Base-Promoted Chemodivergent Formation of 1,4-Benzoxazepin-5(4H)-ones and 1,3-Benzoxazin-4(4H)-ones Switched by Solvents.

Qian Chen,Yunpeng Wang,Ruimao Hua

doi:10.3390/molecules24203773

Qian Chen, Yunpeng Wang + Show 1 more

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https://doi.org/10.3390/molecules24203773

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Journal: Molecules (Basel, Switzerland)	Publication Date: Oct 19, 2019
Citations: 12	License type: CC BY 4.0

Affiliation: Tsinghua University

Abstract

The KOH-promoted chemodivergent benzannulation of ortho-fluorobenzamides with 2-propyn-1-ol can afford either 1,4-benzoxazepin-5(4H)-ones or 1,3-benzoxazin-4(4H)-ones in good yields with high selectivity, depending greatly upon the use of solvents. In the case of using DMSO, the intermolecular benzannulation produced seven-membered benzo-fused heterocycles of 1,4-benzoxazepin-5(4H)-ones, whereas in MeCN, the six-membered benzo-fused heterocycles of 1,3-benzoxazin-4(4H)-ones were formed. The KOH-promoted benzannulation proceeded most probably through the C–F nucleophilic substitution of ortho-fluorobenzamides with 2-propyn-1-ol to give the intermediate of ortho-[(2-propynyl)oxy]benzamide, which underwent the intramolecular hydroamidation in a different manner to afford either seven- or six-membered benzo-fused heterocycles.

Highlights

Chemodivergent reactions are interesting and efficient protocols that form the structurally different heterocyclic compounds from the same starting materials through simple change of reaction conditions [1,2,3,4,5,6,7,8,9,10]
The solvent-dependent or solvent-controlled chemodivergent reactions have been well applied in the synthesis of heterocyclic compounds [11,12,13,14,15,16,17,18,19,20,21]
We firstly examined the reaction of 1a with 2-propyn-1-ol (1.2 equivalents) in the presence presence of KOH (3.0 equivalents) in DMSO at 50 °C for 12 h

Summary

Introduction

Chemodivergent reactions are interesting and efficient protocols that form the structurally different heterocyclic compounds from the same starting materials through simple change of reaction conditions [1,2,3,4,5,6,7,8,9,10]. As the structures shown in Scheme 1, 1,4-benzoxazepin-5(4H)-one is the useful and potential precursor for the synthesis of its derivatives by simple transformation. The known procedures for the formation of the seven-membered benzo-fused heterocycle either are multi-step with low atom-utilization or using uneasily available starting materials catalyzed by palladium complexes [33,34,35]

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Results

Conclusion