Synthesis of an Isoindoline-Annulated, Tricyclic Sultam Library via Microwave-Assisted, Continuous-Flow Organic Synthesis (MACOS)

Abstract A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of an isoindoline-annulated, tricyclic sultam library, utilizing a Heck–aza-Michael (HaM) strategy, is reported. This sequence involves a Heck reaction on vinylsulfonamides with batch microwave heatin...

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Bibliographic Details
Published in:Synthesis (Stuttgart) 2012, Vol.44 (16), p.2547-2554
Main Authors: Ullah, Farman, Zang, Qin, Javed, Salim, Porubsky, Patrick, Neuenswander, Benjamin, Lushington, Gerald H., Hanson, Paul R., Organ, Michael G.
Format: Article
Language:English
Subjects:
Chemistry
Exact sciences and technology
Heterocyclic compounds
Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms
Heterocyclic compounds with only one n hetero atom and condensed derivatives
Organic chemistry
Preparations and properties
special topic
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Summary:Abstract A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of an isoindoline-annulated, tricyclic sultam library, utilizing a Heck–aza-Michael (HaM) strategy, is reported. This sequence involves a Heck reaction on vinylsulfonamides with batch microwave heating followed by a one-pot, sequential intramolecular aza-Michael cyclization/Boc-deprotection using MACOS. Subsequent cyclization with either 1,1′-carbonyldiimidazole or chloromethyl pivalate using MACOS provided an array of tricyclic sultams. This efficient three-step protocol requires only a few hours to produce the target sultams starting from simple starting materials. Using this strategy, a 38-member library of isoindoline-annulated sultams was generated in good to excellent overall yields (53–87%).
ISSN:0039-7881
1437-210X
DOI:10.1055/s-0031-1289791