Palladium‐Catalyzed Base‐Promoted Arylation of Unactivated C(sp³)–H Bonds by Aryl Iodides: A Practical Approach To Synthesize β‐Aryl Carboxylic Acid Derivatives

Abstract

A highly efficient protocol for the β‐arylation of carboxylic amides by aryl iodides under PdCl2(CH3CN)2/CsOAc catalysis was developed. This method was found to tolerate a broad scope of substrates and was successfully employed in the preparation of a variety of β‐aryl α‐amino and γ‐amino acid derivatives. The utility of this method was further illustrated in the synthesis of the psychotropic drug (±)‐phenibut and β‐aryl bile acid analogues.

Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

“…A further demonstration of synthetic utility is demonstrated through the preparation of cholesterol amides (42) in good to excellent yields via the iodinated cholesterol ( Table 3). The amides were obtained in 1:1 dr and 42c-e were isolated as the enantiopure diastereoisomers following chromatographic purification.…”

Synthesis of β3‐Aryl‐Alaninyl Derivatives by sp3 C‐H Activation with Pd(OAc)2 Catalyst/Pivalic Acid in DCE and Their Structural Studies in Solid State

“…Experimental procedure of synthesized compounds are provided in Supporting Information. Spectral Data ( 1 H-NMR, 13 C-NMR & ESI-HRMS) of newly synthesized compounds and X-ray data given crystals are also depicted 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 Table 3. Backbone torsion angles for monomer, dipeptide and tripeptides.…”

“…The activation of α ‐C−H adjacent to N ‐atom in α ‐amino acid have been reported with CuI/TBHP conditions . Recently, β ‐arylation of carboxylic amides by aryl iodides under PdCl 2 (CH 3 CN) 2 /CsOAc catalysis was developed and has been succefully employed in the preparation of a variety of β‐arylα‐amino and γ‐amino acid derivatives . Hence we hypothesied the synthesis of aryl‐β 3 ‐amino acid from β‐alanine through palladium catalysed reaction.…”

“…[12] Recently, β-arylation of carboxylic amides by aryl iodides under PdCl 2 (CH 3 CN) 2 /CsOAc catalysis was developed and has been succefully employed in the preparation of a variety of β-arylα-amino and γ-amino acid derivatives. [13] Hence we hypothesied the synthesis of aryl-β 3amino acid from β-alanine through palladium catalysed reaction. But very recently, Chowdury etal has reported palladium-catalyzed auxiliary-directed regioselective βmethylene bond arylation of β-alanine with Pd(OAC) 2 /AgoAc system in BuOH-TCE solvent at 140°C.…”

Direct Lactamization of β‐Arylated δ‐Aminopentanoic Acid Carboxamides: En Route to 4‐aryl‐2‐Piperidones, Piperidines, Antituberculosis Molecule Q203 (Telacebec) and its Analogues

“…Of particular interest, Daugulis, [13a] Qin, [15a,b] Bach, [15c] and Babu [15d] have independently reported examples of Pd(II)‐catalyzed, 8‐aminoquinoline‐directed arylation of the β ‐C(sp 3 )−H bonds of various short/medium/long chain‐based amino alkanoic acid derivatives 3 (Scheme 2). In our earlier paper, [15d] we reported some synthetic transformations with the newly assembled β ‐C−H arylated N ‐(quinolin‐8‐yl)butanamides ( 4′ , γ ‐aminobutyric acid derivatives).…”