Directed ortho metalation-cross coupling strategies. N-cumyl arylsulfonamides. Facile deprotection and expedient route to 7- and 4,7-substituted saccharins.
By using the powerful N-cumylsulfonamide directed metalation group (DMG), a series of 2-substituted derivatives were prepared according to the directed ortho metalation (DoM) tactic (Table 1). Mild conditions for N-decumylation and other simple transformations of the products have been achieved (Scheme 2). The 3-silyloxy sultam 12 undergoes further DoM to give formyl, thiomethyl, iodo, and amide derivatives 13a-g of potential value for saccharin synthesis (Table 2). An effective route to target 7-aryl saccharins via Suzuki cross coupling (Table 3) followed by further metalation-carbamoylation and cyclization (Table 5) is described. 4,7-Disubstituted saccharins have been obtained by similar sequences (Scheme 3). Mild TFA-mediated N-decumylation furnishes substituted primary arylsulfonamides (Table 4).
Blanchet
Jérôme
J
Department of Chemistry, Queen's University, 90 Bader Lane, Kingston, Ontario K7L 3N6, Canada.
Macklin
Todd
T
Ang
Patrick
P
Metallinos
Costa
C
Snieckus
Victor
V
D002625:Chemistry, Organic / Q000379:methods*; D008670:Metals / Q000737:chemistry; D012439:Saccharin / Q000138:chemical synthesis / Q000737:chemistry*; D013449:Sulfonamides / Q000737:chemistry*; D013843:Thiazines / Q000737:chemistry
D008670:Metals; D013449:Sulfonamides; D013843:Thiazines; D012439:Saccharin