Bio‐inspired Domino oxa‐Michael/Diels–Alder/oxa‐Michael Dimerization of para‐Quinols

Abstract

A bio-inspired, pyrrolidine-mediated, dimerization of para-quinols has been developed. It represents one of the most complex, yet general, dimerization reactions ever disclosed, selectively forming four new bonds, four new rings, and eight new contiguous stereogenic centres. The para-quinol starting materials are easily handled, bench-stable compounds, accessed in just one step from aromatic feedstocks. The reaction can be scaled up to give grams of polycyclic material, primed for further elaboration.

Tracking the Process of a Solvothermal Domino Reaction Leading to a Stable Triheteroarylmethyl Radical: A Combined Crystallographic and Mass‐Spectrometric Study

“…This reaction meets the criteria of domino reactions. Although the classification of the reaction steps in this domino reaction is not straightforward, based on the chemical bond breaking and forming, this is a 14 step domino reaction . This sequence involves more steps than the longest previously reported 12 step cascade reaction .…”

Bio‐inspired Domino oxa‐Michael/Diels–Alder/oxa‐Michael Dimerization of para‐Quinols

“…Thed iversity of functional groups available presented an umber of options.C onversion of tetracycle 2a into hexacycle 3a is easily achieved thermally,o rt hrough treatment with acid or base.The tertiary alcohol in tetracycle 2a can, if required, be protected with phenyl isocyanate to afford carbamate 12.H ydrogenation of tetracycle 2a gives saturated polycycle 13,a nd reaction of 2a with hydrogen peroxide selectively delivers epoxide 14 (Scheme 5). [9] In summary,abio-inspired strategy has resulted in one of the most complex, yet general, dimerizations ever disclosed. Scheme 2.…”

“…[9] Thec omplexity this collection of polycyclic compounds exhibits,w ith seven or eight newly formed contiguous stereogenic centres and numerous fused and bridged (hetero)cycles,i st ruly remarkable given that they are made from aromatic feedstocks in two simple and general steps. p-Quinols with ortho and/or meta substituents failed to produce dimers when subjected to our conditions.T he structure of each dimer was assigned using extensive NMR spectroscopy,a nd crystal structures for both at etracycle and hexacycle (2a and 3f,r espectively) were obtained (Scheme 2).…”

“…[9] In summary,abio-inspired strategy has resulted in one of the most complex, yet general, dimerizations ever disclosed. We employed scaled-up reactions (subject to slight modification, see the Supporting Information for details) to provide gram-scale quantities of both tetracycle 2a and hexacycle 3a (Scheme 5).…”

“…p-Quinols with ortho and/or meta substituents failed to produce dimers when subjected to our conditions.T he structure of each dimer was assigned using extensive NMR spectroscopy,a nd crystal structures for both at etracycle and hexacycle (2a and 3f,r espectively) were obtained (Scheme 2). [9] Thec omplexity this collection of polycyclic compounds exhibits,w ith seven or eight newly formed contiguous stereogenic centres and numerous fused and bridged (hetero)cycles,i st ruly remarkable given that they are made from aromatic feedstocks in two simple and general steps.…”