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Enantioselective Copper‐Catalysed Propargylic Substitution: Synthetic Scope Study and Application in Formal Total Syntheses of (+)‐Anisomycin and (−)‐Cytoxazone
Author(s) -
Detz Remko J.,
Abiri Zohar,
le Griel Remi,
Hiemstra Henk,
van Maarseveen Jan H.
Publication year - 2011
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201003727
Subject(s) - anisomycin , enantioselective synthesis , substitution (logic) , scope (computer science) , formal synthesis , copper , chemistry , total synthesis , combinatorial chemistry , stereochemistry , computer science , organic chemistry , catalysis , programming language , biochemistry , protein biosynthesis
A copper catalyst with a chiral pyridine‐2,6‐bisoxazoline (pybox) ligand was used to convert a variety of propargylic esters with different side chains (R=Ar, Bn, alkyl) into their amine counterparts in very high yields and with good enantioselectivities (up to 90 % enantiomeric excess ( ee )). Different amine nucleophiles were applied in the reactions and the highest enantioselectivities were obtained for aniline and its analogues. Interestingly, some carbon nucleophiles could also be used and with indoles excellent ee values were obtained (up to 98 % ee ). The versatility of the propargylic amines obtained was demonstrated by their further elaboration to formal total syntheses of the antibiotic (+)‐anisomycin and the cytokine modulator (−)‐cytoxazone.