Synthesis of Isoquinolines via Rhodium(III)‐Catalyzed Dehydrative CC and CN Coupling between Oximines and Alkynes

Abstract

Isoquinolines have been synthesized from the redox-neutral dehydrative C À N and C À C crosscoupling between oximines and alkynes using a catalytic amount of (pentamethylcyclopentadiene)rhodium dichloride dimer {[RhCp*Cl 2 ] 2 } and cesium acetate (CsOAc), a process that involves ortho C À H activation of oximines and subsequent functionalization with alkynes. This redox-neutral catalytic isoquinoline synthesis operates under mild conditions, and is insensitive to moisture or air. A broad scope of coupling partners has been established, and a likely mechanism has been suggested.

A Coupling of Benzamides and Donor/Acceptor Diazo Compounds To Form γ-Lactams via Rh(III)-Catalyzed C–H Activation

“…1 This concept has been extensively explored in the Rh(III) catalyzed synthesis of nitrogen containing heterocycles mediated by C–H activation. 2 A wide swath of unsaturated heterocycles can be accessed though coupling amides, amines, oximes, and anilines with alkynes to access isoquinolones, 3 pyridones, 3d,4 isoquinolines, 5 pyridines, 5g,6 indoles, 7 and pyrroles. 7b,8 …”

Facile Rh(III)-Catalyzed Synthesis of Fluorinated Pyridines

“…16-17 However, we found that the nucleophilic alcoholic solvents utilized in their protocols, MeOH or 2,2,2-trifluoroethanol (TFE), posed a problem for the construction of fluorinated analogues due to alcohol displacement of the fluorine under the basic reaction conditions (Table 1, entries 1–2). To avoid fluoride displacement we examined a range of nonhydroxylic solvents, and while most proved to be ineffective (see Table S1 in the SI), ethyl acetate resulted in complete conversion to fluoropyridine 3a with minimal byproduct formation as determined by 19 F NMR (entry 3).…”

An efficient synthesis of isoquinolines via rhodium-catalyzed direct C–H functionalization of arylhydrazines

“…In 2010, Chiba described a rhodium-catalyzed synthesis of isoquinolines from ketone Oacyloximes and internal alkynes with the use of NaOAc as an effective additive and an external co-oxidant was not needed. 7 Later, Li reported the use of oxime as directing group and CsOAc as the additive also leading to the rapid formation of isoquniolines. 7 The oximes have been thought as oxidizing-directing groups during the rhodium-catalyzed procedures.…”

“…7 Later, Li reported the use of oxime as directing group and CsOAc as the additive also leading to the rapid formation of isoquniolines. 7 The oximes have been thought as oxidizing-directing groups during the rhodium-catalyzed procedures. By replacing the rhodium catalysts with ruthenium complexes, Jeganmohan 8 and Ackermann 9 independently realized the synthesis of isoquinolines synthesize isoquinolines.…”