Ruthenium-Catalyzed Synthesis of Isoquinolones with 8-Aminoquinoline as a Bidentate Directing Group in C–H Functionalization

Abstract

Ruthenium-catalyzed oxidative annulation of N-quinolin-8-yl-benzamides with alkynes in open air has been achieved using 8-aminoquinolinyl moiety as a bidentate directing group in the presence of Cu(OAc)2·H2O as an oxidant. This reaction offers a broad substrate scope, and both symmetrical and unsymmetrical alkynes can be applied. High regioselectivity was achieved in the case of unsymmetrical (aryl)alkynes. Reaction with heteroaryl amides was also successful in this catalytic process. A ruthenium-N-quinolin-8-yl-benzamide complex was isolated in the absence of alkyne; in the absence of both N-quinolin-8-yl-benzamide and alkyne, in contrast to literature, only the monoacetate complex RuCl(OAc)(p-cymene), but not the bis-acetate complex Ru(OAc)2(p-cymene), was isolated. These data suggest that this reaction may proceed via N,N-bidentate chelate complex. Key products were characterized by X-ray crystallography.

C–H Functionalization of Aromatic Amides

“…In 2014, Allu and Swamy reported the ruthenium‐catalyzed oxidative annulation of aromatic amides with alkynes using 8‐aminoquinoline as directing group (Scheme ) . The reaction is unique in that Cu(OAc) 2 ⋅H 2 O is used here as an oxidant rather than a catalyst.…”

“…In 2014, Allu and Swamy reported the rutheniumcatalyzed oxidative annulation of aromatic amides with alkynes using 8-aminoquinoline as directing group (Scheme 46). [72] Ther eactioni su nique in that Cu(OAc) 2 ·H 2 Oi su sedh ere as an oxidantr ather than ac atalyst. At the same time,t he rhodiumc omplex needstoexchange ligands with Cu(OAc) 2 ·H 2 Otoproduce activity before it exerts ac atalytic role.T he reasonable mechanism is as follows:[ RuCl 2 (p-cymene)] 2 reacts with Cu(OAc) 2 Scheme46.…”

Ruthenium‐Catalyzed Synthesis of Heterocycles via CH Bond Activation

“…In some cases, products with insertion of two alkynes were also isolated. [50]. A similar reaction using 2-pyridinylmethylamine has been explored by using Ni(cod) 2 as catalyst [51].…”

Nickel-Catalyzed C–H Bond Functionalization Utilizing an N,N′-Bidentate Directing Group

“…Instead, an alkyne functioned as the hydrogen acceptor. Later, Pd(II) [25] and Ru(II) were also found to catalyze oxidative cycloaddition of aromatic amides to internal alkynes leading to isoquinolones [26] (for the Ru(II)-catalyzed isoquinolone synthesis utilizing an 8-aminoquinoline directing group, see [27]). However, the use of an inexpensive and abundant metal, such as Ni as the catalyst, is significant.…”