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 sulfonamides 1 and 2 using n-BuLi have been carried out. While both 1 and 2 show kinetic ortho-metalation, thermodynamic conditions lead to ortho and benzylic deprotonation, respectively (Figures 1 and 2). Metalation of 1 using the n-BuLi/KOtBu superbase led to regioselective benzylic metalation (Figure 4); LDA deprotonation was also briefly explored. Application of the developed conditions allows the synthesis of diverse sulfonamide products 5a-e, 6a-e, 7a,b, and 8a-e. Ipso-bromo desilylation reactions afford sulfonamides 9a,b while Suzuki cross-coupling reactions furnish biaryl sulfonamides 11a-c.
MacNeil
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SL
Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, University of Waterloo, Waterloo, ON, Canada, N2L 3G1.
Familoni
O B
OB
Snieckus
V
V