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

نویسندگان

  • Farman Ullah
  • Qin Zang
  • Salim Javed
  • Patrick Porubsky
  • Benjamin Neuenswander
  • Gerald H Lushington
  • Paul R Hanson
  • Michael G Organ
چکیده

A microwave-assisted, continuous-flow organic synthesis (MACOS) protocol for the synthesis of an isoindoline-annulat-ed, tricyclic sultam library, utilizing a Heck-aza-Michael (HaM) strategy, is reported. This sequence involves a Heck reaction on vi-nylsulfonamides with batch microwave heating followed by a one-pot, sequential intramolecular aza-Michael cyclization/Boc-deprot-ection 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%).

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عنوان ژورنال:
  • Synthesis

دوره 44 16  شماره 

صفحات  -

تاریخ انتشار 2012