We have provided a critical review that focuses on key developments in the area of 3-substituted phthalides and their role in the development of important biologically active natural products. 3-Substituted phthalides are vital molecules owing to their fascinating biological activity. The scope, isolation, and characterization of various naturally occurring racemic and chiral 3-substituted phthalides have been covered. We have put significant emphasis on recently developed research methodologies for the synthesis of racemic and chiral 3-substituted phthalides. These newer approaches are essential for the development of newer and elegant strategies for the synthesis of phthalide-based or similar molecular architecture with broader substrate scope and higher stereoselectivities. Also, we have discussed the application of 3-substituted phthalides as a precursor for the synthesis of natural products and their analogs.
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http://dx.doi.org/10.1039/d0ra00701c | DOI Listing |
Photochem Photobiol Sci
November 2024
Faculty of Sciences and Letters, Department of Chemistry, Istanbul Technical University, Istanbul, 34469, Turkey.
Org Biomol Chem
February 2024
Graduate School of Pharmaceutical Sciences, Tokushima University, Shomachi, Tokushima 770-8505, Japan.
We developed a novel thiourea Lewis-base catalyst with phenol moieties for the enantioselective 5--bromolactonization of stilbenecarboxylic acids to afford chiral 3-substituted phthalides. The phenol moieties are crucial for the enantio- and regio-selectivity.
View Article and Find Full Text PDFJ Org Chem
September 2023
Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, P. R. China.
A facile new method for the synthesis of 3,3-disubstituted phthalides is reported. A successive reaction process begins with the TfOH-catalyzed cyclization of -alkynylbenzoic acids followed by an -regioselective electrophilic alkylation of various electron-rich aromatic compounds or alkenes, which has been successfully developed. The corresponding regioselective products of 3-substituted phthalide were obtained in good to high yields.
View Article and Find Full Text PDFJ Org Chem
April 2022
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208016, India.
Herein, we report the asymmetric Ru/cinchonine dual catalysis that provides straightforward access to enantioselective synthesis of C-3 substituted phthalides via tandem C-H activation/Michael addition cascade. The use of readily accessible and less expensive [RuCl(p-cym)] and cinchonine catalyst for the one-pot assembly of chiral phthalides greatly overcomes the present trend of using highly sophisticated catalysts. The developed method provides access to both enantiomers of a product using pseudoenantiomeric cinchona alkaloids as catalysts streamlining the synthesis of phthalide in both the optically active forms.
View Article and Find Full Text PDFChem Commun (Camb)
June 2021
CAS Key Laboratory of Receptor Research, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zuchongzhi Road, Pudong, Shanghai 201203, China. and University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing 100049, China and School of Pharmaceutical Science and Technology, Hangzhou Institute of Advanced Study, Hangzhou 310024, China.
Merging both C-H and C-C activation in a tandem process is a marked challenge. A novel Rh(iii)-catalyzed C-H activation/ring opening C-C cleavage/cyclization of carboxylic acids with cyclopropanols was developed for the synthesis of 3-substituted phthalides and α,β-butenolides. This reaction displays excellent functional group tolerance with respect to both carboxylic acids and cyclopropanols and features relatively mild conditions.
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