One-pot Synergistic Alkylation-sulfonylation of Diphenol

Diphenol, occurring in various pharmaceutical and natural molecules, has been concerned as efficient substrates or precursors for derivation of aromatic moiety [1]. Due to the broad synthetic application and highly sensitive reactivities, the selectivity-controlling of protection and derivatization of hydroxyl groups is an innegligible challenge to achieve the desired chemical conversion [2]. In addition, alkylation of hydroxyl group in phenol is not only the protection methods [3,4], the alkyloxy groups are key scaffolds in a great deal of functional molecules [5]. However, the common alkylation reagents, such as halides, alkyl sulfates and sulfonates have been confined for their environmental toxicity, potential danger to health [7,8].

Utilizing alcohols as green alkylating reagents, sulfonyl chloride-promoted directed alkylation of monophenols were achieved. Based on such results, a one-pot synergistic alkylation-sulfonylation reaction of diphenol was developed in the presence of the weak base, potassium carbonate, and sulfonyl chlorides using alcohols as alkylating reagents (Scheme 1). Based on this method, the hydroxyls in resveratrol could be functionalized definitely to produce compound 3 in good yield (Figure 1).

Scheme 1. One-pot synergistic alkylation-sulfonylation of diphenol

Figure 1. Synergistic alkylation-sulfonylation of resveratrol

Therefore, a novel method was provided for efficiently synergistic alkylation-sulfonylation of hydroxyl groups in diphenols, which had the potential application in the unsymmetrical derivatization of multiple hydroxyls in polyphenols.