Synthesis and Diels–Alder reactions of thioisobenzofurans

Abstract

Anions prepared by deprotonation of benzofused thionolactones reacted with alkylating agents preferentially on sulfur. The resulting isobenzofurans underwent Diels–Alder reactions with dienophiles. This chemistry was developed as a one-pot procedure for the synthesis of bridged precursors of polycyclic aromatic compounds. The structure of one of the adducts, dimethyl 9-exo-10-endo-1-methylsulfanyl-8-phenyl-11-oxatricyclo[6.2.1.0^2.7]undeca-2,4,6-triene-9,10-dicarboxylate 5a, was determined by single-crystal X-ray diffraction. The versatility of this approach was extended by lithiation of the intermediate anion whereby alkylation introduced a further substituent on the aromatic nucleus. This methodology may be appropriate for the synthesis of anti-tumour prodrugs.