Reaction of singlet oxygen with enol ethers in the presence of acetaldehyde. Formation of 1,2,4-trioxanes

A Vibrational Study of Some 1,2,4‐Trioxanes

“…-Ever since the discovery that arteannuin (1) is a potent antimalarial agent [ 1-31, there has been a growing interest in the synthesis, chemistry, and physical properties of the intrinsic structural feature of this unique natural product, namely the 1,2,4-trioxane ring and its congeners [4][5][6][7][8][9][10][11][12][13][14][15][16][17]. From a study of the vibrational spectra of 1 and its lactol derivatives, it has been concluded [18] that the peroxide linkage contained therein is characterized by a frequency at 722 cm-'.…”

“…Rf0.47 (CH2CI,). 'H-NMR (360 MHz): 1.21 (3, 3 H); 1.30 (s, 3 H); 1.76 (s, 3 H) 39 (s, 3 H); 1.50 (s, H) (5). The procedures employed for the synthesis of 2 and 4 were followed, except that 1,4-('80,)epidioxy-l,4-dihydro-1,4-dimethylnaphthalene was used as a starting material [30] [31].…”

Synthesis of Cyclic Peroxides

“…Alkyl(or aryl)oxy-spirocyclic and fused 1,2-dioxetanes as well as unsaturated bridged bicyclic 5-and 6-membered endoperoxides are commonly used in these reactions. For example, 2-(methoxymethylene)adamantane 591a in solution of acetaldehyde at −78 • C easily undergoes [2 + 2]-cycloaddition with singlet oxygen to form the thermally unstable dioxetane 592a that subsequently reacts with acetaldehyde to give 1,2,4-trioxane 593a (total 53%) as a mixture of C5 epimers (Scheme 168) 508,509 . While reactions of more robust 3-aryloxy-1,2-dioxetanes 592b-e, deriving from the corresponding aryloxyethens 591b-e, with excess acetaldehyde in the presence of TMSOTf afford the corresponding trioxanes 593b and 593f-i in good yields, the couplings of 592b with other aliphatic and aromatic aldehydes were found to be less efficient (Scheme 168) 509, 510 .…”

From Carbenes to Peroxidic Antimalarial Drugs. Highlights from the Scientific Work of Charles William Jefford

“…In a noteworthy study the hitherto enigmatic sensitised photooxygenation of adamantylideneadamantane (5) was reexamined and elucidated. [5] This doublecage alkene gives with sensitizers such as methylene blue (MB) or meso-tetraphenylporphine (m-TPP) almost exclusively the expected dioxetane (6). However, when rose bengal (RB) was used as sensitizer, the epoxide (7) became the main product (Scheme 2).…”

“…This led eventually to the finding that aldehydes can be incorporated into the photooxygenation process to give 1,2,4-trioxanes. [6] An illustration, outlined in Scheme 3, is the behaviour of 2-(methoxymethylene)adamantane (8). This enol ether undergoes in aprotic solvents dye-sensitized photooxidation to give the dioxetane 9, or after work-up, adamantanone (10).…”