Tf₂NH-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with Dioxazoles: A Metal-Free Approach to Polysubstituted 4-Aminooxazoles

Abstract

An unprecedented TfNH-catalyzed formal [3 + 2] cycloaddition of ynamides with dioxazoles was developed to construct various polysubstituted 4-aminooxazoles. This approach features a metal-free catalytic bimolecular assembly of oxazole motifs, a low-cost catalyst, exceptionally mild reaction conditions, a very short reaction time, a broad substrate scope, and high efficiency. This metal-free protocol may find applications in pharmaceutical-oriented synthesis.

Alkynyl Thioethers in Gold‐Catalyzed Annulations To Form Oxazoles

“…No reaction was seen between 1 a and 2 a in the presence of Tf 2 NH. Using the dioxazole 7 , in place of 2 a led to the formation of 3 aa′ and no trace of 3 aa (Scheme ). In the presence of a cationic Au I catalyst 3 aa was formed as the major isomer, thus ruling out the nitrenoid's role in switching regioselectivity.…”

Keteniminium Ions: Unique and Versatile Reactive Intermediates for Chemical Synthesis

“…98 Switching to dioxazoles, 153 promotes another rearrangement from aminovinyldioxazolium ions 154 affording 4-aminooxazoles 155 resulting from a formal [3+2] cycloaddition. 99 The successful outcome of these two reactions in which an activated keteniminium ion is trapped with azides or dioxazoles is actually based on the electrophilic character of ketene acetals cations 150 and 154. An interesting and particularly relevant extension of this reactivity was reported in 2017 by the Shin group, who devised a remarkable oxidative intermolecular Friedel-Crafts-type coupling of electron-rich arenes or silyl enol ethers (Scheme 32).…”

“…Such reactions have been extensively studied since 2015 and representative examples are summarized in Scheme 37: they include the use of dioxazoles 153, 110 isoxazoles 191, 111 anthranils 196, 112 oxadiazoles 199, 113 pyridoindazoles 202, 114 or azirines 205 115 which result in the formation of various heterocyclic scaffolds. It is important to note that some reactions were also shown to be efficiently catalyzed by an acid instead of a gold catalyst (e.g., reaction of ynamides and dioxazoles 153 in Schemes 31 99 and 37 109 ), and both the nature of the metal catalyst and the starting…”

Rh‐Catalyzed Annulation of ortho‐C−H Bonds of 2‐Arylimidazoles with 1,4,2‐Dioxazol‐5‐ones toward 5‐Arylimidazo[1,2‐c]quinazolines

“…Meanwhile, with the development of organometallic chemistry, 1,4,2‐dioxazol‐5‐ones were applied in C−H amidation reactions . Moreover, in combined with the sequential cyclization step, they served as subunits to access polysubstituted 4‐aminooxazoles, benzimidazoles, quinazolines and their derivatives, functionalized oxazoles, and azolopyrimidines . These aforementioned elegant examples spurred us to test the feasibility of the reaction between 2‐arylimidazoles and 1,4,2‐dioxazol‐5‐ones toward imidazo[1,2‐ c ]quinazolines whereby the sequential C−H amidation and cyclization (Scheme , eq 5).…”