2H-Azirines as C–C Annulation Reagents in Cu-Catalyzed Synthesis of Furo[3,2-c]quinolone Derivatives

Abstract

A method of furo-annulation of 4-hydroxy-2oxoquinoline-3-carboxylates with 3-arylazirines under Cu(II) catalysis was developed to synthesize a variety of 2,3dihydrofuro[3,2-c]quinolones bearing a carbamate group at the C2 position. The reaction involves an azirine ring opening across the N−C2 bond and formation of a dihydrofuran ring with the inclusion of two azirine carbon atoms, accompanied by a shift of the ester group to the nitrogen. The discovered reaction is the first example of the use of 2H-azirines for furo-annulation.

Design, Synthesis, in vitro and in silico Characterization of 2‐Quinolone‐L‐alaninate‐1,2,3‐triazoles as Antimicrobial Agents

“…In this context, the antimicrobial importance of polyheterocyclic systems such as 2‐quinolones is well established. The 2‐quinolone moiety is among the most widely used synthetic scaffolds that researchers have used for successful design of new antimicrobial agents [11–25] . One useful strategy has been to create hybrid molecules [26] using two different pharmacophoric moieties with antimicrobial effects.…”

“…The 2‐quinolone moiety is among the most widely used synthetic scaffolds that researchers have used for successful design of new antimicrobial agents. [ 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 ] One useful strategy has been to create hybrid molecules [26] using two different pharmacophoric moieties with antimicrobial effects. 2‐Quinolones could be combined with, for example, the privileged scaffolds of 1,2,3‐ or 1,2,4‐triazoles[ 27 , 28 , 29 ] that have both been widely applied not only in medicinal chemistry[ 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ] but also in material science.…”

Copper(II)-Catalyzed (3+2) Cycloaddition of 2H-Azirines to Six-Membered Cyclic Enols as a Route to Pyrrolo[3,2-c]quinolone, Chromeno[3,4-b]pyrrole, and Naphtho[1,8-ef]indole Scaffolds

“…However, attempts to extend this method to six-membered enols of the quinoline-3-carboxylate series unexpectedly encountered a serious problem associated with the involvement of the ester substituent in the transformation ( Scheme 1 , reaction 2a). This reaction also proceeds through azirine N1-C2 bond cleavage under both Cu(I) and Cu(II) catalysis, but exclusively produces the furo-annulation product [ 29 ]. A visible-light-promoted (3+2) cycloaddition of azirines, derived in situ from vinyl azides, to α-hydroxybenzoquinones is the only successful example of azirine cycloaddition to a multiple bond of a six-membered cyclic enol to date ( Scheme 1 , reaction 2b) [ 30 ].…”

Regiodivergent Synthesis of Butenolide-Based α- and β-Amino Acid Derivatives via Base-Controlled Azirine Ring Expansion

“…The first example of the formation of the furan ring using carbon atoms of the azirine intermediate was the synthesis of 2-aminobenzofurans from vinyl azides under visible light irradiation (Scheme , reaction 1) . Recently, we reported the first example of the use of stable azirines for ortho -annulation of the dihydrofuran ring to the 4-quinolin-2-one ring (reaction 2) . Both of the above reactions proceed through the azirine N1–C2 bond cleavage.…”

“…7 Recently, we reported the first example of the use of stable azirines for ortho-annulation of the dihydrofuran ring to the 4quinolin-2-one ring (reaction 2). 8 Both of the above reactions proceed through the azirine N1−C2 bond cleavage. Examples of the use of 2H-azirines for the formation of the unfused furan derivatives, including furanones, are hitherto unknown.…”