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 3 N 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 ). Graphic