New Synthesis of Diarylmethanes, Key Building Blocks for SGLT2 Inhibitors

[Image: see text] Synthesis of diarylmethanes, a key building block for SGLT2 inhibitors, has been developed through ketone synthesis by Friedel–Crafts acylation with TiCl(4), followed by reduction with TiCl(4)/NaBH(4). The new protocol proceeded more cleanly than the previous methods employing AlCl(3) and BF(3)·OEt(2)/Et(3)SiH to provide the diarylmethanes corresponding to canagliflozin, empagliflozin, and luseogliflozin in a highly expedient and affordable manner. In the case of a diarylmethane for the synthesis of dapagliflozin, the reduction step took place by an alternative method using InCl(3)/Al/BF(3)·OEt(2).