Selective Ortho and Benzylic Functionalization of Secondary and Tertiary p-Tolylsulfonamides. Ipso-Bromo Desilylation and Suzuki Cross Coupling Reactions
Stephen L. MacNeil, O. B. Familoni, Victor Snieckus*
*Departement of Chemistry, Queen's University, Kingston, ON, Canada, K7L3N6,
Email: snieckus
chem.queensu.ca
S. L. MacNeil, O. B. Familoni, V. Snieckus, J. Org. Chem, 2001, 66, 3662-3670.
DOI: 10.1021/jo001402s
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Abstract
Kinetic vs thermodynamic deprotonation studies on secondary and tertiary sulfonamides using n-BuLi have been carried out. Application of the developed conditions allows the synthesis of diverse sulfonamide products. Subsequent Suzuki cross-coupling reactions of iodo derivatives furnish various biaryl sulfonamides.
| Boronic Acid |
eq. |
t (h) |
Yield (%,
isol.) |
| PhB(OH)2 | 2.2 | 24 | 95 |
 |
3 | 26 | 92 |
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Details
The study by Stephen L. MacNeil, O. B. Familoni, and Victor Snieckus focuses on the selective ortho and benzylic functionalization of secondary and tertiary p-tolylsulfonamides. Using n-BuLi, kinetic deprotonation leads to ortho-metalation for both secondary and tertiary sulfonamides, while thermodynamic conditions result in ortho and benzylic deprotonation, respectively. The n-BuLi/KOtBu superbase achieves regioselective benzylic metalation. The research explores the synthesis of various sulfonamide products and demonstrates the utility of ipso-bromo desilylation and Suzuki cross-coupling reactions to produce biaryl sulfonamides. The study highlights the potential of sulfonamides as Directed Metalation Groups (DMGs) and their application in synthetic chemistry. The findings include the preparation of functionalized derivatives and the successful execution of Suzuki-Miyaura cross-coupling reactions, which are significant for pharmaceutical applications. The research provides a systematic approach to achieving selective metalation and functionalization, contributing valuable insights into the development of synthetically useful anionic aromatic reactions.
Key Words
DoM, Directed Ortho Metalation, Suzuki Coupling, Iodination, Benzylic Alcohols
ID: J42-Y2001-020
