Stewart, ScottHarfoot, GwionMcRae, KennethTeng, YinglaiYu, Li-JuanChen, BoCammi, RobertoCoote, MichelleBanwell, MartinWillis, Anthony2022-10-120022-3263http://hdl.handle.net/1885/274489cis-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.The ANU Major Equipment Committee is thanked for providing the funds to purchase the high-pressure reactor used in these studies, while S.G.S., G.J.H., and K.J.M. gratefully acknowledge the Research School of Chemistry, ANU, for providing Ph.D. scholarships.application/pdfen-AU© 2020 The authors202010.1021/acs.joc.0c017672021-11-28