3, characteristic absorptions) {4.97
(br s, 1H) 4.90 (br s, 1H), 3.88 (d, 1H, J¼6.5 Hz), 1.72 (s,
3H)}; threo secondary hydroperoxide (as alcohol obtained
after reduction with PPh3, characteristic absorptions) {4.93
(br s, 1H), 4.88 (br s, 1H), 3.79 (d, 1H, J¼6.5 Hz), 1.73 (s,
3H)}. Photooxygenation of 5 (or 5d3): tertiary hydroperox-
ide (as alcohol obtained after reduction with PPh3, character-
istic absorptions) {5.85 (dd, 1H, J1¼16.0 Hz, J2¼7.0 Hz),
5.61 (d, 1H, J¼16.0 Hz), 3.45 (m, 1H), 1.46 (s, 6H), 1.41
(d, 3H, J¼7.5 Hz)}; main diastereomeric secondary hydro-
peroxide (as alcohol obtained after reduction with PPh3,
characteristic absorptions) {4.90 (d, 1H, J¼1.5 Hz) 4.80
(d, 1H, J¼1.5 Hz), 3.84 (dd, 1H, J1¼8.5 Hz, J2¼4.5 Hz),
2.99 (m, 1H), 1.78–1.90 (m, 2H), 1.70 (s, 3H), 1.29 (d,
3H, J¼7.0 Hz)}; minor diastereomeric secondary hydroper-
oxide (as alcohol obtained after reduction with PPh3, charac-
teristic absorptions) {4.88 (d, 1H, J¼1.5 Hz), 4.86 (d, 1H,
J¼1.5 Hz), 4.04 (t, 1H, J¼8.5 Hz), 2.85 (m, 1H), 1.78–
1.90 (m, 2H), 1.76 (s, 3H), 1.29 (d, 3H, J¼7.0 Hz)}. Photo-
oxygenation of 6 (or 6d3): tertiary hydroperoxide (character-
istic absorptions) {5.62 (dt, 1H, J1¼16 Hz, J2¼7.5 Hz), 5.41
(d, 1H, J¼16.0 Hz), 2.85 (m, 1H), 2.37 (m, 2H), 1.27 (s,
6H)}; secondary hydroperoxides (characteristic absorptions)
{5.03 (br s, 1H), 5.00 (br s, 1H), 4.31 (t, 1H, J¼7.5 Hz) cor-
responding to the one diastereomer, 4.30 (t, 1H, J¼7.5 Hz)
corresponding to the other diastereomer, 2.72 (m, 2H), 1.70
(s, 3H) corresponding to the one diastereomer, 1.66 (s, 3H)
corresponding to the other diastereomer}. Photooxygenation
of 7: tertiary hydroperoxide (characteristic absorptions)
{5.87 (dd, 1H, J1¼16 Hz, J2¼7.5 Hz), 5.53 (d, 1H,
J¼16.0 Hz), 2.94 (t, 1H, J¼9.0 Hz), 1.34 (s, 3H), 1.31 (s,
3H)}; major secondary hydroperoxide (characteristic ab-
sorptions) {7.65 (s, 1H, –OOH), 4.90 (br s, 1H), 4.85 (br s,
1H), 3.98 (m, 1H), 2.60 (m, 1H), 1.62 (s, 3H)}; minor second-
ary hydroperoxide (characteristic absorptions) {7.56 (s,
1H, –OOH), 5.05 (br s, 1H), 4.79 (br s, 1H), 4.00 (m, 1H),
2.21 (m, 1H), 1.73 (s, 3H)}.
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This work was supported by the community initiative
INTERREG IIIB, MEDOCC programme (Aquatex project).
This European programme supports projects aimed at trans-
lational co-operation in the field of territorial development
of Mediterranean countries. The authors are indebted to Pro-
fessors Michael Orfanopoulos and Georgios Vassilikogian-
nakis for fruitful discussions and productive collaboration
in the field of singlet oxygen chemistry for the past 15–20
years.

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M. Stratakis et al. / Tetrahedron 62 (2006) 10623–10632
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