Efficient Palladium-Catalyzed Cross-Coupling of β-Chloroalkylidene/arylidene Malonates Using Microwave Chemistry

Abstract

A general method for the synthesis of beta-aryl/alkylarylidene malonates is reported. The key step involves the coupling of an arylboronic acid to a beta-chloroalkyl/arylidene malonate, in the presence of K2CO3 and 1 mol % of the air-stable palladium catalyst (POPd) under microwave irradiation, to afford beta-aryl/alkylarylidene malonates in good yields. The combination of mild reaction conditions, air stable catalyst, microwave-enhanced chemistry, and high levels of functional group compatibility make this an attractive synthetic approach to this class of compounds.

Microwave-Assisted Palladium-Catalyzed Cross-Coupling Reactions: Generation of Carbon–Carbon Bond

“…The coupling of an arylboronic acid to a β-chloroalkyl/arylidene malonate in the presence of K2CO3 and 1 mol% of the air-stable palladium catalyst, [(t-Bu)2P(OH)]2PdCl2, under microwave irradiation affords β-aryl/alkylarylidene malonates, which were synthesized mainly upon Knoevenagel condensation. The mild reaction conditions allow a variety of arylboronic acids bearing electron-rich, electron-deficient, sterically demanding systems, amino and hydroxyl functionality to afford the products in good yields, Scheme 20 [54]. Schotten's group has reported that palladium acetate catalyzes the cross-coupling reaction of poly(ethylene glycol) (PEG) ester of bromo-, iodo-, and triflate-para-substituted benzoates with aryl boronic acids in water under microwave irradiation for 2-4 min (Scheme 19).…”

“…The coupling of an arylboronic acid to a β-chloroalkyl/arylidene malonate in the presence of K2CO3 and 1 mol% of the air-stable palladium catalyst, [(t-Bu)2P(OH)]2PdCl2, under microwave irradiation affords β-aryl/alkylarylidene malonates, which were synthesized mainly upon Knoevenagel condensation. The mild reaction conditions allow a variety of arylboronic acids bearing electron-rich, electron-deficient, sterically demanding systems, amino and hydroxyl functionality to afford the products in good yields, Scheme 20 [54]. The coupling of an arylboronic acid to a β-chloroalkyl/arylidene malonate in the presence of K 2 CO 3 and 1 mol% of the air-stable palladium catalyst, [(t-Bu) 2 P(OH)] 2 PdCl 2 , under microwave irradiation affords β-aryl/alkylarylidene malonates, which were synthesized mainly upon Knoevenagel condensation.…”

Evolution of microwave irradiation and its application in green chemistry and biosciences

“…The formation of 15-membered meta, meta-cyclophane, biphenomycin B have several biological activities, such as antimuscarinic activity, antibacterial activity, and antifungal activity 106, featuring a key microwave-induced intramolecular Suzuki-Miyaura reaction step, which was carried out by using controlled microwave heating to increase the cyclization efficiency in the key C-C coupling reaction of the tripeptide 105 precursor [90]. The best yield was obtained when using a toluene-water solvent system in the presence of TBAB (tetrabutylammonium bromide) as an additive (Scheme 35).…”

Studies of Anti‐HIV Transcription Inhibitor Quinolones: Identification of Potent N1‐Vinyl Derivatives

“…2‐Methyl quinolone 2 a was prepared as outlined in Scheme through a Gould–Jacob procedure. The reaction of 3‐chloro‐4‐nitroaniline with diethyl 2‐(1‐chloroethylidene)malonate 13 8 gave intermediate 14 which, following cyclization with refluxing diphenylether, furnished the desired ethyl 7‐chloro‐2‐methyl‐6‐nitro‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate, along with 30 % of its regioisomer (ethyl 5‐chloro‐2‐methyl‐6‐nitro‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylate). The mixture was difficult to separate and was, therefore, used directly in the successive methylation step to yield desired N ‐methyl derivative 15 following purification.…”