Intermolecular and Selective Synthesis of 2,4,5‐Trisubstituted Oxazoles by a Gold‐Catalyzed Formal [3+2] Cycloaddition

Abstract

Oxazole new world: A gold‐catalyzed intermolecular reaction of pyridine‐N‐aminides with ynamides can be used to prepare trisubstituted 1,3‐oxazoles with a variety of functional groups. This formal [3+2] cycloaddition employs robust conjugated N‐ylides as N‐nucleophilic N‐acyl nitrene equivalents for a highly chemoselective and regioselective addition across electron‐rich CC triple bonds.

Highly regioselective synthesis of 2,4,5-(hetero)aryl substituted oxazoles by intermolecular [3+2]-cycloaddition of unsymmetrical internal alkynes

“…5 We reported a synthesis of 4-amido-/4-alkoxy-oxazoles from ynamides/ ynol ethers in a formal [3+2]-cycloaddition strategy. 6 Gold activation of the ynamide triggers a process in which pyridine-N-aminides 2 react as dipolar cycloaddition-selective acyl nitrene equivalents.…”

Transition Metal-Mediated Synthesis of Monocyclic Aromatic Heterocycles

“…The reaction proceeds well with a variety of diversely-substituted reactants, providing the coresponding oxazoles 5-76 in good to excellent yields (Scheme 349). 548 …”

Meeting the Challenge of Intermolecular Gold(I)‐Catalyzed Cycloadditions of Alkynes and Allenes

“…56 In this case, the nucleophilic counterpart contained functionalities that formed the gold α-imidocarbenoid complex and could also close the ring though a 1,3- N , O -dipolar cycloaddition. The two-center reactants employed were pyridine- N -amidines that reacted with a wide range of functionalized ynamides or enol ethers.…”

“…The resulting cationic intermediate ( 41 - I ) cyclizes, forming the new C–O bond (Scheme 41). 56 Subsequent elimination of the pyridine moiety through N–N bond cleavage and demetalation furnishes the oxazoles. More recently, the same procedure has been applied to non-symmetrical internal alkynes affording 2,4,5-(hetero)aryl-substituted oxazoles 57…”