Cyclization of ortho-hydroxycinnamates to coumarins under mild conditions: A nucleophilic organocatalysis approach

Abstract

Summary(E)-Alkyl ortho-hydroxycinnamates cyclize to coumarins at elevated temperatures of 140–250 °C. We find that the use of tri-n-butylphosphane (20 mol %) as a nucleophilic organocatalyst in MeOH solution allows cyclization to take place under much milder conditions (60–70 °C). Several coumarins were prepared, starting from ortho-hydroxyarylaldehydes, by Wittig reaction with Ph3P=CHCO2Me to (E)-methyl ortho-hydroxycinnamates, followed by the phosphane catalyzed cyclization.

A One‐Pot Synthesis of Pyranocoumarins Through Microwave‐Promoted Propargyl Claisen Rearrangement/Wittig Olefination

“…We were confident that our preferred reaction temperature of 250 °C could not be substantially lowered, because both our research group and that of Pospíšil recently found that E/Z isomerization of the intermediate cinnamates, a prerequesite for the cyclization into coumarin, does not efficiently proceed at temperatures lower than 200 °C. There is literature precedent for the conversion of preformed cinnamates into coumarins through an E/Z isomerization/cyclization sequence at temperatures below 100 °C, but this method requires the presence of air‐sensitive trialkylphosphines as catalysts . Nevertheless, we submitted 12a under otherwise identical conditions to microwave irradiation at 200 °C for 1 h (Table , Entry 6).…”

“…There is literature precedent for the conversion of preformed cinnamates into coumarins through an E/Z isomerization/cyclization sequence at temperatures below 100°C, but this method requires the presence of air-sensitive trialkylphosphines as catalysts. [44] Nevertheless, we submitted 12a under otherwise identical conditions to microwave irradiation at 200°C for 1 h (Table 2, Entry 6). This resulted in complete consumption of the starting material but, not surprisingly, with very poor selectivity, as a complex mixture of products was observed.…”

Visible-Light Photocatalytic E to Z Isomerization of Activated Olefins and Its Application for the Syntheses of Coumarins

“…Coumarins, the important structural motifs in natural products and bioactive compounds, exhibiting broad biological activities, have been the targets for many organic syntheses [32][33][34]. Among many successful methods developed over the years, cyclization of ortho-hydroxycinnamates via double-bond isomerization was the one which was generally convenient from easily obtained starting material and afforded the coumarins in very good yields.…”

tert‐Butoxide‐Mediated Synthesis of 3,4′‐Biquinolines from 2‐Aminochalcones

“…In our previously reported synthesis of quinolines 2 from 2‐aminochalcones 1 with a nucleophilic catalyst, the nucleophile undergoes conjugate addition to 2‐aminochalcones 1 to give the corresponding enolates 4 , which subsequently abstract a proton to form the saturated ketones 5 bearing the nucleophile at the β‐position. Condensation between the amino and carbonyl groups in 5 followed by elimination of the nucleophile would provide the desired quinoline products 2 (Scheme ) ,. Based on the reaction mechanism for the synthesis of quinolines 2 from 2‐aminochalcones 1 , we hypothesized that if enolates 4 underwent Michael addition to another molecule of 2‐aminochalcones 1 instead of the proton abstraction, dimeric intermediates 7 of 2‐aminochalcones, connected through the C α −C β’ bond, would be generated after protonation.…”