Titanium reagents for the synthesis of 2-substituted benzo[b]thiophenes on the solid phase

Titanium(IV) benzylidenes (Schrock carbenes) bearing a masked sulfur nucleophile in the ortho position were generated from thioacetals with use of low-valent titanocene complex Cp(2)TiP(OEt)(3)](2) and alkylidenated Merrifield resin-bound esters to give enol ethers. Treatment of the resin-bound enol ethers with a 5:5:90 mixture of TFA, TFAA, and dichloromethane led to cleavage from resin, removal of the tert-butyldimethylsilyl (TBDMS) protecting group, and concomitant cyclization to complete the traceless solid-phase synthesis (SPS) of benzothiophenes. Switching the nature of the linker from acid-stable to acid-sensitive ensured good purity.