Gold‐Catalyzed [4+2]‐ and [3+3]‐Annulations of Ynamides with 1‐Yn‐3‐ols to Access Six‐Membered Carbocycles and Oxacycles via Three Distinct Cyclizations

Abstract

Three distinct strategies for catalytic annulations between ynamides and 1‐yn‐3‐ols are described; the resulting carbo‐ and heterocycles were produced efficiently in one‐pot operations using a gold catalyst. The chemoselectivities of these annulations are controlled by variations of the substituents of the ynamides and the 1‐yn‐3‐ols. This reaction sequence involves initial alkoxylations of ynamides, followed by Claisen rearrangement of propargylic enol ethers, and ends with 6‐endo‐trig cyclizations of 1‐allenyl‐5‐amide intermediates. Among these cascade annulations, the cyclizations of 5‐allenyl‐1‐amides to yield 5,6‐dihydro‐2‐pyranones and 6‐alkylenecyclohex‐2‐ene‐1‐carboxamides are unprecedented in the literature.magnified image

Gold‐Catalyzed Carboxylative Cyclization Reactions: Recent Advances

“…Liu group disclosed gold‐catalyzed multicomponent cyclization reactions between ynamides 6 and 1‐yn‐3‐ols 3 via [4+2] and [3+3]‐cascade annulation reaction. The carbo‐ and heterocyclic product could be obtained from one pot synthesis in presence of 10 mol% PPh 3 AuCl, 10 mol% AgOTf in 1,2‐dichloroethane solvent at 25 °C for 4–22 h with moderate to good yields [21] . Phenyl substituted ynamides smoothly afforded pyranone derivatives 7 in 68–82% yield (Scheme 7).…”

“…The carbo-and heterocyclic product could be obtained from one pot synthesis in presence of 10 mol% PPh 3 AuCl, 10 mol% AgOTf in 1,2-dichloroethane solvent at 25 °C for 4-22 h with moderate to good yields. [21] Phenyl substituted ynamides smoothly afforded pyranone derivatives 7 in 68-82% yield (Scheme 7). In addition, alkyl substituted ynamides and alkyl group bearing 1-yn-3-ols could be subjected to the cyclization reactions, forming the product in moderate yield.…”

Gold-Catalyzed Reactions of Specially Activated Alkynes, Allenes, and Alkenes

“…In a similar report, the same group took advantage of the well-known Claisen rearrangement pathway using ynamides 197 and propargylic alcohols 198 to synthesize functionalized cyclohexene carboxamides 199a,b and α,β-unsaturated δlactones 200 (Scheme 47). 107 The product distribution was found to be highly dependent on the substitution pattern of the ynamide and alcohol reaction partners. The authors propose a common allenyl-gold complex intermediate 201 as the divergence point for the synthesis of the three types of products.…”