Chemistry of Ketene N,S-Acetals: An Overview

Abstract

Push-pull alkenes, which bear electron-donating and -accepting group(s) at both termini of a C═C double bond, respectively, are of interest not only for their unique electronic properties but also for their importance as versatile building blocks in organic synthesis. In the world of ketene acetals having the push-pull alkene skeleton, ketene N,S-acetal is most likely the biggest family according to the number and types of these compounds. The first ketene N,S-acetal compound was reported in 1956. As a cyclic ketene N,S-acetal compound, nithiazine, the first lead structure of neonicotinoid insecticides, was reported in 1978. The characteristics of ketene N,S-acetals, which have the structural feature of ketene S,S-acetals and enaminones, make them versatile and easy to use, especially in cyclization and multicomponent reactions for the synthesis of various heterocyclic systems and related natural products. There has been an increasing wealth of information about the synthesis and synthetic applications of ketene N,S-acetals, especially, in recent years. This review provides comprehensive knowledge on the chemistry of ketene N,S-acetals.

Synthesis of fused hydroxy dihydropyrroles and unexpected dihydropyrazine and dihydroquinoxaline derivatives based on heterocyclic ketene aminals

“…For example, the 1 H NMR spectrum of 6e showed two singlets for the NMe 2 (δ = 3.36, 2.95 ppm) and one signal for the NH group (δ = 11.85), which was exchanged with deuterium, along with characteristic signals for the phenyl moiety. Initial addition of 1,n-diamine to 1,1-bis (methylsulfanyl)-2-nitroethene leads to HKA 11, [40] which is protonated by the C-H acid to afford 12, followed by intramolecular proton transfer and elimination of diamine leads to 14. The 13 C NMR spectrum of 6e showed 18 resonances in agreement with the proposed structure.…”

“…[39,40] Herein, we report four-component domino reaction for the synthesis of highly substituted fused dihydropyrroles and dihydropyrazines via reaction of 1,1-bis (methylsulfanyl)-2-nitroethene 1, various diamines 2, arylglyoxal monohydrates 3, and C-H acids 4 (Scheme 1). [39,40] Herein, we report four-component domino reaction for the synthesis of highly substituted fused dihydropyrroles and dihydropyrazines via reaction of 1,1-bis (methylsulfanyl)-2-nitroethene 1, various diamines 2, arylglyoxal monohydrates 3, and C-H acids 4 (Scheme 1).…”

Carbene‐Catalyzed Enantioselective Aromatic N‐Nucleophilic Addition of Heteroarenes to Ketones

“…For example, the nitrogen atoms of indole molecules can undergo addition reactions with reactive ketones to form N , O ‐acetals . Acetals are versatile structural motifs with applications in organic synthesis and pharmaceutical research . Most acetal‐forming reactions can be made very efficient.…”

“…[1,2] Acetals are versatile structural motifs with applications in organic synthesis [3,4] and pharmaceutical research. [5][6][7][8][9] Most acetal-forming reactions can be made very efficient. Themain challenges,however,lies on controlling the enantioselectivities of these transformations.I nt he field of transition-metal-free catalysis,c hiral phosphoric-acid catalysts have found impressive success in the mediation of asymmetric acetal formations,aspioneered by Antilla, [10] List, [11] and others.…”

4-Trifluoromethyl-p-quinols as dielectrophiles: three-component, double nucleophilic addition/aromatization reactions

“…This reaction enables two different nucleophiles, a thiol and a carbonucleophile generated in-situ from ketene dithioacetals3637, to be introduced on “aromatic to be” carbons3132333435 in the ortho and para positions of the CF 3 group of 4-(trifluoromethyl)- p -quinols via a novel meta -double functionalization fashion (Fig. 2b)32.…”