View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Archivio della ricerca - Università degli studi di Napoli Federico II Current Organic Chemistry, 2007, 11, 1053-1075 1053 Photooxygenation of Non-Aromatic Heterocycles M. Rosaria Iesce*, F. Cermola, M. Rubino Dipartimento di Chimica Organica e Biochimica, Università di Napoli Federico II, Complesso Universitario Monte S. Angelo, via Cinthia 4, I-80126 – Napoli, Italy Abstract: Photooxygenation of non-aromatic heterocycles and cyclic compounds containing non-usual heteroatoms, namely silicon, germanium and tellurium has been reviewed. All three types of photooxygenation (Types I-III) can take place. Moreover the heteroatom can be frequently involved endorsing electron-transfer reactions which turn out to be the main pathways, even in singlet oxygen oxygenation. A vast collection of novel and unexpected products are often formed, sometimes in a stereocontrolled manner. 1. INTRODUCTION sources; aromatic ketones, as benzophenone, or cyanoaro- Since the first experiments by enthusiastic Ciamician [1] matic compounds, as 9,10-dicyanoanthracene (DCA), are on the roof of his institute in Bononia (Bologna) University, used in photooxygenation of Type I or III, respectively and a pletora of papers and books have been made regarding in- mercury-lamps (preferably UV filtered) are used as light teraction of light with matter, and in this context photooxy- sources [2, 4c, 4d]. genation, combination of light and oxygen generally in the In 2005 we published a review on the photooxygenation presence of a suitable conjugated molecule (sensitized pho- of heterocyclic aromatic compounds with the aim to bring tooxygenation), has been widely used to introduce oxygen- up-to-date on the latest twenty-year results [2]. In this review ated functions in organic molecules. we focus our attention on the photooxygenation of non- aromatic heterocycles (unsaturated where bonds to the het- Three common mechanisms are invoked for the sensi- tized photooxygenation which differ essentially by the dif- eroatom are directly involved or saturated) [11] and have ferent role of the sensitizer [2, 3]. So, the photoexcitated expanded the discussion to cyclic compounds containing sensitizer can interact with the molecule by extracting hy- non-usual heteroatoms, namely silicon, germanium and tellu- drogen (Type I) or an electron (Type III), and the radical or rium [12]. the radical cation of the substrate so formed react with triplet oxygen or superoxide anion to give the oxygenated products. 2. PHOTOOXYGENATION OF UNSATURATED HET- In Type II an energy transfer from the excited sensitizer to EROCYCLES triplet ground state oxygen can occur generating singlet The nucleophilicity of a double bond is enhanced by the 1 oxygen ( O2), a highly reactive species, whose behaviour presence of the heteroatom so that partially saturated deriva- towards organic molecules is continuously under investiga- tives as cyclic enol ethers or enamines react easily with sin- tion due to the chemical [4] and biochemical [5] implica- glet oxygen by [2+2] cycloaddition and afford the character- tions. The electrophilicity of this species and its alkene-type istic cleavage products from thermally unstable dioxetanes. character promote addition reactions to unsaturated systems The dioxetane-mode however competes with ene mode in ([4+2] cycloaddition [6], [2+2] cycloaddition [6], or ene-like the presence of adjacent allylic hydrogens. The nature of reaction [7]). Singlet oxygen may also react at electron pair heteroatom, ring size, substitution as well as environmental bearing heteroatom centers, e.g. sulfur, to give the corre- factors influence the product distribution. So, in the pho- sponding oxide [4]. Sometime reactions with electron-rich tooxygenation of dihydropyran 1, both dicarbonyl compound substrates, such as amines [8], sulfides [9] and phenols [10], 4, the product expected from cleavage of the dioxetane 2, may proceed by electron transfer from the electron-rich sub- and dihydropyrone 5, the dehydration product from the hy- strate to singlet oxygen to give a cation radical-superoxide ion pair or charge-transfer complex. Coupling reaction of the 1 1 ion pair could give the oxygenated product or a back- O O2 O2 electron transfer could occur producing triplet oxygen and O ene OOH the starting compound. The latter route is particularly impor- O [2+2] OO tant for nitrogen-containing molecules, and some suitable H derivatives, e.g. diazabicyclo[2.2.2]octane (DABCO), are 2 1 3 specifically used as singlet–state oxygen inactivators [2, 4]. - H2O Typical sensitizers for singlet oxygen reactions are dyes as methylene blue (MB) or Rose Bengal (RB) or tetraphenyl- O porphine (TPP) and tungsten-halogen lamps are used as light OO O O 4 5 Address correspondence to this author at the Dipartimento di Chimica Or- ganica e Biochimica, Università di Napoli "Federico II" Complesso Univer- 4/5 ratio increases up to 58-fold from C H to CH CN sitario Monte S. Angelo, Via Cinthia, 4, I-80126 Napoli Italy; Tel: +39-081- 6 6 3 674-334; Fax: +39-081- 674-393; E-mail: [email protected] Scheme 1. 1385-2728/07 $50.00+.00 © 2007 Bentham Science Publishers Ltd. 1054 Current Organic Chemistry, 2007, Vol. 11, No. 12 Iesce et al. droperoxide 3, are formed and the product ratio 4/5 varies the preferred products [15]. It is interesting to note that hy- over a 58-fold as the solvent changes from benzene to aceto- droperoxides 10 (for n=1) undergo straightforward H2O2 nitrile with polar solvent favouring the 1,2-addition (Scheme elimination to give furans [14]. 1) [13]. The solvent effect however seems to be associated A different behaviour is observed in the singlet oxygena- with the unsymmetrical character of the enol ether substrate tion of thio-analogues. Indeed, they essentially lead to dicar- [13a]. bonyl derivatives via dioxetanes. Less than 5% of allylic Small rings and electron-donor substitution appear to fa- hydroperoxides is formed starting from five-membered de- vour the formation of dioxetanes at the expense of allylic rivatives as dihydrothiophene 13 while dioxetane mode is the hydroperoxides [14, 15]. Scheme 2 and Table 1 report the unique route in six-membered derivatives as in 3,4-dihydro- trend observed in oxygenated systems (dihydrofurans and 2H-thiopyran 16 which gives exclusively compound 18 dihydropyrans). (Scheme 3) [16]. The nature of heteroatom plays a role also Significant is the strong substituent effect in the oxygena- in the thermal stability of dioxetane intermediate. S- tion of ethyl 3,4-dihydro-6-methyl-2H-pyran-5-carboxylate substituted dioxetanes result more thermally unstable than O- (Table 1) and 5-acetyl analogue [15]. These compounds un- analogues, and have been spectroscopically detected at very dergo the exclusive ene-reaction due to the presence of the low temperatures (< -70 °C), if any [16]. electron-withdrawing ester and acetyl groups which further The selective formation of dicarbonyl derivatives via di- address the formation of the conjugated hydroperoxides as oxetanes is obviously observed in the presence of two het- R O O O O R n O Me n O Me 8 7 R OOH n CH2 1 O O2 9 R R R 1O n= 1 2 OOH n O Me n O Me O Me H2O2 6 10 11 CH2 R= Me OOH n O Me 12 Scheme 2. Table 1. CCl4 CH3CN entry n R Products (%)a 8 9 10 12 8 9 10 12 a14 1 Me 80 - 13 7 87 - 7 6 14 b 1 CO2Me 3 14 83 - 44 6 50 - c14 2 Me 28 52 - 20 35 55 - 10 15 d 2 CO2Et - 17 83 - - 65 35 - a By 1H NMR. Photooxygenation of Non-Aromatic Heterocycles Current Organic Chemistry, 2007, Vol. 11, No. 12 1055 CO Me CO2Me 2 O O , h, Sens Me SCO2Me 2 O + < 5% of ene products Me S S Me O O 13 14 15 (>90%) O O , h, Sens S 2 S Ph S Ph CH2Cl2, -78 °C Ph Ph O Ph Ph OO 18 (quant.) 16 17 Scheme 3. O 1 O2 X Y X Y Ph X Y Ph CH2Cl2, -78 °C Ph Ph O Ph Ph OO 21 19 20 a; X= Y= O b; X= Y= S c; X= O, Y= S d; X= Y= NMe Scheme 4. eroatoms on the double bond as in 19 (Scheme 4) [17]. Once usual decomposition of dioxetanes. However peculiar rear- more the nature of the heteroatoms affects the thermal stabil- rangements have also been observed. So, oxygenation of ity of the corresponding dioxetanes. A mechanism involving compound 22 sometime leads to diketone 24 derived from an intramolecular electron-transfer process has been pro- the decomposition of dioxetane 23 via C-S bond cleavages posed for the cleavage of unstable S- and N-substituted di- [18], as also observed in bis-, tris- and tetrakis-1,2- oxetanes [17]. This mechanism requires that the stability of ethylthioethylenes (Scheme 5) [19]. dioxetanes is related to the oxidation potential of the heteroa- The presence of suitable substituents at appropriate posi- tom substituents. So, dioxetanes bearing easily oxidized tions may induce peculiar rearrangements. So, in the oxy- groups such as N- or S-substituents are dramatically less genation of 5,6-dihydro-1,4-oxathiins 25 (X=O) [20] and stable than a similar dioxetane with an O-group possessing a 5,6-dihydro-1,4-dithiins 25 (X=S) [21] the formation of keto much higher oxidation potential [17]. sulfoxides 28 and/or 30 has been observed in the presence of As observed in above Schemes, fragmentation to dicar- an electron withdrawing group at the double bond (Scheme bonyl compounds via O-O and C-C bond breakage is the 6). It has been suggested that in the dioxetanes 26 the in- O S 1 S H O2 O H OMe O OMe S S O 22 23 24 Scheme 5.