Copper(II)‐Catalyzed Three‐Component Cascade Annulation of Diaryliodoniums, Nitriles, and Alkynes: A Regioselective Synthesis of Multiply Substituted Quinolines

Abstract

Three become one: Multiply substituted quinolines were synthesized from diaryliodoniums, alkynes, and nitriles by a CuII‐catalyzed method. This cascade annulation is highly regioselective, step‐economic, flexible with regard to the functional groups, and could potentially be applied to the synthesis of complex molecules.

Diaryliodonium Salts in Organic Syntheses: A Useful Compound Class for Novel Arylation Strategies

“…Rearomatization and deprotonation followed by reductive elimination would provide metasubstituated products (76). Theoretical and experimental studies by DFT calculations suggest that meta-arylated products are formed via a Heck-like four-membered-ring transition state through a Cu(III)-Ph intermediate.…”

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

“…In particular, the arylation–cyclisation reactions promoted by the highly electrophilic Cu(III)–aryl intermediates 3 can allow access to aryl-functionalised carbocyclic and heterocyclic molecules 8 with valuable functionalities [9,29–44]. The mechanistic details of these cascade reactions are not clear as evidenced by the different mechanistic proposals (see, e.g., [18,30,40,44]). These mechanisms suggest the presence and existence of vinyl cation 7 , alkynyl–Cu(III) 5 , or alkenyl–Cu(III) complexes 6 before the C–O bond formation in the ring closing step (see Scheme 1).…”

Diaryliodonium Salts: Aryl Transfer Reagents for Alkyne Difunctionalization

“…[9] A three-component reaction featuring a diaryliodonium salt, an alkyne, and a nitrile was applied to the synthesis of substituted quinolines (Scheme 3b). [10] By tethering the alkyne and nitrile portion, the method could be extended to the construction of tricyclic quinolines (Scheme 3c). [11] In addition, the nitrile moiety could be replaced by a thiocyanate, which was also shown to be a compatible and efficient reaction partner.…”