Palladium-Catalyzed Regioselective C-5 Arylation of Protected l-Histidine: Microwave-Assisted C–H Activation Adjacent to Donor Arm

Abstract

An efficient, microwave-assisted direct C-H arylation at the C-5 position of fully protected L-histidine has been achieved via a palladium-catalyzed transformation reaction. This highly regioselective reaction has been applied to synthesize a series of protected 5-aryl-L-histidines using aryl iodides as coupling partners, in good to excellent yields. The reaction is compatible with substrates possessing electron-donating or electron-withdrawing substituents and offers high reactive functional group tolerance.

Site‐Selective C–H Bond Activation/Functionalization of Alpha‐Amino Acids and Peptide‐Like Derivatives

“…Alternatively, the group of Jain realized the C(sp 2 )–H arylation of N ‐benzyl protected histidine 33 derivatives using a Pd 0 catalysts under microwave conditions (Scheme ) . Different phosphines were screened with Pd(CH 3 CN) 2 as optimal catalysts, resulting PCy 3 the most effective ligand.…”

“…Alternatively, the group of Jain realized the C(sp 2 )-H arylation of N-benzyl protected histidine 33 derivatives using a Pd 0 catalysts under microwave conditions (Scheme 11). [27] Different phosphines were screened with Pd(CH 3 CN) 2 as optimal catalysts, resulting PCy 3 the most effective ligand. Hence, the more nucleophilic C5-position of the pyrazole ring was selectively arylated with various iodoarenes with different steric and elec-Scheme 11.…”

Recent Advances on Amino Acid Modifications via C–H Functionalization and Decarboxylative Functionalization Strategies

“…Here Pd(CH 3 CN) 2 ‐PCy 3 was used as the effective catalytic system. However under heating conditions the protocol did not result in any reaction …”

Homogeneous Catalysis: A Powerful Technology for the Modification of Important Biomolecules

“…The CÀHa rylationo fN ,C-protected histidine 137 under microwavei rradiation conditions was first reported by Mahindra and co-workers. [94] The more-nucleophilic C5-position of AcÀ His(Bn)ÀOMe was selectively arylated with aryl/heteroaryl iodides 138,t hereby affording the products (139)i ng ood yields (Scheme 39). Aryl bromidesa lso gave the desired products, albeit in poor yields (< 18 %).…”