Iridium(III) Photocatalysis: A Visible‐Light‐Induced Dearomatizative Tandem [4+2] Cyclization to Furnish Benzindolizidines

Abstract

A photocatalytic dearomatizative tandem [4+2] cyclization between N-(2-iodoethyl)indoles and a variety of alkenes leads to tri- and tetracyclic benzindolizidines with high diastereoselectivity and yield. The intermolecular annulation reaction is performed under visible-light irradiation and employs [Ir(ppy)3] or [Ir(dtbbpy)(ppy)2] PF6 as photocatalysts, in combination with tertiary amines as electron and hydrogen atom donors.

Photoredox‐Induced Radical 6‐exo‐trig Cyclizations onto the Indole Nucleus: Aromative versus Dearomative Pathways

“…Indole substrates 3 bearing C-3 acceptor substituents (R = CO 2 R, COR, CN) efficiently underwent dearomatization under our reaction conditions, and products 5 were obtained with excellent diastereoselectivity. [5] Our results in the tandem (4+2) cyclizations of substrates 3 with alkenes 4 conditions. A combined experimental and computational study revealed that only very subtle structural changes in the substrate-reactant complexes of the key radical intermediates with amine radical cations steer the divergent product selectivities, instead of the usual reactivity parameters such as ionization potentials or partial charges.…”

“…[5] The reductive quench of the electronically excited photocatalyst by the amine generates an amine radical cation 11 and the monoreduced catalyst [PC] -to reduce iodide 3. The resulting primary carbon radical undergoes 1,4-addition with the alkene 4 followed by intramolecular 6-exo-trig ring closure.…”

“…Further, a conceivable single-electron reduction of radical 7b can be ruled out, because the resulting enolates undergo an instantaneous retro-Michael ring-opening, which is not observed under photoredox conditions. [5] The 1 H NMR spectra of crude reaction mixtures from the aromative intramolecular cyclizations of bromomalonate 1a in the presence of triethylamine (Table 1, Entries 2 and 3) showed that 1 equiv. of triethylamine hydrobromide (14a) is formed per cyclization product 2a (Scheme 4).…”

“…The photocatalytic (4+2) cyclization between alkyl iodide 3a and methyl acrylate (4a) to give product 5b was performed as described previously. [5] The cyclization of α-bromo ester 9 according to the above general procedure similarly led to product 5b. The cyclization of substrate 1a gave product 2a, for which the analytical data were reported previously.…”

“…(a) Photoredox-induced intramolecular aromative radical cyclization of bromomalonate-tethered indoles 1 [2] and (b) photoredox intermolecular dearomative (4+2) cyclization between N-(2-iodoethyl)indoles 3 and alkenes 4. [5] Assuming that both annulation pathways involve the generation of an open-chain radical 6, which then undergoes a subsequent intramolecular 6-exo-trig ring closure to form 3-indolyl radical 7 (Scheme 2), and considering that the only structural difference between the two species is the substituent Y, a question arises about why the bromomalonate-derived radical 6a is converted exclusively to aromatic products 2, whereas radical 6b is reduced to products 5 under otherwise similar reaction conditions. Consequently, we set out to investigate the putatively elusive factors governing the divergent product-formation pathways in these reactions.…”