High-Pressure-Promoted and Facially Selective Diels-Alder Reactions of Enzymatically Derived cis-1,2-Dihydrocatechols and Their Acetonide Derivatives: Enantiodivergent Routes to Homochiral and Polyfunctionalized Bicyclo[2.2.2]octenes

Scott G. Stewart, Gwion J. Harfoot, Kenneth J. McRae, Yinglai Teng, Li Juan Yu, Bo Chen, Roberto Cammi, Michelle L. Coote, Martin G. Banwell, Anthony C. Willis

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

cis-1,2-Dihydrocatechols 5 (X = Me and Cl), which are available in the homochiral form through the whole-cell biotransformation of toluene and chlorobenzene, respectively, undergo Diels-Alder cycloaddition reactions with a range of electron-deficient dienophiles at 19 kbar (1.9 GPa). The favored products of such reactions are adducts of the general form 7 and that arise through the operation of a contrasteric or syn-addition pathway. In contrast, the acetonide derivatives of metabolites 5 undergo anti-selective addition reactions under the same conditions and so producing adducts of the general form 11. Bicyclo[2.2.2]octenes 7 and 11, which embody carbocyclic frameworks of opposite enantiomeric form, are useful scaffolds for chemical synthesis. Computational studies reveal that syn-adduct formation is kinetically and normally thermodynamically favored over anti-adduct formation when the free diols 5 are involved, but the reverse is so when the corresponding acetonides participate as the 4?-addend. Furthermore, the reactions become more exothermic as pressure increases while, concurrently, the activation barrier diminishes and at 6 GPa (60 kbar) almost vanishes.

Original languageEnglish (US)
Pages (from-to)13080-13095
Number of pages16
JournalJournal of Organic Chemistry
Volume85
Issue number20
DOIs
StatePublished - Oct 16 2020

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Fingerprint Dive into the research topics of 'High-Pressure-Promoted and Facially Selective Diels-Alder Reactions of Enzymatically Derived cis-1,2-Dihydrocatechols and Their Acetonide Derivatives: Enantiodivergent Routes to Homochiral and Polyfunctionalized Bicyclo[2.2.2]octenes'. Together they form a unique fingerprint.

Cite this