Silver‐Catalyzed Synthesis of Substituted Pyridine Derivatives from N‐Propargylic α‐Enamino Esters

Abstract

A wide range of substituted pyridine derivatives were synthesized in moderate to good yields from N‐propargylic α‐enamino esters. The synthetic strategy involved regioselective addition of a propargylamine to the α‐carbon atom of an alkynyl ester to produce the N‐propargylic α‐enamino ester, which acted as the key intermediate in the synthesis.

One-Pot Sequential Hydroamination Protocol for N-Heterocycle Synthesis: One Method To Access Five Different Classes of Tri-Substituted Pyridines

“…To further demonstrate the versatility of this one-pot sequential reaction, the scope for 2,3,4-trisubstituted pyridines was investigated (Scheme ). This substitution pattern is generally accessed via ring substitution reactions by sequential cross-couplings as there are few synthetic routes available. − With our one-pot protocol, 2,3,4-trisubstituted pyridine derivatives were obtained by using N -triphenylsilylamine, internal alkynes, and 3-substituted α,β-unsaturated aldehydes, which were either commercially available or readily synthesized using a Wittig reaction. A variety of internal alkynes were screened for altering the substituents at 2- and 3-positions.…”

“…Recent advances in the synthesis of multisubstituted pyridines include transition metal-catalyzed intermolecular cyclization to access functionalized pyridine derivatives from pre-functionalized substrates. ,,, A variety of intermolecular cyclization methodologies have been developed to access tri-substituted pyridines, including [2+2+2], [2+2+1+1], [3+3], [3+2+1], and [4+2] cycloadditions and cycloisomerizations. ,,, A majority of the reported methodologies focus on the synthesis of 2,3,6-, 2,3,5-, and 2,4,6-trisubstituted pyridines with fewer methodologies focusing on 2,3,4- and 2,4,5-trisubstituted pyridines (Scheme ). ,,− Only a limited number of synthetic strategies are available to access 3,4,5-trisubstituted pyridines, making it a challenging substitution pattern, which is generally accessed with sequential cross-coupling reactions. ,− Diverse tri-substitution patterns of pyridines are found in a number of FDA-approved drugs such as etoricoxib (2,3,5-), lansoprazole (2,3,4-), and netupitant (2,4,5-) (Figure ). The development of a new, facile strategy to access the less explored pyridine substitution patterns from readily available substrates may enable the development of alternatively substituted pyridines for exploration in medicinal chemistry.…”

Preliminary Study on Novel Expedient Synthesis of 5-Azaisocoumarins by Transition Metal-Catalyzed Cycloisomerization

“…The structure of 4a was confirmed by comparison of its NMR spectrum with previously reported data ( Table S1 ) (Hellal et al, 2008 ). Recently, many research groups have continuously reported the efficiency of various transition-metal Lewis acid catalysts for alkyne activation in cycloisomerization reaction (Abbiati et al, 2003 ; Yan et al, 2007 ; Cacchi et al, 2008 ; Saito et al, 2009 ; Jiang et al, 2010 ; Fei et al, 2011 ; Mikušek et al, 2016 ; Vessally et al, 2016 ; Nizami and Hua, 2017 ; Sakthivel et al, 2017 ; Gianni et al, 2018 ; Lyubov'N et al, 2018 ; Mancuso et al, 2018 ; Ahn et al, 2019 ). To increase the product yield, cycloisomerization was performed in the presence of various metal catalysts, including Ag(I), Au(I), Cu(I), Cu(II), and In(III).…”

Stereoselective Construction of (E,Z)‐1,3‐Dienes and Its Application in Natural Product Synthesis

“…Initially used by Nakagawa in 1977, [228] the 1,6‐addition of nucleophiles to 4‐yn‐2‐en‐one derivatives is an efficient method for constructing conjugated Z,E ‐dienes; however, they exhibit variable Z selectivities [229–233] . Furthermore, Ooi described in 2018 a spectacular organocatalysed 1,6‐Michael addition of azlactones ( 235 ) to enynyl N ‐acyl pyrazoles ( 236 ) [234] .…”

“…however, they exhibit variable Z selectivities. [229][230][231][232][233] Furthermore, Ooi described in 2018 a spectacular organocatalysed 1,6-Michael addition of azlactones (235) to enynyl N-acyl pyrazoles (236). [234] The use of a P-spiro chiral triaminoiminophosphorane catalyst not only allows the perfect control of the addition regioselectivity (1,6 vs 1,4), but also the Z,Econfiguration of the diene and the enantioselectivity of the quaternary centre in the resulting compounds (237, Scheme 92).…”