Synthesis of 3‐Unsubstituted Phthalides from Aryl Amides and Paraformaldehyde via Ruthenium(II)‐Catalyzed C–H Activation

Abstract

A straightforward and convenient route has been developed for the synthesis of 3‐unsubstituted phthalide derivatives from aryl amides and paraformaldehyde by ruthenium(II)‐catalyzed C–H activation. The reaction proceeds through tandem ortho‐hydroxymethylation of aryl amide and subsequent intramolecular lactonization.

Asymmetric Ruthenium‐Catalyzed C−H Activation by a Versatile Chiral‐Amide‐Directing Strategy

“…[24,25b] It is worth noting that transition-metal-catalyzed direct addition of aryl CÀ H to aldehyde/ketones followed by lactonization emerged as a highly efficient strategy for the construction of various phthalides. [26] Attractively, reactants are simple and readily available. However, the asymmetric variants remain rare.…”

An Overview of Natural and Synthetic Phthalides Involved in Cancer Studies: Past, Present, and Future

“…[91] Since the classical synthesis of phthalides between 2-formylbenzoic acids with phenols, [16] many different synthetic routes have been added to the literature giving rise to the synthesis and derivatization of phthalides such as Diels-Alder reaction between furanones and dienes from Watanabe et al in 1989, [92] one-pot intramolecular reactions, [93] palladium-catalyzed intramolecular benzannulation of bis-enyne and enynen-diyne systems, [94] Rh III -catalyzed regioselective synthesis with water as the solvent, [95] asymmetric domino multicatalysis oxidation/oxa Michael addition reaction, [96] reactions between hydroxycoumarins and 2-formylbenzoic acid derivatives in water as an environmentally friendly solvent, [97] o-phthaldehydic acid with amino compounds, [98] etc. [99][100][101][102] In 2014, Karmakar and co-workers published a review in which the specific syntheses of naturally occurring phthalides are featured. [3] In 2019 Renzetti and co-workers reviewed the methods for the synthesis of phthalides and α,β-butenolides by CÀ H bond functionalization from non-halogenated starting materials.…”