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

S L MacNeil; O B Familoni; V Snieckus

doi:10.1021/jo001402s

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

J Org Chem. 2001 Jun 1;66(11):3662-70. doi: 10.1021/jo001402s.

Authors

S L MacNeil¹, O B Familoni, V Snieckus

Affiliation

¹ Guelph-Waterloo Centre for Graduate Work in Chemistry and Biochemistry, University of Waterloo, Waterloo, ON, Canada, N2L 3G1.

PMID: 11374982
DOI: 10.1021/jo001402s

Abstract

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.