Synthesis of Benzothiophene Derivatives by Pd-Catalyzed or Radical-Promoted Heterocyclodehydration of 1-(2-Mercaptophenyl)-2-yn-1-ols

Novel and convenient approaches to benzothiophene derivatives 3and 5 have been developed, based on heterocyclization reactions of 1-(2-mercaptophenyl)-2-yn-1-ols 2 or 4, respectively, readily available from alkynylation of 2-mercaptobenzaldehydes or 1-(2-mercaptophenyl) ketones 1. In particular, 1-(2-mercaptophenyl)-2-yn-1-ols 2, bearing a CH2R substituent on the triple bond (R = alkyl, aryl), were conveniently converted in fair to good yields (55- 82%) into (E)-2-(1-alkenyl)benzothiophenes 3 when allowed to react in the presence of catalytic amounts (2 mol %) of PdI2 in conjunction with KI (KI:PdI2molar ratio =10) at 80- 100 °C in MeCN as the solvent, through a heterocyclodehydration process. On the other hand, 2-alkoxymethylbenzothiophenes 5 were selectively obtained in fair to excellent yields (49- 98%) via a radical promoted substitutive heterocyclodehydration process, by reacting 1-(2-mercaptophenyl)-2-yn-1-ols 4 (bearing an alkyl or aryl substituent on the triple bond) in alcoholic media at 80- 100 °C in the presence of a radical initiator, such as AIBN.