Rhodium(III)-Catalyzed Isoquinolone Synthesis: The N−O Bond as a Handle for C−N Bond Formation and Catalyst Turnover

Abstract

An external-oxidant-free process to access the isoquinolone motif via cross-coupling/cyclization of benzhydroxamic acid with alkynes is described. The reaction features a regioselective cleavage of a C-H bond on the benzhydroxamic acid coupling partner as well as a regioselective alkyne insertion. Mechanistic studies point out the important involvement of a N-O bond as a tool for C-N bond formation and catalyst turnover.

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

“…A similar transformation was previously reported Scheme 2 Cyclometalation using NiBr 2 Scheme 3 Imidazolium C-H/alkene coupling reaction Fig. 1 Representative substrates applicable to the Ni-catalyzed functionalization of C-H bonds Nickel-Catalyzed C-H Bond Functionalization Utilizing an N,N using Rh(III) as the catalyst [23,24]. However, the reaction does not require the addition of a metal oxidant or an intramolecular sacrificed oxidizing substituent in the substrate, in contrast to the Rh(III) system.…”

Metal‐Catalyzed Annulations through Activation and Cleavage of C−H Bonds

“…Recently the group of Ackermann demonstrated that the reaction can be carried out with a Ru(II) catalyst under mild conditions and using oxygen as sole oxidant. 24c Benzamides can also undergo similar annulation reactions, as has been extensively demonstrated using rhodium, 25 or ruthenium catalysts. 26 These methods provide a step-economic and direct access to isoquinolones starting from readily available benzamides.…”

Rh(III)- and Ir(III)-Catalyzed C–C Bond Cross Couplings from C–H Bonds

“…bearing X-H moieties, a commonly proposed catalytic cycle consists of four fundamental steps: (1) DG-orientated metalation via baseassisted C-H activation, (2) coordination of an alkyne and its consecutive insertion into the C-M bond, (3) oxidative C-X bond forming reductive elimination and release of the reduced catalyst, and (4) oxidative regeneration of the catalyst (Scheme 2). Following such a catalytic scenario, highly valuable scaffolds such as indoles [26], pyrroles [27], isoquinolines [28,29], isoquinolones [30][31][32], pyridinium salts [33], isocoumarins [34], carbazoles [35], indolo [2,1-a] isoquinolines [36], isochromenes [37], pyridones [38,39], pyrones [40], phosphaisocoumarins [41], and indenones [42] could be constructed. Alternatively, if aromatic substrates bearing nonpolar DGs are employed, C-H activation followed by double insertion of an alkyne is observed, hence delivering naphthalene scaffolds (Scheme 2) [19,43,44].…”