gem-Bishydroperoxides

Johannes grew up in the diamond city Kimberley, South Africa. He pursued his interest in science by obtaining a B.Sc. degree in chemistry and biology in 2004 from the University of the Free State. His fondness for organic chemistry led him to procure a M.Sc. degree from the same institution in 2008. He is currently completing a Ph.D. degree under the supervision of Professor B. C. B. Bezuidenhoudt at the University of the Free State.

Introduction

The relevance of gem-dihydroperoxides to peroxidic antimalarial agents stimulated initial interest in this class of compounds.[1] [2] [3] [4] [5] Apart from their biological activities,[6,7] gem-dihydroperoxides have been established as important building blocks in synthetic chemistry, for example the preparation of organic peroxides, trioxanes, tetraoxanes, spirobisperoxyketals, and dicarboxylic diesters.[4] [7] [8] gem-Dihydroperoxides can also be employed as oxidizing agents under various conditions to perform transformations such as epoxidation[1] [2] [3] [4] [5] and sulfoxidation.[2] [3] [4] [5] [9] In addition, in situ decomposition of gem-dihydroperoxides can generate singlet oxygen as the active oxidant[8] [10] in olefin oxidation, for example.[11] The ability of gem-dihydroperoxides to generate radicals allows them to be furthermore exploited as radical initiators,[2] [3] [4] [5] for example methyl ethyl ketone peroxide is used in the manufacturing of acrylic resins, reinforced plastics, and unsaturated polyester resins.[6]

Itoh and co-workers established two catalyst-free preparative protocols for gem-dihydroperoxides, of which the one employs hydrogen peroxide[12] as terminal oxidant and the other molecular oxygen.[13] [14] The latter is achieved in combination with a photosensitizer (anthracene[13] or anthraquinone[14]) and exposure of the reaction mixture to light.

Reaction times can generally be reduced upon introduction of a catalyst, amongst which molecular iodine[15] as well as numerous transition-metal Lewis acids have proven effective.[4] [5] [8] [16] [17] Brønsted acids are comparably active as either homogeneous (sulfuric acid[3]) or heterogeneous catalysts, for example silica-sulfuric acid[2] or triflic-acid-functionalized silica-coated ferromagnetic nanoparticles.[18]

Abstracts

(A) Dussault and co-workers[19] prepared primary and secondary alkyl hydroperoxides in moderate to high yields (48–79%) via double alkylation of 1,1-dihydroperoxides, followed by acid-catalyzed hydrolysis of the resulting strained cyclic alkylated gem-bishydroperoxides (bisperoxyacetals).
(B) 1-Hydroxy-1′-alkoxyperoxides were prepared by Terent’ev et al.[6] in moderate yield (40–64%) through iodine-catalyzed cross-coupling of gem-bishydroperoxides and acetals. This cross-coupling is also effective upon substitution of the acetal with an enol ether.
(C) Symmetrical and asymmetrical tetraoxanes can be prepared from gem-dihydroperoxides. The combination of a gem-dihydroperoxide and its carbonyl analogue in the presence of fluoroboric acid and hydrogen peroxide favors formation of symmetrical tetra­oxanes.[20] Similarly, asymmetrical tetraoxanes are obtained when two non-identical carbonyl compounds are introduced.[7]
(D) Jakka et al.[1] reported the epoxidation of various α,β-unsaturated ketones utilizing cyclohexylidene-bishydroperoxide as a stoichiometric oxidant under Weitz–Scheffer reaction conditions (aqueous, alkaline).
(E) Sulfoxidation of thiophenol ethers can be achieved under neutral conditions at ambient temperature, producing sulfoxides in high yields (79–93%) in less than two hours.[9]
(F) Subsequent to observing the oxidation of triphenylphosphine to triphenylphosphine oxide in the presence of 1,1-dihydroperoxy­cyclododecane, Sekine and co-workers[21] prepared oligodeoxyribonucleotides in a similar fashion via the oxidation of phosphite intermediates to their respective phosphate analogues.
(G) Dussault and co-workers reported the liberation of singlet oxygen when monoactivated gem-dihydroperoxide derivatives were exposed to anhydrous alkaline conditions.[22] If this degradation is performed in the presence of an organic substrate, an oxidative transformation of the substrate is observed.[10] This protocol also allows for oxidative cleavage of olefinic substrates to yield aldehydes or ­ketones in moderate to high yields (35–82%).[11]

• References

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