Total synthesis of the alkoxydioxines (+)- and (-)-chondrillin and (+)- and (-)-plakorin via singlet oxygenation/radical rearrangement

Patrick H. Dussault, C. Todd Eary, Kevin R. Woller

Research output: Contribution to journalArticle

40 Citations (Scopus)

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 1O2 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.

Original languageEnglish (US)
Pages (from-to)1789-1797
Number of pages9
JournalJournal of Organic Chemistry
Volume64
Issue number6
DOIs
StatePublished - Mar 19 1999

Fingerprint

Oxygenation
Biological Products
Optical rotation
tert-Butylhydroperoxide
Photoisomerization
Dimerization
Enantiomers
Hydroxyl Radical
Hydrogen Peroxide
Hydrogen bonds
Substrates
perhydroxyl radical
allyl alcohol

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Total synthesis of the alkoxydioxines (+)- and (-)-chondrillin and (+)- and (-)-plakorin via singlet oxygenation/radical rearrangement. / Dussault, Patrick H.; Eary, C. Todd; Woller, Kevin R.

In: Journal of Organic Chemistry, Vol. 64, No. 6, 19.03.1999, p. 1789-1797.

Research output: Contribution to journalArticle

@article{c9dfbadcd47f43ac811308fb83cc0855,
title = "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 1O2 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.",
author = "Dussault, {Patrick H.} and Eary, {C. Todd} and Woller, {Kevin R.}",
year = "1999",
month = "3",
day = "19",
doi = "10.1021/jo981128q",
language = "English (US)",
volume = "64",
pages = "1789--1797",
journal = "Journal of Organic Chemistry",
issn = "0022-3263",
publisher = "American Chemical Society",
number = "6",

}

TY - JOUR

T1 - Total synthesis of the alkoxydioxines (+)- and (-)-chondrillin and (+)- and (-)-plakorin via singlet oxygenation/radical rearrangement

AU - Dussault, Patrick H.

AU - Eary, C. Todd

AU - Woller, Kevin R.

PY - 1999/3/19

Y1 - 1999/3/19

N2 - 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 1O2 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.

AB - 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 1O2 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.

UR - http://www.scopus.com/inward/record.url?scp=0033583002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033583002&partnerID=8YFLogxK

U2 - 10.1021/jo981128q

DO - 10.1021/jo981128q

M3 - Article

C2 - 11674266

AN - SCOPUS:0033583002

VL - 64

SP - 1789

EP - 1797

JO - Journal of Organic Chemistry

JF - Journal of Organic Chemistry

SN - 0022-3263

IS - 6

ER -