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Chemoselective Synthesis of N ‐Protected Alkoxyprolines under Specific Solvation Conditions
Author(s) -
Mihali Voichita,
Foschi Francesca,
Penso Michele,
Pozzi Gianluca
Publication year - 2014
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.201402429
Subject(s) - chemistry , tetrahydrofuran , alkylation , nucleophile , stereocenter , alkoxy group , dimethyl sulfoxide , solvation , solvent , medicinal chemistry , sulfoxide , ion , stereochemistry , organic chemistry , enantioselective synthesis , alkyl , catalysis
N ‐Protected hydroxyprolines (Hyp) were transformed chemoselectively into alkoxyproline derivatives by direct O ‐alkylation. The starting Hyp was transformed into the corresponding dianion in a mixture of dimethyl sulfoxide and tetrahydrofuran (1:16 v / v ) as solvent. Under these conditions, the carboxy‐anion showed reduced nucleophilicity because it was specifically solvated, and the more reactive oxy‐anion was selectively alkylated. N ‐Protected trans ‐4‐alkoxy‐, cis ‐4‐alkoxy‐ and trans ‐3‐alkoxyprolines were thus obtained in a single step in very high overall yields and with complete stability of the stereogenic center configuration.