Photoinduced Atom Transfer Radical Addition/Cyclization Reaction between Alkynes or Alkenes with Unsaturated α-Halogenated Carbonyls

Abstract

We have developed a photochemical ATRA/ATRC reaction that is mediated by halogen bonding interactions. This reaction is caused by the reaction of malonic acid ester derivatives containing bromine or iodine with unsaturated compounds such as alkenes and alkynes in the presence of diisopropylethylamine under visible light irradiation. As a result of various control experiments, it was found that the formation of complexes between amines and halogens by halogen-bonding interaction occurs in the reaction system, followed by the cleavage of the carbon–halogen bonds by visible light, resulting in the formation of carbon radicals. In this reaction, a variety of substrates can be used, and the products, cyclopentenes and cyclopentanes, were obtained by intermolecular addition and intramolecular cyclization.

Shining light on halogen-bonding complexes: a catalyst-free activation mode of carbon–halogen bonds for the generation of carbon-centered radicals

“…To extend the synthetic utility of the HB activation of α-bromomalonates, Yamaguchi and Itoh reported also in 2021 a radical cascade cyclization employing α-allyl-α-bromomalonate 162 and styrenes or arylacetylenes as starting materials for the synthesis of functionalized cyclopentanes 163 and cyclopentenes 164 through an atom-transfer radical addition/atom-transfer radical cyclization (ATRA/ATRC) protocol ( Scheme 26 ). 50 In this case a stoichiometric amount of DIPEA was used as the promoter for the generation of the initial radical through the HB-complex formation/PET/fragmentation sequence. Thus, upon photoinduced fragmentation of the HB complex 165 the radical intermediates 166 and 167 are proposed to be formed.…”

Ketyl Radical Enabled Synthesis of Oxetanes

“…It is known that halogen bonding of a Lewis base with a suitably weak carbon-halogen bond can induce bond homolysis under visible-light irradiation. [67][68][69][70][71][72][73][74][75][76][77] With this new mechanistic hypothesis, we evaluated a series of amine additives that can undergo halogen bonding and identified DIPEA as the most suitable, producing oxetane 19 in 70% yield (entries 2-5). Increasing the reaction concentration to 2.0 M further improved the yield to 72% (entry 6).…”

“…Based on literature precedent and our observation that no photocatalyst is needed to promote the ATRA, we propose a halogen bonding radical chain mechanism for formation of the initial ATRA adduct (Scheme 4). [67][68][69][70][71][72][73][74][75][76][77] First, DIPEA (35) and the -oxy iodide (17) form a halogen bonding complex 36. Upon being irradiated with light, carbon-iodine bond homolysis can occur to produce a ketyl radical (38) and a DIPEA-iodine adduct (37).…”

Photochemical Synthesis of Lactones, Cyclopropanes and ATRA Products: Revealing the Role of Sodium Ascorbate**

“…In more detail, Itoh and coworkers reported in 2020 a photochemical ATRA reaction between olefins and carbon tetrabromide via an in‐situ formed halogen‐bonding complex, using 4‐phenyl‐pyridine (Scheme 1, E ) [17a] . A year later, the same research group developed two photoinduced ATRA protocols, where unsaturated compounds (alkenes or alkynes) reacted with halogen‐malonic acid ester derivatives via a visible‐light formed XB‐complex between DIPEA or 4‐phenylpyridine and halogenated products that promoted the cleavage of the carbon‐halogen bonds via visible light, generating carbon radicals (Scheme 1, F and G) [17b,c] . In 2022, Takemoto and Nanjo suggested a photochemical cleavage of C−Br bonds via XB ‐complex formation between a pyridine‐based donor‐acceptor molecule and alkyl bromides [17d] .…”