Utility of 4-Amino-2,1,3-benzothiadiazole Directing Group in the Pd(II)-catalyzed Arylation of γ-C−H Bonds of Carboxamides and β-C-H Bonds of Amino Acid Carboxamides

Abstract

Expanding the availability, scope, and limitations of directing groups (DGs) for executing the site-selective C−H activation and functionalization and substrate scope development are valuable efforts. This paper reports the scope and extension of the utility of the 4-amino-2,1,3-benzothiadiazole (ABTD) directing group in the Pd(II)-catalyzed arylation of remote sp2/sp3 γ-C−H bonds of aromatic carboxamides and sp3 β-C−H bonds of amino acid carboxamides. The performance of the ABTD DG in the arylation of remote γ-C−H bonds of carboxamides and sp3 β-C−H bonds of amino acid carboxamides was compared with other known DGs. For example, we have observed that the mono arylation of the methyl sp3 β-C−H bonds of alanine carboxamide possessing the ABTD DG with iodopyridine yielded the pyridylalanine derivative. Conversely, the same reaction using 8-AQ DG did not yield the expected pyridylalanine derivative. Furthermore, 2,1,3-benzothiadiazole moiety-containing compounds are an important class of molecules in materials chemistry and medicinally relevant molecules. While this work reveals the utility of ABTD as the DG in the Pd(II)-catalyzed C−H arylation of carboxamides including amino acid derivatives. On the other hand, indirectly the process of ABTD-aided C−H arylation reactions has enabled to accomplish the synthesis of a library of 2,1,3-benzothiadiazole moiety containing new carboxamides.