Palladium-Catalyzed Asymmetric 6-Endo Cyclization of Dienamides with Substituent-Driven Activation

Abstract

Chiral 2-piperidinone compounds with various C-6 substituents were successfully synthesized via a Pd-catalyzed asymmetric 6-endo cyclization of dienamides, which were evidently activated by both N-p-toluenesulfonyl and C-3 ester substituents.

Hydrogen Bond-Assisted 6π-Azaelectrocyclization of Penta-2,4-dienamides: Synthesis of Dihydropyridin-2(3H)-ones

“…Over the past decades, extensive experimental and theoretical work had demonstrated that the substituents in the triene precursors had a distinct effect on facilitating the electrocyclization. , This “substituent-driven activation” was clarified by Katsumura and co-workers on rapid 6π-azaelectrocyclization of dienamides to substituted pyridines and chiral piperidines (Scheme ). The cyclization was realized by the remarkable substituent effect due to the enhancement of the HOMO–LUMO interaction in the 6π-electron system, which mainly derived from the C-4 ester substituent and the additional electron-withdrawing group at the nitrogen. , In contrast, our present cyclic reaction of penta-2,4-dienamides, carrying an electron-withdrawing acyl group at C-3 position and an aryl or alkyl group at the nitrogen, proceeded smoothly without any catalyst. The results imply that the activation to the electrocyclization of 1-azatrienes might not merely originate from the electronic effect of the substituents or their position.…”

“…6π-Electrocyclization, one of the well-known concerted pericyclic reactions, represents an elegant annulation approach for the synthesis of heterocycles and has gained great interest in the synthesis of pyridines, chromene, nicotinamide and pyridinium bisretinoid . Recently, Katsumura and co-workers reported the synthesis of dihydropyridin-2­(3 H )-ones via a Pd-catalyzed 6-endo type cyclization of N -sulfonyldienamide . Soon after, they revealed that analogous reactions could successfully proceed in the absence of transition metal catalysts following a thermal 6π-azaelectrocyclization mechanism.…”

Rapid Access to Azabicyclo[3.3.1]nonanes by a Tandem Diverted Tsuji–Trost Process

“…Related conjugateda ddition processesh ave been observed to occur under palladiumc atalysis. [24] In conclusion, we have demonstrated that ad iverted Ts uji-Trost process provides rapid access to biologically important ring systems. This occurs via an unusual Pd-catalysedm echanism, exploiting processes often regarded as unwanted side reactions that is, proto-dehalogenation, b-hydridee limination and Pd O-enolate equilibration.…”

“…These species undergo acid/base‐promoted isomerization to the observed product. Related conjugated addition processes have been observed to occur under palladium catalysis [24] …”

Recent advances in Pd-catalyzed asymmetric cyclization reactions

“…Using a BINAP-Pd catalyst system, an asymmetric 6- endo type cyclization of dienamide 818 to synthesize chiral 2-piperidinone compounds 819 was described by Katsumura, Tsuchikawa and co-workers in 2012 (Scheme 194). 369 It was notable that both N-p -toluenesulfonyl and C-3 ester substituents were essential for activating this cyclization reaction. This transformation was proposed to proceed via the key activated 1-azatriene intermediate Int-A , followed by an immediate aza-electrocyclization to give the 2-piperidinone compound, but the other possibility via Pd(0)-catalyzed intramolecular amidation could not be ruled out.…”