Reduction-induced access to novel functionalized quinoline allylic alcohols via Baylis–Hillman chemistry

Abstract

Quinoline derivatives are valuable scaffolds in medicinal and synthetic organic chemistry. In this work, a series of 3-formyl-2-allyloxyquinolines were synthesized from 2-chloro-3-formylquinolines prepared via the Meth-Cohn protocol, followed by acetal protection and alkoxide substitution. The Baylis-Hillman reaction of these quinolinic aldehydes with methyl acrylate in the presence of DABCO afforded the corresponding β-hydroxy acrylate adducts in good yields. To prevent undesired transformations of the hydroxyl functionality, these adducts were protected as tert -butyldimethylsilyl ethers. However, reduction of the silylated Baylis-Hillman adducts with LiAlH 4 did not furnish the anticipated allylic alcohols. Instead, the reaction proceeded through a competing reduction-elimination pathway, leading to mixtures of unsaturated esters and primary alcohols. The product distribution was influenced by the substitution pattern of the quinoline framework.