Unusual Sterically Controlled Regioselective Lithiation of 3-Bromo-5-(4,4‘-dimethyl)oxazolinylpyridine. Straightforward Access to Highly Substituted Nicotinic Acid Derivatives

Abstract

[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.