Stereoselectivity in Ene Reactions with ^sup 1^O2: Matrix Effects in Polymer Supports, Photo-oxygenation of Organic Salts and Asymmetric Synthesis
The ene reaction of chiral allylic alcohols is applied as a tool for the investigation of intrapolymer effects by means of the stereoselectivity of the singlet-oxygen addition. The diastereo selectivity strongly depends on the structure of the polymer, the substrate loading degree and also on the degree of conversion demonstrating additional supramolecular effects evolving during the reaction. The efficiency and the stability of polymer-bound sensitizers were evaluated by the ene reaction of singlet oxygen with citronellol. The ene reaction with chiral ammonium salts of tiglic acid was conducted under solution phase conditions or in polystyrene beads under chiral contact ion-pair conditions. The products thus obtained precipitate during the photoreaction as ammonium salts. Moderate asymmetric induction was observed for this procedure for the first time.
Singlet oxygen is a versatile reagent in organic oxidation chemistry. Because this molecule can be generated by numerous thermal methods, singlet-oxygen chemistry is often not considered per se as a photochemical topic. The most practical method to generate singlet oxygen in solution, however, is triplet sensitization by use of electronically excited triplet states of dye molecules. Furthermore, singlet oxygen is an electronically excited molecule and can decay to its ground state by radiation-less or radiative processes in addition to chemical reactions. The chemical process that leads to the oxidation of organic substrates by transfer of both oxygen atoms is termed Type-II photo-oxygenation (1-3). The atom economy of such a process is 100%, a major advantage over other oxidants, such as hydrogen peroxide, that can only reach an atom economy of 48%, if calculated for the formation of epoxides from alkenes (4). The primary peroxidic products from Type-II photo-oxygenation can be reduced to numerous polyoxygenated derivatives either with loss of the original oxygen content (allylic alcohols from allylic hydroperoxides) or with conservation of the oxygen content (1,2-and 1,4-diols from dioxetanes and endoperoxides, respectively, or epoxy-alcohols from allylic hydroperoxides by means of titanium[IV]-catalyzed oxygen transfer).
Singlet-oxygen reaction media
In the last decade, the area of polymer-supported organic reactions (5-7) and polymer-supported catalysts (8,9) has impressively increased. This is obvious for solid-phase synthetic chemistry, where reactions are carried out in resins and/or catalyzed by supported catalysts. Photo-oxygenation in solution with the use of insoluble polymer-bound sensitizers facilitates the problem of dye recovery. The first polymer-bound sensitizer was the now commercially available polystyrene-bound Rose Bengal developed by Schaap et al. (10) followed by a series of immobilized sensitizers, e.g. the immobilized fullerene C^sub 60^ (11,12), ionic porphyrins immobilized on cationically functionalized polystyrene (13), tetrakis(4-hydroxyphenyl)porphyrin supported to polyethylene glycol (14), aluminum(III) tetracarboxyphthalocyanine bound to poly(styrene-co-chloromethylstyrene) (15), polystyrene-bound benzophenones (16), immobilized pyrylium salts on Merrifield resins (17), sensitizer-incorporated nation membranes (18), or ion-exchange resins ionically bound to photosensitizers (19). Other heterogeneous catalysts using clay (20), silica (21), and zeolites (22,23) as support materials were also recently developed. From the viewpoint of solution photochemistry, the use of nonpolar solvents enhances dye oxidation and bleeding, especially if long reaction times are needed, which decreases the singlet-oxygen quantum yield and hence the reaction efficiency. On the other hand, photo-oxygenation reactions carried out in aqueous solutions are also not favored, due to low solubility of most organic substrates, the low singlet-oxygen lifetime, and hydrophobic aggregations of nonpolar sensitizers (leading to self quenching), which as a consequence reduces the triplet lifetime (24,25), We have recently reported a solution to circumvent some of the mentioned technical problems: Under solvent-free reaction conditions, in which the substrates are embedded in a porphyrin-loaded polystyrene polymer matrix, irradiation and product isolation accompanied by complete sensitizer separation by extraction with ethanol offers a shortcut to green photo-oxygenation reactions (26).
Two major problems in photo-oxygenation chemistry appeared unsolved until recently: (a) altering the regio- and diastereoselectivity of singlet-oxygen ene or [4+2]-cycloadditions by optimizing the reaction media, and (b) making singlet oxygen chiral, i.e. introducing high enantioselectivity into singlet-oxygen ene or [4+2]-cycloaddition reactions by catalytic methods.
The singlet-oxygen ene reaction
The singlet-oxygen ene reaction was discovered in 1943 by G. O. Schenck (27,28). In the course of this reaction, ^sup 1^O^sub 2^ attacks one center of a CC double bond with abstraction of an allylic hydrogen atom and shift of the double bond (Scheme 1). As a result of this reaction, allylic hydroperoxides are formed, compounds that are versatile intermediates for the synthesis of allylic alcohols, epoxides, epoxyalcohols, 1,2-diols, and 1,2,3-triols. Several mechanisms have been postulated for this reaction, most recently the two-step no-intermediate mechanism involving a bifurcating transition state with perepoxide structure (29), as well as 1,4-biradicals (30), 1,4-zwitterions (31), perepoxide (32), dioxetane or exciplex intermediates.