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Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.

Lorenc C, Saurí J, Moser A, Buevich AV, Williams AJ, Williamson RT, Martin GE, Peczuh MW - ChemistryOpen (2015)

Bottom Line: Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out".Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series.Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Connecticut 55 N. Eagleville Road, U3060, Storrs, CT, 06269, USA.

ABSTRACT
Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization-dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out". Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

No MeSH data available.


Mechanisms depicting the conversion of 3 to 7 and 11 to 14 via epoxidation, ring opening and oxocarbenium ion formation, and trapping by nucleophiles.
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fig04: Mechanisms depicting the conversion of 3 to 7 and 11 to 14 via epoxidation, ring opening and oxocarbenium ion formation, and trapping by nucleophiles.

Mentions: Consideration of the mechanisms for conversion of 3 to 7 and 11 to 14 accounted for the novel rearrangements (Figure 4). They were triggered by the instability of the highly oxygenated epoxide intermediates that initially form (i.e., I and V),3,24 especially in light of the acidity of the medium.25,26 The epoxidation, which follows a “majority rules” model,27 appears to have been highly diastereoselective because we were only able to detect and isolate one product from each reaction. Following epoxidation, a cascade of steps including oxocarbenium ion formation and attack by nucleophiles occurred en route to both 7 and 14. Whereas V opened to oxocarbenium ion VI and was trapped by the hydroxyl group of the erstwhile hemiketal, the pathway followed by epoxide I was more complex. Oxocarbenium II is regioisomerically different than VI and likely reflected the influence of the ketone unit in the reaction trajectory. The ketone acted as the initial nucleophile followed by formation of a second oxocarbenium (IV) and trapped with m-chlorobenzoic acid to give 7.


Turning Spiroketals Inside Out: A Rearrangement Triggered by an Enol Ether Epoxidation.

Lorenc C, Saurí J, Moser A, Buevich AV, Williams AJ, Williamson RT, Martin GE, Peczuh MW - ChemistryOpen (2015)

Mechanisms depicting the conversion of 3 to 7 and 11 to 14 via epoxidation, ring opening and oxocarbenium ion formation, and trapping by nucleophiles.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4608522&req=5

fig04: Mechanisms depicting the conversion of 3 to 7 and 11 to 14 via epoxidation, ring opening and oxocarbenium ion formation, and trapping by nucleophiles.
Mentions: Consideration of the mechanisms for conversion of 3 to 7 and 11 to 14 accounted for the novel rearrangements (Figure 4). They were triggered by the instability of the highly oxygenated epoxide intermediates that initially form (i.e., I and V),3,24 especially in light of the acidity of the medium.25,26 The epoxidation, which follows a “majority rules” model,27 appears to have been highly diastereoselective because we were only able to detect and isolate one product from each reaction. Following epoxidation, a cascade of steps including oxocarbenium ion formation and attack by nucleophiles occurred en route to both 7 and 14. Whereas V opened to oxocarbenium ion VI and was trapped by the hydroxyl group of the erstwhile hemiketal, the pathway followed by epoxide I was more complex. Oxocarbenium II is regioisomerically different than VI and likely reflected the influence of the ketone unit in the reaction trajectory. The ketone acted as the initial nucleophile followed by formation of a second oxocarbenium (IV) and trapped with m-chlorobenzoic acid to give 7.

Bottom Line: Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out".Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series.Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry, University of Connecticut 55 N. Eagleville Road, U3060, Storrs, CT, 06269, USA.

ABSTRACT
Spiroketals organize small molecule structures into well-defined, three-dimensional configurations that make them good ligands of proteins. We recently discovered a tandem cycloisomerization-dimerization reaction of alkynyl hemiketals that delivered polycyclic, enol-ether-containing spiroketals. Here we describe rearrangements of those compounds, triggered by epoxidation of their enol ethers that completely remodel their structures, essentially turning them "inside out". Due to the high level of substitution on the carbon skeletons of the substrates and products, characterization resorted to X-ray crystallography and advanced computation and NMR techniques to solve the structures of representative compounds. In particular, a new proton-detected ADEQUATE NMR experiment (1,1-HD-ADEQUATE) enabled the unequivocal assignment of the carbon skeleton of one of the new compounds. Solution of the structures of the representative compounds allowed for the assignment of product structures for the other compounds in two separate series. Both the rearrangement and the methods used for structural determination of the products are valuable tools for the preparation of characterization of new small molecule compounds.

No MeSH data available.