Excited‐State Copper Catalysis for the Synthesis of Heterocycles

Abstract

Heterocycles are one of the largest groups of organic moieties with significant medicinal, chemical, and industrial applications. Herein, we report the discovery and development of visible‐light‐induced, synergistic excited‐state copper catalysis using a combination of Cu(IPr)I as a catalyst and rac‐BINAP as a ligand, which produces more than 10 distinct classes of heterocycles. The reaction tolerates a broad array of functional groups and complex molecular scaffolds, including derivatives of peptides, natural products, and marketed drugs. Preliminary mechanistic investigation suggests in situ generations of [Cu(BINAP)2]+ and [Cu(IPr)2]+ catalysts that work cooperatively under visible‐light irradiation to facilitate catalytic carbo‐aroylation of unactivated alkenes, affording a wide range of useful heterocycles.

Photoactive Copper Complexes: Properties and Applications

“…As a last example that will be described in this section, the Ngai group recently described a general carbo-aroylation of alkenes 192 with aroyl chlorides 193 in presence of [Cu­(IPr)]­I ([Cu­( C 1 )]­I) as copper source and Binap ( PP 41 ) as ligand under blue LED irradiation (Scheme ). Several heterocyclic scaffolds 194 , such as indole derivatives (including indolines, oxindoles, isoquinolines, thiazines, and tetrahydroindolizines) and benzopyrans (including isochromans) to cite a few, could be obtained through this process in good to excellent yields. It is noteworthy that the reaction proceeded regardless of the electron density of aroyl chloride, which was further validated through postfunctionalization of several biologically relevant molecules.…”

One-Metal/Two-Ligand for Dual Activation Tandem Catalysis: Photoinduced Cu-Catalyzed Anti-hydroboration of Alkynes

“… 2 A simpler strategy allowing distinct mechanisms to operate in tandem is to use a single metal in combination with two ligands (ML 1 /L 2 ), each one with a specific role to induce the desired reactivity to the metal. Despite impressive recent accomplishments, 3 the full potential of this concept is yet to be revealed.…”

“… 9 Collins used heteroleptic Cu complexes such as Cu(bphen)(Xantphos)BF 4 as PSs for isomerization of a range of di- and trisubstituted alkenes, including 1,3-enynes. 10 However, the use of these Cu PSs for the modulation of olefin geometry is yet limited to styrene-type alkenes, for which deconjugation of the aromatic unit with the olefin driven by A 1 , 3 interaction ensures directionality. 11 …”

Synthesis of Ketonylated Carbocycles via Excited‐State Copper‐Catalyzed Radical Carbo‐Aroylation of Unactivated Alkenes

“…For example, using ecologically benign and cost‐effective copper complexes (Cu: US$0.512/mol) [11] as photocatalysts as compared to the widely studied ruthenium (Ru: US$2,015/mol) and iridium (Ir: US$30,282/mol) based complexes are attractive due to their diverse role, variable oxidation states (0, +1, +2, +3), flexible ligand environments, and the possibility of inner sphere catalysis. [12‐14] With our continuing interest in exploring synthetic applications of the Umpolung reactivity of acyl radicals and expanding the reaction profile of excited‐state Cu catalysis, [15] we have recently developed a Cu(IPr)I/BINAP [IPr=1,3‐bis(2,6‐diisopropylphenyl)‐1,3‐dihydro‐2 H ‐imidazol‐2‐idene; BINAP=(2,2’‐bis(diphenylphosphino)‐1,1’‐binaphthyl] catalytic system for the synthesis of more than 10 distinct classes of heterocycles under photo‐irradiation conditions [15d] . We questioned whether simple copper (I) catalysts such as CuI in the presence of rac‐ BINAP could be used to generate acyl radicals for the synthesis of the desired carbocycles.…”