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; Farah Al-Marzooq; Mohamad Hamad; Monther A. Khanfar; Mani Ramanathan; Nelson C. Soares; Taleb H. Al-Tel

doi:10.1055/s-0040-1706006

Synthesis, Table of Contents

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

^aSharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE

,

Farah Al-Marzooq

^dDepartment of Medical Microbiology and Immunology, College of Medicine and Health Sciences, UAE University, Al Ain, UAE

,

Mohamad Hamad

^aSharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE

^bCollege of Health Sciences, University of Sharjah, 27272, Sharjah, UAE

,

Monther A. Khanfar

^aSharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE

^eDepartment of Chemistry, University of Jordan, 11942, Amman, Jordan

,

Mani Ramanathan

^fDepartment of Biology, Chemistry and Environmental Sciences, American University of Sharjah, 26666, Sharjah, UAE

,

Nelson C. Soares

^aSharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE

^cCollege of Pharmacy, University of Sharjah, 27272, Sharjah, UAE

,

Taleb H. Al-Tel ∗

^aSharjah Institute for Medical Research, University of Sharjah, 27272, Sharjah, UAE

^cCollege of Pharmacy, University of Sharjah, 27272, Sharjah, UAE

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Abstract

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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

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References

References

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