Palladium Catalyst Recycling for Heck‐Cassar‐Sonogashira Cross‐Coupling Reactions in Green Solvent/Base Blend. Issue 12 (11th May 2021)

• Record Type: Journal Article
• Authors: Fantoni, Tommaso; Bernardoni, Sara; Mattellone, Alexia; Martelli, Giulia; Ferrazzano, Lucia; Cantelmi, Paolo; Corbisiero, Dario; Tolomelli, Alessandra; Cabri, Walter; Vacondio, Federica; Ferlenghi, Francesca; Mor, Marco; Ricci, Antonio
• Is Part Of: ChemSusChem. Volume 14:Issue 12(2021)
• Page Start: 2591
• Page End: 2600
• Publication Date: 2021-05-11
• Subjects: cross-coupling -- green chemistry -- Heck-Cassar-Sonogashira -- homogeneous catalysis -- TPPTS; Green chemistry -- Periodicals; Sustainable engineering -- Periodicals; Chemistry -- Periodicals; Chemical engineering -- Periodicals; 660
• DOI: 10.1002/cssc.202100623
• Languages: English
• ISSNs: 1864-5631

Abstract

Abstract: The identification of a green, versatile, user‐friendly, and efficient methodology is necessary to facilitate the use of Heck‐Cassar‐Sonogashira (HCS) cross‐coupling reaction in drug discovery and industrial production in the pharmaceutical segment. The Heck‐Cassar and Sonogashira protocols, using N ‐hydroxyethylpyrrolidone (HEP)/water/ N, N, N′, N′ ‐tetramethyl guanidine (TMG) as green solvent/base mixture and sulfonated phosphine ligands, allowed to recycle the catalyst, always guaranteeing high yields and fast conversion under mild conditions, with aryl iodides, bromides, and triflates. No catalyst leakage or metal contamination of the final product were observed during the HCS recycling. To our knowledge, a turnover number (TON) up to 2375, a turnover frequency (TOF) of 158 h −1, and a process mass intensity (PMI) around 7 that decreased around 3 after solvent, base, and palladium recovery, represent one of the best results to date using a sustainable protocol. The Heck‐Cassar protocol using sSPhos was successfully applied to the telescoped synthesis of Erlotinib (TON: 1380; TOF: 46 h −1 ). Abstract : Recycle and reuse : Heck‐Cassar‐Sonogashira cross‐coupling using the green N ‐hydroxyethylpyrrolidone (HEP)/H2 O/ N, N, N′, N′ ‐tetramethyl guanidine (TMG) blend, sulfonate phosphines, and aryl iodides, bromides, and triflates affords the corresponding products in high yield free from metal contamination. The catalyst/HEP/H2 O solution can be recycled, increasing turnover number and frequency up to 2375 and 158 h −1, respectively, with a low process mass intensity close to 3 after solvent, base, and palladium recovery. Additionally, Erlotinib synthesis is described.