Pericyclic Cascade toward Isochromenes: Application to the Synthesis of Alkaloid Benzosimuline

Abstract

The synthesis of biologically active alkaloid benzosimuline, isolated from the shrub Zanthoxylum simulans, is reported. Key transformation involves an oxa-6π electrocyclic ring-opening/hetero-Diels-Alder pericyclic cascade. Although the last aromatization step proved to be cumbersome, this work unfolds a unique route to access interesting molecules from simple precursors.

Palladium-Catalyzed Aerobic Dehydrogenation of Cyclic Hydrocarbons for the Synthesis of Substituted Aromatics and Other Unsaturated Products

“…62 The natural product was obtained in relatively low yield (34%), but this approach proved superior to more classical dehydrogenation methods, using chloranil or Pd/C (Scheme 32). This creative application highlights both the utility and the need for continued catalyst development efforts.…”

One-Pot Total Synthesis of Cannabinol via Iodine-Mediated Deconstructive Annulation

“…The three compounds formed in the pyrolytic study had already been described from the treatment of CBC and other cannabinoids with acids and/or by heating or irradiation . The formal [2π + 2π] thermal cyclization of CBC ( 3 ) to CBL ( 8 ) was, nevertheless, mechanistically intriguing, and a similar transformation is documented also for other homoisoprenylchromenes. − The reaction has been considered a Gassman-type cationic [2π + 2π] cyclization, but the anti-Markovnikow regiochemistry is at odds with the considerations of carbocation stability that governs this type of cycloaddition. , An alternative, and more plausible mechanism, is presented in Figure . The reaction might involve a cyclopropane intermediate ( 9 ), the result of a concerted process triggered by electrophilic (acidic) activation of the carbonyl tautomer of the resorcinyl moiety, and terminated by electrophilic Markovnikov addition to the electron-rich homoisoprenyl terminal double bond (Figure ).…”

Biomimetic Total Synthesis of the Rubiginosin Meroterpenoids

“…Of these, only the chromenylation method developed by Snieckus and co-workers (stoichiometric PhB­(OH) 2 in AcOH/PhMe) was effective in pushing the cascade further than the initial chromene products to give rubiginosin A ( 4 ) in 10% yield, alongside the undesired regioisomer “iso-rubiginosin A” ( 26 ) in 31% yield. This disappointing regioselectivity was surprising, as orcinol ( 13 ) is known to react selectively at C-2, rather than C-4, in several previous chromenylations . Nevertheless, there is a significant increase in molecular complexity during the cascade, with the construction of 5 stereocenters, 4 covalent bonds and 3 rings.…”