Synlett 2020; 31(09): 871-877
DOI: 10.1055/s-0040-1707997
letter
© Georg Thieme Verlag Stuttgart · New York

Ultrasound-Activated Atom-Economical Approach to the Synthesis of Highly Substituted Pyrrolidin-2-ones through a Four-Component Ugi/5-endo-trig Intramolecular Radical Cyclization Reaction

Atena Nashta Rahimi
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
,
Helya Janatian Ghazvini
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
,
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
b   Medical Biology Research Center, Kermanshah University of Medical Sciences, P. O. Box 6715847141, Kermanshah, Iran
,
Frank Rominger
c   Organisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg, Germany
,
Hossein Zahedian Tejeneki
a   Peptide Chemistry Research Center, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran
,
Hamid R. Bijanzadeh
d   Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Tehran, Iran   Email: balalaie@kntu.ac.ir
› Author Affiliations
We thank the Iran National Science Foundation (INSF, Grant No 97020936) for financial support.
Further Information

Publication History

Received: 27 January 2020

Accepted after revision: 21 February 2020

Publication Date:
13 March 2020 (online)


Abstract

An efficient and diversity-oriented access to functionalized pyrrolidin-2-ones through an Ugi reaction of readily available starting materials with a subsequent transformation is described. A two-step reaction sequence of a four-component Ugi reaction and an intramolecular radical-cyclization reaction leads to the chemo- and regioselective formation of a single product with high atom economy and good to high yields. The radicalization of the pseudopeptides generated from the first step by a cavitational mechanism produces the key intermediate for the ultrasound-activated formation of γ-lactams as the final products by β-Michael addition. Among the advantages of this approach are its use of cavitation bubble implosion as an exclusive path to radicalization of the polyfunctional Ugi adduct, its high selectivity, and its short reaction times.

Supporting Information

 
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