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Regioselectivity in lateral deprotonation of an isoxazolecarboxamide of ( S )‐prolinol. Conformational correlation by crystal structure solid state solution 13 C NMR
Author(s) -
Schlicksupp Ludwig,
Natale N. R.
Publication year - 1987
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570240522
Subject(s) - chemistry , metalation , deprotonation , amide , moiety , hydroxymethyl , stereochemistry , substituent , ether , crystallography , crystal structure , organic chemistry , ion
The conformation at the amide functional group in 3,5‐dimethylisoxazole‐4‐( S ‐2′‐hydroxymethyl‐ N ‐pyrrolidino) carboxamide (1) has been determined by a single crystal X‐ray determination. The 13 C nmr in both deuteriochloroform solution and solid state show close agreement. The metalation behaviour of the amide is dependent upon the substitution on the 2′‐hydroxymethyl moiety. Dianion studies indicate C‐5 lateral metalation under both thermodynamic and kinetic conditions. Protection of this substituent as the methyl ether, 2 , gives rise to predominant C‐3 lateral metalation under kinetic conditions and C‐5 lateral metalation on equilibration. These observations can be explained using the Ireland‐Evans model for chelation directed deprotonation.