Total Synthesis of the Alkoxydioxines (+)- and (−)-Chondrillin and (+)- and (−)-Plakorin via Singlet Oxygenation/Radical Rearrangement

Abstract

The sequential application of singlet oxygenation and peroxyl radical rearrangement provides an asymmetric entry to 4-peroxy-2-enols and 4-peroxy-2-enones. Enantiomerically enriched 2-hydroperoxy-3-alkenols, obtained via hydroxyl-directed addition of (1)O(2) to Z-allylic alcohols, undergo stereospecific radical rearrangement to form 4-hydroperoxy-2-alkenols. The yields of the rearrangement are improved in the presence of excess tert-butyl hydroperoxide, which limits dimerization of the substrate peroxyl radicals. However, the rearrangement equilibrium is unaffected by the presence of polar co-solvents or by the incorporation of a group able to selectively hydrogen bond to the product hydroperoxide. Photoisomerization of the (E)-4-hydroperoxy-2-enone rearrangement products results in irreversible ring closure to furnish diastereomeric mixtures of enantiomerically enriched dioxinols. The strategy is applied to the total synthesis of the alkoxydioxine natural products chondrillin and plakorin. Comparison of the optical rotation of the synthetic material against literature reports indicates that the natural products are either enantiomerically pure or highly enriched in one enantiomer. In addition, our results conclusively demonstrate that the reported configuration of chondrillin is in error.

Stereoselective Allylation of Chiral Monoperoxyacetals.

“…13 All new compounds were determined to be >95% pure based upon 1 H or 13 C NMR. Unless otherwise noted NMR spectra were recorded at 500 ( 1 H) or 125 ( 13 C) MHz in CDCl3.…”

Recent Advances in the Chemistry of Cyclic Peroxides

“…As a consequence of this work, the absolute configuration of (+)-Chondrillin 83 has been revised as 3R,6S (cf. Plakorin 84 which is confirmed as 3S,6S) [58]. 3 AcOH, dry air, r.t.…”

“…a mixture of hydroperoxide 76 (20%) and hydroxy derivative 77 (31%) is obtained from the ozonolysis of hydroperoxyacetal 74b in TFE-CH 2 Cl 2 (Scheme 22) [53]. The Lewis acid-catalysed cyclisation of unsaturated monoperoxyketals , in which a C-C rather than a C-O ring bond is formed, proceeds via a 6-endo/exo pathway to give the 1,2-dioxanes 82 (Scheme 25) [ accomplished as outlined in Scheme 26 [57,58]. Crucial to the success of this strategy was the partial isomerisation of the hydroxyallylic hydroperoxides and the successful deprotection and irreversible photocyclisation of intermediate peroxy enones.…”

Synthesis of Conjugates of Oligonucleotides and 11,11-D2-Linoleic Acid Derivatives via Azide-Alkyne Cycloaddition

“…1-(Триизопропилсилилокси)пентин-4 (2). Реакцию проводили по опубликованной методике [32]. К раствору пентин-4-ола-1 (1) (5,00 г, 59,5 ммоль) в ДМФА (200 мл) добавили имидазол (6,07 г, 89,3 ммоль) и триизопропилхлорсилан (14,0 мл, 65,5 ммоль).…”