Combinatorial Library of Biaryl-Based Sulfonamides

Significance

A combinatorial library of biaryl-based sulfonamides (9 amines x 7 sulfonyl chlorides x 13 boronic acids = 819 compounds) was prepared on a solid support through a four-step split-and-pool sequence. Thus, the reductive amination of a solid-supported aldehyde 1 with primary amines was performed with TiCl(Oi-Pr)₃/NaBH(OAc)₃ to give the corresponding amines 2. Subsequently, the supported amines 2 were treated with sulfonyl chlorides in the presence of DMAP in CHCl₃-pyridine to give the amides 3. The Suzuki cross-coupling reaction of 3 and boronic acids was carried out with PdCl₂(dppf) and aqueous Na₂CO₃ in DME at 100 °C to give the amides 4. The desired library of the sulfonamides 5 was obtained from 4 via TFA-mediated cleavage.