COMMUNICATIONS
doi.org/10.1002/adsc.202100432
Copper(I)-Catalyzed Intramolecular Cyclization of
o-Propargyloxy Diketopiperazines to Access Diverse Diazabicyclic
and Spiro-Diketopiperazinochromanes
Bita Manavi,a Hossein Zahedian Tejeneki,a Frank Rominger,b Mahsa Armaghan,c
Walter Frank,c Hamid Reza Bijanzadeh,d and Saeed Balalaiea, e,*
a
Peptide Chemistry Research Institute, K. N. Toosi University of Technology, P. O. Box 15875-4416, Tehran, Iran,
Tel: +98-21-23064226
Fax: +98-21-22889403
E-mail: balalaie@kntu.ac.ir
b
Organisch-Chemisches Institut der Universität Heidelberg, Im Neuenheimer Feld 270, D-69120 Heidelberg
Institut für Anorganische Chemie und Strukturchemie, Heinrich-Heine-Universität Düsseldorf, Universitätsstraße 1, 40225
c
Düsseldorf, Germany
d
Department of Environmental Sciences, Faculty of Natural Resources and Marine Sciences, Tarbiat Modares University, Tehran,
Iran
e
Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran
Manuscript received: April 6, 2021; Revised manuscript received: June 26, 2021;
Version of record online: ■■■, ■■■■
preferred in many cases based on their unique
advantages including that they are readily available,
Abstract: In this report, two distinctive intramolec-
ular cyclizations of o-propargyloxy diketopipera-
zines (achieved from a one-pot Ugi post-trans-
formation) is achieved via a copper(I)-catalyzed
cost-effective, and the fact that they have low
toxicity.[2] In this context, metal-catalyzed cycloaddi-
tion reactions of unsaturated CÀ C bonds with dipolar
intramolecular reaction of azomethine ylide and
species in general, and azomethine ylides in particular,
alkyne moiety. The presence of internal alkyne in
have been developed into striking and integral trans-
the starting materials directed the reaction towards
formations for the synthesis of complex N-hetero-
through [3+2]-cycloaddition, while terminal alkyne
cycles, especially when they are performed in an
led to a spirocyclization reaction between azome-
intramolecular setting.[3]
thine ylide and terminal unsaturated CÀ C bond.
Considering the significance of azomethine ylides,
there are a variety of methods for in situ preparation of
these intermediates. However, the formation of these
This method offering an opportunity for the syn-
thesis of challenging Diazabicyclics and Spiro-
Diketopiperazinochromanes in high yields with
dipolar species is mostly limited to the carboxylative
exclusive diastereoselectivity.
condensation of aldehydes with amino acids or amino
esters. Moreover, most of the cycloaddition reactions
of azomethine ylides and dienophiles involve sub-
Keywords: Copper; Cyclization; Cycloaddition; Het-
erocycles; Homogeneous catalyst; Multicomponent
reactions
strates encompassing electron-withdrawing groups
(EWGs) to the unsaturated CÀ C bond.[3] In this project,
we successfully present a new generation of azome-
thine ylide surrogates (Scheme 1). These intermediates
were subsequently incorporated in an intramolecular
Over the past decades, there has been significant
[3+2]-cycloaddition reaction with an inactive triple
progress in the Lewis acid-catalyzed cycloaddition CÀ C bond. Recently, Ugi post-transformation reactions
reaction and it has become the method of choice for have proved to be a powerful synthetic method for the
the rapid synthesis of complex structural building synthesis of a wide range of carbocycles, heterocycles,
blocks using simple raw materials with high atom and bridge rings that are not easily accessible by
economy in a single step.[1] One of the most important traditional synthetic routes through careful selection
factors in these formations is the selection of a proper starting materials.[4] Inspired by prior reports, we
metal catalyst. Nowadays, earth-abundant metals are envisaged that an intramolecular [3+2]-cycloaddition
Adv. Synth. Catal. 2021, 363, 1–8
1
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