Copper Catalyzed Atom Transfer Radical Cyclization Reactions

Abstract

Atom transfer radical cyclization (ATRC) is a powerful technique to prepare functionalized 4–10 membered ring systems using transition metal catalysts. In this review recent advances in the use of copper complexes are described. In particular the effect of different ligands on reactivity, selectivity and product outcome are illustrated with application to heterocycle and natural product synthesis. New approaches that increase catalyst efficiency with supplemental reducing agents are reviewed and examples using green solvents, benign reducing agents (e.g. ascorbic acid) and with catalyst loadings as low as 0.05 mol‐% are highlighted. Radical addition to aromatic rings and rearrangement reactions under ATRC conditions as well as application to radical‐polar crossover reactions are also described.

β,β,β‐Trichloroethyl‐NH‐Enamine as Viable System for 5‐Endo‐trig Radical Cyclization via Multifaceted CuI−CuII Redox Catalysis: Single Step Synthesis of Multi‐Functionalized NH‐Pyrroles

“…First, a very high geometrical constraint in the occurrence of 5‐endo radical cyclization step of enamine 20 a necessitates a continuous regeneration of active Cu(I)‐catalyst by continuous supply of IBN radicals. Second, the Cu(I)‐catalyst performs the radical generation in enamine 20 a and the double dehydrohalogenation reactions in the 5‐ endo‐trig product (pyrrolidine intermediate) to give an aromatic product (Scheme ) while undergoing HCl‐catalyst‐deactivation –…”

“…Over the years, Copper(I)‐catalyzed halogen atom transfer radical cyclization (HATRC) of unsaturated polyhalomethyl substrates has emerged as a mild, catalytic, cost‐effective and high yielding strategy to synthesize various heterocycles with wider substrate scope, 100% atom efficiency and functional group tolerance including halogens . AIBN and ascorbic acid (ARGET), and platinum electrode surface (eATRC) regenerate an active Cu(I)‐catalyst by reducing a Cu(II)‐complex to decrease the catalyst loading drastically even below 1 mol % –. However, there is a scarcity of radical cyclization approaches to access an aromatic ring in single step .…”

“…Aza‐Michael addition of 1‐phenyl‐2,2,2‐trichloroethyl amine 19 a to dimethyl acetylenedicarboxylate(DMAD) afforded dimethyl 2‐(2,2,2‐trichloro‐1‐phenyl‐ethylamino)fumerate 20 a as the representative precursor. The reactions of enamine 20 a were performed with redox active CuCl‐ and CuCl 2 ‐[complexes with 2,2′‐bipyridine (bpy), tetramethylethylenediamine (TMEDA), pentamethyldiethylenetriamine (PMDETA) and tris(2‐pyridylmethyl)amine (TPMA) ligands–], Ni(OAc) 3 , Mn/AcOH, and reductive n Bu 3 SnH/AIBN radical initiators using various solvents and additives under a nitrogen atmosphere (Table ) to explore the suitable catalytic system.…”

Auto‐Tandem Catalysis: Activation of Multiple, Mechanistically Distinct Process by a Single Catalyst

“…Asymmetric allylic substituted of allylchlorides 30 by α‐haloamides 31 catalysed by the planar‐chiral ruthenium complex 34 gave allylamides 32 . Atom transfer radical cyclisation catalysed by the same ruthenium complex afforded anti ‐substituted γ‐lactams 33 in good yields and ee's.…”

Combination of a Cyano Migration Strategy and Alkene Difunctionalization: The Elusive Selective Azidocyanation of Unactivated Olefins

“…[1] Relying on the recent advances in chemo-and regio-selective radical reactions,t he radical-mediated difunctionalization of alkenes has made great progress. [2] Mechanistically,t his type of reactions is initiated by the free-radical addition to an olefin moiety and the generation of the C-centered radical intermediate.The Ccentered radical can be subsequently coupled with an extrinsic radical donor (Scheme 1A)o rf urther single-electron oxidized to carbonium and trapped by an ucleophile (Scheme 1B). In both cases,the reaction feasibility is largely dependent on the stability of the in situ formed radical or cation intermediate.Inthis scenario,activated alkenes such as aryl, carbonyl, and heteroatom-substituted alkenes become favorable substrates for alkene difunctionalization because of the p-p conjugate effect, which thus stabilizes the nascent radical intermediate.…”