Current Organic Synthesis, 2005, 2, 281-299
281
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation Manolis Stratakis* Department of Chemistry, University of Crete, 71409 Iraklion, Greece Abstract: This review focuses on the recent achievements towards the selective formation of allylic hydroperoxides by the reaction of singlet molecular oxygen (1 O 2 ) with alkenes adsorbed in the cavities of zeolite Na-Y. The product distribution by zeolite confinement is often dramatically different compared to the photooxygenation reaction in a homogeneous medium. Cation – π interactions and cation – singlet oxygen interactions, in the rate-limiting transition states, are most likely responsible for the changes in product selectivity within Na-Y.
Keywords: Singlet oxygen, allylic hydroperoxides, regioselectivity, diastereoselectivity, zeolite Na-Y, cation – π interactions. STRUCTURAL FEATURES OF FAUJASITES Zeolites are crystalline aluminosilicates whose primary structure is formed by SiO44- and AlO45- tetrahedra sharing the edges [1]. Their tertiary structure forms strictly uniform channels and cavities of molecular dimensions that are repeated along the zeolite lattice. Due to the lower valence of the aluminum relative to silicon, the excess negative charge (one per Al atom) is balanced by alkali metal cations, mainly Na+. The cations are placed in the interior of cavities and can be easily exchanged. The cation-exchange process leads to new type of materials having interesting properties [2], and it is expected in the near future that the metalsupported zeolites will find significant applications in applied chemistry. An important class of the zeolite family are the faujasites, known as zeolites X and Y, which have the typical composition for the unit cell as follows: Type Na-X
Na86(AlO2)86(SiO2)106 · x H2O
Type Na-Y
Na56(AlO2)56(SiO2)136 · x H2O
Fig. (1). Structure of the faujasite supercage assembled by the sodalite cages (the arrows indicate the positions of the cations).
The faujasite framework consists of two main cages, the supercage, and the sodalites (Fig. 1). The supercage results from the assembly of the smaller sodalite cages. The access to the supercages occurs by four 12-membered ring “windows”, of approximately 7-8 Å in diameter. The “windows” are tetrahedrally distributed around the centre of the supercages, which are approximately 13 Å in diameter. The charge-compensating cations in faujasites occupy three different positions as shown in Fig. 1, namely Type I-III [3]. Only cations at sites II and III can interact to the hosted organic compounds. Depending on the size of the cation, the supercages in the alkali metal exchanged Y zeolites (M-Y) have enough net volume to host relatively large organic molecules. For example, Na-Y can adsorb molecules even of the size of a steroid. On the other hand, for type X faujasites, the free volume of the supercages is more limited due to the extra compensating cations, and finds less applications in organic chemistry. The performance of organic reactions in organized media, e.g. by zeolite confinement [4-6], and the use of zeolites as selective and “green” catalysts [7] for organic transformations has been popularized in recent years. The main advantage of the zeolites to be tested as media or catalysts for carrying out organic reactions, is the so called “shape selectivity” [8]. The shape selectivity can be categorized into 3 types: (i)
Reactant selectivity; from a mixture of reactants only the molecules with the appropriate shape can be adsorbed into the cavities.
(ii)
Product selectivity; only those products, produced from the intrazeolite reaction, having the appropriate shape can diffuse out of the pores, and
(iii)
Transition state shape selectivity; due to the zeolite confinement, the relative stability of transition states for the possible reaction pathways can be significantly altered.
PHOTOOXYGENATION ORGANIZED MEDIA *Address correspondence to these authors at the Department of Chemistry, University of Crete, 71409 Iraklion, Greece; E-mail:
[email protected] 1570-1794/05 $50.00+.00
REACTIONS
IN
The partial exchange of the Na+ cations within the zeolite Na-Y supercages by dye molecules that have the structure of © 2005 Bentham Science Publishers Ltd.
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organic cations (e.g. methylene blue, thionin, etc.) [9] triggered the interest to examine the dye-sensitized photooxygenation of organic compounds within the confined environment of the faujasite Y cavities. The reaction of singlet oxygen with organic compounds has attracted a significant attention in the scientific community, not only because of their biological role [10], but also due to their mechanistic interest and the valuable synthetic applications as well [11]. The study of singlet oxygen reactions with alkenes using alternative supramolecular systems as microreactors [12], such as pentasil zeolites [13], nafion membranes [14] and surfactant vesicles [15], has also attracted a considerable attention recently, but will not be presented in the present review article.
For the achievement of mass balances in intrazeolite photooxygenation reaction >80%, loading levels of 0.1-0.3 adsorbed molecules per zeolite supercage have been successfully used in the past. However, the recent observation by Clennan and Pace [19], that replacing the solvent hexane with perfluorohexane was very crucial for the efficiency of the reaction, allowed the zeolite medium to be used for preparative scale photooxygenation reactions (500 mgr of alkene), without loss of the product selectivity or the reduction of the mass balance. The fluorophobicity of alkenes in perfluorohexane allows the facile migration of the reactant molecules into the zeolite cavities. In hexane, on the other hand, the affinity of a simple alkene such as 2-methyl2-heptene for entering into the interior of Na-Y decreases by ~50% relative to the fluorinated solvent. In the same study, the authors extrapolated the upper limit for the 1O2 lifetime within Na-Y to be 7.5 µ s. Based on this value, it was estimated that singlet oxygen can migrate through 5,000 supercages, before it deactivates to 3 O 2 or react with the adsorbed substrate.
For the success of the dye-sensitized singlet oxygen reactions within zeolite Na-Y, the loading level of the dye and the water content [16] in the interior of zeolite are crucial. At increased loading levels, the dye tend to dimerize and do not emit [17], thus, inefficiently producing 1O2 upon excitation by energy transfer to the triplet molecular oxygen. At an approximate loading level of 1 thionin cation per 100 zeolite supercages, irradiation under a constant flow of oxygen gas produces singlet oxygen efficiently, leading to rapid oxidation of tri- and tetrasubstituted alkenes to form ene allylic hydroperoxides [18] as shown for the photooxygenation of tetramethylethylene (1) in Scheme 1. H3 C H3 C
CH3
Thionin/Na-Y
H2C
CH3
hv/O2
H3C
COMPLEXITIES OF THE INTRAZEOLITE PHOTOOXYGENATION REACTIONS It is well-known that faujasites (Na-Y or Na-X) contain small concentration of both Brönsted [20] and Lewis acid sites [21]. The acidic sites may cause significant problems, such as the decomposition or rearrangement of product and reactants, giving often poor reaction mass balances. Acidsensitive alkenes, such as terpenes, upon adsorption within Na-Y undergo isomerization and skeletal rearrangements. Ramamurthy and co-workers have reported such problems in the intrazeolite photooxygenation of limonene [16]. In addition, tertiary allylic hydroperoxides, formed in the
CH3 OOH CH3
1
Scheme 1. Ene hydroperoxidation of tetramethylethylene within thionin-supported Na-Y.
2
3
Na-Y 4
5
9
6
7
8
monoterpene
Scheme 2. Transformation of monoterpenes to p-cymene within Na-Y under thermal conditions.
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation
photooxygenation of trisubstituted alkenes do not persist within the Na-Y cages [18]. The unwanted side-reactions and complexities, attributable to acid catalysis can be minimized or completely suppressed by treatment of the zeolite with bases such as pyridine or triethylamine for a few minutes prior to the photooxygenation reaction. We studied [22] the fate of several monoterpenes within thionin-supported Na-Y under thermal conditions, and found that the intrazeolite transformations of the adsorbed molecules are most probably consonant with an electron transfer pathway subordinated to the presence of the acidic sites. For example, upon loading of several monoterpenes within thionin-supported Na-Y (monocyclic, bicyclic or acyclic), in the absence of oxygen or visible light irradiation, immediate isomerization takes place with main formation of α-terpinene (2), isoterpinolene (5) and p-cymene (9). The aromatic component p-cymene, was postulated to arise from the dehydrogenation of the monoterpenes, initiated by formation of their radical cations [23] (Scheme 2). In addition, the initially formed isomeric terpenes such as 2 or 5, finally transform to 9 after prolonged intrazeolite treatment (1-2 hours). The formation of radical ion pairs under thermal conditions within Na-Y is more likely associated with the presence of acidic sites [24]. Pyridine or triethylamine most probably react with the acidic sites, and therefore destroy the “electron holes” that initiate the electron transfer-induced pathway. CATION - π INTERACTIONS WITHIN Na-Y Alkali metal cations have been known to bind strongly to the π face of aromatics [25]. For example, the Na+ -
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benzene binding enthalpy is roughly equivalent to the binding enthalpy between Na+ and H2O. The adsorption of alkenes or arenes into the interior of the zeolites is mainly driven by their quadrupolar interaction with the alkali metal cations present in the cages. Haw and co-workers [26] have presented experimental evidence for the Li+ - benzene interaction within zeolite LiZSM-5 using solid state NMR. Cations not only play a significant role in the adsorption efficiency of the porous materials, but they have also proposed [27] to play a major role in intrazeolite reactions by affecting the relative energies of the possible transition states through substrate binding [28]. To have a deep knowledge of the factors affecting the product distribution in intrazeolite photooxygenation reactions, it was necessary to perform theoretical calculations on the interaction of alkali metal cations with olefins. We [29] and others [30] performed a systematic study on the interaction of Na+ and Li+ with several alkenes in the gas phase using the DFT and the MP2 method or Ab initio calculations. Two predominant binding trends were mainly recognized. The first was that for the majority of the alkenes, the cations do not bind on top of the π system, but close to it. Thus, for trisubstituted alkenes, the binding site resides either towards the more or the less substituted side of the olefin. A typical example is trimethylethylene, whose interaction with Li+ was calculated to give the two almost isoenergetic minima presented in Fig. 2. This unexpected type of interaction was found even with highly symmetric alkenes such as tetramethylethylene. The second trend was that there is a relatively strong interaction for both cations (Li+ or Na+) to the alkyl chains of the double bond, at the homoallylic position. A typical example is cis-3-hexene
Fig. (2). Local minima structures of Li+ binding to trimethylethylene at the B3LYP/6-31G* level of theory.
Fig. (3). Local minima structures of Li+ binding to cis-3-hexene at the B3LYP/6-31G* level of theory.
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(Fig. 3), in which the structure where the Li+ interacts with both alkyl chains is more stable compared to the structure where it sits at the antiperiplanar position by 3.0 kcal/mol. The two binding trends of the alkali metal cations to alkenes were rationalized taking into account the polarization of the double bond by the cation, polarization of the alkyl chains and steric effects as well. Recently, Gal and coworkers [31] reported a similar alkyl chain - Li + attraction in alkylbenzenes, namely the “scorpion effect”.
The mechanism of this reaction has been extensively studied in the past [35], and found to proceed via formation of an intermediate perepoxide. The energy profile of the reaction depends on the degree of the alkyl substitution. Recent theoretical and experimental work by Singleton and coworkers [36], however, proposed a two step no-intermediate mechanism, with a rate-limiting transition state resembling that for the formation of a perepoxide in the initially proposed stepwise process. Photooxygenation of the isomeric cis, trans and gemtetramethylethylenes-d6 (1-d6) is an ideal tool (Stephenson’s isotope effect test) [37] to study the mechanism of ene-type reactions. For cis-1-d6 Clennan and Sram [38] had reported a negligible isotope effect of kH/kD = 1.04 for the intrazeolite reaction with 1O 2 within methylene blue-supported Na-Y. We performed the thionin-sensitized intrazeolite photooxygenation of trans-1-d6 and gem-1-d6, and found [39] for the trans-1-d6 a kH /kD = 1.52 ± 0.05, whereas for the gem-1-d6 it was kH /kD = 1.62 ± 0.05 (Scheme 4). The measured intrazeolite isotope effects were very similar to those reported for the photooxygenation in solution [37], and therefore, consonant with a Type II photooxygenation process for tetrasubstituted alkenes, in which singlet oxygen forms irreversibly a perepoxide or a perepoxide-type intermediate in the rate-limiting step of the reaction. A scenario, involving radical ion pairs as precursors of the ene allylic hydroperoxides is unlikely to occur upon visible light irradiation within the thionin-supported Na-Y.
MECHANISM OF THE ENE HYDROPEROXIDATION IN THE DYE-SENSITIZED INTRAZEOLITE PHOTOOXYGENATION OF ALKENES Ene type allylic hydroperoxides can be formed in photooxygenation reactions by two alternative pathways, namely the Type I and Type II processes [32]. Type I involves formation of a radical ion pair between the alkene and molecular oxygen, while in Type II photooxygenation process, singlet oxygen (1O2) is the reacting species. Type I intrazeolite photooxygenation of alkenes has been reported by Frei [33] and others [34] to give mainly allylic hydroperoxides (Scheme 3). In this process, the charge transfer band of the alkene - O2 complex within Na-Y was irradiated to form the alkene radical cation and superoxide ion. The radical ion pair in turn gives the allylic hydroperoxides via an allylic radical intermediate. On the other hand, for the Type II pathway, singlet molecular oxygen (1O2) is produced by energy transfer from the triplet excited state of a photosensitizer to 3O2 [32]. Singlet oxygen is a highly reactive enophile that reacts with alkenes possessing allylic hydrogens to form allylic hydroperoxides.
In addition, to elucidate the energy reaction profile in the intrazeolite photooxygenation of trisubstituted alkenes, the competing photooxygenation of 1-phenyl-3-methyl-2-butene and its deuterated at the geminal methyl analog (Scheme 5)
Type I
H3C
CH3
hv/3O2
H2C
CH3
H3C
CH3
Na-Y
H3C
CH3
H2C
CH3
H3C
CH3
O2
H2 C HOO
+
CH3 OOH CH3
H3 C
Type II
hv
3O 2
3sensitizer*
sensitizer
1O
2
CH3 H3C
CH3
O
1
O2
O H3C
CH3
CH3
H2C H3C
H3 C CH3
Scheme 3. Type I and Type II intrazeolite photooxygenation processes.
CH3 OOH CH3
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation H3C
CD3
H3C
H2C
hv/O2 thionin/Na-Y
CD3
CD3 OOH CD3
H3C
H3C
CH3
D3C
CD3
H2C
hv/O2 thionin/Na-Y
D3C
CD2
CD3
D2C
hv/O2 thionin/Na-Y
H3C DOO D3C
+
CH3
H3C
kH/kD = 1.04
CD2 kD
CH3 OOD CD3
trans-1-d 6
kH /kD = 1.62
CD3
kH
CH3
285
kD
CH3 OOH CD3
cis-1-d6
H3C
H3C DOO H3C
+
kH
gem-1-d6
D3C
Current Organic Synthesis, 2005, Vol. 2, No. 2
D3C HOO H3C
+
CH2 kH/kD = 1.52
CD3
kH
kD
Scheme 4. Intrazeolite photooxygenation of the isomeric tetramethylethylenes-d6.
was studied [39]. A negligible intermolecular isotope effect of kH/kD = 1.03 ± 0.02 indicated that also for trisubstituted alkenes, formation of a perepoxide-type transition state is the rate-limiting step. H3C
CH3
D3C
CD3 hv/O2
versus
kH /kD = 1.03
thionin/Na-Y Ph kH
Ph kD
Scheme 5. Intermolecular kinetic isotope effect in the intrazeolite photooxygenation of 1-phenyl-3-methyl-2-butene.
REGIOSELECTIVITY IN THE INTRAZEOLITE PHOTOOXYGENATION OF TRISUBSTITUTED ALKENES For geminal dimethyl trisubstituted alkenes, such as 10 or 13, photooxygenation in solution gives a nearly solvent
almost independent ratio of secondary to tertiary allylic hydroperoxides ~ 1/1 [40]. In addition, for the case of 1methyl-1-cycloalkenes [41], such as 14 and 15, the more substituted side of the alkene is the more reactive (“cis effect” selectivity). Ramamurthy and Li reported [42] that in contrast to the reaction in solution, the thionin-sensitized intrazeolite photooxygenation of trisubstituted alkenes is highly regioselective, giving the secondary allylic hydroperoxide as the major or only product (Table 1). Furthermore, 1-methyl-1-cycloalkenes give mainly ene product with hydrogen atom abstraction from the methyl group. The regioselectivity was significantly affected by the size of the cation present in the supercage (Table 2) [43]. For example, in the photooxygenation of 13 within Li-Y, the secondary hydroperoxide was formed in 100% relative yield, while in Cs-Y, the ratio secondary to tertiary hydroperoxide was 66/34, very close to what is found in solution. It was
Table 1. Intrazeolite Photooxygenation of Trisubstituted Alkenes (the Values in Parentheses Indicate the Relative Reactivity of the Ene Reaction in Solution) CH3 H3 C
CH3
CH3
100 (50)
CH3 28 (50)
0 (50) 10
11 CH3 CH3
0 (54)
CH3 100 (46)
85 (40) Ph
CH3 15 (60) 13
12 10 (45) CH3
2 (15) 14
72 (50)
88 (40)
0 (45)
CH3 100 (6)
0 (48) 15
286 Current Organic Synthesis, 2005, Vol. 2, No. 2
Table 2.
Manolis Stratakis
Cation-Dependent Regiochemical Control in the Intrazeolite Photooxygenation of 1- Phenyl-3-methyl-2-butene CH3
HOO
hv/O2
+ Ph
CH3
thionin/M-Y
Ph
13
13b
M
13a (%)
13b (%)
Li
100
0
Na
85
15
Rb
80
20
Cs
66
34
To shed light to the factors affecting the product distribution of the ene reaction, it was necessary to measure the regioselectivity for the hydrogen atom abstraction from each of two geminal methyl groups (twin or twix) [44] in trisubstituted alkenes such as 10-13. This was accomplished by stereoselective deuterium labelling of the twin methyl group. Independent studies by us [43] and Clennan’s group [45] revealed that the so-called “cis effect” [46] selectivity found in solution, no longer operates within the zeolite. As seen in Table 3, for the case of 16-19, the twin methyl group reactivity increases up to 14 times (see substrate 18) by zeolite confinement. Several models were invoked to explain the low intrazeolite reactivity of the allylic hydrogen atoms at the lone position, and the increased reactivity of the twin methyl group as well (Scheme 6). Originally, Ramamurthy and coworkers proposed [42,43] that steric effects inside the cavity place the bulkier alkyl group (R) at the lone position away from the cation; therefore, the methylene hydrogen atoms cannot react with the electrophile (Model A). Later, it was postulated [18] that polarization of the alkene by interaction of the double bond with the cation occurs in such a way that Table 3.
Ph
CH2 13a
postulated that the cation-dependent change in the regioselectivity is proportional to the magnitude of the cation – π interactions. Li+ being the smallest alkali metal cation is expected to bind the substrate very strong and affect the relative energy of the transition states leading to the secondary or tertiary allylic hydroperoxides. For the case of the largest Cs+ , cation – π interactions are less important, and product distribution is zeolite-unaffected.
CH3 OOH CH3
CH3
the more substituted carbon atom bears a partial positive charge (Model B). Thus, the electrophilic 1O 2 attacks the more nucleophilic monosubstituted olefinic carbon atom, and allylic hydrogen abstraction occurs from the alkyl substituents at the geminal disubstituted site. For alkene 13 (Table 1) in which R = Ph, we proposed [45] a simultaneous interaction of the cation with the phenyl group and the alkene double bond, that results in a conformation in which none of the allylic hydrogen atoms at the benzylic position are perpendicular to the olefinic plane to become reactive for abstraction by 1O2 (Model C). Later, however, Ramamurthy and co-workers performed theoretical calculations and suggested [48] that for the phenyl-substituted alkenes at the lone position, simultaneous interaction of the cation to the phenyl group and to alkene double bond as well is unlikely to occur. According to the regioselectivity results from the photooxygenation of some tetrasubstituted alkenes, Clennan and Sram [38] proposed the mechanistic Model D. They argued that the alkali-metal cation forms a complex with the pendant oxygen in the intermediate perepoxide, which leads to a greater positive charge on the carbon framework, while steric interactions between the cation and the alkyl substituents affect the stability of thetransition states that lead to the intermediate. In the perepoxide intermediate of Model D, the C-O bonds are highly unsymmetrical due to polarization effects and therefore, accounts for the Markovnikov-type selectivity. Finally, based on theoretical calculations of the interaction of the Li+ and Na+ to 2methyl-2-hexene at the B3LYP/6-31G* level of theory [29], we postulated that cation – π interactions place the alkyl group R towards the cation (scorpion effect [31], Model E).
Regioselectivity in the Intrazeolite Photooxygenation of Deuterium Labeled Trisubstituted Alkenes (the Values in Parentheses Indicate the Relative Reactivity in Solution)
H3C
CD3
33 (8)
CH3
61 (48)
6 (44)
CD3 42 (14) H3C
18
58 (36)
CD3
37 (8)
CH3
41 (38)
0 (50)
16
Ph 10 (60)
CH3
17
CD3
57 (4)
CH3
33 (36)
22 (54) 19
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation Model A 1O
Model B
2
1O
H
H
H
Na Ph CH3
H3C
CH3 Na
Model E innapropriate conformation for abstraction
1
O2
δ+ O δO
H
R H3 C
H
H3C
Model D
innapropriate conformation for abstraction
2
R H
H Na CH3
287
Model C
1O 2
R H3 C
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Na CH3
H3C
H
Na R CH3
Scheme 6. Proposed models for the intrazeolite photooxygenation of trisubstituted alkenes.
Thus, the allylic methylene hydrogens have inappropriate conformations for abstraction since they cannot adopt perpendicular orientations with respect to plane of the double bond. In fact, Model E resembles Model C, which is applicable to phenyl-substituted alkenes such as 13. Generally, all models are working hypotheses, and further experimental results are necessary to tune the role of the zeolite medium in the regioselectivity of the ene reaction. To explain the enhanced reactivity of the allylic hydrogen atoms at the less substituted side of the trisubstituted alkenes (twin position), it was proposed [45,46] that the electrostatic interaction of the pendant negatively charged oxygen atom in the intermediate perepoxide with an alkali metal cation within the cages of Na-Y stabilizes the transition state in which the oxygen is directed towards the less substituted side of the alkene (Scheme 7). In the absence of the cation-stabilizing interaction, the intermediate in which oxygen can interact only with one allylic hydrogen atom (twin-oriented perepoxide) is not favorable due to entropic reasons, as has been suggested by Schuster and coworkers (cis-effect selectivity) [49]. δ+ O
O
δD2C
CH3
D H3C R
R H
Na
OOD
twin selectivity
Scheme 7. Cation-directing t w i n regioselectivity in the intrazeolite photooxygenation of trisubstituted alkenes.
Despite the complexity of the proposed heuristic models, it is widely accepted that cation – oxygen interaction is significant for the intrazeolite singlet oxygen ene reactions with olefins. It has been proposed that cations play a major role in the rate acceleration and product distribution for the intrazeolite photooxygenation of sulfides [50], or the
dramatic increase in the reactivity of the sulfide functionality relative to an alkene double in substrates containing both the sulfide and olefinic linkages [51]. An electrostatic interaction between Na+ and the negatively charged oxygen of the persulfoxide intermediate [52] was invoked by Clennan and co-workers (Scheme 8).
R
S
1O 2
R'
O
Na-Y
R
S
O Na + R'
Na+ - persulfoxide interaction
R
S
O
R' 2
R
S
R'
Scheme 8. Cation-stabilizing persulfoxide intermediate within Na-Y.
INTRAZEOLITE ASYMMETRIC PHOOTOXYGENATION OF ALKENES The confined spaces of Na-Y may induce enantioselective reactions if appropriately modified with chiral inductors [53]. By suitably mixing chiral compounds such as (-)ephedrine, (-)-pseudoephedrine or (-)-norephedrine, a “chiral zeolite” can be produced. Ramamurthy and co-workers have successfully used this approach to perform a variety of enantioselective photochemical reactions with Na-Y, obtaining remarkable enantioselectivities in certain cases [54]. The attempts to achieve an enantioselective photooxygenation within a chirally-modified zeolite Na-Y are very limited. Only the photooxygenation of 1-phenyl-3methyl-2-butene (13) was studied within thionin-supported zeolite Na-Y modified by (+)-ψ-ephedrine, to give [55] approximately 15% e.e. for the formation of the major secondary allylic hydroperoxides (Scheme 9).
288 Current Organic Synthesis, 2005, Vol. 2, No. 2
CH3
Manolis Stratakis
Ph
hv/O2
CH3
Ph
thionin/Na-Y (+)-ψ-ephedrine
13
CH3 OOH + CH3
HOO
CH3
Ph
CH2 15% e.e
Scheme 9. Asymmetric photooxygenation of an alkene in a chirally-modified zeolite Na-Y.
10, with [A] > [B]). The Na+ - bound alkenes are expected to be highly unreactive due to the electron depletion from the double bond. Assuming that the dynamic equilibrium between the Na+ complexed or uncomplexed species is fast, and applying the Curtin-Hammett principle, the reaction is expected to occur mainly via the uncomplexed alkene, therefore, similar regioselectivity results are expected to those found in solution [57]. On the other hand, if the carbonyl functionality is shifted from the α - to the γposition with respect to the double bond (substrate 23), the alkenes give the expected regiochemical outcome (predominant formation of the secondary allylic hydroperoxides), as found in the intrazeolite photooxygenation of non-functionalized trisubstituted alkenes [39].
It might be tempting to examine the photooxygenation of alkenes bearing polar substituents in such chirallymodified media. The expected stronger interactions between the polar substituents of the substrates and the chiral inductors in the confined environment of Na-Y, might lead to increased enantioselectivity for the formation of the chiral allylic hydroperoxides. INTRAZEOLITE PHOTOOXYGENATION ELECTRON-POOR ALKENES
OF
Clennan and co-workers [56] reported that the intrazeolite environment is unable to influence the regiochemistry in the photooxygenation of electron-poor alkenes such as α,βunsaturated carbonyl compounds, relative to the photooxygenation in solution. The regioselectivity results are presented in Table 4. To explain the lack of changes in the regioselectivity on going to the zeolite environment, it was suggested that only the alkenes, which were not complexed to the cation, are reactive, although they are the minor component in a dynamic equilibrium involving uncomplexed and complexed substrates (A and B in Scheme
REMOTE SUBSTITUENT EFFECTS IN THE REGIOSELECTIVITY OF TRISUBSTITUTED ALKENES Due to the confined environment and cation – π interactions within the zeolite cavities as well, it is expected
Table 4. Regiochemistry in the Intrazeolite Photooxygenation of Electron-Poor Alkenes (the Values in Parentheses Indicate the Relative Reactivity in Solution) MeO O H3C
H3 C
H3C
O
O
29(15) CH3
CH3
6 (2)
MeO
MeO
6 (3)
H3C
CH3 71 (85)
94 (97)
94 (98) 20
22
21 15 (47) H3C O
85 (53) H3C
H3 C 23
Complex B
Complex A Na+
Na+
MeO R1
O
R2
CH3 1O
MeO
R1
COOM e
R1
R2
CH3
R2
1 2
High population (less reactive)
Uncomplexed substrate
O2
Low population (less reactive)
O CH3 1O 2
Low population (more reactive)
Scheme 10. Multicomplexation model for the intrazeolite photooxygenation of electron-poor alkenes.
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation
that the regioselectivity in the photooxygenation of trisubstituted alkenes might be influenced by remote substituents relative to the reaction center (alkene double bond) specially if they can strongly bind to the cation. We performed [39] the intrazeolite photooxygenations in a series of deuterium-labeled gem-dimethyl trisubstituted alkenes, by varying the position of a phenyl or a cyclohexyl substituent at the end of the alkyl chain at the lone position. We chose the phenyl and cyclohexyl groups as substituents because they have similar steric demands, but different electronic character. The phenyl group can strongly coordinate to the Na+ cations within the Na-Y supercages. The regioselectivity results are presented in Table 5. For the phenyl-substituted alkenes 18 and 24-26, there is a significant variation of the reactivity at the allylic positions (twin, twix or lone) by changing the length of the phenyl-substituted alkyl chain. For example, the reactivity at the lone position is 10% for 18, slightly drops to 7% for 24, then increases significantly to 44% in 25 and finally drops to 22% in 26. Similarly, significant variations were found for the ratio of twin/twix allylic hydroperoxides. While for 18 twin/twix = 63/37, by increasing the length of the alkyl chain the ratio drops to 30/70 in 24, to 32/68 in 25, and finally for alkene 26 it is 50/50. Contrary, for the cyclohexyl-substituted alkenes 19 and 27-28, the intrazeolite variation of the lone/twin/twix reactivity ratio is quite similar (approximately 22/37/41). On the other hand, the regioselectivity results for the photooxygenation of all alkenes (phenyl or cyclohexylsubstituted) in solution, is quite similar (lone/twin/twix ~ 50/5/45). The novel feature of the intrazeolite regioselectivities for the phenyl-substituted alkenes is that the lone and the twin/twix reactivity ratios depend significantly on the position of phenyl group. This effect is absent for the case of the cyclohexyl-substituted alkenes.
Table 5.
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289
It was proposed [39] that the changes in the ene reactivity at the lone position for the phenyl-substituted alkenes are controlled by cation - π interactions and conformational effects within the Na-Y supercages. Depending on the remoteness of the phenyl ring from the reaction centre, simultaneous coordination of the Na+ with the phenyl ring and the alkene double bond, probably places the allylic methylene hydrogen atoms in a favorable (perpendicular to the double bond) or unfavorable position for ene reaction (Scheme 11). For the cyclohexyl-substituted alkenes, however, coordination of the Na+ to the alkene double bond affords similar conformations for the allylic methylene hydrogen atoms and, therefore, they are approximately equally reactive. This is also corroborated by the fact that the twix/twin reactivity ratio is the same for all cyclohexylsubstituted alkenes, while for the phenyl-substituted compounds it changes remarkably. 1O
appropriate or innapropriate conformation for allylic hydrogen atom abstraction
2
H
H
Ph
H3C CH3
n
Na
Scheme 11. Possible interaction of Na+ to phenyl-substituted alkenes within Na-Y.
INTRAZEOLITE PHOTOOXYGENATION ISOBUTENYLARENES AND STILBENES
OF
Photooxygenation of 1-aryl-2-methylpropenes in solution proceeds slowly, and affords a complex mixture of products
Substituent Effects in the Intrazeolite Photooxygenation of Trisubstituted Alkenes (the Values in Parentheses Indicate the Relative Reactivity in Solution)
Ph 10 (60)
CD3
57 (4)
CH3
33 (36)
CD3
37 (8)
CH3
41 (38)
22 (54) 18
19 CD3
28 (5)
CH3
65 (49)
CD3 35 (5)
Ph 7 (46)
CH3
40 (46)
25 (49)
24
27 CD3 18 (5)
CD3
37 (7)
CH3
42 (42)
Ph CH3 38 (47)
44 (48) 25
Ph 22 (45) 26
21 (51) 28
CD3
39 (4)
CH3
39 (51)
290 Current Organic Synthesis, 2005, Vol. 2, No. 2
Manolis Stratakis
O O
CH3 Ph
1O 2
CH3
CH3 solvent O
29
O
+
O
CH3
O
CH3 O
HOO
CH2
Ph
CH3
+
CH3
O
H +
O Ph
major
CH3
CH2
H3C CH3 HOO
CH3 1O
O
2
CHO
CH3
O
+
+
solvent 30
major
Scheme 12. Photooxygenation of isobutenylarenes in solution.
arising mainly from [4+2] or [2+2] addition to the double bond [58]. The ene pathway is less favorable or even absent. For example, β,β-dimethylstyrene (29) affords the ene adduct in approximately 20% yield, benzaldehyde (from a [2+2] pathway), and mainly two diastereomeric di-endoperoxides (from a [4+2] pathway) in a ratio 2/1 (Scheme 1 2 ) . Table 6.
Similarly, for 1-(2-methylpropenyl)naphthalene (30), apart from the minor ene product, an 1,4-endoperoxide is mainly formed [59]. The intrazeolite photooxygenation in a series of isobutenylarenes [60], bearing either electron-withdrawing or electron-deficient substituents on the aryl ring affords rapidly
Photooxygenation of Isobutenylarenes within the Thionin-Supported Zeolite Na-Y
CH3 Ar
1O
CH3
2
Na-Y
HOO
CH2
Ar
CH3
>85% relative yield
CH3 CH3
CH3
CH3
CH3 CH3 CH3 CH3 CH3
H3C CH3
33
MeO
34
CH3 CH3 CF 3 CF 3 37
CH3
CH3
CH3
H3 C
31
30
29
CH3
38
32
CH3
CH3
CH3
CH3
F3C
35
36
CH3
CH3
CH3
CH3
F 39
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation
the ene allylic hydroperoxides as the major or even exclusive products (Table 6). The relative yield of the ene adduct was always higher than 85%. It is remarkable that isobutenylarenes whose photooxygenation in solution requires many hours to go to completion, only requires 3-5 minutes to react to same extend in the confined space of the zeolite (for the same amount of reactants). For example, the ortho-CF 3 substituted styrene 38 gives after 4 minutes of intrazeolite photooxygenation the ene product in >97% relative yield. In contrast, photooxygenation in solution proceeds at a remarkably slow rate (less than 5% conversion after 45 min of irradiation) with formation of a complex reaction mixture. To explain the remarkable chemoselectivity, two possible intermediates were invoked, the perepoxide [58], that leads to ene product and the open 1,4-zwitterionic intermediate [61], which gives the [4+2] or [2+2] adducts. Na+-binding to the aryl ring within Na-Y, destabilizes the open zwitterionic intermediate (ZI), because upon cation complexation the aryl ring is losing electron density and is less capable to stabilize the positive charge at the benzylic position (Scheme 13). On the other hand, for the perepoxide intermediate, complexation of the aryl ring to the cation is expected to cause significantly less destabilization compared to the open zwitterion. An alternative explanation for the lack of Diels-Alder cycloadduct formation, could be that encapsulation of the alkene within the zeolite, places the aryl group at an inappropriate conformation for a concerted [4+2] reaction to take place (s-cis conformation between the alkene double bond and the aryl ring). This rationalization, however, requires a synchronous mechanism for the 1 O 2 addition to the arylalkene, which is unlikely [61] to occur.
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291
Similarly, for the o-CF3 substituted styrene 45, in solution twin/twix = 77/23, while within Na-Y, twin/twix = 32/68. Again, for the naphthyl-substituted alkene 42, the reaction in zeolite is twin selective, however, in solution is twix selective (twin/twix = 82/18). The unexpected increased reactivity of the twix methyl group for the photooxygenation of β,β-dimethyl styrenes in solution has been rationalized [58,63] in terms of attractive arene-oxygen interactions in the transition state for the formation of the twix-oriented intermediate. For the intrazeolite photooxygenation reactions, cation – π interactions have been primarily examined as the major reason to dictate the site selectivity for the ene pathway. DFT calculations at the B3LYP/6-31G* level of theory revealed that the binding site of Na+ to the substrates of Table 7 is controlled significantly by the presence of substituents capable of interacting to the cation via nonbonded electron pairs (e.g. fluorine or oxygen atoms). The Na+ - F interaction, for example, is highly exothermic and is the driving force for the facile adsorption of fluorinated compounds within Na-Y [64]. Although for the parent β,βdimethyl styrene 29, the cation binds approximately in the middle and on top of the phenyl ring, for the para-CF 3 substituted styrene 36, binding occurs in between the middle of the aryl ring and the fluorine atoms (Fig. 4). For the
δO
δ+ O
H2 C
CH3
Ar Na H3 C
CH3
perepoxide (PE)
Ar
OOH
ene product
O Ar
O H3C
CH3
[4+2] or [2+2] adducts
Na
open zwitterion (ZI)
Scheme 13. Destabilization of the zwitterionic intermediate by coordination to a Na+.
The intrazeolite photooxygenation of some stereoselectively deuterium-labeled 1-aryl-2-methylpropenes, revealed that the site selectivity for the ene pathway (ratio twin/twix) is significantly affected by cation – arene interactions within the zeolite cavities. The site selectivity for some isobutenylarenes are presented in Table 7 [62]. It is evident that remarkable changes occur by zeolite confinement relative to the reaction in solution. For example, for the pCF 3 substituted styrene 43, although in solution the ratio twin/twix = 26/74, within Na-Y it becomes 82/18.
Fig. (4). Calculated minima structures for the Na+ interaction to p-and o-CF 3 substituted β,β-dimethyl styrenes at the B3LYP/631G* level of theory.
292 Current Organic Synthesis, 2005, Vol. 2, No. 2
Manolis Stratakis
ortho-CF3 substituted styrene 38, however, the binding site changes dramatically, and resides closely to the alkene double bond.
binding site closer to the CF3 functionality (see the structures of Fig. 4). The distance between the Na+ and the double bond of the alkene is higher, therefore, the stabilizing electrostatic interaction between and the incoming oxygen and the cation less important (transition state TS3, Scheme 14). Therefore, transition state TS 4 predominates (twin allylic hydrogen atom abstraction). For the case of the orthosubstituted CF3-styrene 45, binding of Na+ to the fluorine atoms shifts the cation very close to the alkene double bond (Fig. 4), thus favoring electrostatic interaction between Na+ and the negatively charged oxygen atom of the twix-oriented perepoxide, which essentially leads to twix selectivity. In addition, binding of Na + to the naphthyl (4 2 ) or pfluorophenyl-substituted (46) alkenes occurs at more remote position from alkene double bond, relative to the parent β,βdimethyl styrene, thus, a twin-selective reaction occurs.
For the intrazeolite photooxidation of the alkenylarenes, we proposed [62] that the relative reactivity of the twin and twix methyl groups for allylic hydrogen atom abstraction is controlled: (i) by electrostatic interactions between Na+ and the styrenes, and (ii) by electrostatic interactions of the negatively charged oxygen of the intermediate perepoxide to the Na+. For the parent β,β-dimethyl styrene 40, the slight preference for the twix product formation was attributed to favorable electrostatic interaction between the negatively charged oxygen of perepoxide and the cation (higher stability of TS 1 compared to the TS 2 in Scheme 14). By placing a CF 3 substituent at the para-position of 40, interaction of Na + to the highly electronegative fluorine atoms shifts the
Table 7.
Site Selectivity for the Photooxygenation of Deuterium-Labeled Isobutenylarenes by Zeolite Confinement (the Values in Parentheses Indicate the Relative Reactivity in Solution)
CD3
DOO
1O 2
CD2 +
Ar
CH3
ene pathway
Ar
CH3 twin
Substrate
Ar
40
41
H3C
42
43
F3C
HOO
CD3
Ar
CH2 twix
Intrazeolite photooxidation (twin/twix)
Photooxidation in solution (twin/twix)
42/58
37/63
43/57
45/55
61/39
18/82
82/18
26/74
38/62
30/70
32/68
77/23
60/40
32/68
F3 C 44
CF 3 45
46
F
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation
δ+ O
TS1
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δO HOO
CD3
Ph D3C
Na
CH3
TS2
δO
CH2 twix
δ+ O
DOO
CD2
Ph D3C CH3
δ+ O
TS 3
293
CH3 twin
Na
δO F F
CD3
Ar
F D3 C
HOO
CH2 twix
Na CH3
TS 4
δO
O δ+
F F F
D3C
Na
DOO
CD2
Ar
CH3 twin
CH3
Scheme 14. Postulated transition states controlling the site selectivity in the intrazeolite photooxygenation of isobutenylarenes.
Significant changes in the product distribution by zeolite confinement, were found in the photooxygenation of stilbenes. Reaction of 1 O 2 with trans-stilbene in solution proceeds very slowly, to give mainly mono or diendoperoxides [65] arising from a non-concerted [4+2] cycloaddition pathway. By contrast, it was reported by Ramamurthy and Li [66], that the dye-sensitized intrazeolite photooxygenation of stilbenes 47 and 48 proceeds via a [2+2] pathway, to form labile 1,2-dioxetanes, which cleave under thermal conditions to benzaldehydes (Scheme 15). The preferential formation of the 1,2-dioxetanes within Na-Y was attributed to an electron transfer pathway. However, a singlet oxygen-involved mechanistic rationalization cannot be ruled out. DIASTEREOSELECTIVITY IN THE INTRAZEOLITE PHOTOOXYGENATION OF CHIRAL ALKENES The study of the diastereoselection in the electrophilic addition of singlet oxygen to the π phase of chiral alkenes is of primary interest for the achievement of a selective oxyfunctionalization reaction. Zeolite confinement and cation – π interactions might be expected to affect
significantly the diastereoselectivity in the photooxygenation of chiral alkenes. Na+ - π interactions have been postulated as a major factor for the dramatic change in the π facial photoreduction of some enone steroids [67] within zeolite Na-Y, relative to the reaction in a homogeneous environment. The diastereoselectivity in the ene reaction of 1O 2 with chiral alkenes bearing a stereogenic center at the α- position with respect to the double bond has been extensively studied in solution [68]. Chiral alkenes which bear a substituent on the asymmetric carbon atom other than the hydroxy or amine functionality afford predominately e r y t h r o allylic hydroperoxides. The erythro selectivity was attributed to steric and electronic repulsions between the incoming oxygen and the substituents on the stereogenic carbon atom, and to a preferable conformational arrangement to minimize the 1,3-allylic strain. For allylic alcohols and amines, the threo diastereoselectivity was rationalized in terms of an oxygen - hydroxy/amine steering effect. We examined [69] the regioselectivity and diastereoselectivity in the photooxygenation of some chiral alkenes, possessing a phenyl group and an alkyl group (R) of various size on the stereogenic carbon atom (R = methyl, 49; R = ethyl, 50 and R = cyclohexyl, 51). The reaction of
294 Current Organic Synthesis, 2005, Vol. 2, No. 2
Manolis Stratakis R
R O
Thionin/Na-Y
O
hv/O2 R = H (47) R= OM e (48) R
R 1O 2
solvent R
R
CHO
O O R
Scheme 15. Photooxygenation of stilbenes in solution and within Na-Y.
chiral alkenes 49-51 with 1O 2 in solution is regioselective with preferential formation of the secondary allylic hydroperoxides. Among the secondary hydroperoxides the erythro isomer prevails (Table 8). It is also notable, that the minor tertiary allylic hydroperoxides has always the (Z)geometrical configuration. For example, in the photooxygenation of 1-cyclohexyl-1-phenyl-3-methyl-2butene 51, the (Z)-tertiary allylic hydroperoxide was formed in 14% relative yield, while for the predominant secondary allylic hydroperoxides, the ratio erythro/threo = 82/18.
allylic hydroperoxides were formed, however, with an inverse diastereoselection trend (Table 8). The threo diastereomer is now predominant, and the ratio threo/erythro increases with increasing the size of the R group. A remarkable example is substrate 5 1 , for which the diastereoselection trend was completely reversed (erythro/threo = 09/91 versus 82/18 in solution). Formation of the major erythro diastereomer for the photooxygenation of the chiral alkenes in solution was explained considering the transition state shown in Scheme 16. The phenyl group is placed to the opposite plane of the double bond with respect to the attacking oxygen, due to the unfavorable
The thionin-sensitized intrazeolite photooxygenation of the 49-51 is highly regioselective, since only the secondary Table 8.
Regioselectivity and Diastereoselectivity in the Photooxygenation of Chiral Alkenes within Zeolite Na-Y and in Solution (Values in Parentheses) CH3
H3 C R = methyl (49) R = ethyl (50) R = cyclohexyl (51)
R Ph
1O
H3 C
OOH CH3
H2C +
Ph
2
CH3
H2C +
R
OOH Ph
R (Z) a
CH3
R
OOH Ph
erythro b
threo c
Alkene
a (%)
b (%)
c (%)
49
>1 (6)
46 (72)
54 (22)
50
>1 (10)
23 (70)
77 (20)
51
>1 (14)
9 (71)
91 (15)
Oxyfunctionalization of Alkenes by Dye-Sensitized Intrazeolite Photooxygenation O
Current Organic Synthesis, 2005, Vol. 2, No. 2
H2C
CH3
H3C
O H
R
R
Ph H3C
+
OOH
OOH CH3
Ph
Ph
CH3
295
R
erythro
(Z)
Scheme 16. Erythro-forming transition state for the photooxygenation of the phenyl-substituted chiral alkenes in solution.
oxygen - arene electronic repulsions. In addition, a minimum 1,3-allylic strain between the tertiary allylic hydrogen and the twix allylic methyl group dictates the preferential 1O2 approach. On the other hand, the remarkable change of the diastereoselection on going from the solution to the confined environment of the zeolite was rationalized taking into account the strong electrostatic interaction of the phenyl ring to the Na+ within the supercages. The alkene most likely adopts the conformation shown in Scheme 17. Preferential attack of singlet oxygen from the less hindered top phase leads to the major threo allylic hydroperoxides. As the size of the R group increases, the energy difference between the threo and erythro forming transition states is expected to increase, in favor of the threo isomer. 1O
top attack: threo (more favorable)
2
low diastereoselectivity (~10% d.e.) was found for the formation of the secondary allylic hydroperoxides. By Na-Y confinement, however, the reaction is 94% regioselective in favor of the secondary hydroperoxides and the diastereomeric excess enhances to 44% d.e. (Scheme 18). It is likely that, upon interaction of the alkene with a Na+ within the cage, the substrate folds, and the chirality is “transferred” close to the reaction center (double bond). As a result, the distribution of the diastereomeric e n e products is significantly affected. CH3 Ph CH3 H3C
94 % d.e. 44% (47 % d.e. 10%)
6 (53) 52
Scheme 18. Regioselectivity/diastereoselectivity in the photooxygenation of 2-methyl-5-phenyl-2-hexene (the values in parentheses indicate the relative reactivity in solution). H3C
H
H3 C
Na R
1O
2
bottom attack: erythro (less favorable)
Scheme 17. Threo and eryhthro-forming transition states for the photooxygenation of phenyl-substituted chiral alkenes by zeolite confinement.
DIASTEREOSELECTIVITY-INDUCED REMOTE CHIRAL SUBSTITUENT
BY
A
Due to the adsorption of the reactant alkenes in confined environment within the zeolite cavities, increased diastereoselectivity might be expected in cases where a chiral center resides at a remote position with respect to the double bond (enzyme-like activity). This aspect of enhancement the diastereoselection of a reaction induced by a remote stereogenic center within zeolite Na-Y has been elegantly shown [70] in the photochemical disrotatory electrocyclic cyclization of a chiral tropolone ether by Ramamurthy and co-workers. For the photooxygenation of chiral alkenes in solution bearing a stereogenic center at the β- or more remote position with respect to the double bond, low or negligible diastereoselection is expected [71]. We studied [72] the photooxygenation of 2-methyl-5-phenyl-2-hexene 52, a chiral alkene that bears a stereogenic center at the β-position with respect to the double bond. As expected, in solution a
The intrazeolite photooxygenation of 2-methyl-5-phenyl2-hexene (substrate 53), specifically labeled at the twin methyl group was performed, to determine the degree of diastereoselection induced by abstraction of an allylic hydrogen atom either from the more (CH3) or the less (CD3) substituted side of the double bond (Scheme 19). It was found that the diastereoselectivity depends on the position of the allylic hydrogen to be abstracted. The twix/twin methyl reactivity was found within Na-Y to be 70/30. Formation of the double bond by reaction of the twin methyl group (Dabstraction) proceeds with moderate diastereoselectivity (18% d.e.), while hydrogen abstraction from the twix methyl group proceeds with 54% d.e. This site differentiation in the diastereoselection was rationalized as follows. Upon folding of the alkene within the zeolite cages, the stereogenic center most probably becomes closer to the more substituted side of the double bond, thus higher diastereoselectivity is expected if the reaction occurs by hydrogen atom abstraction from the twix methyl group. A remarkable enhanced diastereoselection for the ene pathway was also reported by our group [73] in the photooxygenation of the monoterpene (R)-(-)-α-phellandrene (54). The oxygenated products for the reaction of 54 with 1O 2 in solution [74] are the two diastereoisomeric endoperoxides 54a and 54b (major products), while five isomeric ene adducts (54c-g) are formed in various amounts (Table 9). Within zeolite Na-Y, the relative ratio of the overall ene adducts increases (ene/[4+2] = 34/66 in solution versus ene/[4+2] = 52/48 in the zeolite). Comparing the Diels-Alder adducts, the diastereomeric ratio of 54a/54b slightly increases in zeolite, while for the ene adducts, for those where the double bond is formed in the interior of the ring, the predominant diastereomer in solution is also the
296 Current Organic Synthesis, 2005, Vol. 2, No. 2
Manolis Stratakis H2C twix
CD3
H2C
H3C
H- abs traction
H3 C
+
OOH
CD3
OOH
Ph
Ph 70% (d.e. 54%)
twin CD3
1O
CH3
Na-Y
2
Ph H3 C
twix
53
CD2
H3C
H3C
CD2
twin H3C
H3C
+
D- abstraction
OOD
OOD
Ph
Ph 30% (d.e. 18%)
Scheme 19. Site-dependent diastereoselectivity in the intrazeolite photooxygenation of 2-methyl-5-phenyl-2-hexene (53). Table 9.
Photooxygenation of (R)-(-)-α-Phellandrene in Zeolite and in Solution H3C CH3
54
H3C 1
O2
CH3
CH3
O
H3 C
O
+
O
CH3
+
O
H3C
54a
HOO CH3
H3C OOH
CH3
+
H3C
54b
H3C
CH3 54c
CH2
CH2
CH3 OOH
+
H3C
CH3
54e
CH3 54d
HOO
HOO
+
+
H3C
CH3 54f
H3C
CH3
54g
Conditions
54a (%)
54b (%)
54c (%)
54d (%)
54e (%)
54f (%)
54g (%)
i-PrOH /RB
39
26
14
9
2
1.5
3
Thionin/Na-Y
33
15
12
5
5
30
90% diastereomeric excess, resulting from allylic hydrogen atom abstraction from the more substituted side of the cycloalkene (Scheme 21). This regiochemistry trend is in contrast to what has been reported for the intrazeolite photooxygenation of 1-methyl-1-cycloalkenes.
H 54a, 54c, 54e CH3
H H
CH3
Favorable transition state within zeolite CH2
O H3 C
HOO
O
H H
H3 C H H Na
H3C
H
CH3 54f
Scheme 20. Transition states leading the major ene adducts in solution and within Na-Y.
> trans) was rationalized in terms of a common perepoxide intermediate shown in Scheme 20, which leads either to the ene or to the Diels-Alder products. In that intermediate, singlet oxygen attacks the more reactive trisubstituted double bond of the more stable conformation from the top phase to interact with an axially oriented allylic hydrogen atom. For the intrazeolite reaction, cation binding to the alkene was used to explain the stereochemical outcome of the reaction. The major ene adduct was proposed to arise from the transition state shown in Scheme 20. Oxygen attacks from the opposite face of the alkene with regard to the bound cation, and is preferentially oriented towards the less substituted side of the double bond, because in the
The dramatic change in the regioselectivity can be explained considering attractive singlet oxygen – cation interactions during the formation of the intermediate perepoxide, that direct 1 O 2 to abstract preferentially an allylic hydrogen atom from the more substituted side of the alkene (transition state of Scheme 22). Most probably, the Na+ cation is bound close to the acetate functionality and at the appropriate position to interact electrostatically with 1O2. The allylic hydrogen at the 3-position has the ideal geometry for abstraction (axial conformation), thus, mainly one diastereomer is formed. OOH
H2 C
1O
CH3
2
Na-Y
H3 C 4
H2C CH2 H3C >97% (d.e. 98%)
Scheme 21. Changes in the regiochemistry and diastereoselection by zeolite confinement due to a remote substituent. δO AcO
H
H3C H3C
297
orientation facing the more substituted side of the alkene, it cannot interact with any axially-oriented allylic hydrogen atom(s).
Favorable transition state in solution H O
Current Organic Synthesis, 2005, Vol. 2, No. 2
O δ+ CH3
H3C AcO H3C
OOH CH3
3 H
Scheme 22. Na+-directing regioselectivity and diastereoselection in the intrazeolite photooxygenation of α-terpinyl acetate.
298 Current Organic Synthesis, 2005, Vol. 2, No. 2
Manolis Stratakis
CONCLUDING REMARKS
[18]
The confined environment of the zeolite supercages can significantly influence the product distribution of singlet oxygen-induced reactions and can lead to the development of novel and stereoselective oxyfunctionalization pathways in the photooxygenation of alkenes. The cations within the supercages are not just inert fillers, but through cation – π interactions can dramatically influence reaction pathways. The experimental results presented herein are an excellent basis for the development of models with predictive capability, in order to tune the behavior of 1O2 reactions by zeolite confinement. In addition, these results reveal clearly that zeolites can no longer be considered as “boiling stones” or adsorbing molecular sieves but can find significant applications in organic chemistry [76]. The environmentally benign nature of the zeolite medium justify further exploration towards new frontiers for selective organic transformations in organized media.
[19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32]
ACKNOWLEDGEMENTS I would like to thank the General Secretariat of Research and Technology and the Greek Ministry of Education (ΕΠΕΑΕΚ program) for financial support during the past 45 years of my research activities in the University of Crete. I am indebted to my graduate and undergraduate students, Giannis Kosmas, Constantinos Rabalakos, Nikoletta Sofikiti, Radim Nencka, Constantinos Tsangarakis, Dimitris Kalaitzakis, Dimitris Stavroulakis, Constantinos Baskakis, Christos Raptis and to professor G. E. Froudakis (theoretical calculations) for participation in the intrazeolite photooxygenation project. Discussions with professors W. Adam, M. Orfanopoulos and G. Vassilikogiannakis are also highly acknowledged.
[33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43]
REFERENCES
[44]
[1]
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Received: October 8, 2003
Accepted: November 3, 2003
299
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