Palladium-Catalyzed Selective γ-Monoarylation of Free Amines Containing Symmetric γ-C–H Controlled by a Transient Directing Group

Abstract

We developed a new transient directing group, N-(2-benzoyl-4-chlorophenyl)-1,1,1-trifluoromethanesulfonamide, which can facilitate the γ-monoarylation of free amines containing symmetric γ-C−H bonds. A variety of amines containing symmetric and identical γ-C(sp 3 )−H and γ-C(sp 2 )−H reacted with a diverse range of aryl and heteroaryl iodides to provide γmonoarylated products exclusively. A mines constitute an important and vast class of organic compounds, which range from bioactive compounds to organic functional materials. 1−3 The transition-metal-catalyzed C−H activation and functionalization of amines has been realized successfully by directing-group-based strategies to provide a direct and facile avenue to afford various amine derivatives. 4−6 Despite directing group strategies exhibiting excellent site selectivity in the C−H functionalization of amines, the γ-C−H functionalization of amines containing symmetric γ-C−H bonds cannot generate the desired monofunctionalized products exclusively but predominantly forms a mixture of mono-, di-, and/or trifunctionalized products (Scheme 1a).Previously, directing groups (DGs) were introduced into substrates by covalent bonds to realize reaction selectivity. The groups of Carretero, 7 Balaraman, 8 and Yu 9 have independently developed the C−H arylation and alkynylation of amines using covalent DGs. However, the amine substrates containing symmetric γ-C−H bonds provided a mixture of mono-and difunctionalized products. Apart from these reports, the native amine-directed γand δ-C−H arylation of amines has been reported by the groups of Yao, 10 Bannister, 11 and Jiao, 12 respectively. The amines containing symmetric γ-C−H bonds still yielded a mixture of mono-, di-, and/or triarylated products.Transient directing groups (TDGs) enabled site-selective C−H functionalization of free amines and have attracted great attention because they avoid the additional steps needed for installation and removal of directing groups. Several TDGs have been successfully developed. However, it is still a