Straightforward Synthesis of Novel Difluorinated 2‐Hydroxyl‐Substituted Dihydroquinolones Through Selectfluor‐triggered Annulation of 2‐Aminoarylenaminones

Abstract

A series of novel difluorinated 2‐hydroxyl‐substituted dihydroquinolones have been firstly synthesized via selectfluor‐triggered tandem cyclizations of 2‐aminoarylenaminones. This new approach could occur under mild reaction conditions, and features easy operation and scalability.

Recent Advances in Reactions Using Enaminone in Water or Aqueous Medium

“…As the general process, the condensation of enaminones with hydrazine first took By employing o-aminophenyl enaminones 48 and selectfluor 49 as main substrates in water/acetone medium, the 3,3-difluoro-2-hydroxyl dihydroquinolones 50 were synthesized in the presence of NaOAc by Yang group. [32] The reactions started from the electrophilic fluorination of 48 with 49 providing Water acted as both the medium and hydroxyl group donor in the reactions (Scheme 20). It was noteworthy that the reactions of structurally similar o-hydroxyphenyl enaminones were later found to undergo halocyclization for the synthesis of 2-amino-3,3difluorochromanones and 2-amino-3,3-dihalochromanones (halogen = Cl, Br) by conducting reactions in the absence of water by Yang [33] and us, [8c] respectively.…”

“…By employing o ‐aminophenyl enaminones 48 and selectfluor 49 as main substrates in water/acetone medium, the 3,3‐difluoro‐2‐hydroxyl dihydroquinolones 50 were synthesized in the presence of NaOAc by Yang group [32] . The reactions started from the electrophilic fluorination of 48 with 49 providing 20 A .…”

Recent Advances in Organic Synthesis Based on N,N-Dimethyl Enaminones

“…In 2018, Yang and co-workers synthesized a series of novel difluorinated 2-hydroxy-substituted dihydroquinolones via Selectfluor-triggered cascade cyclizations of 2-aminoarylenaminones for the first time (Scheme 59). 62 From the results of substrate scope studies, the electronic character of the N-substituent had a considerable impact on the Selectfluor-triggered tandem cyclization process. The introduction of electron-withdrawing substituents (Boc, Ac) onto the nitrogen atom of the 2-aminoarylenaminone gave the corresponding products in higher yields compared to those with electron-donating substituents (Bn, allyl).…”

A Straightforward Approach to Fluorinated Pyrimido[1,2-b]indazole Derivatives via Metal/Additive-Free Annulation with Enaminones, 3-Aminoindazoles, and Selectfluor

“…Enaminones, as easily available and versatile building blocks with highly active sites and structural diversity, have been widely used in organic synthesis . Recently, electrophilic fluorination of enaminones with Selectfluor has become a powerful strategy for the synthesis of fluorine-containing heterocycle compounds. − For example, Yang’s, and Song’s groups have achieved the preparation of difluorinated dihydrochromones using o -hydroxyl enaminones with Selectfluor through the electrophilic fluorination and intramolecular cyclization processes, respectively. Later on, Yang and co-workers developed the first example of synthesizing difluorinated 2-hydroxyl-substituted quinolones via a tandem process .…”

“…Recently, electrophilic fluorination of enaminones with Selectfluor has become a powerful strategy for the synthesis of fluorine-containing heterocycle compounds. − For example, Yang’s, and Song’s groups have achieved the preparation of difluorinated dihydrochromones using o -hydroxyl enaminones with Selectfluor through the electrophilic fluorination and intramolecular cyclization processes, respectively. Later on, Yang and co-workers developed the first example of synthesizing difluorinated 2-hydroxyl-substituted quinolones via a tandem process . In addition, the same group also reported a BHT-regulated protocol for the construction of monofluorinated chromones using o -hydroxyl enaminones with Selectfluor .…”