Auto-Tandem Catalysis

The Nobel prize-winning Mizoroki-Heck reaction is one of the premier methods for carbon-carbon bond formation, allowing for inter- or intramolecular cross-coupling of activated aryl or vinyl electrophiles and alkenes.

Application of this reactivity to unactivated alkyl electrophiles has been a long-standing challenge in organic synthesis due to the reluctance of electron-rich alkyl electrophiles to participate in oxidative addition with transition metal catalysts and to the propensity with which alkylmetal intermediates undergo unproductive β-hydride elimination.

As part of their ongoing investigations into the Mizoroki-Heck-type reaction of unactivated electrophiles, scientists in the Alexanian Group, published in JACS, recently reported the first general Mizoroki-Heck-type carbocyclization of alkenes involving unactivated alkyl bromides. This new methodology allows easy access to a diverse array of carbo- and heterocyclic products. Mechanistic studies are consistent with auto-tandem catalysis involving an atom transfer radical cyclization, ATRC, intermediate.