Palladium(II)‐Catalyzed Sp3/Sp2γ‐ and δ‐C‐H Functionalization of Aryl Amines using 5‐Methylisoxazole‐3‐Carboxamide as Directing Group

Abstract

A dual objective‐based study comprising exploration of 5‐methylisoxazole‐3‐carboxamide (MICA) as a directing group (DG) for the Pd(II)‐catalyzed sp3/sp2 γ‐ and δ‐C−H activation/functionalization of aryl amines and assembling of various MICA motifs are reported. The Pd(II)‐catalyzed MICA‐aided γ‐C(sp3)‐H arylation/acetoxylation of ortho‐toluidines gave various 2‐aminodiphenylmethanes and 2‐aminobenzyl acetates, respectively. The Pd(II)‐catalyzed MICA‐aided γ‐C(sp2)‐H arylation/acetoxylation of benzylamines gave the corresponding arylated/acetoxylated products. Furthermore, the Pd(II)‐catalyzed MICA‐aided δ‐C(sp2)‐H amidation/alkenylation of phenethylamines were also explored. Representative control reactions were done to assess the relative effectiveness of MICA for the γ‐C(sp3)‐H arylation and MICA is a removable DG. Apart from the usage of MICA as a DG for the sp2/sp3 C−H functionalization of aryl amines, indirectly this process has led to the construction of a library of MICA motifs. This is an added advantage to note as the MICA‐based motifs are valuable small molecules in medicinal chemistry.