Formal [4+2] annulation of enaminones and cyanomethyl sulfur ylide: one-pot access to polysubstituted pyridin-2(1H)-ones

Abstract

A facile and efficient one-pot synthesis of polysubstituted pyridin-2(1H)-ones from readily available enaminones and the cyanomethyl sulfonium bromide salt in the presence of cesium carbonate is developed, and a mechanism involving sequential nucleophilic vinylic substitution (S(N)V), intramolecular nucleophilic cyclization and dealkylation reactions is proposed.

Chemistry of Ketene N,S-Acetals: An Overview

“…Ketene N , S -acetals, which possess structural features that enable the olefinic linkage to be activated by electron-releasing alkylthio and amino groups through p−π conjugation, are more reactive toward electrophiles than ethylene. Functionalized ketene N , S -acetals, for example C , having structural features of polarized α-oxo ketene S , S -acetals − ,− and enaminones (Figure ), − have proved to be particularly useful intermediates in organic synthesis. In addition, the incorporation of multiple reactive sites as in enaminones and ketene S , S -acetals, including a good leaving group (alkylthio group) in ketene N , S -acetals along with varied sorts of functional groups (FGs) on the carbon atom adjacent to the acetal moiety (also known simply as the acceptor end) and N -alkyl or N -aryl group, gives ketene N , S -acetals rise to a variety of chemical transformations and allows them to be used easily in the construction of a wide variety of heterocycles. ,,− …”

A Formal [3+2] Annulation of β‐Oxoamides and 3‐Alkyl‐ or 3‐Aryl‐Substituted Prop‐2‐Ynyl Sulfonium Salts: Substrate‐Controlled Chemoselective Synthesis of Substituted γ‐Lactams and Furans

“…All reagents were purchased from commercial sources and used without purification, unless otherwise indicated. 1 H NMR and 13 C NMR spectra were recorded at 25°C at 300 MHz (or Table 2. Formal [3 + 2] annulation of α-unsubstituted β-oxoamides 1 and prop-2-ynyl sulfonium salts 2.…”

“…Reddish solid (169.9 mg, 87%), m.p. 45-46°C; 1 H NMR (300 MHz, CDCl 3 ): δ 8.19 (s, 1H), 6.49 (d, J = 0.9 Hz, 1H), 3.37 (q, J = 6.6 Hz, 2H), 2.30 (s, 3H), 2.12 (d, J = 0.9 Hz, 3H), 1.54-1.63 (m, 2H), 1.32-1.45 (m, 2H), 0.93 (t, J = 7.2 Hz, 3H); 13 C NMR (75 MHz, CDCl 3 ): 191. 2, 164.6, 129.0, 118.8, 99.1, 41.2, 32.2, 28.1, 19.9, 13.7, 11.5;IR (KBr): 2960.3, 2932.9, 2873.6, 1641.8, 1565.9, 1455.1, 1397.4, 1078…”

“…[10] During the course of our studies on the synthesis and applications of varied β-oxoamides and their derivatives, [11] we achieved efficient synthesis of γlactams via a formal [4 + 1] annulation of α,α-dialkylβ-oxoamides and trimethyl sulfoxonium iodide in the presence of NaH (Scheme 1b) [12] and synthesis of substituted pyridin-2(1H)-ones via a formal [4 + 2] annulation of α-acyl acrylamides and cyanomethyl sulfonium salt in the presence of cesium carbonate (Cs 2 CO 3 ), respectively. [13] Inspired by these results and our continued research interest in developing new synthetic methods for highly valuable heterocycles, we set out to explore the reactions of β-oxoamides with 3alkyl/arylprop-2-ynyl sulfonium salts. After a series of detailed investigation, we achieved efficient synthesis of substituted γ-lactams and furans under very mild conditions (Scheme 1c).…”

[3 + 2]-Annulation of Prop-2-ynylsulfonium Salts: Access to Hydroindol-5-ones Containing a Methylthio Group

“…Subsequent protonation of B give intermediate C . The methyl group of the Me 2 S sulfonium would be attacked by Br – to yield intermediate D , which then undergoes double-bond isomerization to afford the final product 3 . The Br – of MeBr proceeds via nucleophilic substitution by the N anion to generate N -methyl product 4 .…”