vinyl-sulfonamide and beta-sultam

From vinyl sulfonamides as precursors to vinyl sulfonamide epoxides, two cascade reaction protocols were developed to synthesize eight-membered ring sultams in water. These protocols employ intermolecular Michael addition by NaOH or NaHS in water, followed by rapid proton transfer and intramolecular 8-endo-tet epoxide ring-opening to give medium-size sultams selectively in one-pot. Novel core structures and high synthetic efficiency make these cascade reactions highly suitable for sultam library production. Both reactions proceeded well and afforded the respective sultams in good yields under environmentally friendly conditions.

Topics: Combinatorial Chemistry Techniques; Epoxy Compounds; Stereoisomerism; Sulfonamides; Water

A diversity-oriented synthesis (DOS) strategy termed "Click, Click, Cyclize" is reported. This approach relies on functional group (FG) pairing between a vinyl sulfonamide and an array of functional groups to synthesize skeletally diverse sultams. Several FG pairing pathways on central tertiary vinyl sulfonamide linchpins have been developed including intramolecular Heck, aza-Michael, ring-closing enyne metathesis, Pauson-Khand, and chemoselective oxidation/Baylis-Hillman reactions.

Topics: Catalysis; Combinatorial Chemistry Techniques; Cyclization; Molecular Structure; Stereoisomerism; Sulfonamides