A Facile Preparation of Hydroxycinnamyl Alcohols withSimultaneous Protection of Phenol Groups as Carbonate

Abstract

A novel procedure for reduction and simultaneous protection of phenol groups of hydroxycinnamic acids to the related alcohols has been developed. During the formation of mixed anhydrides from the acids and an alkyl chloroformate, the phenol was protected as carbonate, and the mixed anhydrides were reduced with an aqueous solution of sodium borohydride. Free phenols were obtained by deprotection under mild conditions with 30% aq. NH4OH in methanol. O‐protected phenolic alcohols can be converted by standard methods into orthogonal protected derivatives. This rapid and efficient synthetic method offers a simple and high‐yield preparation of these important fine chemicals, overcoming the tedious and costly procedures associate with the use of strong reducing agents such as LiAlH4 and DIBAL−H.

Sustainable Chemical Derivatization of Hydroxycinnamic Acids

“…Our laboratory used alkyl chloroformates in THF to convert trans‐HCAm to protected mixed anhydrides. We then reduced them to alcohols using NaBH 4 in water [23] . These chloroformates are cost‐effective and reactive reagents and can be used under well‐ventilated conditions, even at room temperature.…”

“…We then reduced them to alcohols using NaBH 4 in water. [23] These chloroformates are cost-effective and reactive reagents and can be used under well-ventilated conditions, even at room temperature. Our interest lies in exploiting these reagents to activate a carboxyl function since they have the unique characteristic of leaving no trace of their action.…”

Protection and Activation of Hydroxycinnamic Acids in Water

“…HCAs were recently reduced in our laboratories into carbonate protected hydroxycinnamyl alcohols using sodium borohydride in tetrahydrofuran/water. This work was carried out to substantiate: 1 ) the compatibility of isobutyl chloroformates in pure water in the protection‐activation of HCAs, just as occurs in organic solvents 2 ) their coupling reactions with amines and C ‐protected α‐amino acids to acquire the related amides, and 3 ) directly coupling them with free α‐amino acids in an effort to obtain N ‐hydroxycinnamoyl‐α‐amino acids.…”

Gram-scale economical synthesis of trans-coniferyl alcohol and its corresponding thiol

“…Based on a recent study (Panzella et al 2018), we report a one-pot, conventional mixed anhydride reduction method for the direct chemoselective reduction of 4-O-acetylated ferulic acid with sodium borohydride, which produces the corresponding coniferyl alcohol in high yields on a large gram scale. Further reaction with thioacetic acid followed by complete deprotection affords the corresponding coniferyl thiol.…”