Unusual sterically controlled regioselective lithiation of 3-bromo-5-(4,4'-dimethyl)oxazolinylpyridine. Straightforward access to highly substituted nicotinic acid derivatives

Nicolas Robert; Anne-Laure Bonneau; Christophe Hoarau; Francis Marsais

doi:10.1021/ol062556i

Unusual sterically controlled regioselective lithiation of 3-bromo-5-(4,4'-dimethyl)oxazolinylpyridine. Straightforward access to highly substituted nicotinic acid derivatives

Org Lett. 2006 Dec 21;8(26):6071-4. doi: 10.1021/ol062556i.

Authors

Nicolas Robert¹, Anne-Laure Bonneau, Christophe Hoarau, Francis Marsais

Affiliation

¹ Laboratoire de Chimie Organique Fine et Hétérocyclique, UMR 6014, INSA et Université de Rouen, IRCOF-INSA Rouen BP08, 76131 Mont Saint Aignan Cedex, France.

PMID: 17165932
DOI: 10.1021/ol062556i

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Lithium / chemistry*
Niacin / analogs & derivatives*
Niacin / chemistry
Pyridines / chemistry*

Substances

Pyridines
Niacin
Lithium