Hydroiodination‐Triggered Cascade Reaction with I₂/PPh₃/H₂O: Metal‐Free Access to 3‐Substituted Phthalides from 2‐Alkynylbenzoates

Abstract

Phthalide is an important scaffold found in several biologically active compounds. Therefore, effective methods for the synthesis of phthalides are strongly desired. Herein, we describe the metal‐free synthesis of 3‐substituted phthalides by the reductive hydroiodination of 2‐alkynylbenzoates through an I2/PPh3/H2O‐triggered cascade reaction. A variety of 3‐substituted phthalides were synthesized in excellent yields by a one‐pot reaction involving four processes: desilylation, hydroiodination, cyclization, and reduction.

Pd-Catalyzed carbonylative lactonization of 2-halidearomatic aldehydes with H2O as a nucleophile

“…2 Therefore, the development of an efficient method for the construction of phthalides is highly demanded. Consequently, numerous efforts have been devoted to this field, and lots of methodologies have become available for the synthesis of phthalides, such as the oxidative cyclization of phthalaldehydes, 3 oxa-Michael addition reaction, 4 aromatic C–H bond activation of aromatic acids, 5 reductive hydroiodination of 2-alkynylbenzoates, 6 Friedel–Crafts alkylation of indoles, 7 aldol-lactonization reactions, 8 etc . 9 Despite the flourishing advancement of phthalide chemistry, the development of new methods to construct complex lactones using different nucleophiles remains of great significance.…”

One-Pot Synthesis of Spiro-isobenzofuran Compounds via the Sequential Condensation/Oxidation Reaction of Ninhydrin with 4-Amino-1,2-naphthoquinones/2-Amino-1,4-naphthoquinones under Mild Conditions

“…Due to the chemical importance and biological applications of isobenzofurans, their synthesis has attracted the interest of various research groups and quite a lot of methods have been developed. Someof the most recently reported methods include the following: Montmorillonite K-10-, ZrOCl 2 –8H 2 O-, and silica-supported Preyssler-nanoparticle-catalyzed condensation and lactonization of phthalaldehydic acid (2-carboxybenzaldehyde) with methylaryl and cyclic ketones; magnetic-nanoparticle-supported 1-methyl-3-(propyl-3-sulfonic acid)­imidazolium triflate-catalyzed reaction of phthalaldehydes, and methylaryl ketones; insertion of aldehydes into a C–H bond of aromatic ketimines using a rhenium complex, [ReBr­(CO) 3 (thf)] 2 ; coupling of o -alkynylbenzoyl derivatives with Fischer carbene complexes; Pd-catalyzed oxidative intramolecular C–H functionalization reactions of 3-(2-(hydroxymethyl)­aryl)- N -methyl- N arylpropiolamides; l -proline-catalyzed cascade Michael-aldol reaction of 4-hydroxy-3-alkyl-5 H -furan-2-ones with alkyl vinyl ketones; silica sulfuric acid- and molecular-iodine-mediated oxidative cleavage of 4b,9b-dihydroxy-4 bH -indeno­[1,2- b ]­benzofuran-10­(9 bH )-ones; Sc­(OTf) 3 -catalyzed reaction of o -dicarbonylbenzenes and hydrosilane; chemoenzymatic bioreduction of 2-acetylbenzonitriles; [Cu]- and [Pd]-catalyzed intermolecular cyanation or carbonylation of o -bromobenzyl alcohols; the reaction of 2-cyanobenzaldehydes with nucleophiles, such as organolithiums or lithium enolates of tert -butyl acetate and N , N -dimethylacetamide; nucleophilic addition of alkynyllithium to benzocyclobutenone and subsequent oxidative ring cleavage of the prepared bicyclo[4.2.0]­octatrien; oxidation of indane derivatives using molecular oxygen and H 2 O 2 in subcritical water; trifluoroacetic acid-mediated lactonization of tert -butyl 2-(1,3-dioxol-2-yl)- or 2-(1,3-dioxan-2-yl)­benzoates; and reductive hydroiodination of 2-alkynylbenzoates through an I 2 /PPh 3 /H 2 O-triggered cascade reaction …”