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Synthesis of a Unique Isoindoline/Tetrahydroisoquinoline-based Tricyclic Sultam Library Utilizing a Heck-aza-Michael Strategy

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journal contribution
posted on 12.03.2012, 00:00 by Qin Zang, Salim Javed, Patrick Porubsky, Farman Ullah, Benjamin Neuenswander, Gerald H. Lushington, Fatima Z. Basha, Michael G. Organ, Paul R. Hanson
The synthesis of a unique isoindoline- and tetrahydroisoquinoline (THIQ)-containing tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy is reported. Both isoindoline and THIQ rings are installed through a Heck reaction on a vinylsulfonamide, followed by one-pot deprotection and intramolecular aza-Michael reaction. Subsequent cyclization with either paraformaldehyde condensation or 1,1′-carbonyldiimidazole coupling generates a variety of tricyclic sultams. Overall, a 160-member library of these sultams, together with their isoindolines/THIQ and secondary sulfonamides precursors, were constructed using this strategy.