O -Tetrahydropyran-2-yloxy ( O -THP) as an ortho -Directing Group in the Lithiation of Pyridines

Rabah Azzouz (1) , Laurent Bischoff (1) , Corinne Fruit (1) , Francis Marsais (2)

1 COBRA - Chimie Organique et Bioorganique : Réactivité et Analyse
2 IRCOF - Institut de Chimie Organique Fine

Herein we report regioselective deprotonations of 3- and 4-(tetrahydropyran-2-yloxy)pyridine with n-butyllithium. Trapping the lithiated species with various electrophiles afforded functionalized pyridines in good yields. A one-pot procedure also allowed the double functionalization at C4 and C2 in the case of 3-O-THP-pyridine. The ortho-metallating ability of this group was examined in comparison with other well-known oxygen-based ortho-directing groups.

Keywords: acetals; pyridines; metallations; lithium; organometallic reagents

Domains: Chemical Sciences; Chemical Sciences; Organic chemistry; Chemical Sciences; Medicinal Chemistry; Chemical Sciences; Radiochemistry; Chemical Sciences; Material chemistry; Chemical Sciences; Inorganic chemistry; Chemical Sciences; Catalysis

Rabah Azzouz, Laurent Bischoff, Corinne Fruit, Francis Marsais. O -Tetrahydropyran-2-yloxy ( O -THP) as an ortho -Directing Group in the Lithiation of Pyridines. SYNLETT, 2006, 2006 (12), pp.1908-1912. ⟨10.1055/s-2006-947340⟩. ⟨hal-02385070⟩