Selective ortho and benzylic functionalization of secondary and tertiary p-tolylsulfonamides. Ipso-bromo desilylation and Suzuki cross-coupling reactions

Kinetic vs thermodynamic deprotonation studies on secondary and tertiary su lfonamides 1 and 2 using n-BuLi have been carried out. While both 1 and 2 s how kinetic ortho-metalation, thermodynamic conditions lead to ortho and be nzylic deprotonation, respectively (Figures 1 and 2). Metalation of 1 using the n-BuLi/KOtBu superbase led to regioselective benzylic metalation (Figu re 4); LDA deprotonation was also briefly explored. Application of the deve loped conditions allows the synthesis of diverse sulfonamide products 5a-e, 6a-e, 7a,b, and 8a-e. Ipso-bromo desilylation reactions afford sulfonamide s 9a,b while Suzuki cross-coupling reactions furnish biaryl sulfonamides 11 a-c.