In this paper, we report 4-amino-2,1,3-benzothiadiazole (ABTD) as a new bidentate directing group for the Pd(II)-catalyzed sp/sp C-H activation/functionalization of various aliphatic/alicyclic/aromatic carboxamide systems. The Pd(II)-catalyzed, ABTD-directed sp C-H arylation/acetoxylation of aliphatic- and alicyclic carboxamides afforded the corresponding β-C-H arylated/acetoxylated carboxamides. The Pd(II)-catalyzed, ABTD-directed sp C-H arylation of cyclobutanecarboxamide with different aryl iodides afforded the corresponding bis β-C-H arylated cyclobutanecarboxamides having all-cis stereochemistry with a high degree of stereocontrol. The Pd(II)-catalyzed, ABTD-directed arylation/benzylation/acetoxylation/alkoxylation of ortho C(sp)-H bonds of various benzamides afforded the corresponding ortho C-H arylated/benzylated/oxygenated benzamides. The observed regio- and stereoselectivity in the Pd(II)-catalyzed, ABTD-directed arylation/benzylation of aliphatic/alicyclic carboxamides and benzamides were ascertained from the X-ray structures of representative compounds 5g (bis-β-C(sp)-H arylated cyclobutanecarboxamide) and 7f (ortho C(sp)-H arylated benzamide). A brief description on the efficiency, scope, and limitations of bidentate directing group ABTD is reported.
In this paper, we report the Pd(II)-catalyzed, picolinamide DG-aided sp2 γ-C-H functionalization and expansion of the library of enantiopure α-methylbenzylamine and phenylglycinol scaffolds. We have shown the synthesis of a wide range of racemic and enantiopure ortho-C-H arylated, alkylated, brominated and iodinated α-methylbenzylamine and phenylglycinol scaffolds. Various racemic and R and S (chiral) sp2 γ-C-H functionalized α-methylbenzylamine and phenylglycinol scaffolds were synthesized with good enantiopurities. Racemic and enantiopure α-methylbenzylamine and phenylglycinol derivatives are important building blocks in organic synthesis and medicinal chemistry. Accordingly, this work contributes to the expansion of the libraries of α-methylbenzylamine and phenylglycinol motifs and substrate scope development through the Pd(II)-catalyzed bidentate directing group picolinamide-aided site-selective C-H activation and functionalization method.
We report the Pd(II)‐catalyzed bidentate directing group 8‐aminoquinoline‐aided sp3 γ‐C−H alkylation of 3‐methyl‐ thiophene/furan‐2‐carboxylic acid and 3‐methyl‐ benzothiophene/benzofuran‐2‐carboxylic acid systems. While the 8‐aminoquinoline‐aided sp3 γ‐C−H functionalization including arylation or amidation or amination of carboxylic acid derivatives are well known, however, the Pd(II)‐catalyzed bidentate directing group 8‐aminoquinoline‐aided sp3 γ‐C−H alkylation is not explored. Notably, 2‐ and/or 3‐alkylated thiophene/furan and benzothiophene/benzofuran motifs are found in pharmaceutically active molecules. Accordingly, this work reveals the scope of the 8‐aminoquinoline‐aided sp3 γ‐C−H alkylation method, and its usefulness by enriching the libraries of 3‐alkylated thiophene/furan and benzothiophene/benzofuran motifs.
Expanding the availability, scope, and limitations of directing groups (DGs) for executing the site-selective CÀ 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 sp 2 /sp 3 γ-CÀ H bonds of aromatic carboxamides and sp 3 β-CÀ H bonds of amino acid carboxamides. The performance of the ABTD DG in the arylation of remote γ-CÀ H bonds of carboxamides and sp 3 β-CÀ H bonds of amino acid carboxamides was compared with other known DGs. For example, we have observed that the mono arylation of the methyl sp 3 β-CÀ 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 CÀ H arylation of carboxamides including amino acid derivatives. On the other hand, indirectly the process of ABTD-aided CÀ H arylation reactions has enabled to accomplish the synthesis of a library of 2,1,3-benzothiadiazole moiety containing new carboxamides.
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