Premium
Specific Solvation as a Tool for the N ‐Chemoselective Arylsulfonylation of Tyrosine and (4‐Hydroxyphenyl)glycine Methyl Esters
Author(s) -
Penso Michele,
Albanese Domenico,
Landini Dario,
Lupi Vittoria,
Tricarico Giovanni
Publication year - 2003
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200300366
Subject(s) - chemistry , chemoselectivity , stereocenter , nucleophile , racemization , medicinal chemistry , glycine , solvent , nucleophilic substitution , organic chemistry , alcohol , protecting group , amino acid , catalysis , enantioselective synthesis , alkyl , biochemistry
The 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)