Oxidations of 3-alkenyltetronic acids with dimethyldioxirane (DMD) and air: regioselectivity and formation of a spirotricyclic hemiketal endoperoxide lactone

Abstract

The endocyclic C᎐ ᎐ C bond of 3-allyltetronic acid 1 can be selectively oxidised with dimethyldioxirane to give 3-allyl-3hydroxydihydrofuran-2,4-dione 2 while 3-exo-alkylidenedihydrofuran-2,4-diones 9 are rapidly autooxidised to furnish the spirotricyclic hemiketal endoperoxide lactones 10. Scheme 2 Normal side-chain epoxidation of 3-allyltetronate 5: a) DMD, Ϫ78 ЊC → rt, 12 h; b) MCPBA, CHCl 3 , NaHCO 3 , rt, 12 h. Scheme 3 Formation and reductive ring opening of endoperoxides 10.

4-Benzyloxy-1-oxaspiro[4.6]undec-3-en-2-one

“…1), the cycloheptane ring adopts a slightly distorted chair conformation with q2 = 0.438 (3) Å and ' = 20.8 (4) . The orientation of the fivemembered ring (O1/C1/C4/C3/C2) with respect to the cycloheptane ring is similar to that reported by Schobert et al (2001) for spiro-compounds with seven membered rings. The mean plane of the five-membered ring forms a dihedral angle of 57.13 (11) with the phenyl ring of the benzyloxy substituent.…”

3-Acyltetramic Acids: A Decades-Long Approach to a Fascinating Natural Product Family

“…All oxidants led to a preferred oxidation at C-3 to give the corresponding 3-hydroxydihydrofuran-2,4-diones. 53 Scheme 9 depicts our 16-step synthesis 54 of macrocidin A which had also been synthesised previously by Pfaltz, Suzuki and coworkers. 55 Retrosynthetically, the 3-octanoyl side chain 56, already featuring the α-methyl group and an ω-bromo epoxide, was to be attached to a doubly protected, L-tyrosine-derived tetramic acid 57 via the Yoshii-Yoda acylation.…”

“…In contrast, 3alk(en)yltetramic and -tetronic acids 67 are oxidised by most agents, e.g., dimethyldioxirane, to give the corresponding 3-hydroxy-3-alk(en)yl derivatives 73. 53 3-Triphenylphosphoranylidenetetronic and -tetramic acids, which are readily available from reaction of the respective α-hydroxy or α-amino acids with Ph 3 PCCO 6, are oxidised by N-p-tosyl-phenyloxaziridine (74) to the corresponding α-keto derivatives or to their hydrates. For instance, proline was converted into the bicyclic bisacyl ylide 75 which did not undergo Wittig alkenations, yet could be oxidised by 74 to afford the trisketone 76 in 50% yield (Scheme 12).…”

α-Substituted organic peroxides: synthetic strategies for a biologically important class of gem-dihydroperoxide and perketal derivatives

“…116 Schobert et al showed another aspect of Snider's protocol in the case of 2,5-dihydrofuran-2,4-dione 146-an important structural element in bioactive compounds that is prone to oxidation when it has an alkylidene group at position 3 (Scheme 38). 117, 118 Reaction was activated by copper(II) sulfate that acts as a photosensitizer and promoter of enolization and proceeds under acidic conditions. Results point to the involvement of a singlet oxygen with [2 + 2] cycloaddition to the enol double bond and [1,3] O-shift to form the dioxen cycle.…”