Metal‐Free Synthesis of Furocoumarins: An Approach via Iodine‐Promoted One‐Pot Cyclization between 4‐Hydroxycoumarins and Acetophenones

Abstract

A transition metal‐free approach was developed to achieve substituted furocoumarins via an iodine‐promoted one‐pot cyclization between 4‐hydroxycoumarins and acetophenones. High yields of furocoumarins were achieved in the presence of NH4OAc as an additive, while neither acidic nor basic additives were effective. The reaction would proceed via a 5‐exo‐tet cyclization but not an O‐alkylation. The fact that commercially available starting materials could be used without the need of a transition metal catalyst could be a significant advantage.

Recent Advances on Sustainable Synthesis of Furocoumarins

“…Phan and co-workers developed a transition metal-free approach for the synthesis of furocoumarins by promoting a one-pot cyclization reaction between 4-hydroxycoumarins and acetophenones in the presence of iodine as a catalyst and ammonium acetate as an additive (Scheme 74). [139] The methodology works well for electronically varied substituents (electron withdrawing and electron donating substituents) present in meta and para position of benzophenone and 4-hydroxycoumarins to afford moderate to good yield of the desired product (54% to 92% yield). The yield of the reaction was found to be lower for ortho-substituted benzophenone (28% yield) due to the possibility of increased steric repulsion.…”

Convenient multicomponent synthesis of furo[3,2-c]coumarins in the promoting medium DIPEAc and assessment of their therapeutic potential through in silico pharmacophore based target screening

“…The literature survey reveals that the synthesis of furocoumarins has already been reported by using catalysts such as Fe 3 O 4 @SiO 2 nanoparticles, 20 I 2 /H 2 O, 21 pyridine or a mixture of AcOH and AcONH 4 , 22 ionic liquid [BMIm]OH, 23 Pd(CF 3 COO) 2 , 24 CuBr 2 , 25 N -methylimidazolium 26 and Et 3 N. 27 However, in spite of their potential benefits, many of these reported methods suffer from drawbacks such as the use of environmentally harmful organic solvents, expensive catalysts, harsh reaction conditions, difficult work-up, non-recyclability of solvents, commercial unavailability and low yields. Given this scenario, the discovery of robust synthetic strategies that enable the one-pot convergent assembly of furocoumarins remains a vibrant research area.…”