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).

Specific solvation as a tool for the N-chemoselective arylsulfonylation of tyrosine and (4-hydroxyphenyl)glycine methyl esters / M. Penso, D. Albanese, D. Landini, V. Lupi, G. Tricarico. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - :23(2003), pp. 4513-4517. [10.1002/ejoc.200300366]

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

D. Albanese
Secondo
;
D. Landini;
2003

Abstract

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).
Amino acids; Arylsulfonylation; Chemoselectivity; Protecting groups; Solvent effects
Settore CHIM/04 - Chimica Industriale
2003
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/188870
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