Gold(I)-Catalyzed Synthesis of Heterocycles via Allene Oxide from Propargylic Alcohols

Abstract

A new mechanistic pathway of propargylic alcohol activation by gold­(I) catalysis has been proposed toward the efficient synthesis of N-protected pyrroles, 5,6-dihydropyridin-3­(4H)-ones from N-protected 5-aminopent-2-yn-1-ol, and 5-aminopent-2-yn-1-ol. Control experiments support that the reaction proceeded via the neighboring group participation of the oxygen atom of propargylic alcohol to form an allene oxide intermediate where the nucleophilic heteroatom attacks intramolecularly. Further, this methodology is successfully extrapolated toward the atom-economic synthesis of hydroxyalkyl indoles and benzofurans. The short reaction time of 30 s, low catalyst loading of 0.5 mol %, high yield, variation in the substrate scope, and procedurally simple open-flask reaction conditions make this methodology highly applied.

Gold(I)-Catalyzed Cascade Cyclization of Alkynyl Indoles for the Stereoselective Construction of the Quaternary Carbon Center of Akuammiline Alkaloids

“…Next, we investigated effect of the free hydroxy and NH indole moieties on the reaction (Scheme ). When using the TBS-protected alcohol 31a as substrates, the cyclization product 32 was obtained in only 22% yield after 24 h. This result suggests that the free hydroxy group promotes the cyclization, presumably through a hydroxy-group-assisted coordination of alkyne to the gold catalyst . In the case using N -methylindole 33 , the yield was also decreased (33%) with prolonged reaction time, which can be attributed to the facile imine formation with NH indole in the first cyclization step.…”

Electrocatalytic Asymmetric Nozaki–Hiyama–Kishi Decarboxylative Coupling: Scope, Applications, and Mechanism

“…Of all compounds listed in Table , only 7 has been previously prepared in an enantioselective fashion, all of which require pyrophoric nucleophiles (alkyl lithium and Grignard species) . Alcohols 30 , 35 , and 38 have been previously prepared in racemic fashion through Grignard additions . It is advantageous in many cases to use carboxylic acid inputs from both a chemoselectivity standpoint and synthetic simplicity as several of the requisite alkyl halides would need to be derived either from alcohol halogenation or Hunsdiecker decarboxylation (i.e., compounds 27 , 28 , and 29 ).…”

Recent Progress in Gold‐Catalyzed Reactions of Alkynes for the Construction of Indole Frameworks

“…During synthesis of diverse heterocyclic scaffolds via goldcatalysis, Sarkar and co-workers derived hydroxyalkyl indole derivatives 110 involving diversely substituted propargylic alcohols 109. [90] A tentative mechamism for the intramolecular annulation is proposed in Scheme Annulation of cyclohexenone tethered propargyl type alcohol 111 with amines 112 could be achieved in the presence of gold-catalyst 113. [91] The 6-hydroxyindole derivatives 114 were obtained via aza-Michael addition followed by rearrangement.…”

“…During synthesis of diverse heterocyclic scaffolds via gold‐catalysis, Sarkar and co‐workers derived hydroxyalkyl indole derivatives 110 involving diversely substituted propargylic alcohols 109 [90] . A tentative mechamism for the intramolecular annulation is proposed in Scheme 27.…”