Pd-Catalyzed\nC(sp<sup>2</sup>)–C(sp<sup>3</sup>) Suzuki Coupling and Synthesis\nof Lumacaftor Using Designed Monophosphine\nLigands

Novel monophosphine ligands <b>L1</b> and <b>L2</b> with a C–P ring were designed and synthesized for\nthe efficient\nPd-catalyzed C(sp<sup>2</sup>)–C(sp<sup>3</sup>) Suzuki coupling.\nWith 0.5 mol % Pd<sub>2</sub>dba<sub>3</sub> and 2 mol % <b>L1</b>, aryl halides coupled with alkylboronic acids to give the products\nin up to 99% yield. The aryl thianthrene salt was further applied\nfor late-stage methylation in 97% yield. The active pharmaceutical\ningredient lumacaftor was synthesized by aryl–alkyl and aryl–aryl\nSuzuki coupling reactions using <b>L1</b> and <b>L2</b>.