AbstractThe methyl esters of L‐tyrosine and D‐(4‐hydroxyphenyl)glycine were directly transformed into the corresponding 2‐arylsulfonamido esters with arylsulfonyl chlorides, without protecting the phenolic hydroxy group. The reaction is conducted in a THF/DMF (8:1) mixture as solvent, and using lyophilized solid sodium carbonate as base. The N‐arylsulfonylation takes place with good yields (62−85%) in a chemoselective fashion, without racemization of the stereogenic carbon centers. The DMF (2.6 mol/mol amino ester) specifically solvates the oxygen atom of the formed N,O‐dianion, reducing its nucleophilicity and dramatically increasing the chemoselectivity of the N‐substitution. In contrast, in the absence of a highly coordinating additive, the phenoxide anion competes unfavorably with the 2‐amino group for the nucleophilic attack, and the N,O‐disulfonyl esters are produced with relevant yields. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)