Base-Controlled Divergent Synthesis of Fluorine-Containing Benzo[4,5]imidazo[2,1-b][1,3]thiazines from 2-Mercaptobenzimidazoles and -CF₃-1,3-Enynes

A base-controlled divergent cyclization between 2-mercaptobenzimidazoles and beta-CF3-1,3-enynes providing either trifluoromethylated or fluorinated benzo-[4,5]-imidazo-[2,1-b]-[1,3]-thiazines has been developed. The beta-CF3-1,3-enyne, as a three-carbon synthon, underwent a 1,8-diazabicyclo[5.4.0] undec-7-ene (DBU)-catalyzed tandem hydroamination/intramolecular hydrothiolation to give CF3-substituted 3,4-dihydro-2H-benzo-[4,5]-imidazo-[2,1-b]-[1,3]-thiazine, whereas reaction with KOH afforded fluorinated 4H-benzo-[4,5]-imidazo-[2,1-b]-[1,3]-thiazine exclusively. In addition, the synthetic utility of this methodology was showcased through a variety of downstream derivatizations.