Gold‐Catalyzed Post‐Ugi Cascade Transformation for the Synthesis of 2‐Pyridones

Abstract

A gold‐catalyzed post‐Ugi cascade transformation for the synthesis of 2‐pyridones is described. The process involves furan–alkyne cyclization followed by furan ring‐opening and cleavage of the isocyanide‐originated fragment. The initially formed cis double bond can isomerize into a more stable trans double bond upon prolonged exposure to a strong Brønsted acid. Thus, the overall strategy provides a viable access towards two types of 2‐pyridones.

Silver(I) Triflate‐Catalyzed Protocol for the Post‐Ugi Synthesis of Spiroindolines

“…Unless otherwise specified, starting materials and solvents were purchased from commercial sources and used as received. 3‐(4‐Fluorophenyl)propiolic acid ( 1 b ), 3‐(4‐chlorophenyl)propiolic acid ( 1 c ), 3‐(4‐methoxyphenyl)propiolic acid ( 1 d ), 3‐(Thiophen‐2‐yl)propiolic acid ( 1 e ) were synthesized following previously described protocol . Melting points were measured using INESA WRR apparatus.…”

Gold Catalysis and Furans: A Powerful Match for Synthetic Connections

“…The fragmentation of intermediate 113, arising from nucleophilic attack of the furan, affords pyridin-2ones 114, in which the double bond is in Z configuration, but slowly undergoes spontaneous isomerization to afford (E)-114 in the reaction mixture (Scheme 33). 52 On the other hand, 3-diazoindolin-2-ones 126 were treated with a gold catalyst to give the corresponding Au carbenes, which reacted with furans 127 (Scheme 36). After 3-alkylideneindolin-2-ones 129 had been formed through nucleophilic attack and ring opening of the furan ring, an asymmetric addition of trimethylsilyl cyanide to the carbonyl group was achieved in one pot by employing a cinchona alkaloid derived chiral organocatalyst.…”

“…The fragmentation of intermediate 113, arising from nucleophilic attack of the furan, affords pyridin-2ones 114, in which the double bond is in Z configuration, but slowly undergoes spontaneous isomerization to afford (E)-114 in the reaction mixture (Scheme 33). 52…”

Heteroarene‐tethered Functionalized Alkyne Metamorphosis

“…The cascade process involves alkyne‐furan cyclization followed by subsequent furan ring opening and C−C bond cleavage (Scheme 120). [141] Pyrrole‐2‐carboxaldehyde 473 and alkynoic acid 475 derived propargylamides 477 were transformed with high regioselectivity by applying a very similar strategy discussed before. Selective formation of pyrrolopyridinones 479 via exo‐dig cyclization was obtained by using Au(PPh 3 )OTf.…”

“…Recently,agold-catalyzed, post-Ugi, transformation was reported by Du et al for the synthesis of 2-pyridones 472.T he cascade process involves alkyne-furan cyclization followed by subsequentf uran ring opening and CÀCb ond cleavage (Scheme 120). [141] Pyrrole-2-carboxaldehyde 473 and alkynoic acid 475 derived propargylamides 477 were transformed with high regioselectivity by applying av ery similar strategy discussed before.S electivef ormation of pyrrolopyridinones 479 via exo-dig cyclization was obtained by using Au(PPh 3 )OTf. By changingt he catalytic system to Pt II , endo-dig cyclization furnished the pyrroloazepinones 478 as major product (Scheme 121).…”