Unusual sterically controlled regioselective lithiation of 3-bromo-5-(4,4'-dimethyl)oxazolinylpyridine. Straightforward access to highly substituted nicotinic acid derivatives.
[Structure: see text] Lithiation of 5-bromonicotinic acid protected as secondary or tertiary amide as well as (4,4'-dimethyl)oxazoline with lithium amides is reported. The unusual C-2 and C-4 regioselective lithiation of 3-bromo-5-(4,4'-dimethyl)oxazolinylpyridine using LTMP versus LDA was observed, providing a new route to substituted nicotinic acid scaffolds. The methodology was applied to the synthesis of novel C-4 and C-6 arylated 5-bromonicotinic acids.
Robert
Nicolas
N
Laboratoire de Chimie Organique Fine et Hétérocyclique, UMR 6014, INSA et Université de Rouen, IRCOF-INSA Rouen BP08, 76131 Mont Saint Aignan Cedex, France.
Bonneau
Anne-Laure
AL
Hoarau
Christophe
C
Marsais
Francis
F
D008094:Lithium / Q000737:chemistry*; D009525:Niacin / Q000031:analogs & derivatives* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*
D011725:Pyridines; D009525:Niacin; D008094:Lithium