Synthesis 2012; 44(16): 2547-2554
DOI: 10.1055/s-0031-1289791
special topic
© Georg Thieme Verlag Stuttgart · New York

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

Farman Ullah
a  Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada, Fax: +1(416)7365936   Email: organ@yorku.ca
c  The 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
b  Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA
c  The 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
b  Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA
c  The 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
c  The 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
c  The 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
b  Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA
c  The 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*
b  Department of Chemistry, University of Kansas, 1251 Wescoe Hall Drive, Lawrence, KS 66045-7582, USA
c  The 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*
a  Department of Chemistry, York University, 4700 Keele Street, Toronto, ON, M3J 1P3, Canada, Fax: +1(416)7365936   Email: organ@yorku.ca
c  The 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
› Author Affiliations
Further Information

Publication History

Received: 17 April 2012

Accepted: 11 May 2012

Publication Date:
04 July 2012 (online)

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%).

Supporting Information

 
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