Recent Advances in Synthesis of 4-Arylcoumarins

Abstract

4-Arylcoumarins (4-aryl-2H-1-benzopyran-2-one), also known as neoflavones, comprise a minor subclass of naturally occurring flavonoids. Because of their broad-spectrum biological activities, arylcoumarins have been attracting the attention of the organic and medicinal chemistry communities, and are considered as an important privileged scaffold. Since the development of Pechmann condensation, a classical acid-catalyzed condensation between phenol and β-keto-carboxylic acid, several versatile and efficient synthetic approaches for 4-arylcoumarins have been reported. This review summarizes recent advances in the synthesis of the 4-arylcoumarin scaffold by classifying them based on the final bond-formation type. In particular, synthetic methods executed under mild and highly efficient conditions, such as solvent-free reactions and transition metal catalysis, are highlighted.

Keywords: 4-arylcoumarins; Pechmann condensation; Wittig-type olefination; aldol-type olefination; cyclocarbonylation; cycloisomerization; hydroarylation; transition-metal-catalysis.

Figure 1

Representative synthetic routes toward 4-arylcoumarin.

Scheme 1

Synthesis of 4-arylcoumarins via FeCl₃-catalyzed intramolecular alkenylation of arenes.

Scheme 2

Pd-catalyzed formation of 4-arylcoumarins via C–H insertion.

Scheme 3

Pd-catalyzed intramolecular (A) and intermolecular (B,C) hydroarylation of C–C triple bonds for the preparation of 4-arylcoumarins.

Scheme 4

Synthesis of 4-arylcoumarins via Au (A)- and Pt (B)-catalyzed intramolecular addition.

Scheme 5

Synthesis of 4-arylcoumarins via Rh-catalyzed C–H bond activation.

Scheme 6

Synthesis of 4-arylcoumarins via Pd-catalyzed cyclocarbonylation.

Scheme 7

Synthesis of 4-arylcoumarins via Cp*Co(III)-catalyzed cyclocarbonylation.

Scheme 8

Synthesis of 4-arylcoumarins via Pd-catalyzed cyclocarboxylation.

Scheme 9

Synthesis of 4-arylcoumarins via transition-metal-free cyclocarboxylation.

Scheme 10

Synthesis of 4-arylcoumarins via Wittig-type reaction (A,B), intramolecular Wittig olefination (C), and Peterson olefination (D).

Scheme 11

Synthesis of 4-arylcoumarins via Kostanecki-Robinson reaction (A) and Knoevenagel condensation (B).

Scheme 12

Synthesis of 4-arylcoumarins via cycloisomerization.

Scheme 13

Synthesis of 4-arylcoumarins by oxidative cyclization.

Scheme 14

Synthesis of 4-arylcoumarins via Pd(0)-catalyzed Stille reaction using 4-triflated coumatins (A), 4-tosylated coumarins (B), 4-stannylcoumarins (C) and 4-chlorocoumarin (D).

Scheme 15

Synthesis of 4-arylcoumarins via Pd(0)-catalyzed Suzuki reaction using 4-halocoumatins (A), 4-tosylated coumarins (B,C), 4-triflated coumarins (D–F) and 4-chlorocoumarin (G).

Scheme 16

Pd(0)-catalyzed introduction of the 4-aryl group via Negishi-type reactions (A,B) and another-type reactions (C–E).

Scheme 17

Ni(II)-catalyzed cross-coupling reactions for 4-arylcoumarin synthesis using 4-diethylphosphonooxycoumarins (A), 4-mesylated coumarins (B), 4-tosylated coumarins (C,D) and 4-carbamoyloxycoumarin (E).

Scheme 18

Synthesis of 4-arylcoumarins via Rh(I)-catalyzed cross-coupling reaction.

Scheme 19

Synthesis of 4-arylcoumarins via oxidative Heck coupling reaction of the 4H-coumarin with aryl boronic acids (A,B) and simple arenes (C).

Scheme 20

Synthesis of 4-arylcoumarins via protodecarboxylation-induced Heck reaction.

Scheme 21

Introduction of 4-aryl group via sequential domino reactions involving Pd(II)-catalyzed oxidative Heck-type arylation (A–C) and Cu(I)-catalyzed 1,4-addition (D).