Efficient, regioselective access to bicyclic imidazo[1,2-x]- heterocycles via gold- and base-promoted cyclization of 1-alkynylimidazoles.
Reactions of 1-alkynylimidazoles involving the formation of their 2-lithio derivatives followed by addition of aldehydes or ketones are presented. The method gives access to 1-alkynyl-2-(hydroxymethyl)imidazoles which undergo 6-endo-dig or 5-exo-dig cyclization under AuCl(3)- or base-catalyzed conditions to yield imidazo[1,2-c]oxazoles and imidazo[2,1-c][1,4]oxazine heterocycles. Under transition metal catalysis, the reaction occurs in a regiospecific manner, leading exclusively to the product of 6-endo-dig attack, whereas under basic conditions, the reaction takes place in a regioselective manner giving preferentially the product from 5-exo-dig attack.
Laroche
Christophe
C
Division of Medicinal Chemistry, College of Pharmacy, The University of Texas at Austin, Austin, Texas 78712, USA.
Kerwin
Sean M
SM
D000447:Aldehydes; D003500:Cyclization; D006046:Gold; D006571:Heterocyclic Compounds / Q000138:chemical synthesis*; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D007659:Ketones; D008094:Lithium; D008722:Methods
D000447:Aldehydes; D006571:Heterocyclic Compounds; D007093:Imidazoles; D007659:Ketones; D006046:Gold; D008094:Lithium