ABSTRACT
An efficient and straightforward method has been developed for the synthesis of ß-benzyl-substituted 5-membered heterocyclic carbaldehydes via transient directing-group-enabled direct γ-C(sp3)-H arylation of 3-methylheteroarene-2-carbaldehydes. A wide range of 3-methylheteroarene carbaldehydes undergo coupling with a variety of aryl iodides, including less reactive iodo pyridine derivatives to provide a library of highly selective functionalized products in good to excellent yields. Some of these products have been successfully utilized in synthesizing useful synthetic intermediates.
ABSTRACT
In this paper, we report 4-amino-2,1,3-benzothiadiazole (ABTD) as a new bidentate directing group for the Pd(II)-catalyzed sp2/sp3 C-H activation/functionalization of various aliphatic/alicyclic/aromatic carboxamide systems. The Pd(II)-catalyzed, ABTD-directed sp3 C-H arylation/acetoxylation of aliphatic- and alicyclic carboxamides afforded the corresponding ß-C-H arylated/acetoxylated carboxamides. The Pd(II)-catalyzed, ABTD-directed sp3 C-H arylation of cyclobutanecarboxamide with different aryl iodides afforded the corresponding bis ß-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(sp2)-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-ß-C(sp3)-H arylated cyclobutanecarboxamide) and 7f (ortho C(sp2)-H arylated benzamide). A brief description on the efficiency, scope, and limitations of bidentate directing group ABTD is reported.
