An Oxidative Dearomatization Approach to Tetrodotoxin via a Masked ortho-Benzoquinone

Abstract
Progress toward a stereoselective synthesis of tetrodotoxin (TTX) is presented. Oxidative dearomatization of a tetrasubstituted guaiacol arene yielded a masked ortho-benzoquinone that intercepted an acyl nitroso species generated in situ by the copper-catalyzed aerobic oxidation of an acyl hydroxylamine. The subsequent alkene dihydroxylation and reduction of a bis-neopentylic ketone proceeded with perfect diastereoselectivity to reveal advanced intermediates toward the synthesis of TTX.

Citation
An Oxidative Dearomatization Approach to Tetrodotoxin via a Masked ortho-Benzoquinone Jacob G. Robins and Jeffrey S. Johnson Organic Letters Article ASAP DOI: 10.1021/acs.orglett.1c03998