Axel G. Griesbeck

Singlet oxygen photooxygenation of furans : Isolation and reactions of (4+2)-cycloaddition products (unsaturated sec.-ozonides)

Tetraphenylporphin-photosensitized oxygenations of furan (19), 2-methylfuran (26), 2-ethylfuran (39), furfurylalcohol (24), 2-acetylfuran (40), 2-methoxyfuran (42), 2,5-dimethylfuran (30), furfural (25) and 5-methylfurfural (41) in non-polar aprotic solvents yield the corresponding monomeric unsaturated secondary ozonides due to a (4+2)-cycloaddition of singlet oxygen to these furans. With the exception of the ozonide derived from 25, the ozonides were isolated and characterized (1H- and 13C-NMR spectra, etc.). In non-polar aprotic solvents, the ozonides derived from 19, 26 and 39 undergo thermal rearrangements to the corresponding cis-diepoxides and epoxylactones. Ozonide 31, derived from 30, however, dimerizes, only above about 60° is a cis-diepoxide formed from either 31 or its dimer. Rose bengal-photosensitized oxygenations of the furans in alcohols (MeOH, EtOH, i-PrOH) also produce the corresponding ozonides as the primary products of (4+2)-cycloadditions of singlet oxygen to these furans. However, reactions of the alcohols with the ozonides are too fast to allow the ozonides to be isolated. Instead, the same products are obtained as are isolated from reactions carried out by dissolving the ozonides in the alcohols. Depending on the structure of the ozonide, three pathways are available to ozonide/alcohol (ROH) interactions:(1) addition of ROH to yield alkoxy hydroperoxides; one out of several possible isomers is formed in a completely stereoselective and regiospecific reaction; (2) elimination of a bridgehead proton by ROH as a base, as observed with the ozonide derived from 19 to give hydroxy butenolide (78) in yields between 20 and 60%, and (3) ROH-attack on a carbonyl side-chain under elimination of the corresponding alkyl ester, as observed with furfural photooxygenation which yielded hydroxy butenolide (78) in high yields (95%). Interaction of ozonide 31 with tert.-butyl alcohol (t-BuOH) yields quantitatively cis-3-oxo-1-butenylacetate (81) by a Baeyer-Villiger-type rearrangement with vinyl group migration Hydrogenbonding between the alcohol and the peroxy group of the ozonides assist the heterolysis of the C—O bonds in the ozonides; the most stabilized cation develops. Front-attack of ROH on this cation explains the stereoselectivity as well as the regiospecificity of the alkoxy hydroperoxide formation; with a bulky alcohol like t-BuOH, ROH-attack on the cation is sterically hindered thus allowing a rearrangement to occur. 1,3-Dipolar cycloaddition of p-nitrophenyl azide to ozonide 31 proceeds stereoselectively to one of the isomers 87a/87b. Finally, kinetic results of furan photooxygenation in methanol show the following order of furan-reactivity towards singlet oxygen: 30 > 42 > 26 > 19 > 41 > 25, with absolute rate constants ranging from 1.8 × 108 (with 30) to 8.4 × 1O4 M-1P-1 (with 25).

Asymmetric photochemistry and photochirogenesis.

One of the most interesting phenomena on Earth is the chirality of biomolecules, the origin of which remains unknown. A challenge arising from this phenomenon is the selective, atom-economic synthesis of enantiomerically pure target molecules from nonchiral starting materials. Herein, new developments in the field of asymmetric photochemistry and photochirogenesis are described with special emphasis on absolute asymmetric synthesis. In this context, the elucidation of the ultimate cause of homochirality phenomena on earth and the possible correlation with physicochemical parameters are also presented.

Photoinduced electron transfer chemistry of phthalimdes: an efficient tool for CC-bond formation

A collection of intra- and intermolecular photoinduced electron transfer (PET) reactions is presented which all are based on the phthalimide chromophore as the oxidizing species. Electron-donating groups versatile for PET processes are ethers, thioethers, amines, alkenes, arenes, and carboxylates as well as α-trialkylsilyl activated heteroatom-substituents. These reactions can be efficiently applied for the synthesis of five- and six-membered ring heterocycles, medium-sized and macrocyclic products such as macrolides, cyclopeptides, crown ethers or thioethers as well as (from intermolecular processes) Grignard-alike products.

Diastereo- and Enantioselective Synthesis of Pyrrolo[1,4]benzodiazepines through Decarboxylative Photocyclization

Memory of chirality in triplet 1,7-diradicals was detected for the first time and to a remarkably high degree in the decarboxylative photocyclization of the proline derivative of N-phthaloyl anthranilic acid 1 into 2 (X=H: 45 % yield, 86 % ee; X=Cl: 50 % yield, 79 % ee).

Sustainable photochemistry: solvent-free singlet oxygen-photooxygenation of organic substrates embedded in porphyrin-loaded polystyrene beadsDedicated to Professor Waldemar Adam on the occasion of his 65th birthday and his retirement from the stage of photooxygenation chemistry.

A solvent-free photooxygenation process that uses organic substrates embedded in porphyrin-loaded polystyrene beads as solid support is described and applied for ene- and [4 + 2]-cycloaddition reactions involving singlet oxygen (1 delta g).

Photoinduced decarboxylation reactions. Radical chemistry in water

Intramolecular photodecarboxylation reactions of potassium ω-phthalimido carboxylates in water or mixtures of water and organic solvents (acetone, acetonitrile) were investigated using an incoherent XeCl excimer radiation source emitting at 308 nm. Electron transfer induced intermolecular addition of alkyl carboxylates to phthalimides likewise proceeded efficiently under these conditions. The reactions can be performed in multigram (i.e. 10–30 g product) quantities using easiliy available substrates such as glutamic acid (for the synthesis of 3), leucine (for 8, 9) or simple alkyl carboxylates (for 11). The advantages of this methodology are: clean and high-yielding reactions, solvent and waste minimization, water-based processes and efficient utilization of photons of defined energy.

Solvent dependence of singlet oxygen / substrate interactions in ene-reactions, (4+2)- and (2+2)-cycloaddition reactions

Abstract Product formation of singlet oxygen reactions with simple olefins occurring as ene-reactions, (4+2)- and (2+2)-cycloaddition reactions is independent on solvent polarity. Thus, 2,3-dimethyl-2-butene (1) and 2-methy]-2-butene (3), 1,3-cyclohexadiene (6), and benzvalene (8) yield allylic hydroperoxides (2) and(4) (54%) + (5) (46%), endoperoxide (7), and dioxetane (9), respectively. The rates of the ene-reactions and (4+2)-cycloaddition reactions are only slightly dependent, those of the (2+2)-cycloaddition reaction, however,are clearly dependent on solvent polarity. “Physical” quenching of singlet oxygen by the olefins is negligible, but substantial by the sensitizer tetraphenylporphin (TPP) in chlorinated solvents.

Interactions of singlet oxygen with 2,5-dimethyl-2,4-hexadiene in polar ano non-polar solvents evidence for a vinylog ene-reaction

Abstract 2,5-Dimethyl-2,4-hexadiene ( 1 )was studied as a singlet oxygen acceptor in various solvents. 1 undergoes concomitantly the three well-known modes of singlet oxygen reactions: (1) the ene-reaction to give the allylic hydroperoxide 3 , (2) the (4+2)-cycloaddition to give the endoperoxide 4 , and (3) the (2+2)-cycloaddition to give the dioxetane 2 . Beyond that (and in contrast to simple olefins), there are (4) “physical” quenching and (5) a “vinylog ene-reaction” to give the twofold-unsaturated hydroperoxide 5 . The latter reaction represents a novel mode of singlet oxygen interaction with a substituted 1,3-diene. - Kinetic analysis shows that “physical” quenching, endoperoxide and vinylog ene-product formations proceed with solvent-inde pendent rates; the rates of dioxetane and ene-product formations, however, are solvent-dependent. - A mechanism (Scheme 3) is proposed, according to which endoperoxide formation is due to a concerted singlet oxygen reaction with the s-cis-conformational isomer 1b ; with the s-trans-isomer 1a , “physical” quenching and the vinylog ene-reaction proceed via a non-polar singlet diradical intermediate, whereas the ene-product formation occurs via a per epoxide-like transition state. In aprotic solvents, the dioxetane is mainly formed via a “tight-geometry intermediate”, in methanolic solution via a solvent-stabilized zwitterion; the latter is also responsible for the formation of the methanol-addition product 6 .

Photooxygenation of allylic alcohols: kinetic comparison of unfunctionalized alkenes with prenol-type allylic alcohols, ethers and acetates

The kinetics of the chemical and physical quenching of the first excited singlet state of oxygen [1O2 (1delta(g))] by unfunctionalized alkenes 1-4, allylic alcohols 5-7 and 9, allylic acetates 8 and 11, and the allylic ether 10 display small solvent-polarity effects on the reactivity. The regioselectivity of the singlet oxygen ene reaction is solvent independent for the unfunctionalized alkenes as well as the prenol-type substrates, the latter showing substantial solvent effects on the diastereoselectivity. Pronounced physical quenching is detected only for the allylic alcohols 5 and 6. These results are interpreted in terms of the interactions between singlet oxygen and the allylic hydroxy groups, conformationally promoted by allylic strain which lead either to chemical activation or to physical quenching. The results for substrate 9 in deuterated v.s non-deuterated methanol are in accord with hydrogen bonding between the allylic alcohol and 1O2, which directs the diastereoselectivity of the ene reaction with chiral allylic alcohols.

Synthetic Organic Photochemistry

With contributions from 24 international authorities, Synthetic Organic Photochemistry offers a leading-edge presentation of the most recent and in-demand applications of photochemical methodologies. Outlining a wide assortment of reaction types entailing cycloadditions, cyclizations, isomerizations, rearrangements, and other organic syntheses, this reference offers unmatched coverage of all reactions in the foreground of organic photochemistry and ties in critical considerations that overlap in modern photochemistry and organic chemistry, such as stereoselectivity. Select experimental procedures demonstrate the industrial and academic value of reactions presented in the text.