Specific solvation as a tool for the N-chemoselective arylsulfonylation of tyrosine and (4-hydroxyphenyl)glycine methyl esters

The methyl esters of L-tyrosine and D-(4-hydroxyphenyl)glycine were directly transformed into the corresponding 2-aryl-sulfonamido 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. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003).