Concise Synthesis of Bicyclic Pyridinol Antioxidants

The recently reported bicyclic pyridinols 1 and 2 are highly effective antioxidants exhibiting 88- and 28-fold greater potency, respectively, than α-tocopherol when assayed for their ability to suppress the autoxidation of methyl linoleate. Described herein is a short, economical, and scalable strategy for the synthesis of this novel group of antioxidants, as well as analogues 3-6. Key reactions involved the cyclocondensation reaction of lactam acetals with enaminone 7 and selective functionalizaton of the heterocyclic systems.