Synthesis of methylated resveratrol and analogues by Heck reactions in organic and aqueous solvents

Abstract

The Heck reaction under phosphane free conditions using oxime-derived palladacycles or Pd(OAc) 2 as catalysts is a general methodology for the synthesis of methoxylated ( E)-stilbene derivatives. Couplings can be performed either with (dicyclohexyl)methylamine as base and TBAB in aqueous DMA or in neat water and with Et 3N as base in DMA in air and under thermal and microwave conditions. The arylation of different styrenes are performed with 3,5-dimethoxyiodobenzene to afford a series of important biologically active ( E)-stilbene derivatives containing the 3,5-dimethoxyphenyl moiety, including resveratrol, piceatannol and pinosilvine, which are efficiently prepared with high regioselectivity and total stereoselectivity (TON up to 10 4).