Microwave‐Assisted Synthesis of Heterocycles by Rhodium(III)‐Catalyzed Annulation of N‐Methoxyamides with α‐Chloroaldehydes

Abstract

α‐Chloroaldehydes have been used as alkyne equivalents in rhodium‐catalyzed syntheses of isoquinolones and 3,4‐dihydroisoquinolins starting from N‐methoxyamides. Compared to the existing technology, a complementary regioselectivity is achieved. Mechanistic investigations have been performed, and it was found that steric effects of both substrate and additive determine the product selectivity. Various other heterocycles, such as isoquinolines and lactones, can be prepared by transformation of the obtained products.

RhIII‐Catalyzed Synthesis of Isoquinolones and 2‐Pyridones by Annulation of N‐Methoxyamides and Nitroalkenes

“…13 C NMR (151 MHz, [D]Chloroform): δ = 157.9, 138.6, 135.9, 132.4, 128.9, 128.8, 128.6, 128.4, 127.7, 127.0, 126.8, 123.7, 115.3, 64.5, 35.6 ppm. Spectral characterization data matches previously reported data for the same compound …”

“…A range of aromatic β‐nitrostyrenes were also effective coupling partners in this reaction, including electron‐neutral ( 3e ), electron‐rich ( 3f ), electron‐poor ( 3g ), and ortho ‐substituted ( 3h ) derivatives. These aryl‐substituted products ( 3e – 3h ) are significant as they have not been prepared with any previously reported C–H functionalization methods, including the recently reported Rh III ‐catalyzed annulation with α‐chloroaldehydes…”

“…In contrast, very few methods are available for the preparation of 4‐monosubstituted isoquinolones . Recently, Bolm reported the Rh III ‐catalyzed synthesis of 4‐substituted isoquinolones using α‐chloroaldehydes (Scheme B.I) . To the best of our knowledge this is the only general method for the selective synthesis of 4‐substituted isoquinolones by C–H functionalization.…”

“…Branched and unbranched aliphatic nitroalkenes were effective inputs for various aromatic and alkenyl N ‐methoxyamide C–H functionalization substrates. Moreover, aromatic nitroalkenes provide isoquinolones with 4‐aryl substitution, a class of substituents that had not been accessed with the α‐chloroaldehyde inputs . Additionally, use of benzoic acid led to the formation of a novel nitro‐dihydroisocoumarin.…”

Reaching Green: Heterocycle Synthesis by Transition Metal‐Catalyzed C−H Functionalization in Sustainable Medium

“…In addition, sulfoximines also participated in the reaction, providing 1,2‐benzothiazines in a green solvent medium. In a similar manner, the annulation reaction of α‐chloroaldehydes 61 with amides afforded isoquinolones 53 d . The reaction offered a complementary regioselectivity from existing annulation reactions with alkynes.…”