Tf₂NH-catalyzed formal [3 + 2] cycloaddition of oxadiazolones with ynamides: a simple access to aminoimidazoles

Abstract

Oxadiazolones are first employed as the three-atom coupling partners in the TfNH-catalyzed cycloaddition with ynamides. This formal [3 + 2] cycloaddition allows a rapid synthesis of aminoimidazoles with a broad substrate scope. The approach also features a metal-free catalytic cycloaddition process, which may find applications in the synthesis of bioactive molecules. Besides, the resulting N-methyl products can further be readily converted to free N-H aminoimidazoles.

Gold-Catalyzed Formal [3 + 2] Cycloaddition of Ynamides with 4,5-Dihydro-1,2,4-oxadiazoles: Synthesis of Functionalized 4-Aminoimidazoles

“…Employing AgSbF 6 , TfOH, or HNTf 2 as the catalyst afforded enamine 4a as the major product derived from the attack of imino nitrogen of 2a to the ynamide (entries 17–19). Increasing the amount of HNTf 2 to 1.0 equiv resulted in the formation of the complex reaction mixture …”

Triflimide (HNTf2) in Organic Synthesis

“…A range of N-sulfonyl ynamides substituted with aryl, heteroaryl, and alkyl groups all proceeded smoothly to afford the corresponding products in good yields (Scheme 18). 64 However, unfortunately, the oxazolidinone-based ynamides could not participate in this process to give the corresponding aminoimidazole 73d. Nevertheless, the authors demonstrated that the typical substituents on the nitrogen, such as sulfonyl and benzyl groups, could be removed successfully, thereby allowing diverse derivatizations when needed.…”

β-Oxidation of Ynamides into N,O-Acetals by mCPBA: Application in Enantioselective Intermolecular Transacetalization

“…The generality of the ynamide oxidation with peroxy acids were then examined (Scheme ). Unlike the necessity of electron-rich aryl groups in the previous acid-catalyzed oxygenative couplings, the reaction tolerated various groups as the alkynyl substituent (R 2 ), including alkenyl ( 6b – c ), aryl ( 6d – q ), heteroaryl ( 6r – t ), and aliphatic groups ( 6u – w ), although in some cases, lower yields were obtained ( 6u and 6v ). Interestingly, a TBDMS-protected alcohol ( 6w ) was compatible with this oxidation.…”

“…Ynamides are useful building blocks in transition-metal and organocatalysis . A particularly noteworthy aspect is their oxidation chemistry as it provides synthetically versatile electrophilic α-oxo carbene equivalents. − For example, transition-metal (Au, Rh, Ir, Ru, or Zn) or Brønsted acid-catalyzed oxidation of ynamides led to a range of reactivity, including addition of N- , O- , C- nucleophiles, cyclopropanations, 1,3-dipolar cycloaddition, and C–H insertions. Here, use of resonance-stabilized oxidants have been typical, including pyridine- N- oxides, nitrones, nitro groups, sulfoxides, azides, N- acylpyridinium N- aminides, and heteroaromatics with an imbedded N–O bond.…”