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

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

doi:10.1055/s-0031-1289791

Synthesis, Table of Contents

Synthesis 2012; 44(16): 2547-2554
DOI: 10.1055/s-0031-1289791

special topic

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

Authors

Farman Ullah

^aDepartment of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada, Fax: +1(416)7365936 Email: organ@yorku.ca

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Qin Zang

^bDepartment of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Salim Javed

^bDepartment of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Patrick Porubsky

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Benjamin Neuenswander

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Gerald H. Lushington

^bDepartment of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Paul R. Hanson*

^bDepartment of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu
Michael G. Organ*

^aDepartment of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada, Fax: +1(416)7365936 Email: organ@yorku.ca

^cThe University of Kansas Center for Chemical Methodologies and Library Development (KU-CMLD), Del Shankel Structural Biology Center, 2034 Becker Drive, Lawrence, KS 66047-3761, USA, Fax: +1(785)8645396 Email: phanson@ku.edu

Abstract

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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%).

Key words

MACOS - continuous flow - sultams - Heck reaction - aza-Michael addition - isoindolines

Full Text

References

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Supplementary Material

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