Synthesis of Isoquinolones and Related Derivatives

In 2010, Fagnou and coworkers reported a cascade method for the synthesis of isoquinolones 58 by Rh-catalyzed annulation of Af-methoxybenzamides with internal alkynes [32]. Both symmetrical and unsymmetrical alkynes were examined as the coupling partners (Eq. (5.56)). This external oxidant-free process used a N-O bond to unlock the C-N bond formation and catalyst release. 

At the same time, similar methodology to succeed the catalytic C-H activation of benzamides under oxidative coupUng conditions resulting in isoquinolones was also reported (Eqs. (5.57) and (5.58)). Both Af-alkyl and Af-aryl secondary benzamides could be employed, whereas primary benzamides reacted differently, and two alkyne units were oxidatively incorporated to give tricyclic products such as 60 [33]. 

The reaction was further extended to the annulation of Af-pivaloxybenzamide with terminal alkynes to give 3-substituted isoquinolones 61 with good regioselectivity under mild conditions (Eq. (5.59)) [34]. If alkenes were used, the reaction gave 3,4-dihydroisoquinolones 62 in good yields (Eq. (5.60)) however, both diaryl- and dialkyl-substituted alkenes failed to react under the same reaction conditions. 

At this stage, many authors focused on different routes for the synthesis of hydroisoquinolone derivatives by utilizing Rh-catalyzed C-H activation and 

An interesting Rh(III)-catalyzed intramolecular annulation of alkyne-tethered benzamides to give isoquinolones was recently developed by Park and coworkers [36a]. The reaction might involve intramolecular insertion of the alkyne moiety with rhodacycle II, which leads to intermediate 12 or 12. Then, reductive elimination, followed by oxidative addition of the N-O bond, gives intermediate 

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