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Synthesis 2021; 53(11): 1911-1922
DOI: 10.1055/s-0040-1706006
paper

Sequencing Groebke–Blackburn–Bienaymé and Aza-Michael Addition Reactions: A Modular Strategy for Accessing a Diverse Collection of Constrained Benzoxazepine and Imidazopyrazine Systems

Vunnam Srinivasulu
a   Sharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE
,
Farah Al-Marzooq
d   Department of Medical Microbiology and Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, UAE
,
Mohamad Hamad
a   Sharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE
b   College of Health Sciences, University of Sharjah, 27272, Sharjah, UAE
,
Monther A. Khanfar
a   Sharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE
e   Department of Chemistry, University of Jordan, 11942, Amman, Jordan
,
Mani Ramanathan
f   Department of Biology, Chemistry and Environmental Sciences, American University of Sharjah, 26666, Sharjah, UAE
,
Nelson C. Soares
a   Sharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE
c   College of Pharmacy, University of Sharjah, 27272, Sharjah, UAE
,
Taleb H. Al-Tel  ∗
a   Sharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE
c   College of Pharmacy, University of Sharjah, 27272, Sharjah, UAE
› Author AffiliationsThis work was supported by generous grants from the Islamic Development Bank (IsDB), Transform Fund (Grant No. 2018-2021) and the Research Funding Department, University of Sharjah, UAE (Grant No. 1801110125-P).
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Sequencing Groebke–Blackburn–Bienaymé and Aza-Michael Addition Reactions: A Modular Strategy for Accessing a Diverse Collection of Constrained Benzoxazepine and Imidazopyrazine SystemsSynthesis 2021; 53(11): e2-e2
DOI: 10.1055/s-0040-1706141

Abstract

We present a divergent strategy that permits access to diversely functionalized benzoxazepinium scaffolds fused to various heterocycles. The described strategy features a one-pot combination of the Groebke–Blackburn–Bienaymé reaction and an aza-Michael addition. Methyl (E)-4-(2-formylphenoxy)but-2-enoate and its derivatives are utilized as central elements in this cascade. These building blocks are reacted with a variety of functionalized amino-azines and tert-butyl isocyanide under ytterbium triflate [Yb(OTf)3] catalysis. The ensuing cascade represents a rapid, modular and atom-economic process that leads to the construction of a diverse collection of constrained benzoxazepinium systems from a wide substrate scope.

Key words

aza-Michael addition - benzoxazepines - indolopyrazines - diversity-oriented synthesis - multicomponent reactions - Groebke–Blackburn–Bienaymé - modular synthesis

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0040-1706006.
  • Supporting Information


Publication History

Received: 01 October 2020

Accepted after revision: 07 December 2020

Article published online:
07 January 2021

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