Rh^III‐Catalyzed Synthesis of Highly Substituted 2‐Pyridones using Fluorinated Diazomalonate

Abstract

AR h III -catalyzed strategy wasd eveloped for the rapid constructiono fh ighly substituted 2-pyridones caffolds using a,b-unsaturated oximes and fluorinated diazomalonate. The reaction proceeds through direct, site-selective alkylation based on migratory insertiona nd subsequent cyclocondensation. Awide substrate scope with different functional groups wase xplored. The requirement of fluorinated diazomalonate was explored for this transformation. The developed methodology was furthere xtended with the synthesis of the bioactive compound.Highly substituted 2-pyridones are considered as one of the most important classes of electron-deficient nitrogen-containing heterocycles due to its often occurrence as pharmaceuticals, bioactive natural products,o rganic-materials (Figure 1). [1] Since the development of classical synthetic strategies with their specific limitations, [2] transition metal catalysis played a crucial role in the development of step-economic strategies for the construction of this core. [3] Chem. Asian J. 2020, 15,360 -364

Straightforward Construction and Functionalizations of Nitrogen‐Containing Heterocycles Through Migratory Insertion of Metal‐Carbenes/Nitrenes

“…The method proceeded via i) the site-selective alkylation of the α, βunsaturated oxime using fluorinated diazo malonate as an alkylating agent ii) nucleophilic attack of oxime N-center towards the highly electrophilic ester carbonyl centre and iii) subsequent rearomatization (Scheme 9). [21] This protocol featured a vast scope, including aryl groups with electrondeficient, electron-withdrawing substituents, and functional groups such as esters and halides.…”

Rhodium‐Catalyzed Cascade Reactions using Diazo Compounds as a Carbene Precursor to Construct Diverse Heterocycles

“…Lastly, a nucleophilic attack of the N-atom present on oxime to the electrophilic carbonyl center present on trifluoroethyl ester occurred followed by deprotonation provided the desired cyclized 2-pyridone product (148). [51] Volla and co-workers demonstrated a method to synthesize biologically relevant indolo[2,3-c]isoquinoline-5-ones (155) derivatives via Rh(III)-catalyzed reaction of N-methoxy benzamides (153) and 3-diazoindolin-2-imines (154) under modest reaction conditions (Scheme 41). [52] During this study, they have screened [Cp*RhCl 2 ] 2 as a catalyst along with different bases and solvents, and found that reaction gave maximum yield of product (155) when employed CsOAc as a base in DCE at 80 °C.…”

“…Samanta et al developed an economic process for the synthesis of 2-pyridone scaffolds (148) via cycloaddition of α, β-unsaturated oximes (146) with fluorinated diazomalonate (147) using (Cp*RhCl 2 ) 2 as a catalyst (Scheme 40). [51] After having optimized reaction conditions i. e., 1 equiv. of 2-pyridone and 1.2 equiv.…”

“…Next, the migratory insertion and protodemetalation occurs leading to a six‐membered rhodacycle ( iii ) and β‐alkylated complex ( iv ) respectively along with the regeneration of active Rh(III)‐catalyst. Lastly, a nucleophilic attack of the N‐atom present on oxime to the electrophilic carbonyl center present on trifluoroethyl ester occurred followed by deprotonation provided the desired cyclized 2‐pyridone product ( 148 ) [51] …”

Redox-Neutral Cobalt(III)-Catalyzed C–H Activation/Annulation of α,β-Unsaturated Oxime Ether with Alkyne: One-Step Access to Multisubstituted Pyridine

“…Reagents and starting materials were purchased from Sigma-Aldrich, TCI, Avra, Spectrochem, and other commercially available sources, used without further purification unless otherwise noted. All aldol condensation derivatives, 28 imine derivative, 29 and alkyne derivatives 30 were prepared according to the reported literature procedure.…”