A Tandem Dehydrogenation‐Driven Cross‐Coupling between Cyclohexanones and Primary Amines for Construction of Benzoxazoles. Issue 30 (7th June 2022)

• Record Type: Journal Article
• Authors: Xu, Biping; Su, Weiping
• Is Part Of: Angewandte Chemie international edition. Volume 61:Issue 30(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-07
• Subjects: Aromatization -- Heterocycles -- Radical -- Reaction Mechanisms -- Synthetic Methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.202203365
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Herein, we report a transition metal‐free, operationally simple, general method for straightforward syntheses of 2‐substituted benzoxazoles from readily available cyclohexanones and aliphatic primary amines by an imine α‐oxygenation‐initiated cascade reaction sequence. The key to achieving high selectivity and excellent functional‐group tolerance is the use of TEMPO as a mild oxidant that selectively oxidizes the reaction intermediates through its multiple reactivity modes, thus facilitating the individual steps to proceed in succession. More than 70 substrate combinations are disclosed, demonstrating the reliability of this protocol to synthesize structurally diverse products, including marketed drugs, drug candidate, and natural products that are unattainable by the existing methods. Abstract : A tandem dehydrogenation‐driven cross‐coupling reaction between cyclohexanones and primary amines is reported for benzoxazole synthesis by TEMPO's multiple reactivity modes (oxygenation and desaturation). This transition metal‐free protocol features broad substrate scope, high functional group tolerance, and is operationally simple, therefore enabling late‐stage functionalization and rapid synthesis of bioactive compounds, including structurally complex marketed drugs and natural products.