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

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 followe...

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Bibliographic Details
Published inSynthesis (Stuttgart) Vol. 44; no. 16; pp. 2547 - 2554
Main Authors Ullah, Farman, Zang, Qin, Javed, Salim, Porubsky, Patrick, Neuenswander, Benjamin, Lushington, Gerald H., Hanson, Paul R., Organa, Michael G.
Format Journal Article
LanguageEnglish
Published STUTTGART Thieme Medical Publishers 2012
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
THIN-FILMS
continuous flow
sultams
aza-Michael addition
STRATEGY
MACOS
Heck reaction
MICROREACTOR
isoindolines
DISCOVERY
CAPILLARIES
CHEMISTRY
SELECTIVE METHOD
AGENTS
INHIBITORS
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Summary: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%).
Bibliography:NIH RePORTER
ISSN:0039-7881
1437-210X
DOI:10.1055/s-0031-1289791