An Apparent Stereochemical Effect in MnO₂ Oxidation of Some Allylic Alcohols

Abstract

3,4-Di-0-acetyl-D-xylal undergoes acid-catalyzed reaction with ethanol to give the anomeric mixture of ethyl 2,3-dideoxy-4-0-acetyl-~-glycero-pent-2-enopyranosides which can be separated after deacetylation.The a-D anomer 1 is readily oxidized by manganese dioxide to the a,p-unsaturated ketone but the p-D anomer 2 is inert. Thorough investigation of the 100 and 220 MHz n.m.r. spectra of 1 and 2, their acetates, and dinitrobenzoates indicates that each exists conformationally pure in the half-chair form having the benefit of the anomeric effect. Hence in the oxidizable anomer 1 the C-4 allylic hydroxyl group is pseudoequatorial; in the unoxidizable one it is pseudoaxial. Hydrogen bonding does not appear to be the reason for failure of 2 to oxidize.The ethoxy groups of 1 and 2 are found to be ABX, system with unusually large separation for the AB protons.Le di-O-acktyl-3,4-~-xylal soumis B une reaction acido-catalysee dans l'ethanol, donne un melange anomtrique de dideoxy-2,3-0-acetyl-4-D glyckro-pentene-2-pyranosides d'kthyle. L'isomere-a-D-1 est rapidement oxyde par le bioxyde de manganese en cetone or,p insaturee, par contre l'isornere P 2 est inerte. L'examen des composCs 1 et 2 iinsi que de leurs derives acetates et dinitrobenzoates, en r.m.n. 100 et 220 MHz a montrC que chacun des isomtres est exclusivement sous forme d'une dernie chaise gr%ce ii "l'effet anomkrique". Ainsi, I'isomere oxydC 1 possede line hydroxyle allylique en C-4 pseudo equatorial. Tandis que dans 2, le rn&me groupe est pseudo axial.Les groupes ethoxy dans 1 et 2 forrnent des systemes ABX, avec une separation inhabituellement grande des protons AB.Canadian Journal of Chemistry, 49,3038 (1971) In a recent publication from this laboratory (1) it was reported that when ethanol reacted with 3,4-di-0-acetyl-D-xylal under boron trifluoride catalysis (2) a mixture was produced which, after deacetylation, could be separated chromatographically into what appeared to be a-and P-anomers of ethyl 2,3-dideoxy-Dglycero-pent-2-enopyranoside. The faster running component l a behaved normally on manganese dioxide oxidation, being converted to an a,P-unsaturated ketone within 8 h. The slower running substance 2a, however, gave no evidence for ketone formation after 14 days of exposure to manganese dioxide.It seemed strange that l a and 2a would display such a difference in oxidizability if the only difference between both compounds was 'Undergraduate research participant, summer 1970. Department of Chemistry, University of Waterloo, Waterloo, Ontario. 2Revision received June 10, 1971. the orientation of the ethoxy group at the remote anomeric center. Both compounds characterized as their dinitrobenzoate esters l b and 2b respectively gave satisfactory microanalyses (3). As expected for an anomeric pair, both l a and 2a lost the aglycon readily (4) to give the same strong ion, 3, corresponding to M+-OCH,CH, at nz/e 99. Structure 4 which could also lead to ion 3 is excluded since 1 and 2 from their n.m.r. and i.r. spectra are not vinyl ethers. The speci...

The algal hepatoxoxin okadaic acid is a substrate for human cytochromes CYP3A4 and CYP3A5

“…While metabolite 2 was oxidized completely to 4 by activated MnO 2 , metabolite 3 was not oxidized under the same conditions. A stereochemical effect has been observed previously in the MnO 2 oxidation of 2-eno-pyranosides (Fraser-Reid, et al, 1971). Equatorial alcohols were readily oxidized whereas axial alcohols were resistant to oxidation.…”

The preparation of amino sugars and branched-chain sugars by palladium-catalyzed, allylic substitution of alkyl hex-2-enopyranosides

“…However, in the parent diacetates 2 and 1 the difference is very small, and in benzene solution 2 is even more dextrorotatory than 1 (+383 vs. +276"), an anomaly that has been suspected (40) before. Deviations from Hudson's rule of isorotation have also been recognized in (nonacetylated) pairs of anomeric alkyl 2,3-dideoxypent-2-enopyranosides (27,29) and in 2-acetylated 3-deoxy-hex-2-enopyranosides (33b). Likewise, the anomeric assignments for the aforementioned hexenopyranosyl phosphonates, originally made on the basis of optical rotations, later had to be revised (21,41).…”

“…No such opposing interaction is present in alkyl 4-0-acetyl-2,3-dideoxypent-2-enopyranosides, e.g. 28 and 32, which on the strength of the anomeric effect alone prefer a conformation wherein the anomeric group is pseudoaxial rather than one wherein it is pseudoequatorial (28' and 32') (27,29). Although in 2 the anomeric effect could be anticipated to favor a similar conformation, it was more difficult to predict whether 1,5-substituent interaction would significantly counteract.…”

Pillaromycin-A: structural and synthetic studies related to the sugar moiety, pillarose

“…Earlier work in our laboratory had reported the surprising result that certain P-D-hex-2-enopyranosides were not oxidized by manganese dioxide (13). Accordingly the anomeric mixture of diols 2lbap was treated with manganese dioxide, whereupon only the a-anomer responded.…”